Hydrocodone Bitartrate and Acetaminophen

WARNING: SERIOUS AND LIFE-THREATENING RISKS FROM USE OF HYDROCODONE BITARTRATE AND ACETAMINOPHEN TABLETS Addiction, Abuse, and Misuse Because the use of Hydrocodone Bitartrate and Acetaminophen Tablets exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death, assess each patient’s risk prior to prescribing and reassess all patients regularly for the development of these behaviors and conditions [see WARNINGS ]. Life-Threatening Respiratory Depression Serious, life-threatening, or fatal respiratory depression may occur with use of Hydrocodone Bitartrate and Acetaminophen Tablets, especially during initiation or following a dose increase. To reduce the risk of respiratory depression, proper dosing and titration of Hydrocodone Bitartrate and Acetaminophen Tablets are essential [see WARNINGS ] . Accidental Ingestion Accidental ingestion of even one dose of Hydrocodone Bitartrate and Acetaminophen Tablets, especially by children, can result in a fatal overdose of hydrocodone [see WARNINGS ]. 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. Reserve concomitant prescribing of Hydrocodone Bitartrate and Acetaminophen Tablets and benzodiazepines or other CNS depressants for use in patients for whom alternative treatment options are inadequate [see WARNINGS , PRECAUTIONS; Drug Interactions ]. Neonatal Opioid Withdrawal Syndrome (NOWS) If opioid use is required for an extended period of time in a pregnant woman, advise the patient of the risk of NOWS, which may be life-threatening if not recognized and treated. Ensure that management by neonatology experts will be available at delivery [see WARNINGS ]. Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS) Healthcare providers are strongly encouraged to complete a REMS-compliant education program and to counsel patients and caregivers on serious risks, safe use, and the importance of reading the Medication Guide with each prescription [see WARNINGS ]. Cytochrome P450 3A4 Interaction The concomitant use of Hydrocodone Bitartrate and Acetaminophen Tablets with all Cytochrome P450 3A4 inhibitors may result in an increase in hydrocodone plasma concentrations, which could increase or prolong adverse reactions 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 concentrations. Monitor patients receiving Hydrocodone Bitartrate and Acetaminophen Tablets and any Cytochrome P450 3A4 inhibitor or inducer for signs of respiratory depression or sedation [see CLINICAL PHARMACOLOGY , WARNINGS , PRECAUTIONS; Drug Interactions ]. Hepatotoxicity Acetaminophen has been associated with cases of acute liver failure, at times resulting in liver transplant and death. Most of the cases of liver injury are associated with the use of acetaminophen at doses that exceed 4,000 milligrams per day, and often involve more than one acetaminophen-containing product [see WARNINGS , OVERDOSAGE ].

Serious Skin Reactions Rarely, acetaminophen may cause serious skin reactions such as acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. Patients should be informed about the signs of serious skin reactions, and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.

Hypersensitivity/Anaphylaxis There have been post-marketing reports of hypersensitivity and anaphylaxis associated with use of acetaminophen. Clinical signs included swelling of the face, mouth, and throat, respiratory distress, urticaria, rash, pruritus, and vomiting. There were infrequent reports of life-threatening anaphylaxis requiring emergency medical attention. Instruct patients to discontinue Hydrocodone Bitartrate and Acetaminophen Tablets immediately and seek medical care if they experience these symptoms. Do not prescribe Hydrocodone Bitartrate and Acetaminophen Tablets for patients with acetaminophen allergy [see PRECAUTIONS; Information for Patients ].

Withdrawal Do not abruptly discontinue Hydrocodone Bitartrate and Acetaminophen Tablets in a patient physically dependent on opioids. When discontinuing Hydrocodone Bitartrate and Acetaminophen Tablets in a physically dependent patient, gradually taper the dosage. Rapid tapering of Hydrocodone Bitartrate and Acetaminophen Tablets in a patient physically dependent on opioids may lead to a withdrawal syndrome and return of pain [see DOSAGE AND ADMINISTRATION , DRUG ABUSE AND DEPENDENCE ]. Additionally, avoid the use of mixed agonist/antagonist (e.g, pentazocine, nalbuphine, and butorphanol) or partial agonist (e.g., buprenorphine) analgesics in patients who are receiving a full opioid agonist analgesic, including Hydrocodone Bitartrate and Acetaminophen Tablets. In these patients, mixed agonist/antagonist and partial agonist analgesics may reduce the analgesic effect and/or precipitate withdrawal symptoms [see PRECAUTIONS; Drug Interactions ].

ADVERSE REACTIONS 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 predominantly 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 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 Cranbury Pharmaceuticals, LLC at (732) 940-0358 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch