HYDROCODONE BITARTRATE AND ACETAMINOPHEN

Hydrocodone bitartrate and acetaminophen, USP is available in tablet 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-3-methoxy-17-methylmorphinan-6-one tartrate (1:1) hydrate (2:5). It has the following structural formula: Hydrocodone Bitartrate- Struct 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: Acetaminophen- Struct Each Hydrocodone Bitartrate and Acetaminophen Tablet, USP contains: Strength Hydrocodone Bitartrate Acetaminophen 5 mg/325 mg 5 mg 325 mg 10 mg/325 mg 10 mg 325 mg In addition, each tablet contains the following inactive ingredients: microcrystalline cellulose, corn starch, colloidal silicon dioxide, crospovidone, pregelatinized starch, povidone, and stearic acid. Hydrocodone Bitartrate and Acetaminophen Tablets, USP complies to USP Dissolution Test 1.

Hydrocodone bitartrate and acetaminophen tablets, USP are indicated for the management of pain severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Limitations of Use Because of the risks of addiction, abuse, and misuse, with opioids, even at recommended doses [see WARNINGS], reserve hydrocodone bitartrate and acetaminophen tablets, USP for use in patients for whom alternative treatment options (e.g., non-opioid analgesics): have not been tolerated, or are not expected to be tolerated, have not provided adequate analgesia, or are not expected to provide adequate analgesia

