These Highlights Do Not Include All The Information Needed To Use Hydrocodone Bitartrate And Homatropine Methylbromide Safely And Effectively. See Full Prescribing Information For Hydrocodone Bitartrate And Homatropine Methylbromide.

Limitations of Use:

• Not indicated for pediatric patients under 18 years of age [see Use in Specific Populations (8.4)].
• Contraindicated in pediatric patients less than 6 years of age [see Contraindications (4)].
• Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses [see Warnings and Precautions (5.1)], reserve hydrocodone bitartrate and homatropine methylbromide for use in adult patients for whom the benefits of cough suppression are expected to outweigh the risks, and in whom an adequate assessment of the etiology of the cough has been made.

Store tablets at controlled room temperature 20°C to 25°C (68°F to 77°F) [See USP Controlled Room Temperature]. Dispense in a tight, light-resistant container, as defined in the USP, with a child-resistant closure.

Hydrocodone bitartrate and homatropine methylbromide is available as a clear red-colored, cherry-flavored oral solution in:

•  
  NDC 64950-371-05: Unit Dose Cup of 5 mL
•  
  NDC 64950-371-45: Case contains 40 unit dose cups of 5 mL (NDC 64950-371-05), packaged in 4 trays of 10 unit dose cups each
•  
  NDC 64950-371-47: Bottle of 473 mL

Store oral solution at controlled room temperature 20°C to 25°C (68°F to 77°F). [See USP Controlled Room Temperature.]

Dispense in a tight, light-resistant container, as defined in the USP, with a child-resistant closure.

Ensure that patients have an oral dosing dispenser that measures the appropriate volume in milliliters.

Counsel patients on how to utilize an oral dosing dispenser and correctly measure the oral suspension as prescribed.

Concomitant use of alcohol with hydrocodone bitartrate and homatropine methylbromide can result in an increase of hydrocodone plasma levels and potentially fatal overdose of hydrocodone. Instruct patients not to consume alcoholic beverages or use prescription or nonprescription products containing alcohol while on hydrocodone bitartrate and homatropine methylbromide therapy [see Warnings and Precautions (5.8), Clinical Pharmacology (12.3)].

Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed.

Hydrocodone bitartrate and homatropine methylbromide tablets and oral solution contain hydrocodone, an opioid agonist; and homatropine, a muscarinic antagonist.

Each tablet or spoonful (5 mL) of hydrocodone bitartrate and homatropine methylbromide oral solution contains 5 mg of hydrocodone bitartrate, USP and 1.5 mg of homatropine methylbromide, USP, for oral administration.

Hydrocodone bitartrate and homatropine methylbromide tablets also contain: calcium phosphate dibasic, colloidal silicon dioxide, lactose, magnesium stearate, pregelatinized starch and stearic acid.

Hydrocodone bitartrate and homatropine methylbromide oral solution also contains: anhydrous citric acid, FD&C Red 40, methylparaben, natural and artificial cherry flavor, propylparaben, purified water, sorbitol solution, sodium citrate dihydrate and sucrose.

Psychological dependence, physical dependence, and tolerance may develop upon repeated administration of opioids; therefore, hydrocodone bitartrate and homatropine methylbromide should be prescribed and administered for the shortest duration that is consistent with individual patient treatment goals and patients should be reevaluated prior to refills [see Dosage and Administration (2.3), Warnings and Precautions (5.1)].

Physical dependence, the condition in which continued administration of the drug is required to prevent the appearance of a withdrawal syndrome, assumes clinically significant proportions only after several weeks of continued oral opioid use, although some mild degree of physical dependence may develope after a few days of opioid therapy.

If hydrocodone bitartrate and homatropine methylbromide is abruptly discontinued in a physically-dependent patient, a withdrawal syndrome may occur. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). Some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis.

Other signs and symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate.

Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see Use in Specific Populations (8.1)].

Hydrocodone bitartrate and homatropine methylbromide tablets and oral solution, for oral use

(HIGH-droe-KOE-dohn by-TAR-trate and hoe-MAT-troe-peen METH-ill-BROE-mide)

CII

What is the most important information I should know about Hydrocodone Bitartrate and Homatropine Methylbromide?

Hydrocodone bitartrate and homatropine methylbromide is not for children under 18 years of age.

Hydrocodone bitartrate and homatropine methylbromide can cause serious side effects, including:

• Addiction, abuse and misuse. Taking hydrocodone bitartrate and homatropine methylbromide or other medicines that contain an opioid can cause addiction abuse, and misuse, which can lead to overdose and death. This can happen even if you take hydrocodone bitartrate and homatropine methylbromide exactly as prescribed by your healthcare provider. Your risk of addiction, abuse, and misuse is increased if you or a family member has a history of drug or alcohol abuse or addiction, or mental health problems.
  • Do not share your hydrocodone bitartrate and homatropine methylbromide with other people.
  • Keep hydrocodone bitartrate and homatropine methylbromide in a safe place away from children.
• Life-threatening breathing problems (respiratory depression). Hydrocodone bitartrate and homatropine methylbromide can cause breathing problems (respiratory depression) that can happen at any time during treatment and can lead to death. Your risk of breathing problems is greatest when you first start taking hydrocodone bitartrate and homatropine methylbromide, are taking other medicines that can cause breathing problems, have certain lung problems, are elderly, or have certain other health problems. Children are at higher risk for respiratory depression. Breathing problems can happen even if you take hydrocodone bitartrate and homatropine methylbromide exactly as prescribed by your healthcare provider.

Call your healthcare provider or get emergency medical help right away if anyone taking hydrocodone bitartrate and homatropine methylbromide has any of the symptoms below:

Keep hydrocodone bitartrate and homatropine methylbromide in a safe place away from children. Accidental use of even 1dose of hydrocodone bitartrate and homatropine methylbromide, especially by a child, is a medical emergency and can cause breathing problems (respiratory depression) which can lead to death. If a child accidentally takes hydrocodone bitartrate and homatropine methylbromide, get emergency medical help right away.

• Overdose and death due to medicine dosing errors. Overdose and death can happen if you measure the wrong dose of hydrocodone bitartrate and homatropine methylbromide. Always use an accurate milliliter (mL) measuring device to measure the correct amount of hydrocodone bitartrate and homatropine methylbromide oral solution. Do not use a household teaspoon to measure your medicine. You may accidentally take too much. You can ask your pharmacist for the measuring device you should use and how to measure the correct dose.
• Breathing problems (respiratory depression) that can lead to death and opioid withdrawal can happen if you start taking or stop taking other medicines while taking hydrocodone bitartrate and homatropine methylbromide, including:
  • certain antibiotics
  • certain medicines to treat a fungal infection
  • certain medicines to treat Human Immunodeficiency Virus (HIV)-1 infection, Acquired Immune Deficiency Syndrome (AIDS), or Hepatitis C
  • rifampin
  • carbamazepine
  • phenytoin

Tell your healthcare provider if you take any of these medicines. Ask your healthcare provider or pharmacist if you are not sure if your medicine is listed above.

• Severe drowsiness, breathing problems (respiratory depression), coma, and death can happen in people who take hydrocodone bitartrate and homatropine methylbromide with benzodiazepines or other central nervous system depressants, including alcohol.
  • Do not take benzodiazepines or any medicine that can cause drowsiness or sleepiness during treatment with hydrocodone bitartrate and homatropine methylbromide.
  • Do not drink alcohol or take prescription or over-the-counter medicines that contain alcohol during treatment with hydrocodone bitartrate and homatropine methylbromide.
• Opioid withdrawal in a newborn. Use of hydrocodone bitartrate and homatropine methylbromide during pregnancy can cause withdrawal symptoms in your newborn baby that could be life-threatening if not recognized and treated. You should not take hydrocodone bitartrate and homatropine methylbromide if you are pregnant. Tell your health care provider right away if you are pregnant or think you may be pregnant.

What is hydrocodone bitartrate and homatropine methylbromide?

• Hydrocodone bitartrate and homatropine methylbromide is a prescription medicine used in adults 18 years of age and older to treat a cough. Hydrocodone bitartrate and homatropine methylbromide contains hydrocodone, an opioid (narcotic) cough suppressant.
• Hydrocodone bitartrate and homatropine methylbromide is a federal controlled substance (C-II) because it contains hydrocodone that can be abused or lead to dependence. Keep hydrocodone bitartrate and homatropine methylbromide in a safe place to prevent misuse and abuse. Selling or giving away hydrocodone bitartrate and homatropine methylbromide may harm others, and is against the law. Tell your healthcare provider if you have ever abused or been dependent on alcohol, prescription medicines or street drugs.

Who should not take hydrocodone bitartrate and homatropine methylbromide?

Hydrocodone bitartrate and homatropine methylbromide is not for children under 18 years of age. See "What is the most important information I should know about hydrocodone bitartrate and homatropine methylbromide?"

Do not take hydrocodone bitartrate and homatropine methylbromide if you:

• have severe breathing problems (respiratory depression) or breathing problems caused by asthma. See "What is the most important information I should know about hydrocodone bitartrate and homatropine methylbromide?"
• have a blockage (obstruction) in your bowel such as a paralytic ileus.
• are allergic to hydrocodone, homatropine, or any of the ingredients in hydrocodone bitartrate and homatropine methylbromide. See the end of this Medication Guide for a complete list of ingredients in hydrocodone bitartrate and homatropine methylbromide.

Ask your healthcare provider if you have any questions about this information.

Before you take hydrocodone bitartrate and homatropine methylbromide, tell your healthcare provider about all of your medical conditions, including if you:

• are pregnant or plan to become pregnant. Hydrocodone bitartrate and homatropine methylbromide can harm your unborn baby. See "What is the most important information I should know about hydrocodone bitartrate and homatropine methylbromide?"
• are breastfeeding or plan to breastfeed. Hydrocodone passes into your breast milk and can cause serious side effects in your baby including increased sleepiness, breathing problems (respiratory depression), and death. You and your healthcare provider should decide if you will take hydrocodone bitartrate and homatropine methylbromide or breastfeed. You should not do both. See "What should I avoid while taking hydrocodone bitartrate and homatropine methylbromide?"
• plan to have children. Hydrocodone bitartrate and homatropine methylbromide may affect the ability to have a child in females and males (fertility problems). It is not known if these fertility problems will be reversible, even after you stop taking hydrocodone bitartrate and homatropine methylbromide. Talk to your healthcare provider if this is a concern for you.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Taking hydrocodone bitartrate and homatropine methylbromide with certain other medicines can cause side effects or affect how well hydrocodone bitartrate and homatropine methylbromide or the other medicines work.

Do not start or stop taking other medicines without talking to your healthcare provider.

Especially tell your healthcare provider if you:

• take pain medicines such as opioids (narcotics).
• take cold or allergy medicines that contain antihistamines or cough suppressants.
• drink alcohol.
• take muscle relaxants.
• take certain medicines used to treat mood, anxiety, psychotic or thought disorders, or depression, including monoamine oxidase inhibitors (MAOIs), tricyclics, selective serotonin reuptake inhibitors (SSRIs), selective serotonin-norepinephrine reuptake inhibitors (SNRIs), or antipsychotics.
• take medicines to lower your blood pressure.
• take water pills (diuretics).
• take medicines called "anticholinergics" used to treat certain health problems including asthma, chronic obstructive pulmonary disease (COPD), or stomach problems.

Ask your healthcare provider if you are not sure if you take one of these medicines.

How should I take hydrocodone bitartrate and homatropine methylbromide?

