hydrocodone bitartrate and acetaminophen oral solution, 10 mg/325 mg per 15 ml, cii

Hydrocodone Bitartrate and Acetaminophen Oral Solution is indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

Hydrocodone Bitartrate and Acetaminophen Oral Solution is a yellow-colored, fruit flavored liquid containing 10 mg hydrocodone bitartrate and 325 mg acetaminophen per 15 mL, with 6.7% alcohol.

It is supplied in the following oral dosage forms:

NDC 64950-375-16: 16 fl oz (473 mL) bottle

Hydrocodone Bitartrate and Acetaminophen Oral Solution is contraindicated in patients with:

• Significant respiratory depression [see WARNINGS ]
• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see WARNINGS ]
• Known or suspected gastrointestinal obstruction, including paralytic ileus [see WARNINGS ]
• Hypersensitivity to hydrocodone or acetaminophen (e.g., anaphylaxis) [see WARNINGS, ADVERSE REACTIONS ]

Hydrocodone bitartrate and acetaminophen is available in liquid form for oral administration.

Hydrocodone bitartrate is an opioid analgesic and occurs as fine, white crystals or as a crystalline powder. It is affected by light. The chemical name is 4, 5α-epoxy-3methoxy-17-methylmorphinan-6-one tartrate (1:1) hydrate (2:5). It has the following structural formula:

Acetaminophen, 4'-hydroxyacetanilide, a slightly bitter, white, odorless, crystalline powder, is a non-opiate, non-salicylate analgesic and antipyretic. It has the following structural formula:

Hydrocodone Bitartrate and Acetaminophen Oral Solution contains:

In addition, the liquid contains the following inactive ingredients: edetate disodium, glycerin, methylparaben, propylene glycol, purified water, saccharin sodium, sorbitol solution, sucrose, with D&C Yellow No. 10 as coloring and natural and artificial flavoring.

Acetaminophen may produce false-positive test results for urinary 5-hydroxyindoleactic acid.

In patients with severe hepatic or renal disease, effects of therapy should be followed with serial liver and/or renal function tests.

There are no adequate and well-controlled studies in pregnant women. Hydrocodone Bitartrate and Acetaminophen Oral Solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Opioids cross the placenta and may produce respiratory depression and psychophysiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. Hydrocodone Bitartrate and Acetaminophen Oral Solution is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including Hydrocodone Bitartrate and Acetaminophen Oral Solution, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression.

Hydrocodone is present in human milk.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Hydrocodone Bitartrate and Acetaminophen Oral Solution and any potential adverse effects on the breastfed infant from Hydrocodone Bitartrate and Acetaminophen Oral Solution or from the underlying maternal condition.

Infants exposed to Hydrocodone Bitartrate and Acetaminophen Oral Solution through breast milk should be monitored for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped.

The safety and effectiveness of Hydrocodone Bitartrate and Acetaminophen Oral Solution in the pediatric population below the age of two years have not been established. Use of Hydrocodone Bitartrate and Acetaminophen Oral Solution in the pediatric patients over the age of 2 years is supported by evidence from adequate and well controlled studies of hydrocodone and acetaminophen combination products in adults, along with additional data which support the development of metabolic pathways in children two years of age and over [see DOSAGE AND ADMINISTRATION ] for pediatric dosage information.

Elderly patients (aged 65 years or older) may have increased sensitivity to Hydrocodone Bitartrate and Acetaminophen Oral Solution. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of Hydrocodone Bitartrate and Acetaminophen Oral Solution slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see WARNINGS ].

Hydrocodone and acetaminophen are 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, care should be taken in dose selection, and it may be useful to follow renal function.

The following adverse reactions have been identified during post approval use of hydrocodone and acetaminophen tablets and oral solution. Because these reactions are 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 frequently reported adverse reactions are light-headedness, dizziness, sedation, nausea and vomiting. Other adverse reactions include:

Cardio-Renal: Bradycardia, cardiac arrest, circulatory collapse, renal toxicity, renal tubular necrosis, hypotension.

Central Nervous System/Psychiatric: Anxiety, dizziness, drowsiness, dysphoria, euphoria, fear, general malaise, impairment of mental and physical performance, lethargy, lightheadedness, mental clouding, mood changes, psychological dependence, sedation, somnolence progressing to stupor or coma.

Endocrine: Hypoglycemic coma.

Gastrointestinal System: Abdominal pain, constipation, gastric distress, heartburn, hepatic necrosis, hepatitis, occult blood loss, nausea, peptic ulcer, and vomiting.