Important Dosage and Administration Instructions Use the lowest effective dosage for the shortest duration consistent with individual patient treatment goals [see WARNINGS]. Initiate the dosing regimen for each patient individually, taking into account the patient's severity of pain, patient response, prior analgesic treatment experience, and risk factors for addiction, abuse, and misuse [see WARNINGS]. Follow patients closely for respiratory depression, especially within the first 24-72 hours of initiating therapy and following dosage increases with hydrocodone bitartrate and acetaminophen tablets and adjust the dosage accordingly [see WARNINGS]. Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver and assess the potential need for access to naloxone, both when initiating and renewing treatment with hydrocodone bitartrate and acetaminophen tablets [see WARNINGS, Life-Threatening Respiratory Depression; PRECAUTIONS, Information for Patients/Caregivers]. Inform patients and caregivers about the various ways to obtain naloxone as permitted by individual state naloxone dispensing and prescribing regulations (e.g., by prescription, directly from a pharmacist, or as part of a community-based program). Consider prescribing naloxone, based on the patients risk factors for overdose, such as concomitant use of CNS depressants, a history of opioid use disorder, or prior opioid overdose. The presence of risk factors for overdose should not prevent the proper management of pain in any given patient [see WARNINGS, Addiction, Abuse, and Misuse, Life-Threatening Respiratory Depression, Risks from Concomitant Use with Benzodiazepines or Other CNS Depressants]. Consider prescribing naloxone when the patient has household members (including children) or other close contacts at risk for accidental ingestion or overdose. Initial Dosage Initiating Treatment with Hydrocodone Bitartrate and Acetaminophen Tablets 2.5 mg/325 mg The usual adult dosage is one or two tablets every four to six hours as needed for pain. The total daily dosage should not exceed 8 tablets. 5 mg/325 mg The usual adult dosage is one or two tablets every four to six hours as needed for pain. The total daily dosage should not exceed 8 tablets. 7.5 mg/325 mg, 10 mg/325 mg The usual adult dosage is one tablet every four to six hours as needed for pain. The total daily dosage should not exceed 6 tablets. Conversion from Other Opioids to Hydrocodone Bitartrate and Acetaminophen Tablets There is inter-patient variability in the potency of opioid drugs and opioid formulations. Therefore, a conservative approach is advised when determining the total daily dosage of hydrocodone bitartrate and acetaminophen tablets. It is safer to underestimate a patient’s 24-hour hydrocodone bitartrate and acetaminophen tablets dosage than to overestimate the 24-hour hydrocodone bitartrate and acetaminophen tablets dosage and manage an adverse reaction due to overdose. Conversion from Hydrocodone Bitartrate and Acetaminophen Tablets to Extended-Release Hydrocodone The relative bioavailability of hydrocodone from hydrocodone bitartrate and acetaminophen tablets compared to extended-release hydrocodone products is unknown, so conversion to extended-release products must be accompanied by close observation for signs of excessive sedation and respiratory depression. Titration and Maintenance of Therapy Individually titrate hydrocodone bitartrate and acetaminophen tablets to a dose that provides adequate analgesia and minimizes adverse reactions. Continually reevaluate patients receiving hydrocodone bitartrate and acetaminophen tablets to assess the maintenance of pain control and the relative incidence of adverse reactions, as well as monitoring for the development of addiction, abuse, or misuse [see WARNINGS]. Frequent communication is important among the prescriber, other members of the healthcare team, the patient, and the caregiver/family during periods of changing analgesic requirements, including initial titration. If the level of pain increases after dosage stabilization, attempt to identify the source of increased pain before increasing the hydrocodone bitartrate and acetaminophen tablets dosage. If unacceptable opioid-related adverse reactions are observed, consider reducing the dosage. Adjust the dosage to obtain an appropriate balance between management of pain and opioid-related adverse reactions. Safe Reduction or Discontinuation of Hydrocodone Bitartrate and Acetaminophen Tablets Do not abruptly discontinue hydrocodone bitartrate and acetaminophen tablets in patients who may be physically dependent on opioids. Rapid discontinuation of opioid analgesics in patients who are physically dependent on opioids has resulted in 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. Patients may also attempt to treat their pain or withdrawal symptoms with illicit opioids, such as heroin, and other substances. When a decision has been made to decrease the dose or discontinue therapy in an opioid-dependent patient taking hydrocodone bitartrate and acetaminophen tablets, there are a variety of factors that should be considered, including the dose of hydrocodone bitartrate and acetaminophen tablets the patient has been taking, the duration of treatment, the type of pain being treated, and the physical and psychological attributes of the patient. It is important to ensure ongoing care of the patient and to agree on an appropriate tapering schedule and follow-up plan so that patient and provider goals and expectations are clear and realistic. When opioid analgesics are being discontinued due to a suspected substance use disorder, evaluate and treat the patient, or refer for evaluation and treatment of the substance use disorder. Treatment should include evidence-based approaches, such as medication assisted treatment of opioid use disorder. Complex patients with co-morbid pain and substance use disorders may benefit from referral to a specialist. There are no standard opioid tapering schedules that are suitable for all patients. Good clinical practice dictates a patient-specific plan to taper the dose of the opioid gradually. For patients on hydrocodone bitartrate and acetaminophen tablets who are physically opioid-dependent, initiate the taper by a small enough increment (e.g., no greater than 10% to 25% of the total daily dose) to avoid withdrawal symptoms, and proceed with dose-lowering at an interval of every 2 to 4 weeks. Patients who have been taking opioids for briefer periods of time may tolerate a more rapid taper. It may be necessary to provide the patient with lower dosage strengths to accomplish a successful taper. Reassess the patient frequently to manage pain and withdrawal symptoms, should they emerge. Common withdrawal symptoms include 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. If withdrawal symptoms arise, it may be necessary to pause the taper for a period of time or raise the dose of the opioid analgesic to the previous dose, and then proceed with a slower taper. In addition, monitor patients for any changes in mood, emergence of suicidal thoughts, or use of other substances. When managing patients taking opioid analgesics, particularly those who have been treated for a long duration and/or with high doses for chronic pain, ensure that a multimodal approach to pain management, including mental health support (if needed), is in place prior to initiating an opioid analgesic taper. A multimodal approach to pain management may optimize the treatment of chronic pain, as well as assist with the successful tapering of the opioid analgesic [see WARNINGS/ Withdrawal, DRUG ABUSE AND DEPENDENCE].

The following adverse reactions have been identified during post approval use of hydrocodone and acetaminophen tablets. 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: Central Nervous System: Drowsiness, mental clouding, lethargy, impairment of mental and physical performance, anxiety, fear, dysphoria, psychological dependence, mood changes. Gastrointestinal System: Constipation. Genitourinary System: Ureteral spasm, spasm of vesical sphincters, and urinary retention. Special Senses: Cases of hearing impairment or permanent loss have been reported predominately in patients with chronic overdose. Dermatological: Skin rash, pruritus, Stevens-Johnson syndrome, toxic epidermal necrolysis, allergic reactions. Hematological: Thrombocytopenia, agranulocytosis. 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 bitartrate and acetaminophen tablets. Androgen deficiency: Cases of androgen deficiency have occurred with chronic use of opioids [see CLINICAL PHARMACOLOGY].