• See "What is the most important information I should know about hydrocodone bitartrate and homatropine methylbromide?"
• Take hydrocodone bitartrate and homatropine methylbromide exactly as your healthcare provider tells you to take it. Do not change your dose without talking to your health care provider.
• Take hydrocodone bitartrate and homatropine methylbromide by mouth only.
• Take hydrocodone bitartrate and homatropine methylbromide oral solution using an accurate milliliter (mL) measuring device. If you do not have one, ask your pharmacist to give you a measuring device to help you measure the correct amount of hydrocodone bitartrate and homatropine methylbromide oral solution. Do not use a household teaspoon to measure your medicine. You may accidently take too much.
• Do not overfill the measuring device.
• Rinse the measuring device with water after each use.
• If you take too much hydrocodone bitartrate and homatropine methylbromide, call your healthcare provider or go to the nearest hospital emergency room right away.
• Tell your healthcare provider if your cough does not get better within 5 days of treatment with hydrocodone bitartrate and homatropine methylbromide.

What should I avoid while taking hydrocodone bitartrate and homatropine methylbromide?

• Avoid driving a car or operating machinery during treatment with hydrocodone bitartrate and homatropine methylbromide. Hydrocodone bitartrate and homatropine methylbromide can cause you to be drowsy, slow your thinking and motor skills, and affect your vision.
• Do not drink alcohol during treatment with hydrocodone bitartrate and homatropine methylbromide. Drinking alcohol can increase your chances of having serious side effects.

Avoid the use of hydrocodone bitartrate and homatropine methylbromide if you:

• are pregnant. Use of hydrocodone bitartrate and homatropine methylbromide during pregnancy can cause withdrawal symptoms in your newborn baby that could be life-threatening if not recognized and treated. Tell your healthcare provider right away if you are pregnant or think you may be pregnant.
• are breastfeeding. Use of hydrocodone bitartrate and homatropine methylbromide while breastfeeding can cause severe breathing problems (respiratory depression) in your breastfed infant that could be life-threatening.
• take a medicine called a monoamine oxidase inhibitor (MAOI). Avoid taking an MAOI within 14 days after you stop taking hydrocodone bitartrate and homatropine methylbromide. Avoid starting hydrocodone bitartrate and homatropine methylbromide if you stopped taking an MAOI in the last 14 days.

What are the possible side effects of hydrocodone bitartrate and homatropine methylbromide?

Hydrocodone bitartrate and homatropine methylbromide can cause serious side effects, including:

• See "What is the most important information I should know about hydrocodone bitartrate and homatropine methylbromide"
• Bowel problems including severe constipation or stomach pain. See "Who should not take hydrocodone bitartrate and homatropine methylbromide?"
• Increased pressure in your head (intracranial). Avoid the use of hydrocodone bitartrate and homatropine methylbromide if you have a head injury or have been told that you have changes in the tissue of your brain (brain lesions) or increased pressure in your head.
• Increased risk of seizures in people with seizure disorders. If you have a seizure disorder, hydrocodone bitartrate and homatropine methylbromide may increase how often you have a seizure.
• Low blood pressure. A sudden drop in blood pressure can happen in some people during treatment with hydrocodone bitartrate and homatropine methylbromide and this may cause you to feel dizzy, faint, lightheaded, or weak, especially when you stand up (orthostatic hypotension). Your risk of having this problem may be increased if you take hydrocodone bitartrate and homatropine methylbromide with certain other medicines that lower blood pressure. If you have any of these symptoms while taking hydrocodone bitartrate and homatropine methylbromide, sit or lie down. Do not change your body position too fast. Get up slowly from sitting or lying down.
• Adrenal gland problems. Hydrocodone bitartrate and homatropine methylbromide can cause serious and life-threatening adrenal gland problems. Your healthcare provider may do blood tests to check for adrenal gland problems. Call your healthcare provider right away if you have any of these symptoms:

The most common side effects of hydrocodone bitartrate and homatropine methylbromide include:

These are not all the possible side effects of hydrocodone bitartrate and homatropine methylbromide.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store hydrocodone bitartrate and homatropine methylbromide?

• Store hydrocodone bitartrate and homatropine methylbromide at room temperature between 68°F to 77°F (20°C to 25°C).
• Store hydrocodone bitartrate and homatropine methylbromide tablets in a tightly closed container, in a dry, cool place away from heat or direct sunlight.
• Keep hydrocodone bitartrate and homatropine methylbromide and all medicines out of the reach of children.

How should I dispose of hydrocodone bitartrate and homatropine methylbromide?

Remove unused hydrocodone bitartrate and homatropine methylbromide from the container and mix it with an undesirable, non-toxic substance such as cat litter or used coffee grounds to make it less appealing to children and pets. Place the mixture in a container such as a sealed plastic bag and throw it away in the household trash. You can also follow your state or local guidelines on how to safely throw away hydrocodone bitartrate and homatropine methylbromide.

General information about the safe and effective use of hydrocodone bitartrate and homatropine methylbromide.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use hydrocodone bitartrate and homatropine methylbromide for a condiition for which it was not prescribed. Do not give hydrocodone bitartrate and homatropine methylbromide to other people, even if they have the same symptoms that you have. It may harm them.

You can ask your pharmacist or healthcare provider for information about hydrocodone bitartrate and homatropine methylbromide that is written for health professionals.

What are the ingredients in hydrocodone bitartrate and homatropine methylbromide?

Active ingredients: hydrocodone bitartrate and homatropine methylbromide

Inactive ingredients in hydrocodone bitartrate and homatropine methylbromide tablets: calcium phosphate dibasic, colloidal silicon dioxide, lactose, magnesium stearate, pregelatinized starch and stearic acid.

Inactive ingredients in hydrocodone bitartrate and homatropine methylbromide oral solution: anhydrous citric acid, FD&C Red 40, methylparaben, natural and artificial cherry flavor, propylparaben, purified water, sorbitol solution, sodium citrate dihydrate and sucrose.

Manufactured by: Genus Lifesciences Inc., Allentown, PA 18102

For more information, go to www.genuslifesciences.com or call 1-866-511-6754.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Revised: 06/2022

Hydrocodone bitartrate and homatropine methylbromide is contraindicated in pediatric patients younger than 6 years of age because of life-threatening respiratory depression and death have occurred in pediatric patients who received hydrocodone [see Contraindications (4), Warnings and Precautions (5.2)].

The safety and effectiveness of hydrocodone bitartrate and homatropine methylbromide has not been established in patients younger than 18 years of age. Hydrocodone bitartrate and homatropine methylbromide is not recommended for use in patients younger than 18 years of age because the benefits of symptomatic treatment of cough associated with allergies or the common cold do not outweigh the risks for use of hydrocodone in these patients [see Indications (1), Warnings and Precautions (5.3)].

Clinical studies have not been conducted with hydrocodone bitartrate and homatropine methylbromide in geriatric populations.

Use caution when considering the use of hydrocodone bitartrate and homatropine methylbromide in patients 65 years of age or older. Elderly patients may have increased sensitivity to hydrocodone; greater frequency of decreased hepatic, renal, or cardiac function; or concomitant disease or other drug therapy [see Warnings and Precautions (5.4)].

Respiratory depression is the chief risk for elderly patients treated with opioids, including hydrocodone bitartrate and homatropine methylbromide. Respiratory depression has occurred after large initial doses of opioids were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration [see Warnings and Precautions (5.4, 5.8)].

Hydrocodone is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, monitor these patients closely for respiratory depression, sedation, and hypotension.

Hydrocodone bitartrate and homatropine methylbromide is contraindicated for:

• All pediatric patients younger than 6 years of age [see Warnings and Precautions (5.2, 5.3), Use in Specific Populations (8.4)].
• Significant respiratory depression [see Warnings and Precautions (5.2)].
• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions (5.4)].
• Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.9)].
• Hypersensitivity to hydrocodone, homatropine, or any of the inactive ingredients in hydrocodone bitartrate and homatropine methylbromide [see Adverse Reactions (6)].

The following clinically significant adverse reactions are described elsewhere in labeling:

• Addiction, abuse, and misuse [see Warnings and Precautions (5.1), Drug Abuse and Dependence (9.3)]
• Life-threatening respiratory depression [see Warnings and Precautions (5.2, 5.3, 5.4, 5.8), Overdosage (10)]
• Accidental overdose and death due to medication errors [see Warnings and Precautions (5.5)]
• Decreased mental alertness with impaired mental and/or physical abilities [see Warnings and Precautions (5.6)]
• Interactions with benzodiazepines and other CNS depressants [see Warnings and Precautions (5.8), Drug Interactions (7.1, 7.4)]
• Paralytic ileus, gastrointestinal adverse reactions [see Warnings and Precautions (5.9)]
• Increased intracranial pressure [see Warnings and Precautions (5.10)].
• Obscured clinical course in patients with head injuries [see Warnings and Precautions (5.10)]
• Seizures [see Warnings and Precautions (5.11)]
• Severe hypotension [see Warnings and Precautions (5.12)]
• Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.13)]
• Adrenal insufficiency [see Warnings and Precautions (5.14)]

The following adverse reactions have been identified during clinical studies, in the literature, or during post-approval use of hydrocodone and/or homatropine. Because these reactions may be reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The most common adverse reactions to hydrocodone bitartrate and homatropine methylbromide include: Sedation (somnolence, mental clouding, lethargy), impaired mental and physical performance, lightheadedness, dizziness, headache, dry mouth, nausea, vomiting, and constipation.

Other reactions include:

Anaphylaxis: Anaphylaxis has been reported with hydrocodone, one of the ingredients in hydrocodone bitartrate and homatropine methylbromide.

Body as a whole: Coma, death, fatigue, falling injuries, lethargy.

Cardiovascular: Peripheral edema, increased blood pressure, decreased blood pressure, tachycardia, chest pain, palpitation, syncope, orthostatic hypotension, prolonged QT interval, hot flush.

Central Nervous System: Facial dyskinesia, insomnia, migraine, increased intracranial pressure, seizure, tremor.

Dermatologic: Flushing, hyperhidrosis, pruritus, rash.

Endocrine/Metabolic: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs. Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Cases of androgen deficiency have occurred with chronic use of opioids.

Gastrointestinal: Abdominal pain, bowel obstruction, decreased appetite, diarrhea, difficulty swallowing, dry mouth, GERD, indigestion, pancreatitis, paralytic ileus, biliary tract spasm (spasm of the sphincter of Oddi).

Genitourinary: Urinary tract infection, ureteral spasm, spasm of vesicle sphincters, urinary retention.

Laboratory: Increases in serum amylase.

Musculoskeletal: Arthralgia, backache, muscle spasm.

Ophthalmic: Miosis (constricted pupils), visual disturbances.

Psychiatric: Agitation, anxiety, confusion, fear, dysphoria, depression.

Reproductive: Hypogonadism, infertility.

Respiratory: Bronchitis, cough, dyspnea, nasal congestion, nasopharyngitis, respiratory depression, sinusitis, upper respiratory tract infection.

Other: Drug abuse, drug dependence, opioid withdrawal syndrome.

No specific drug interaction studies have been conducted with hydrocodone bitartrate and homatropine methylbromide.

The concomitant use of hydrocodone bitartrate and homatropine methylbromide and CYP3A4 inducers such as rifampin, carbamazepine, or phenytoin, can decrease the plasma concentration of hydrocodone [see Clinical Pharmacology (12.3)], resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to hydrocodone [see Warnings and Precautions (5.7)]. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the hydrocodone plasma concentration will increase [see Clinical Pharmacology (12.3)], which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression.

Avoid the use of hydrocodone bitartrate and homatropine methylbromide in patients who are taking CYP3A4 inducers. If concomitant use of a CYP3A4 inducer is necessary, follow the patient for reduced efficacy.

Hydrocodone may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. Avoid the use of hydrocodone bitartrate and homatropine methylbromide in patients taking muscle relaxants. If concomitant use is necessary, monitor patients for signs of respiratory depression that may be greater than otherwise expected.

The pharmacokinetics of hydrocodone bitartrate and homatropine methylbromide has not been characterized in patients with renal impairment. Patients with renal impairment may have higher plasma concentrations than those with normal function [see Clinical Pharmacology (12.3)]. Hydrocodone bitartrate and homatropine methylbromide should be used with caution in patients with severe impairment of renal function, and patients should be monitored closely for respiratory depression, sedation, and hypotension.

Adults 18 years of age and older: One (1) tablet or 5 mL of the oral solution every 4 to 6 hours as needed; not to exceed six (6) tablets or 30 mL in 24 hours.

The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation. Discontinue hydrocodone bitartrate and homatropine methylbromide if serotonin syndrome is suspected.

The pharmacokinetics of hydrocodone bitartrate and homatropine methylbromide has not been characterized in patients with hepatic impairment. Patients with severe hepatic impairment may have higher plasma concentrations than those with normal hepatic function [see Clinical Pharmacology (12.3)]. Therefore, hydrocodone bitartrate and homatropine methylbromide should be used with caution in patients with severe impairment of hepatic function, and patients should be monitored closely for respiratory depression, sedation, and hypotension.

Hydrocodone bitartrate and homatropine methylbromide is indicated for the symptomatic relief of cough in adult patients 18 years of age and older.

Hydrocodone bitartrate and homatropine methylbromide may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) [see Drug Interactions (7.4)]. Monitor these patients for signs of hypotension after initiating hydrocodone bitartrate and homatropine methylbromide.

In patients with circulatory shock, hydrocodone bitartrate and homatropine methylbromide may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of hydrocodone bitartrate and homatropine methylbromide in patients with circulatory shock.

Hydrocodone bitartrate and homatropine methylbromide contains hydrocodone, a Schedule II controlled substance.

The concomitant use of anticholinergic drugs with hydrocodone bitartrate and homatropine methylbromide may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus [see Warnings and Precautions (5.9)]. Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone bitartrate and homatropine methylbromide is used concomitantly with anticholinergic drugs.

• Life-threatening respiratory depression in patients with chronic pulmonary disease or in elderly, cachectic, or debilitated patients: Monitor closely, particularly during initiation of therapy. (5.4)
• Activities requiring mental alertness: Avoid engaging in hazardous tasks requiring mental alertness such as driving or operating machinery. (5.6)
• Risks of use in patients with head injury, impaired consciousness, increased-intracranial pressure, or brain tumors: Avoid use. May increase intracranial pressure and obscure the clinical course of head injuries. (5.10)
• Seizures in patients with seizure disorders: Monitor during therapy. (5.11)
• Severe hypotension: Monitor during initiation of therapy. Avoid use in patients with circulatory shock. (5.12)
• Adrenal insufficiency : If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. (5.14)

Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.

• Adults 18 years of age and older: One (1) tablet or 5 mL of the oral solution every 4 to 6 hours as needed; not to exceed six (6) tablets or 30 mL in 24 hours. (2.2)
• Measure hydrocodone bitartrate and homatropine methylbromide oral solution with an accurate milliliter measuring device. (2.1, 5.5)
• Do not increase the dose or dosing frequency. (2.1)
• Prescribe for the shortest duration consistent with treatment goals. (2.3)
• Reevaluate patients with unresponsive cough in 5 days or sooner for possible underlying pathology. (2.3)
• Reevaluate patient prior to refilling. (2.3)

• Tablets: 5 mg of hydrocodone bitartrate and 1.5 mg of homatropine methylbromide per tablet, white colored, biconvex, one face bisected and debossed with "205", and the other face plain [see Description (11)].
• Oral solution: 5 mg of hydrocodone bitartrate and 1.5 mg of homatropine methylbromide per 5 mL, a clear red-colored, cherry-flavored [see Description (11)].

• Pregnancy: Avoid use in pregnant women. May cause fetal harm. (8.1)
• Lactation: Breastfeeding not recommended. (8.2)
• Renal Impairment : Use with caution in patients with severe renal impairment. (8.6)
• Hepatic Impairment: Use with caution in patients with severe hepatic impairment. (8.7)

• Hydrocodone bitartrate and homatropine methylbromide contains hydrocodone, a Schedule II controlled substance. As an opioid, hydrocodone bitartrate and homatropine methylbromide exposes users to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence (9)], which can lead to overdose and death [see Overdosage (10)].
• Reserve hydrocodone bitartrate and homatropine methylbromide for use in adult patients for whom the benefits of cough suppression are expected to outweigh the risks, and in whom an adequate assessment of the etiology of the cough has been made.
• Assess each patient's risk prior to prescribing hydrocodone bitartrate and homatropine methylbromide, prescribe hydrocodone bitartrate and homatropine methylbromide for the shortest duration that is consistent with individual patient treatment goals, monitor all patients regularly for the development of addiction or abuse, and refill only after reevaluation of the need for continued treatment.
• Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed hydrocodone bitartrate and homatropine methylbromide. Addiction can occur at recommended dosages and if the drug is misused or abused. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression).
• Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing hydrocodone bitartrate and homatropine methylbromide. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug [see Patient Counseling Information (17)]. Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

The concomitant use of hydrocodone bitartrate and homatropine methylbromide and CYP3A4 inhibitors, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), or protease inhibitors (e.g., ritonavir), can increase the plasma concentration of hydrocodone, resulting in increased or prolonged opioid effects. These effects could be more pronounced with concomitant use of hydrocodone bitartrate and homatropine methylbromide and CYP2D6 and CYP3A4 inhibitors, particularly when an inhibitor is added after a stable dose of hydrocodone bitartrate and homatropine methylbromide is achieved [see Warnings and Precautions (5.7)]. After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the hydrocodone plasma concentration will decrease [see Clinical Pharmacology (12.3)], resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to hydrocodone.

Avoid the use of hydrocodone bitartrate and homatropine methylbromide while taking a CYP3A4 or CYP2D6 inhibitor. If concomitant use is necessary, monitor patients for respiratory depression and sedation at frequent intervals.

Hydrocodone bitartrate and homatropine methylbromide is supplied as a white-colored, biconvex tablet, one face bisected and debossed with "205", and the other face plain, available in:

Because opioid agonists may increase biliary tract pressure, with resultant increase in plasma amylase or lipase levels, determination of these enzyme levels may be unreliable for 24 hours after administration of a dose of hydrocodone bitartrate and homatropine methylbromide.

Hydrocodone bitartrate and homatropine methylbromide is not recommended for use in pregnant women. Prolonged use of hydrocodone bitartrate and homatropine methylbromide during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Use in Specific Populations (8.1), Patient Counseling Information (17)].

Avoid the use of hydrocodone bitartrate and homatropine methylbromide in patients who are taking monoamine oxidase inhibitors (MAOIs) or have taken MAOIs within 14 days. The use of MAOIs or tricyclic antidepressants with hydrocodone, one of the active ingredients in hydrocodone bitartrate and homatropine methylbromide, may increase the effect of either the antidepressant or hydrocodone. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma).

• Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, including hydrocodone, one of the active ingredients in hydrocodone bitartrate and homatropine methylbromide. Hydrocodone produces dose related respiratory depression by directly acting on the brain stem respiratory center that controls respiratory rhythm and may produce irregular and periodic breathing. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression includes discontinuation of hydrocodone bitartrate and homatropine methylbromide, close observation, supportive measures, and use of opioid antagonists (e.g., naloxone), depending on the patient's clinical status [see Overdosage (10)]. Carbon dioxide (CO₂) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
• While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of hydrocodone bitartrate and homatropine methylbromide, the risk is greatest during the initiation of therapy, when hydrocodone bitartrate and homatropine methylbromide is used concomitantly with other drugs that may cause respiratory depression [see Warnings and Precautions (5.8)], in patients with chronic pulmonary disease or decreased respiratory reserve, and in patients with altered pharmacokinetics or altered clearance (e.g., elderly, cachectic, or debilitated patients) [see Warnings and Precautions (5.4)].
• To reduce the risk of respiratory depression, proper dosing of hydrocodone bitartrate and homatropine methylbromide is essential [see Dosage and Administration (2.1), Warnings and Precautions (5.5)]. Monitor patients closely, especially within the first 24 to 72 hours of initiating therapy or when used in patients at higher risk.
• Overdose of hydrocodone in adults has been associated with fatal respiratory depression, and the use of hydrocodone in pediatric patients younger than 6 years of age has been associated with fatal respiratory depression when used as recommended. Accidental ingestion of even one dose of hydrocodone bitartrate and homatropine methylbromide, especially by children, can result in respiratory depression and death.

• Pediatric patients are particularly sensitive to the respiratory depressant effects of hydrocodone [see Warnings and Precautions (5.2)]. Because of the risk of life-threatening respiratory depression and death, hydrocodone bitartrate and homatropine methylbromide is contraindicated in pediatric patients less than 6 years of age [see Contraindications (4)].
• Use of hydrocodone bitartrate and homatropine methylbromide in pediatric patients also exposes them to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence (9)], which can lead to overdose and death [see Warnings and Precautions (5.1), Overdosage (10)]. Because the benefits of symptomatic treatment of cough associated with allergies or the common cold do not outweigh the risks of use of hydrocodone in pediatric patients, hydrocodone bitartrate and homatropine methylbromide is not indicated for use in patients younger than 18 years of age [see Indications (1), Use in Specific Populations (8.4)].

NDC 64950-371-47

Hydrocodone Bitartrate

and Homatropine

Methylbromide

Oral Solution

CII

5 mg/1.5 mg per 5 mL

"Dispense the accompanying Medication

Guide to each patient."

Rx Only

473 mL

Genus

Lifesciences Inc.

Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, and other opioids, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. Avoid the use of hydrocodone bitartrate and homatropine methylbromide in patients who are taking benzodiazepines or other CNS depressants [see Warnings and Precautions (5.8)], and instruct patients to avoid consumption of alchohol while on hydrocodone bitartrate and homatropine methylbromide [see Drug Interactions (7.1), Patient Counseling Information (17)].

NDC 64950-206-03

Hydrocodone Bitartrate

and Homatropine

Methylbromide

Tablets

CII

5 mg/1.5 mg

"Dispense the accompanying Medication

Guide to each patient."

Rx Only

30 tablets

Genus

Lifesciences Inc.

Administer hydrocodone bitartrate and homatropine methylbromide by the oral route only.

Always use an accurate milliliter measuring device when administering hydrocodone bitartrate and homatropine methylbromide oral solution to ensure that the dose is measured and administered accurately. A household teaspoon is not an accurate measuring device and could lead to overdosage [see Warnings and Precautions (5.5)]. For prescriptions where a measuring device is not provided, a pharmacist can provide an appropriate measuring device and can provide instructions for measuring the correct dose. Do not overfill. Rinse the measuring device with water after each use.

Advise patients not to increase the dose or dosing frequency of hydrocodone bitartrate and homatropine methylbromide because serious adverse events such as respiratory depression may occur with overdosage [see Warnings and Precautions (5.2), Overdosage (10)]. The dosage of hydrocodone bitartrate and homatropine methylbromide should not be increased if cough fails to respond; an unresponsive cough should be reevaluated for possible underlying pathology [see Dosage and Administration (2.3), Warnings and Precautions (5.4)].

Carcinogenicity, mutagenicity, and fertility studies have not been conducted with hydrocodone bitartrate and homatropine methylbromide; however, published information is available for the individual active ingredients or related active ingredients.