Genitourinary System: Spasm of vesical sphincters, ureteral spasm, and urinary retention.

Hematologic: Agranulocytosis, hemolytic anemia, iron deficiency anemia, prolonged bleeding time, thrombocytopenia.

Hypersensitivity: Allergic reactions.

Musculoskeletal: Skeletal muscle flaccidity.

Respiratory Depression: Acute airway obstruction, apnea, dose-related respiratory depression [see OVERDOSAGE ], shortness of breath.

Special Senses: Cases of hearing impairment or permanent loss have been reported predominantly in patients with chronic overdose.

Skin: Cold and clammy skin, diaphoresis, pruritus, rash.

• Serotonin syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs.
• Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.
• Anaphylaxis: Anaphylaxis has been reported with ingredients contained in hydrocodone and acetaminophen tablets.
• Androgen deficiency: cases of androgen deficiency have occurred with use of opioids for an extended period of time [see CLINICAL PHARMACOLOGY ].
• Hyperalgesia and Allodynia: Cases of hyperalgesia and allodynia have been reported with opioid therapy of any duration [see WARNINGS ].
• Hypoglycemia: Cases of hypoglycemia have been reported in patients taking opioids. Most reports were in patients with at least one predisposing risk factor (e.g., diabetes).

To report SUSPECTED ADVERSE REACTIONS, contact Allucent at 1-866-511-6754 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Hydrocodone Bitartrate and Acetaminophen Oral Solution contains hydrocodone, a Schedule II controlled substance.

Hydrocodone Bitartrate and Acetaminophen Oral Solution contains hydrocodone, a substance with high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see WARNINGS ].

Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed.

Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects.

Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence.

Misuse and abuse of Hydrocodone Bitartrate and Acetaminophen Oral Solution increases risk of overdose, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death. The risk is increased with concurrent abuse of Hydrocodone Bitartrate and Acetaminophen Oral Solution with alcohol and other CNS depressants. Abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. In addition, abuse of opioids can occur in the absence of addiction.

All patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. Patients at high risk of Hydrocodone Bitartrate and Acetaminophen Oral Solution abuse include those with a history of prolonged use of any opioid, including products containing hydrocodone, those with a history of drug or alcohol abuse, or those who use Hydrocodone Bitartrate and Acetaminophen Oral Solution in combination with other abused drugs.

"Drug-seeking" behavior is very common in persons with substance use disorders. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated "loss" of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating health care provider(s). "Doctor shopping" (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control.

Hydrocodone Bitartrate and Acetaminophen Oral Solution, like other opioids, can be diverted for nonmedical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised.

Proper assessment of the patient, proper prescribing practices, periodic reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Both tolerance and physical dependence can develop during use opioid therapy.

Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose).

Physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug.

Withdrawal may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued use.

Do not abruptly discontinue Hydrocodone Bitartrate and Acetaminophen Oral Solution in a patient physically dependent on opioids. Rapid tapering of Hydrocodone Bitartrate and Acetaminophen Oral Solution in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse.

When discontinuing Hydrocodone Bitartrate and Acetaminophen Oral Solution, gradually taper the dosage using a patient-specific plan that considers the following: the dose of Hydrocodone Bitartrate and Acetaminophen Oral Solution the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. To improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. In patients taking opioids for an extended period of time at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see DOSAGE AND ADMINISTRATION, WARNINGS ].

Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see Pregnancy ].

Following an acute overdosage, toxicity may result from hydrocodone or acetaminophen.

I0771C0224

R02/24

Revised: February 2024

Issued 02/2024

Hydrocodone is a semi-synthetic opioid agonist with relative selectivity for the mu-opioid (µ) receptor, although it can interact with other opioid receptors at higher doses. Hydrocodone acts as a full agonist, binding to and activating opioid receptors at sites in the peri-aquaductal and peri-ventricular gray matter, the ventro-medial medulla and the spinal cord to produce analgesia. The analgesia, as well as the euphoriant, respiratory depressant and physiologic dependence properties of μ agonist opioids like hydrocodone, result principally from agonist action at the μ receptors.

The precise mechanism of the analgesic properties of acetaminophen is not established but is thought to involve central actions.

The behavior of the individual components is described below.

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

Store Hydrocodone Bitartrate and Acetaminophen Oral Solution securely and dispose of properly [see PRECAUTIONS/Information for Patients ].

NDC 64950-375-16

Hydrocodone Bitartrate

and Acetaminophen

Oral Solution CII

10 mg/325 mg per 15 mL

Rx ONLY

16 fl oz (473 mL)

Genus

Lifesciences Inc.