• Prescribe hydrocodone bitartrate and homatropine methylbromide for the shortest duration that is consistent with individual patient treatment goals [see Warnings and Precautions (5.1)].
• Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy [see Warnings and Precautions (5.2)].
• Reevaluate patients with unresponsive cough in 5 days or sooner for possible underlying pathology, such as foreign body or lower respiratory tract disease [see Warnings and Precautions (5.4)]. If a patient requires a refill, reevaluate the cause of the cough and assess the need for continued treatment with hydrocodone bitartrate and homatropine methylbromide, the relative incidence of adverse reactions, and the development of addiction, abuse, or misuse [see Warnings and Precautions (5.1)].
• Do not abruptly discontinue hydrocodone bitartrate and homatropine methylbromide in a physically-dependent patient [see Drug Abuse and Dependence (9.3)]. When a patient who has been taking hydrocodone bitartrate and homatropine methylbromide regularly and may be physically dependent no longer requires therapy with hydrocodone bitartrate and homatropine methylbromide, taper the dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal. If the patient develops these signs or symptoms, raise the dose to the previous level and taper more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both.

• Hydrocodone bitartrate and homatropine methylbromide is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus [see Contraindications (4)]. The use of hydrocodone in hydrocodone bitartrate and homatropine methylbromide may obscure the diagnosis or clinical course of patients with acute abdominal conditions.
• The concurrent use of anticholinergics with hydrocodone bitartrate and homatropine methylbromide may produce paralytic ileus [see Drug Interactions (7.9)].
• The hydrocodone in hydrocodone bitartrate and homatropine methylbromide may result in constipation or obstructive bowel disease, especially in patients with underlying intestinal motility disorders. Use with caution in patients with underlying intestinal motility disorders.
• The hydrocodone in hydrocodone bitartrate and homatropine methylbromide may cause spasm of the sphincter of Oddi, resulting in an increase in biliary tract pressure. Opioids may cause increases in serum amylase [see Warnings and Precautions (5.15)]. Monitor patients with biliary tract disease, including acute pancreatitis for worsening symptoms.

The hydrocodone in hydrocodone bitartrate and homatropine methylbromide may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during hydrocodone bitartrate and homatropine methylbromide therapy.

• Dosing errors can result in accidental overdose and death. To reduce the risk of overdose and respiratory depression, ensure that the dose of hydrocodone bitartrate and homatropine methylbromide is communicated clearly and dispensed accurately [see Dosage and Administration (2.1)].
• Advise patients to always use an accurate milliliter measuring device when measuring and administering hydrocodone bitartrate and homatropine methylbromide oral solution. Inform patients that household teaspoon is not an accurate measuring device and such use could lead to overdosage and serious adverse reactions [see Overdosage (10)]. For prescriptions where a measuring device is not provided, a pharmacist can provide an appropriate calibrated measuring device and can provide instructions for measuring the correct dose.

• Concomitant use of opioids, including hydrocodone bitartrate and homatropine methylbromide, with benzodiazepines, or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Because of these risks, avoid use of opioid cough medications in patients taking benzodiazepines, other CNS depressants, or alcohol [see Drug Interactions (7.1, 7.4)].
• Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. Because of similar pharmacologic properties, it is reasonable to expect similar risk with concomitant use of opioid cough medications and benzodiazepines, other CNS depressants, or alcohol.
• Advise both patients and caregivers about the risks of respiratory depression and sedation if hydrocodone bitartrate and homatropine methylbromide is used with benzodiazepines, alcohol, or other CNS depressants [see Patient Counseling Information (17)].
• Patients must not consume alcoholic beverages, or prescription or non-prescription products containing alcohol, while on hydrocodone bitartrate and homatropine methylbromide therapy. The co-ingestion of alcohol with hydrocodone bitartrate and homatropine methylbromide may result in increased plasma levels and a potentially fatal overdose of hydrocodone [see Drug Interactions (7.1)].

Hydrocodone, one of the active ingredients in hydrocodone bitartrate and homatropine methylbromide, may produce marked drowsiness and impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. Advise patients to avoid engaging in hazardous tasks requiring mental alertness and motor coordination after ingestion of hydrocodone bitartrate and homatropine methylbromide. Avoid concurrent use of hydrocodone bitartrate and homatropine methylbromide with alcohol or other central nervous system depressants because additional impairment of central nervous system performance may occur [see Warnings and Precautions (5.8)].

• Concomitant use of hydrocodone bitartrate and homatropine methylbromide with a CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of hydrocodone and prolong opioid adverse reactions, which may cause potentially fatal respiratory depression [see Warnings and Precautions (5.2)], particularly when an inhibitor is added after a stable dose of hydrocodone bitartrate and homatropine methylbromide is achieved. Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in hydrocodone bitartrate and homatropine methylbromide-treated patients may increase hydrocodone plasma concentrations and prolong opioid adverse reactions.
• Concomitant use of hydrocodone bitartrate and homatropine methylbromide with CYP3A4 inducers or discontinuation of a CYP3A4 inhibitor could decrease hydrocodone plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to hydrocodone.
• Avoid the use of hydrocodone bitartrate and homatropine methylbromide in patients who are taking a CYP3A4 inhibitor or inducer. If concomitant use of hydrocodone bitartrate and homatropine methylbromide with a CYP3A4 inhibitor or inducer is necessary, monitor patients for signs and symptoms that may reflect opioid toxicity and opioid withdrawal [see Drug Interactions (7.2, 7.3)].

Avoid the use of hydrocodone bitartrate and homatropine methylbromide in patients with head injury, intracranial lesions, or a pre-existing increase in intracranial pressure. In patients who may be susceptible to the intracranial effects of CO₂ retention (e.g., those with evidence of increased intracranial pressure or brain tumors), hydrocodone bitartrate and homatropine methylbromide may reduce respiratory drive, and the resultant CO₂ retention can further increase intracranial pressure. Furthermore, opioids produce adverse reactions that may obscure the clinical course of patients with head injuries.

Addiction, Abuse, and Misuse

Hydrocodone bitartrate and homatropine methylbromide exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Reserve hydrocodone bitartrate and homatropine methylbromide for use in adult patients for whom the benefits of cough suppression are expected to outweigh the risks, and in whom an adequate assessment of the etiology of the cough has been made. Assess each patient's risk prior to prescribing hydrocodone bitartrate and homatropine methylbromide, prescribe hydrocodone bitartrate and homatropine methylbromide for the shortest duration that is consistent with individual patient treatment goals, monitor all patients regularly for the development of addiction or abuse, and refill only after reevaluation of the need for continued treatment [see Warnings and Precautions (5.1)].

Life-Threatening Respiratory Depression

Serious, life-threatening, or fatal respiratory depression may occur with use of hydrocodone bitartrate and homatropine methylbromide. Monitor for respiratory depression, especially during initiation of hydrocodone bitartrate and homatropine methylbromide therapy or when used in patients at higher risk [see Warnings and Precautions (5.2)].

Accidental Ingestion

Accidental ingestion of even one dose of hydrocodone bitartrate and homatropine methylbromide, especially by children, can result in a fatal overdose of hydrocodone [see Warnings and Precautions (5.2)].

Risk of Medication Errors

Ensure accuracy when prescribing, dispensing, and administering hydrocodone bitartrate and homatropine methylbromide. Dosing errors can result in accidental overdose and death. Always use an accurate milliliter measuring device when measuring and administering hydrocodone bitartrate and homatropine methylbromide oral solution [see Dosage and Administration (2.1), Warnings and Precautions (5.5)].

Cytochrome P450 3A4 Interaction

The concomitant use of hydrocodone bitartrate and homatropine methylbromide with all cytochrome P450 3A4 inhibitors may result in an increase in hydrocodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in hydrocodone plasma concentration. Avoid the use of hydrocodone bitartrate and homatropine methylbromide in patients taking a CYP3A4 inhibitor or inducer [see Warnings and Precautions (5.7), Drug Interactions (7.2, 7.3)].

Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants

Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Avoid the use of hydrocodone bitartrate and homatropine methylbromide in patients taking benzodiazepines, other CNS depressants, or alcohol [see Warnings and Precautions (5.8), Drug Interactions (7.5)].

Interaction with Alcohol

Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products that contain alcohol while taking hydrocodone bitartrate and homatropine methylbromide. The co-ingestion of alcohol with hydrocodone bitartrate and homatropine methylbromide may result in increased plasma levels and a potentially fatal overdose of hydrocodone [see Warnings and Precautions (5.8), Drug Interactions (7.1)].

Neonatal Opioid Withdrawal Syndrome

Hydrocodone bitartrate and homatropine methylbromide is not recommended for use in pregnant women [see Use in Specific Populations (8.1)]. Prolonged use of hydrocodone bitartrate and homatropine methylbromide during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If hydrocodone bitartrate and homatropine methylbromide is used for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Warnings and Precautions (5.13)].

Limitations of Use:

• Not indicated for pediatric patients under 18 years of age [see Use in Specific Populations (8.4)].
• Contraindicated in pediatric patients less than 6 years of age [see Contraindications (4)].
• Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses [see Warnings and Precautions (5.1)], reserve hydrocodone bitartrate and homatropine methylbromide for use in adult patients for whom the benefits of cough suppression are expected to outweigh the risks, and in whom an adequate assessment of the etiology of the cough has been made.

Store tablets at controlled room temperature 20°C to 25°C (68°F to 77°F) [See USP Controlled Room Temperature]. Dispense in a tight, light-resistant container, as defined in the USP, with a child-resistant closure.

Hydrocodone bitartrate and homatropine methylbromide is available as a clear red-colored, cherry-flavored oral solution in:

•  
  NDC 64950-371-05: Unit Dose Cup of 5 mL
•  
  NDC 64950-371-45: Case contains 40 unit dose cups of 5 mL (NDC 64950-371-05), packaged in 4 trays of 10 unit dose cups each
•  
  NDC 64950-371-47: Bottle of 473 mL

Store oral solution at controlled room temperature 20°C to 25°C (68°F to 77°F). [See USP Controlled Room Temperature.]

Dispense in a tight, light-resistant container, as defined in the USP, with a child-resistant closure.

Ensure that patients have an oral dosing dispenser that measures the appropriate volume in milliliters.

Counsel patients on how to utilize an oral dosing dispenser and correctly measure the oral suspension as prescribed.

Concomitant use of alcohol with hydrocodone bitartrate and homatropine methylbromide can result in an increase of hydrocodone plasma levels and potentially fatal overdose of hydrocodone. Instruct patients not to consume alcoholic beverages or use prescription or nonprescription products containing alcohol while on hydrocodone bitartrate and homatropine methylbromide therapy [see Warnings and Precautions (5.8), Clinical Pharmacology (12.3)].

Opioids can reduce the efficacy of diuretics by inducing the release of antidiuretic hormone. Monitor patients for signs of diminished diuresis and/or effects on blood pressure and increase the dosage of the diuretic as needed.

Hydrocodone bitartrate and homatropine methylbromide tablets and oral solution contain hydrocodone, an opioid agonist; and homatropine, a muscarinic antagonist.

Each tablet or spoonful (5 mL) of hydrocodone bitartrate and homatropine methylbromide oral solution contains 5 mg of hydrocodone bitartrate, USP and 1.5 mg of homatropine methylbromide, USP, for oral administration.

Hydrocodone bitartrate and homatropine methylbromide tablets also contain: calcium phosphate dibasic, colloidal silicon dioxide, lactose, magnesium stearate, pregelatinized starch and stearic acid.