Patients with renal impairment may have higher plasma hydrocodone concentrations than those with normal function. Use a low initial dose Hydrocodone Bitartrate and Acetaminophen Oral Solution in patients with renal impairment and follow closely for adverse events such as respiratory depression and sedation.

Patients with hepatic impairment may have higher plasma hydrocodone concentrations than those with normal function. Use a low initial dose of Hydrocodone Bitartrate and Acetaminophen Oral Solution in patients with hepatic impairment and follow closely for adverse events such as respiratory depression and sedation.

Hydrocodone Bitartrate and Acetaminophen Oral Solution is indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate.

Hydrocodone Bitartrate and Acetaminophen Oral Solution is a yellow-colored, fruit flavored liquid containing 10 mg hydrocodone bitartrate and 325 mg acetaminophen per 15 mL, with 6.7% alcohol.

It is supplied in the following oral dosage forms:

NDC 64950-375-16: 16 fl oz (473 mL) bottle

Hydrocodone Bitartrate and Acetaminophen Oral Solution is contraindicated in patients with:

• Significant respiratory depression [see WARNINGS ]
• Acute or severe bronchial asthma in an unmonitored setting or in the absence of resuscitative equipment [see WARNINGS ]
• Known or suspected gastrointestinal obstruction, including paralytic ileus [see WARNINGS ]
• Hypersensitivity to hydrocodone or acetaminophen (e.g., anaphylaxis) [see WARNINGS, ADVERSE REACTIONS ]

Hydrocodone bitartrate and acetaminophen is available in liquid form for oral administration.

Hydrocodone bitartrate is an opioid analgesic and occurs as fine, white crystals or as a crystalline powder. It is affected by light. The chemical name is 4, 5α-epoxy-3methoxy-17-methylmorphinan-6-one tartrate (1:1) hydrate (2:5). It has the following structural formula:

Acetaminophen, 4'-hydroxyacetanilide, a slightly bitter, white, odorless, crystalline powder, is a non-opiate, non-salicylate analgesic and antipyretic. It has the following structural formula:

Hydrocodone Bitartrate and Acetaminophen Oral Solution contains:

In addition, the liquid contains the following inactive ingredients: edetate disodium, glycerin, methylparaben, propylene glycol, purified water, saccharin sodium, sorbitol solution, sucrose, with D&C Yellow No. 10 as coloring and natural and artificial flavoring.

Acetaminophen may produce false-positive test results for urinary 5-hydroxyindoleactic acid.

In patients with severe hepatic or renal disease, effects of therapy should be followed with serial liver and/or renal function tests.

There are no adequate and well-controlled studies in pregnant women. Hydrocodone Bitartrate and Acetaminophen Oral Solution should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Opioids cross the placenta and may produce respiratory depression and psychophysiologic effects in neonates. An opioid antagonist, such as naloxone, must be available for reversal of opioid-induced respiratory depression in the neonate. Hydrocodone Bitartrate and Acetaminophen Oral Solution is not recommended for use in pregnant women during or immediately prior to labor, when other analgesic techniques are more appropriate. Opioid analgesics, including Hydrocodone Bitartrate and Acetaminophen Oral Solution, can prolong labor through actions which temporarily reduce the strength, duration, and frequency of uterine contractions. However, this effect is not consistent and may be offset by an increased rate of cervical dilation, which tends to shorten labor. Monitor neonates exposed to opioid analgesics during labor for signs of excess sedation and respiratory depression.

Hydrocodone is present in human milk.

The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Hydrocodone Bitartrate and Acetaminophen Oral Solution and any potential adverse effects on the breastfed infant from Hydrocodone Bitartrate and Acetaminophen Oral Solution or from the underlying maternal condition.

Infants exposed to Hydrocodone Bitartrate and Acetaminophen Oral Solution through breast milk should be monitored for excess sedation and respiratory depression. Withdrawal symptoms can occur in breastfed infants when maternal administration of an opioid analgesic is stopped, or when breast-feeding is stopped.

The safety and effectiveness of Hydrocodone Bitartrate and Acetaminophen Oral Solution in the pediatric population below the age of two years have not been established. Use of Hydrocodone Bitartrate and Acetaminophen Oral Solution in the pediatric patients over the age of 2 years is supported by evidence from adequate and well controlled studies of hydrocodone and acetaminophen combination products in adults, along with additional data which support the development of metabolic pathways in children two years of age and over [see DOSAGE AND ADMINISTRATION ] for pediatric dosage information.

Elderly patients (aged 65 years or older) may have increased sensitivity to Hydrocodone Bitartrate and Acetaminophen Oral Solution. In general, use caution when selecting a dosage for an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy.

Respiratory depression is the chief risk for elderly patients treated with opioids, and has occurred after large initial doses were administered to patients who were not opioid-tolerant or when opioids were co-administered with other agents that depress respiration. Titrate the dosage of Hydrocodone Bitartrate and Acetaminophen Oral Solution slowly in geriatric patients and frequently reevaluate the patient for signs of central nervous system and respiratory depression [see WARNINGS ].

Hydrocodone and acetaminophen are 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, care should be taken in dose selection, and it may be useful to follow renal function.

The following adverse reactions have been identified during post approval use of hydrocodone and acetaminophen tablets and oral solution. Because these reactions are 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 frequently reported adverse reactions are light-headedness, dizziness, sedation, nausea and vomiting. Other adverse reactions include:

Cardio-Renal: Bradycardia, cardiac arrest, circulatory collapse, renal toxicity, renal tubular necrosis, hypotension.

Central Nervous System/Psychiatric: Anxiety, dizziness, drowsiness, dysphoria, euphoria, fear, general malaise, impairment of mental and physical performance, lethargy, lightheadedness, mental clouding, mood changes, psychological dependence, sedation, somnolence progressing to stupor or coma.

Endocrine: Hypoglycemic coma.

Gastrointestinal System: Abdominal pain, constipation, gastric distress, heartburn, hepatic necrosis, hepatitis, occult blood loss, nausea, peptic ulcer, and vomiting.

Genitourinary System: Spasm of vesical sphincters, ureteral spasm, and urinary retention.

Hematologic: Agranulocytosis, hemolytic anemia, iron deficiency anemia, prolonged bleeding time, thrombocytopenia.

Hypersensitivity: Allergic reactions.

Musculoskeletal: Skeletal muscle flaccidity.

Respiratory Depression: Acute airway obstruction, apnea, dose-related respiratory depression [see OVERDOSAGE ], shortness of breath.

Special Senses: Cases of hearing impairment or permanent loss have been reported predominantly in patients with chronic overdose.

Skin: Cold and clammy skin, diaphoresis, pruritus, rash.

• Serotonin syndrome: Cases of serotonin syndrome, a potentially life-threatening condition, have been reported during concomitant use of opioids with serotonergic drugs.
• Adrenal insufficiency: Cases of adrenal insufficiency have been reported with opioid use, more often following greater than one month of use.
• Anaphylaxis: Anaphylaxis has been reported with ingredients contained in hydrocodone and acetaminophen tablets.
• Androgen deficiency: cases of androgen deficiency have occurred with use of opioids for an extended period of time [see CLINICAL PHARMACOLOGY ].
• Hyperalgesia and Allodynia: Cases of hyperalgesia and allodynia have been reported with opioid therapy of any duration [see WARNINGS ].
• Hypoglycemia: Cases of hypoglycemia have been reported in patients taking opioids. Most reports were in patients with at least one predisposing risk factor (e.g., diabetes).

To report SUSPECTED ADVERSE REACTIONS, contact Allucent at 1-866-511-6754 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Hydrocodone Bitartrate and Acetaminophen Oral Solution contains hydrocodone, a Schedule II controlled substance.

Hydrocodone Bitartrate and Acetaminophen Oral Solution contains hydrocodone, a substance with high potential for misuse and abuse, which can lead to the development of substance use disorder, including addiction [see WARNINGS ].

Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a healthcare provider or for whom it was not prescribed.

Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects.

Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence.

Misuse and abuse of Hydrocodone Bitartrate and Acetaminophen Oral Solution increases risk of overdose, which may lead to central nervous system and respiratory depression, hypotension, seizures, and death. The risk is increased with concurrent abuse of Hydrocodone Bitartrate and Acetaminophen Oral Solution with alcohol and other CNS depressants. Abuse of and addiction to opioids in some individuals may not be accompanied by concurrent tolerance and symptoms of physical dependence. In addition, abuse of opioids can occur in the absence of addiction.

All patients treated with opioids require careful and frequent reevaluation for signs of misuse, abuse, and addiction, because use of opioid analgesic products carries the risk of addiction even under appropriate medical use. Patients at high risk of Hydrocodone Bitartrate and Acetaminophen Oral Solution abuse include those with a history of prolonged use of any opioid, including products containing hydrocodone, those with a history of drug or alcohol abuse, or those who use Hydrocodone Bitartrate and Acetaminophen Oral Solution in combination with other abused drugs.