Hydrocodone bitartrate and homatropine methylbromide oral solution also contains: anhydrous citric acid, FD&C Red 40, methylparaben, natural and artificial cherry flavor, propylparaben, purified water, sorbitol solution, sodium citrate dihydrate and sucrose.

Psychological dependence, physical dependence, and tolerance may develop upon repeated administration of opioids; therefore, hydrocodone bitartrate and homatropine methylbromide should be prescribed and administered for the shortest duration that is consistent with individual patient treatment goals and patients should be reevaluated prior to refills [see Dosage and Administration (2.3), Warnings and Precautions (5.1)].

Physical dependence, the condition in which continued administration of the drug is required to prevent the appearance of a withdrawal syndrome, assumes clinically significant proportions only after several weeks of continued oral opioid use, although some mild degree of physical dependence may develope after a few days of opioid therapy.

If hydrocodone bitartrate and homatropine methylbromide is abruptly discontinued in a physically-dependent patient, a withdrawal syndrome may occur. Withdrawal also may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone, nalmefene), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). Some or all of the following can characterize this syndrome: restlessness, lacrimation, rhinorrhea, yawning, perspiration, chills, myalgia, and mydriasis.

Other signs and symptoms also may develop, including irritability, anxiety, backache, joint pain, weakness, abdominal cramps, insomnia, nausea, anorexia, vomiting, diarrhea, or increased blood pressure, respiratory rate, or heart rate.

Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see Use in Specific Populations (8.1)].

Hydrocodone bitartrate and homatropine methylbromide tablets and oral solution, for oral use

(HIGH-droe-KOE-dohn by-TAR-trate and hoe-MAT-troe-peen METH-ill-BROE-mide)

CII

What is the most important information I should know about Hydrocodone Bitartrate and Homatropine Methylbromide?

Hydrocodone bitartrate and homatropine methylbromide is not for children under 18 years of age.

Hydrocodone bitartrate and homatropine methylbromide can cause serious side effects, including:

• Addiction, abuse and misuse. Taking hydrocodone bitartrate and homatropine methylbromide or other medicines that contain an opioid can cause addiction abuse, and misuse, which can lead to overdose and death. This can happen even if you take hydrocodone bitartrate and homatropine methylbromide exactly as prescribed by your healthcare provider. Your risk of addiction, abuse, and misuse is increased if you or a family member has a history of drug or alcohol abuse or addiction, or mental health problems.
  • Do not share your hydrocodone bitartrate and homatropine methylbromide with other people.
  • Keep hydrocodone bitartrate and homatropine methylbromide in a safe place away from children.
• Life-threatening breathing problems (respiratory depression). Hydrocodone bitartrate and homatropine methylbromide can cause breathing problems (respiratory depression) that can happen at any time during treatment and can lead to death. Your risk of breathing problems is greatest when you first start taking hydrocodone bitartrate and homatropine methylbromide, are taking other medicines that can cause breathing problems, have certain lung problems, are elderly, or have certain other health problems. Children are at higher risk for respiratory depression. Breathing problems can happen even if you take hydrocodone bitartrate and homatropine methylbromide exactly as prescribed by your healthcare provider.

Call your healthcare provider or get emergency medical help right away if anyone taking hydrocodone bitartrate and homatropine methylbromide has any of the symptoms below:

Keep hydrocodone bitartrate and homatropine methylbromide in a safe place away from children. Accidental use of even 1dose of hydrocodone bitartrate and homatropine methylbromide, especially by a child, is a medical emergency and can cause breathing problems (respiratory depression) which can lead to death. If a child accidentally takes hydrocodone bitartrate and homatropine methylbromide, get emergency medical help right away.

• Overdose and death due to medicine dosing errors. Overdose and death can happen if you measure the wrong dose of hydrocodone bitartrate and homatropine methylbromide. Always use an accurate milliliter (mL) measuring device to measure the correct amount of hydrocodone bitartrate and homatropine methylbromide oral solution. Do not use a household teaspoon to measure your medicine. You may accidentally take too much. You can ask your pharmacist for the measuring device you should use and how to measure the correct dose.
• Breathing problems (respiratory depression) that can lead to death and opioid withdrawal can happen if you start taking or stop taking other medicines while taking hydrocodone bitartrate and homatropine methylbromide, including:
  • certain antibiotics
  • certain medicines to treat a fungal infection
  • certain medicines to treat Human Immunodeficiency Virus (HIV)-1 infection, Acquired Immune Deficiency Syndrome (AIDS), or Hepatitis C
  • rifampin
  • carbamazepine
  • phenytoin

Tell your healthcare provider if you take any of these medicines. Ask your healthcare provider or pharmacist if you are not sure if your medicine is listed above.

• Severe drowsiness, breathing problems (respiratory depression), coma, and death can happen in people who take hydrocodone bitartrate and homatropine methylbromide with benzodiazepines or other central nervous system depressants, including alcohol.
  • Do not take benzodiazepines or any medicine that can cause drowsiness or sleepiness during treatment with hydrocodone bitartrate and homatropine methylbromide.
  • Do not drink alcohol or take prescription or over-the-counter medicines that contain alcohol during treatment with hydrocodone bitartrate and homatropine methylbromide.
• Opioid withdrawal in a newborn. Use of hydrocodone bitartrate and homatropine methylbromide during pregnancy can cause withdrawal symptoms in your newborn baby that could be life-threatening if not recognized and treated. You should not take hydrocodone bitartrate and homatropine methylbromide if you are pregnant. Tell your health care provider right away if you are pregnant or think you may be pregnant.

What is hydrocodone bitartrate and homatropine methylbromide?

• Hydrocodone bitartrate and homatropine methylbromide is a prescription medicine used in adults 18 years of age and older to treat a cough. Hydrocodone bitartrate and homatropine methylbromide contains hydrocodone, an opioid (narcotic) cough suppressant.
• Hydrocodone bitartrate and homatropine methylbromide is a federal controlled substance (C-II) because it contains hydrocodone that can be abused or lead to dependence. Keep hydrocodone bitartrate and homatropine methylbromide in a safe place to prevent misuse and abuse. Selling or giving away hydrocodone bitartrate and homatropine methylbromide may harm others, and is against the law. Tell your healthcare provider if you have ever abused or been dependent on alcohol, prescription medicines or street drugs.

Who should not take hydrocodone bitartrate and homatropine methylbromide?

Hydrocodone bitartrate and homatropine methylbromide is not for children under 18 years of age. See "What is the most important information I should know about hydrocodone bitartrate and homatropine methylbromide?"

Do not take hydrocodone bitartrate and homatropine methylbromide if you:

• have severe breathing problems (respiratory depression) or breathing problems caused by asthma. See "What is the most important information I should know about hydrocodone bitartrate and homatropine methylbromide?"
• have a blockage (obstruction) in your bowel such as a paralytic ileus.
• are allergic to hydrocodone, homatropine, or any of the ingredients in hydrocodone bitartrate and homatropine methylbromide. See the end of this Medication Guide for a complete list of ingredients in hydrocodone bitartrate and homatropine methylbromide.

Ask your healthcare provider if you have any questions about this information.

Before you take hydrocodone bitartrate and homatropine methylbromide, tell your healthcare provider about all of your medical conditions, including if you:

• are pregnant or plan to become pregnant. Hydrocodone bitartrate and homatropine methylbromide can harm your unborn baby. See "What is the most important information I should know about hydrocodone bitartrate and homatropine methylbromide?"
• are breastfeeding or plan to breastfeed. Hydrocodone passes into your breast milk and can cause serious side effects in your baby including increased sleepiness, breathing problems (respiratory depression), and death. You and your healthcare provider should decide if you will take hydrocodone bitartrate and homatropine methylbromide or breastfeed. You should not do both. See "What should I avoid while taking hydrocodone bitartrate and homatropine methylbromide?"
• plan to have children. Hydrocodone bitartrate and homatropine methylbromide may affect the ability to have a child in females and males (fertility problems). It is not known if these fertility problems will be reversible, even after you stop taking hydrocodone bitartrate and homatropine methylbromide. Talk to your healthcare provider if this is a concern for you.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Taking hydrocodone bitartrate and homatropine methylbromide with certain other medicines can cause side effects or affect how well hydrocodone bitartrate and homatropine methylbromide or the other medicines work.

Do not start or stop taking other medicines without talking to your healthcare provider.

Especially tell your healthcare provider if you:

• take pain medicines such as opioids (narcotics).
• take cold or allergy medicines that contain antihistamines or cough suppressants.
• drink alcohol.
• take muscle relaxants.
• take certain medicines used to treat mood, anxiety, psychotic or thought disorders, or depression, including monoamine oxidase inhibitors (MAOIs), tricyclics, selective serotonin reuptake inhibitors (SSRIs), selective serotonin-norepinephrine reuptake inhibitors (SNRIs), or antipsychotics.
• take medicines to lower your blood pressure.
• take water pills (diuretics).
• take medicines called "anticholinergics" used to treat certain health problems including asthma, chronic obstructive pulmonary disease (COPD), or stomach problems.

Ask your healthcare provider if you are not sure if you take one of these medicines.

How should I take hydrocodone bitartrate and homatropine methylbromide?

• See "What is the most important information I should know about hydrocodone bitartrate and homatropine methylbromide?"
• Take hydrocodone bitartrate and homatropine methylbromide exactly as your healthcare provider tells you to take it. Do not change your dose without talking to your health care provider.
• Take hydrocodone bitartrate and homatropine methylbromide by mouth only.
• Take hydrocodone bitartrate and homatropine methylbromide oral solution using an accurate milliliter (mL) measuring device. If you do not have one, ask your pharmacist to give you a measuring device to help you measure the correct amount of hydrocodone bitartrate and homatropine methylbromide oral solution. Do not use a household teaspoon to measure your medicine. You may accidently take too much.
• Do not overfill the measuring device.
• Rinse the measuring device with water after each use.
• If you take too much hydrocodone bitartrate and homatropine methylbromide, call your healthcare provider or go to the nearest hospital emergency room right away.
• Tell your healthcare provider if your cough does not get better within 5 days of treatment with hydrocodone bitartrate and homatropine methylbromide.

What should I avoid while taking hydrocodone bitartrate and homatropine methylbromide?

• Avoid driving a car or operating machinery during treatment with hydrocodone bitartrate and homatropine methylbromide. Hydrocodone bitartrate and homatropine methylbromide can cause you to be drowsy, slow your thinking and motor skills, and affect your vision.
• Do not drink alcohol during treatment with hydrocodone bitartrate and homatropine methylbromide. Drinking alcohol can increase your chances of having serious side effects.

Avoid the use of hydrocodone bitartrate and homatropine methylbromide if you:

• are pregnant. Use of hydrocodone bitartrate and homatropine methylbromide during pregnancy can cause withdrawal symptoms in your newborn baby that could be life-threatening if not recognized and treated. Tell your healthcare provider right away if you are pregnant or think you may be pregnant.
• are breastfeeding. Use of hydrocodone bitartrate and homatropine methylbromide while breastfeeding can cause severe breathing problems (respiratory depression) in your breastfed infant that could be life-threatening.
• take a medicine called a monoamine oxidase inhibitor (MAOI). Avoid taking an MAOI within 14 days after you stop taking hydrocodone bitartrate and homatropine methylbromide. Avoid starting hydrocodone bitartrate and homatropine methylbromide if you stopped taking an MAOI in the last 14 days.

What are the possible side effects of hydrocodone bitartrate and homatropine methylbromide?

Hydrocodone bitartrate and homatropine methylbromide can cause serious side effects, including:

• See "What is the most important information I should know about hydrocodone bitartrate and homatropine methylbromide"
• Bowel problems including severe constipation or stomach pain. See "Who should not take hydrocodone bitartrate and homatropine methylbromide?"
• Increased pressure in your head (intracranial). Avoid the use of hydrocodone bitartrate and homatropine methylbromide if you have a head injury or have been told that you have changes in the tissue of your brain (brain lesions) or increased pressure in your head.
• Increased risk of seizures in people with seizure disorders. If you have a seizure disorder, hydrocodone bitartrate and homatropine methylbromide may increase how often you have a seizure.
• Low blood pressure. A sudden drop in blood pressure can happen in some people during treatment with hydrocodone bitartrate and homatropine methylbromide and this may cause you to feel dizzy, faint, lightheaded, or weak, especially when you stand up (orthostatic hypotension). Your risk of having this problem may be increased if you take hydrocodone bitartrate and homatropine methylbromide with certain other medicines that lower blood pressure. If you have any of these symptoms while taking hydrocodone bitartrate and homatropine methylbromide, sit or lie down. Do not change your body position too fast. Get up slowly from sitting or lying down.
• Adrenal gland problems. Hydrocodone bitartrate and homatropine methylbromide can cause serious and life-threatening adrenal gland problems. Your healthcare provider may do blood tests to check for adrenal gland problems. Call your healthcare provider right away if you have any of these symptoms:

The most common side effects of hydrocodone bitartrate and homatropine methylbromide include:

These are not all the possible side effects of hydrocodone bitartrate and homatropine methylbromide.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store hydrocodone bitartrate and homatropine methylbromide?

• Store hydrocodone bitartrate and homatropine methylbromide at room temperature between 68°F to 77°F (20°C to 25°C).
• Store hydrocodone bitartrate and homatropine methylbromide tablets in a tightly closed container, in a dry, cool place away from heat or direct sunlight.
• Keep hydrocodone bitartrate and homatropine methylbromide and all medicines out of the reach of children.

How should I dispose of hydrocodone bitartrate and homatropine methylbromide?

Remove unused hydrocodone bitartrate and homatropine methylbromide from the container and mix it with an undesirable, non-toxic substance such as cat litter or used coffee grounds to make it less appealing to children and pets. Place the mixture in a container such as a sealed plastic bag and throw it away in the household trash. You can also follow your state or local guidelines on how to safely throw away hydrocodone bitartrate and homatropine methylbromide.

General information about the safe and effective use of hydrocodone bitartrate and homatropine methylbromide.

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use hydrocodone bitartrate and homatropine methylbromide for a condiition for which it was not prescribed. Do not give hydrocodone bitartrate and homatropine methylbromide to other people, even if they have the same symptoms that you have. It may harm them.

You can ask your pharmacist or healthcare provider for information about hydrocodone bitartrate and homatropine methylbromide that is written for health professionals.

What are the ingredients in hydrocodone bitartrate and homatropine methylbromide?

Active ingredients: hydrocodone bitartrate and homatropine methylbromide

Inactive ingredients in hydrocodone bitartrate and homatropine methylbromide tablets: calcium phosphate dibasic, colloidal silicon dioxide, lactose, magnesium stearate, pregelatinized starch and stearic acid.

Inactive ingredients in hydrocodone bitartrate and homatropine methylbromide oral solution: anhydrous citric acid, FD&C Red 40, methylparaben, natural and artificial cherry flavor, propylparaben, purified water, sorbitol solution, sodium citrate dihydrate and sucrose.

Manufactured by: Genus Lifesciences Inc., Allentown, PA 18102

For more information, go to www.genuslifesciences.com or call 1-866-511-6754.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Revised: 06/2022

Hydrocodone bitartrate and homatropine methylbromide is contraindicated in pediatric patients younger than 6 years of age because of life-threatening respiratory depression and death have occurred in pediatric patients who received hydrocodone [see Contraindications (4), Warnings and Precautions (5.2)].

The safety and effectiveness of hydrocodone bitartrate and homatropine methylbromide has not been established in patients younger than 18 years of age. Hydrocodone bitartrate and homatropine methylbromide is not recommended for use in patients younger than 18 years of age because the benefits of symptomatic treatment of cough associated with allergies or the common cold do not outweigh the risks for use of hydrocodone in these patients [see Indications (1), Warnings and Precautions (5.3)].

Clinical studies have not been conducted with hydrocodone bitartrate and homatropine methylbromide in geriatric populations.

Use caution when considering the use of hydrocodone bitartrate and homatropine methylbromide in patients 65 years of age or older. Elderly patients may have increased sensitivity to hydrocodone; greater frequency of decreased hepatic, renal, or cardiac function; or concomitant disease or other drug therapy [see Warnings and Precautions (5.4)].

Respiratory depression is the chief risk for elderly patients treated with opioids, including hydrocodone bitartrate and homatropine methylbromide. Respiratory depression has occurred after large initial doses of opioids were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration [see Warnings and Precautions (5.4, 5.8)].

Hydrocodone is known to be substantially excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, monitor these patients closely for respiratory depression, sedation, and hypotension.

Hydrocodone bitartrate and homatropine methylbromide is contraindicated for:

• All pediatric patients younger than 6 years of age [see Warnings and Precautions (5.2, 5.3), Use in Specific Populations (8.4)].
• Significant respiratory depression [see Warnings and Precautions (5.2)].
• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see Warnings and Precautions (5.4)].
• Known or suspected gastrointestinal obstruction, including paralytic ileus [see Warnings and Precautions (5.9)].
• Hypersensitivity to hydrocodone, homatropine, or any of the inactive ingredients in hydrocodone bitartrate and homatropine methylbromide [see Adverse Reactions (6)].

The following clinically significant adverse reactions are described elsewhere in labeling:

• Addiction, abuse, and misuse [see Warnings and Precautions (5.1), Drug Abuse and Dependence (9.3)]
• Life-threatening respiratory depression [see Warnings and Precautions (5.2, 5.3, 5.4, 5.8), Overdosage (10)]
• Accidental overdose and death due to medication errors [see Warnings and Precautions (5.5)]
• Decreased mental alertness with impaired mental and/or physical abilities [see Warnings and Precautions (5.6)]
• Interactions with benzodiazepines and other CNS depressants [see Warnings and Precautions (5.8), Drug Interactions (7.1, 7.4)]
• Paralytic ileus, gastrointestinal adverse reactions [see Warnings and Precautions (5.9)]
• Increased intracranial pressure [see Warnings and Precautions (5.10)].
• Obscured clinical course in patients with head injuries [see Warnings and Precautions (5.10)]
• Seizures [see Warnings and Precautions (5.11)]
• Severe hypotension [see Warnings and Precautions (5.12)]
• Neonatal Opioid Withdrawal Syndrome [see Warnings and Precautions (5.13)]
• Adrenal insufficiency [see Warnings and Precautions (5.14)]

The following adverse reactions have been identified during clinical studies, in the literature, or during post-approval use of hydrocodone and/or homatropine. Because these reactions may be reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

The most common adverse reactions to hydrocodone bitartrate and homatropine methylbromide include: Sedation (somnolence, mental clouding, lethargy), impaired mental and physical performance, lightheadedness, dizziness, headache, dry mouth, nausea, vomiting, and constipation.

Other reactions include:

Anaphylaxis: Anaphylaxis has been reported with hydrocodone, one of the ingredients in hydrocodone bitartrate and homatropine methylbromide.

Body as a whole: Coma, death, fatigue, falling injuries, lethargy.

Cardiovascular: Peripheral edema, increased blood pressure, decreased blood pressure, tachycardia, chest pain, palpitation, syncope, orthostatic hypotension, prolonged QT interval, hot flush.

Central Nervous System: Facial dyskinesia, insomnia, migraine, increased intracranial pressure, seizure, tremor.

Dermatologic: Flushing, hyperhidrosis, pruritus, rash.

Endocrine/Metabolic: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs. Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Cases of androgen deficiency have occurred with chronic use of opioids.

Gastrointestinal: Abdominal pain, bowel obstruction, decreased appetite, diarrhea, difficulty swallowing, dry mouth, GERD, indigestion, pancreatitis, paralytic ileus, biliary tract spasm (spasm of the sphincter of Oddi).

Genitourinary: Urinary tract infection, ureteral spasm, spasm of vesicle sphincters, urinary retention.

Laboratory: Increases in serum amylase.

Musculoskeletal: Arthralgia, backache, muscle spasm.

Ophthalmic: Miosis (constricted pupils), visual disturbances.

Psychiatric: Agitation, anxiety, confusion, fear, dysphoria, depression.

Reproductive: Hypogonadism, infertility.

Respiratory: Bronchitis, cough, dyspnea, nasal congestion, nasopharyngitis, respiratory depression, sinusitis, upper respiratory tract infection.

Other: Drug abuse, drug dependence, opioid withdrawal syndrome.

No specific drug interaction studies have been conducted with hydrocodone bitartrate and homatropine methylbromide.

The concomitant use of hydrocodone bitartrate and homatropine methylbromide and CYP3A4 inducers such as rifampin, carbamazepine, or phenytoin, can decrease the plasma concentration of hydrocodone [see Clinical Pharmacology (12.3)], resulting in decreased efficacy or onset of a withdrawal syndrome in patients who have developed physical dependence to hydrocodone [see Warnings and Precautions (5.7)]. After stopping a CYP3A4 inducer, as the effects of the inducer decline, the hydrocodone plasma concentration will increase [see Clinical Pharmacology (12.3)], which could increase or prolong both the therapeutic effects and adverse reactions, and may cause serious respiratory depression.

Avoid the use of hydrocodone bitartrate and homatropine methylbromide in patients who are taking CYP3A4 inducers. If concomitant use of a CYP3A4 inducer is necessary, follow the patient for reduced efficacy.

Hydrocodone may enhance the neuromuscular blocking action of skeletal muscle relaxants and produce an increased degree of respiratory depression. Avoid the use of hydrocodone bitartrate and homatropine methylbromide in patients taking muscle relaxants. If concomitant use is necessary, monitor patients for signs of respiratory depression that may be greater than otherwise expected.

The pharmacokinetics of hydrocodone bitartrate and homatropine methylbromide has not been characterized in patients with renal impairment. Patients with renal impairment may have higher plasma concentrations than those with normal function [see Clinical Pharmacology (12.3)]. Hydrocodone bitartrate and homatropine methylbromide should be used with caution in patients with severe impairment of renal function, and patients should be monitored closely for respiratory depression, sedation, and hypotension.

Adults 18 years of age and older: One (1) tablet or 5 mL of the oral solution every 4 to 6 hours as needed; not to exceed six (6) tablets or 30 mL in 24 hours.

The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. If concomitant use is warranted, carefully observe the patient, particularly during treatment initiation. Discontinue hydrocodone bitartrate and homatropine methylbromide if serotonin syndrome is suspected.

The pharmacokinetics of hydrocodone bitartrate and homatropine methylbromide has not been characterized in patients with hepatic impairment. Patients with severe hepatic impairment may have higher plasma concentrations than those with normal hepatic function [see Clinical Pharmacology (12.3)]. Therefore, hydrocodone bitartrate and homatropine methylbromide should be used with caution in patients with severe impairment of hepatic function, and patients should be monitored closely for respiratory depression, sedation, and hypotension.

Hydrocodone bitartrate and homatropine methylbromide is indicated for the symptomatic relief of cough in adult patients 18 years of age and older.

Hydrocodone bitartrate and homatropine methylbromide may cause severe hypotension including orthostatic hypotension and syncope in ambulatory patients. There is increased risk in patients whose ability to maintain blood pressure has already been compromised by a reduced blood volume or concurrent administration of certain CNS depressant drugs (e.g., phenothiazines or general anesthetics) [see Drug Interactions (7.4)]. Monitor these patients for signs of hypotension after initiating hydrocodone bitartrate and homatropine methylbromide.