"Drug-seeking" behavior is very common in persons with substance use disorders. Drug-seeking tactics include emergency calls or visits near the end of office hours, refusal to undergo appropriate examination, testing, or referral, repeated "loss" of prescriptions, tampering with prescriptions, and reluctance to provide prior medical records or contact information for other treating health care provider(s). "Doctor shopping" (visiting multiple prescribers to obtain additional prescriptions) is common among people who abuse drugs and people with substance use disorder. Preoccupation with achieving adequate pain relief can be appropriate behavior in a patient with inadequate pain control.

Hydrocodone Bitartrate and Acetaminophen Oral Solution, like other opioids, can be diverted for nonmedical use into illicit channels of distribution. Careful record-keeping of prescribing information, including quantity, frequency, and renewal requests, as required by state and federal law, is strongly advised.

Proper assessment of the patient, proper prescribing practices, periodic reevaluation of therapy, and proper dispensing and storage are appropriate measures that help to limit abuse of opioid drugs.

Both tolerance and physical dependence can develop during use opioid therapy.

Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose).

Physical dependence is a state that develops as a result of a physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug.

Withdrawal may be precipitated through the administration of drugs with opioid antagonist activity (e.g., naloxone), mixed agonist/antagonist analgesics (e.g., pentazocine, butorphanol, nalbuphine), or partial agonists (e.g., buprenorphine). Physical dependence may not occur to a clinically significant degree until after several days to weeks of continued use.

Do not abruptly discontinue Hydrocodone Bitartrate and Acetaminophen Oral Solution in a patient physically dependent on opioids. Rapid tapering of Hydrocodone Bitartrate and Acetaminophen Oral Solution in a patient physically dependent on opioids may lead to serious withdrawal symptoms, uncontrolled pain, and suicide. Rapid discontinuation has also been associated with attempts to find other sources of opioid analgesics, which may be confused with drug-seeking for abuse.

When discontinuing Hydrocodone Bitartrate and Acetaminophen Oral Solution, gradually taper the dosage using a patient-specific plan that considers the following: the dose of Hydrocodone Bitartrate and Acetaminophen Oral Solution the patient has been taking, the duration of treatment, and the physical and psychological attributes of the patient. To improve the likelihood of a successful taper and minimize withdrawal symptoms, it is important that the opioid tapering schedule is agreed upon by the patient. In patients taking opioids for an extended period of time at high doses, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper [see DOSAGE AND ADMINISTRATION, WARNINGS ].

Infants born to mothers physically dependent on opioids will also be physically dependent and may exhibit respiratory difficulties and withdrawal signs [see Pregnancy ].

Following an acute overdosage, toxicity may result from hydrocodone or acetaminophen.

I0771C0224

R02/24

Revised: February 2024

Issued 02/2024

Hydrocodone is a semi-synthetic opioid agonist with relative selectivity for the mu-opioid (µ) receptor, although it can interact with other opioid receptors at higher doses. Hydrocodone acts as a full agonist, binding to and activating opioid receptors at sites in the peri-aquaductal and peri-ventricular gray matter, the ventro-medial medulla and the spinal cord to produce analgesia. The analgesia, as well as the euphoriant, respiratory depressant and physiologic dependence properties of μ agonist opioids like hydrocodone, result principally from agonist action at the μ receptors.

The precise mechanism of the analgesic properties of acetaminophen is not established but is thought to involve central actions.

The behavior of the individual components is described below.

Store at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature].

Store Hydrocodone Bitartrate and Acetaminophen Oral Solution securely and dispose of properly [see PRECAUTIONS/Information for Patients ].

NDC 64950-375-16

Hydrocodone Bitartrate

and Acetaminophen

Oral Solution CII

10 mg/325 mg per 15 mL

Rx ONLY

16 fl oz (473 mL)

Genus

Lifesciences Inc.

Patients with renal impairment may have higher plasma hydrocodone concentrations than those with normal function. Use a low initial dose Hydrocodone Bitartrate and Acetaminophen Oral Solution in patients with renal impairment and follow closely for adverse events such as respiratory depression and sedation.

Patients with hepatic impairment may have higher plasma hydrocodone concentrations than those with normal function. Use a low initial dose of Hydrocodone Bitartrate and Acetaminophen Oral Solution in patients with hepatic impairment and follow closely for adverse events such as respiratory depression and sedation.