In patients with circulatory shock, hydrocodone bitartrate and homatropine methylbromide may cause vasodilation that can further reduce cardiac output and blood pressure. Avoid the use of hydrocodone bitartrate and homatropine methylbromide in patients with circulatory shock.

Hydrocodone bitartrate and homatropine methylbromide contains hydrocodone, a Schedule II controlled substance.

The concomitant use of anticholinergic drugs with hydrocodone bitartrate and homatropine methylbromide may increase risk of urinary retention and/or severe constipation, which may lead to paralytic ileus [see Warnings and Precautions (5.9)]. Monitor patients for signs of urinary retention or reduced gastric motility when hydrocodone bitartrate and homatropine methylbromide is used concomitantly with anticholinergic drugs.

• Life-threatening respiratory depression in patients with chronic pulmonary disease or in elderly, cachectic, or debilitated patients: Monitor closely, particularly during initiation of therapy. (5.4)
• Activities requiring mental alertness: Avoid engaging in hazardous tasks requiring mental alertness such as driving or operating machinery. (5.6)
• Risks of use in patients with head injury, impaired consciousness, increased-intracranial pressure, or brain tumors: Avoid use. May increase intracranial pressure and obscure the clinical course of head injuries. (5.10)
• Seizures in patients with seizure disorders: Monitor during therapy. (5.11)
• Severe hypotension: Monitor during initiation of therapy. Avoid use in patients with circulatory shock. (5.12)
• Adrenal insufficiency : If diagnosed, treat with physiologic replacement of corticosteroids, and wean patient off of the opioid. (5.14)

Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use. Presentation of adrenal insufficiency may include non-specific symptoms and signs including nausea, vomiting, anorexia, fatigue, weakness, dizziness, and low blood pressure. If adrenal insufficiency is suspected, confirm the diagnosis with diagnostic testing as soon as possible. If adrenal insufficiency is diagnosed, treat with physiologic replacement doses of corticosteroids. Wean the patient off of the opioid to allow adrenal function to recover and continue corticosteroid treatment until adrenal function recovers. Other opioids may be tried as some cases reported use of a different opioid without recurrence of adrenal insufficiency. The information available does not identify any particular opioids as being more likely to be associated with adrenal insufficiency.

• Adults 18 years of age and older: One (1) tablet or 5 mL of the oral solution every 4 to 6 hours as needed; not to exceed six (6) tablets or 30 mL in 24 hours. (2.2)
• Measure hydrocodone bitartrate and homatropine methylbromide oral solution with an accurate milliliter measuring device. (2.1, 5.5)
• Do not increase the dose or dosing frequency. (2.1)
• Prescribe for the shortest duration consistent with treatment goals. (2.3)
• Reevaluate patients with unresponsive cough in 5 days or sooner for possible underlying pathology. (2.3)
• Reevaluate patient prior to refilling. (2.3)

• Tablets: 5 mg of hydrocodone bitartrate and 1.5 mg of homatropine methylbromide per tablet, white colored, biconvex, one face bisected and debossed with "205", and the other face plain [see Description (11)].
• Oral solution: 5 mg of hydrocodone bitartrate and 1.5 mg of homatropine methylbromide per 5 mL, a clear red-colored, cherry-flavored [see Description (11)].

• Pregnancy: Avoid use in pregnant women. May cause fetal harm. (8.1)
• Lactation: Breastfeeding not recommended. (8.2)
• Renal Impairment : Use with caution in patients with severe renal impairment. (8.6)
• Hepatic Impairment: Use with caution in patients with severe hepatic impairment. (8.7)

• Hydrocodone bitartrate and homatropine methylbromide contains hydrocodone, a Schedule II controlled substance. As an opioid, hydrocodone bitartrate and homatropine methylbromide exposes users to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence (9)], which can lead to overdose and death [see Overdosage (10)].
• Reserve hydrocodone bitartrate and homatropine methylbromide for use in adult patients for whom the benefits of cough suppression are expected to outweigh the risks, and in whom an adequate assessment of the etiology of the cough has been made.
• Assess each patient's risk prior to prescribing hydrocodone bitartrate and homatropine methylbromide, prescribe hydrocodone bitartrate and homatropine methylbromide for the shortest duration that is consistent with individual patient treatment goals, monitor all patients regularly for the development of addiction or abuse, and refill only after reevaluation of the need for continued treatment.
• Although the risk of addiction in any individual is unknown, it can occur in patients appropriately prescribed hydrocodone bitartrate and homatropine methylbromide. Addiction can occur at recommended dosages and if the drug is misused or abused. Risks are increased in patients with a personal or family history of substance abuse (including drug or alcohol abuse or addiction) or mental illness (e.g., major depression).
• Opioids are sought by drug abusers and people with addiction disorders and are subject to criminal diversion. Consider these risks when prescribing or dispensing hydrocodone bitartrate and homatropine methylbromide. Strategies to reduce these risks include prescribing the drug in the smallest appropriate quantity and advising the patient on the proper disposal of unused drug [see Patient Counseling Information (17)]. Contact local state professional licensing board or state controlled substances authority for information on how to prevent and detect abuse or diversion of this product.

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

The concomitant use of hydrocodone bitartrate and homatropine methylbromide and CYP3A4 inhibitors, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), or protease inhibitors (e.g., ritonavir), can increase the plasma concentration of hydrocodone, resulting in increased or prolonged opioid effects. These effects could be more pronounced with concomitant use of hydrocodone bitartrate and homatropine methylbromide and CYP2D6 and CYP3A4 inhibitors, particularly when an inhibitor is added after a stable dose of hydrocodone bitartrate and homatropine methylbromide is achieved [see Warnings and Precautions (5.7)]. After stopping a CYP3A4 inhibitor, as the effects of the inhibitor decline, the hydrocodone plasma concentration will decrease [see Clinical Pharmacology (12.3)], resulting in decreased opioid efficacy or a withdrawal syndrome in patients who had developed physical dependence to hydrocodone.

Avoid the use of hydrocodone bitartrate and homatropine methylbromide while taking a CYP3A4 or CYP2D6 inhibitor. If concomitant use is necessary, monitor patients for respiratory depression and sedation at frequent intervals.

Hydrocodone bitartrate and homatropine methylbromide is supplied as a white-colored, biconvex tablet, one face bisected and debossed with "205", and the other face plain, available in:

Because opioid agonists may increase biliary tract pressure, with resultant increase in plasma amylase or lipase levels, determination of these enzyme levels may be unreliable for 24 hours after administration of a dose of hydrocodone bitartrate and homatropine methylbromide.

Hydrocodone bitartrate and homatropine methylbromide is not recommended for use in pregnant women. Prolonged use of hydrocodone bitartrate and homatropine methylbromide during pregnancy can result in withdrawal in the neonate. Neonatal opioid withdrawal syndrome, unlike opioid withdrawal syndrome in adults, may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. Observe newborns for signs of neonatal opioid withdrawal syndrome and manage accordingly. Advise pregnant women using opioids for a prolonged period of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Use in Specific Populations (8.1), Patient Counseling Information (17)].

Avoid the use of hydrocodone bitartrate and homatropine methylbromide in patients who are taking monoamine oxidase inhibitors (MAOIs) or have taken MAOIs within 14 days. The use of MAOIs or tricyclic antidepressants with hydrocodone, one of the active ingredients in hydrocodone bitartrate and homatropine methylbromide, may increase the effect of either the antidepressant or hydrocodone. MAOI interactions with opioids may manifest as serotonin syndrome or opioid toxicity (e.g., respiratory depression, coma).

• Serious, life-threatening, or fatal respiratory depression has been reported with the use of opioids, including hydrocodone, one of the active ingredients in hydrocodone bitartrate and homatropine methylbromide. Hydrocodone produces dose related respiratory depression by directly acting on the brain stem respiratory center that controls respiratory rhythm and may produce irregular and periodic breathing. Respiratory depression, if not immediately recognized and treated, may lead to respiratory arrest and death. Management of respiratory depression includes discontinuation of hydrocodone bitartrate and homatropine methylbromide, close observation, supportive measures, and use of opioid antagonists (e.g., naloxone), depending on the patient's clinical status [see Overdosage (10)]. Carbon dioxide (CO₂) retention from opioid-induced respiratory depression can exacerbate the sedating effects of opioids.
• While serious, life-threatening, or fatal respiratory depression can occur at any time during the use of hydrocodone bitartrate and homatropine methylbromide, the risk is greatest during the initiation of therapy, when hydrocodone bitartrate and homatropine methylbromide is used concomitantly with other drugs that may cause respiratory depression [see Warnings and Precautions (5.8)], in patients with chronic pulmonary disease or decreased respiratory reserve, and in patients with altered pharmacokinetics or altered clearance (e.g., elderly, cachectic, or debilitated patients) [see Warnings and Precautions (5.4)].
• To reduce the risk of respiratory depression, proper dosing of hydrocodone bitartrate and homatropine methylbromide is essential [see Dosage and Administration (2.1), Warnings and Precautions (5.5)]. Monitor patients closely, especially within the first 24 to 72 hours of initiating therapy or when used in patients at higher risk.
• Overdose of hydrocodone in adults has been associated with fatal respiratory depression, and the use of hydrocodone in pediatric patients younger than 6 years of age has been associated with fatal respiratory depression when used as recommended. Accidental ingestion of even one dose of hydrocodone bitartrate and homatropine methylbromide, especially by children, can result in respiratory depression and death.

• Pediatric patients are particularly sensitive to the respiratory depressant effects of hydrocodone [see Warnings and Precautions (5.2)]. Because of the risk of life-threatening respiratory depression and death, hydrocodone bitartrate and homatropine methylbromide is contraindicated in pediatric patients less than 6 years of age [see Contraindications (4)].
• Use of hydrocodone bitartrate and homatropine methylbromide in pediatric patients also exposes them to the risks of addiction, abuse, and misuse [see Drug Abuse and Dependence (9)], which can lead to overdose and death [see Warnings and Precautions (5.1), Overdosage (10)]. Because the benefits of symptomatic treatment of cough associated with allergies or the common cold do not outweigh the risks of use of hydrocodone in pediatric patients, hydrocodone bitartrate and homatropine methylbromide is not indicated for use in patients younger than 18 years of age [see Indications (1), Use in Specific Populations (8.4)].

NDC 64950-371-47

Hydrocodone Bitartrate

and Homatropine

Methylbromide

Oral Solution

CII

5 mg/1.5 mg per 5 mL

"Dispense the accompanying Medication

Guide to each patient."

Rx Only

473 mL

Genus

Lifesciences Inc.

Due to additive pharmacologic effect, the concomitant use of benzodiazepines or other CNS depressants, including alcohol, other sedatives/hypnotics, anxiolytics, tranquilizers, muscle relaxants, general anesthetics, antipsychotics, and other opioids, can increase the risk of hypotension, respiratory depression, profound sedation, coma, and death. Avoid the use of hydrocodone bitartrate and homatropine methylbromide in patients who are taking benzodiazepines or other CNS depressants [see Warnings and Precautions (5.8)], and instruct patients to avoid consumption of alchohol while on hydrocodone bitartrate and homatropine methylbromide [see Drug Interactions (7.1), Patient Counseling Information (17)].

NDC 64950-206-03

Hydrocodone Bitartrate

and Homatropine

Methylbromide

Tablets

CII

5 mg/1.5 mg

"Dispense the accompanying Medication

Guide to each patient."

Rx Only

30 tablets

Genus

Lifesciences Inc.

Administer hydrocodone bitartrate and homatropine methylbromide by the oral route only.

Always use an accurate milliliter measuring device when administering hydrocodone bitartrate and homatropine methylbromide oral solution to ensure that the dose is measured and administered accurately. A household teaspoon is not an accurate measuring device and could lead to overdosage [see Warnings and Precautions (5.5)]. For prescriptions where a measuring device is not provided, a pharmacist can provide an appropriate measuring device and can provide instructions for measuring the correct dose. Do not overfill. Rinse the measuring device with water after each use.

Advise patients not to increase the dose or dosing frequency of hydrocodone bitartrate and homatropine methylbromide because serious adverse events such as respiratory depression may occur with overdosage [see Warnings and Precautions (5.2), Overdosage (10)]. The dosage of hydrocodone bitartrate and homatropine methylbromide should not be increased if cough fails to respond; an unresponsive cough should be reevaluated for possible underlying pathology [see Dosage and Administration (2.3), Warnings and Precautions (5.4)].

Carcinogenicity, mutagenicity, and fertility studies have not been conducted with hydrocodone bitartrate and homatropine methylbromide; however, published information is available for the individual active ingredients or related active ingredients.

• Prescribe hydrocodone bitartrate and homatropine methylbromide for the shortest duration that is consistent with individual patient treatment goals [see Warnings and Precautions (5.1)].
• Monitor patients closely for respiratory depression, especially within the first 24 to 72 hours of initiating therapy [see Warnings and Precautions (5.2)].
• Reevaluate patients with unresponsive cough in 5 days or sooner for possible underlying pathology, such as foreign body or lower respiratory tract disease [see Warnings and Precautions (5.4)]. If a patient requires a refill, reevaluate the cause of the cough and assess the need for continued treatment with hydrocodone bitartrate and homatropine methylbromide, the relative incidence of adverse reactions, and the development of addiction, abuse, or misuse [see Warnings and Precautions (5.1)].
• Do not abruptly discontinue hydrocodone bitartrate and homatropine methylbromide in a physically-dependent patient [see Drug Abuse and Dependence (9.3)]. When a patient who has been taking hydrocodone bitartrate and homatropine methylbromide regularly and may be physically dependent no longer requires therapy with hydrocodone bitartrate and homatropine methylbromide, taper the dose gradually, by 25% to 50% every 2 to 4 days, while monitoring carefully for signs and symptoms of withdrawal. If the patient develops these signs or symptoms, raise the dose to the previous level and taper more slowly, either by increasing the interval between decreases, decreasing the amount of change in dose, or both.

• Hydrocodone bitartrate and homatropine methylbromide is contraindicated in patients with known or suspected gastrointestinal obstruction, including paralytic ileus [see Contraindications (4)]. The use of hydrocodone in hydrocodone bitartrate and homatropine methylbromide may obscure the diagnosis or clinical course of patients with acute abdominal conditions.
• The concurrent use of anticholinergics with hydrocodone bitartrate and homatropine methylbromide may produce paralytic ileus [see Drug Interactions (7.9)].
• The hydrocodone in hydrocodone bitartrate and homatropine methylbromide may result in constipation or obstructive bowel disease, especially in patients with underlying intestinal motility disorders. Use with caution in patients with underlying intestinal motility disorders.
• The hydrocodone in hydrocodone bitartrate and homatropine methylbromide may cause spasm of the sphincter of Oddi, resulting in an increase in biliary tract pressure. Opioids may cause increases in serum amylase [see Warnings and Precautions (5.15)]. Monitor patients with biliary tract disease, including acute pancreatitis for worsening symptoms.

The hydrocodone in hydrocodone bitartrate and homatropine methylbromide may increase the frequency of seizures in patients with seizure disorders, and may increase the risk of seizures occurring in other clinical settings associated with seizures. Monitor patients with a history of seizure disorders for worsened seizure control during hydrocodone bitartrate and homatropine methylbromide therapy.

• Dosing errors can result in accidental overdose and death. To reduce the risk of overdose and respiratory depression, ensure that the dose of hydrocodone bitartrate and homatropine methylbromide is communicated clearly and dispensed accurately [see Dosage and Administration (2.1)].
• Advise patients to always use an accurate milliliter measuring device when measuring and administering hydrocodone bitartrate and homatropine methylbromide oral solution. Inform patients that household teaspoon is not an accurate measuring device and such use could lead to overdosage and serious adverse reactions [see Overdosage (10)]. For prescriptions where a measuring device is not provided, a pharmacist can provide an appropriate calibrated measuring device and can provide instructions for measuring the correct dose.

• Concomitant use of opioids, including hydrocodone bitartrate and homatropine methylbromide, with benzodiazepines, or other CNS depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Because of these risks, avoid use of opioid cough medications in patients taking benzodiazepines, other CNS depressants, or alcohol [see Drug Interactions (7.1, 7.4)].
• Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. Because of similar pharmacologic properties, it is reasonable to expect similar risk with concomitant use of opioid cough medications and benzodiazepines, other CNS depressants, or alcohol.
• Advise both patients and caregivers about the risks of respiratory depression and sedation if hydrocodone bitartrate and homatropine methylbromide is used with benzodiazepines, alcohol, or other CNS depressants [see Patient Counseling Information (17)].
• Patients must not consume alcoholic beverages, or prescription or non-prescription products containing alcohol, while on hydrocodone bitartrate and homatropine methylbromide therapy. The co-ingestion of alcohol with hydrocodone bitartrate and homatropine methylbromide may result in increased plasma levels and a potentially fatal overdose of hydrocodone [see Drug Interactions (7.1)].

Hydrocodone, one of the active ingredients in hydrocodone bitartrate and homatropine methylbromide, may produce marked drowsiness and impair the mental and/or physical abilities required for the performance of potentially hazardous tasks such as driving a car or operating machinery. Advise patients to avoid engaging in hazardous tasks requiring mental alertness and motor coordination after ingestion of hydrocodone bitartrate and homatropine methylbromide. Avoid concurrent use of hydrocodone bitartrate and homatropine methylbromide with alcohol or other central nervous system depressants because additional impairment of central nervous system performance may occur [see Warnings and Precautions (5.8)].

• Concomitant use of hydrocodone bitartrate and homatropine methylbromide with a CYP3A4 inhibitor, such as macrolide antibiotics (e.g., erythromycin), azole-antifungal agents (e.g., ketoconazole), and protease inhibitors (e.g., ritonavir), may increase plasma concentrations of hydrocodone and prolong opioid adverse reactions, which may cause potentially fatal respiratory depression [see Warnings and Precautions (5.2)], particularly when an inhibitor is added after a stable dose of hydrocodone bitartrate and homatropine methylbromide is achieved. Similarly, discontinuation of a CYP3A4 inducer, such as rifampin, carbamazepine, and phenytoin, in hydrocodone bitartrate and homatropine methylbromide-treated patients may increase hydrocodone plasma concentrations and prolong opioid adverse reactions.
• Concomitant use of hydrocodone bitartrate and homatropine methylbromide with CYP3A4 inducers or discontinuation of a CYP3A4 inhibitor could decrease hydrocodone plasma concentrations, decrease opioid efficacy or, possibly, lead to a withdrawal syndrome in a patient who had developed physical dependence to hydrocodone.
• Avoid the use of hydrocodone bitartrate and homatropine methylbromide in patients who are taking a CYP3A4 inhibitor or inducer. If concomitant use of hydrocodone bitartrate and homatropine methylbromide with a CYP3A4 inhibitor or inducer is necessary, monitor patients for signs and symptoms that may reflect opioid toxicity and opioid withdrawal [see Drug Interactions (7.2, 7.3)].

Avoid the use of hydrocodone bitartrate and homatropine methylbromide in patients with head injury, intracranial lesions, or a pre-existing increase in intracranial pressure. In patients who may be susceptible to the intracranial effects of CO₂ retention (e.g., those with evidence of increased intracranial pressure or brain tumors), hydrocodone bitartrate and homatropine methylbromide may reduce respiratory drive, and the resultant CO₂ retention can further increase intracranial pressure. Furthermore, opioids produce adverse reactions that may obscure the clinical course of patients with head injuries.

Addiction, Abuse, and Misuse

Hydrocodone bitartrate and homatropine methylbromide exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Reserve hydrocodone bitartrate and homatropine methylbromide for use in adult patients for whom the benefits of cough suppression are expected to outweigh the risks, and in whom an adequate assessment of the etiology of the cough has been made. Assess each patient's risk prior to prescribing hydrocodone bitartrate and homatropine methylbromide, prescribe hydrocodone bitartrate and homatropine methylbromide for the shortest duration that is consistent with individual patient treatment goals, monitor all patients regularly for the development of addiction or abuse, and refill only after reevaluation of the need for continued treatment [see Warnings and Precautions (5.1)].

Life-Threatening Respiratory Depression

Serious, life-threatening, or fatal respiratory depression may occur with use of hydrocodone bitartrate and homatropine methylbromide. Monitor for respiratory depression, especially during initiation of hydrocodone bitartrate and homatropine methylbromide therapy or when used in patients at higher risk [see Warnings and Precautions (5.2)].

Accidental Ingestion

Accidental ingestion of even one dose of hydrocodone bitartrate and homatropine methylbromide, especially by children, can result in a fatal overdose of hydrocodone [see Warnings and Precautions (5.2)].

Risk of Medication Errors

Ensure accuracy when prescribing, dispensing, and administering hydrocodone bitartrate and homatropine methylbromide. Dosing errors can result in accidental overdose and death. Always use an accurate milliliter measuring device when measuring and administering hydrocodone bitartrate and homatropine methylbromide oral solution [see Dosage and Administration (2.1), Warnings and Precautions (5.5)].

Cytochrome P450 3A4 Interaction

The concomitant use of hydrocodone bitartrate and homatropine methylbromide with all cytochrome P450 3A4 inhibitors may result in an increase in hydrocodone plasma concentrations, which could increase or prolong adverse drug effects and may cause potentially fatal respiratory depression. In addition, discontinuation of a concomitantly used cytochrome P450 3A4 inducer may result in an increase in hydrocodone plasma concentration. Avoid the use of hydrocodone bitartrate and homatropine methylbromide in patients taking a CYP3A4 inhibitor or inducer [see Warnings and Precautions (5.7), Drug Interactions (7.2, 7.3)].

Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants

Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death. Avoid the use of hydrocodone bitartrate and homatropine methylbromide in patients taking benzodiazepines, other CNS depressants, or alcohol [see Warnings and Precautions (5.8), Drug Interactions (7.5)].

Interaction with Alcohol

Instruct patients not to consume alcoholic beverages or use prescription or non-prescription products that contain alcohol while taking hydrocodone bitartrate and homatropine methylbromide. The co-ingestion of alcohol with hydrocodone bitartrate and homatropine methylbromide may result in increased plasma levels and a potentially fatal overdose of hydrocodone [see Warnings and Precautions (5.8), Drug Interactions (7.1)].

Neonatal Opioid Withdrawal Syndrome

Hydrocodone bitartrate and homatropine methylbromide is not recommended for use in pregnant women [see Use in Specific Populations (8.1)]. Prolonged use of hydrocodone bitartrate and homatropine methylbromide during pregnancy can result in neonatal opioid withdrawal syndrome, which may be life-threatening if not recognized and treated, and requires management according to protocols developed by neonatology experts. If hydrocodone bitartrate and homatropine methylbromide is used for a prolonged period in a pregnant woman, advise the patient of the risk of neonatal opioid withdrawal syndrome and ensure that appropriate treatment will be available [see Warnings and Precautions (5.13)].