FDA label 6ddbfb7d-838d-4cc9-8538-532ccfc976ce

WARNINGS There have been numerous cases of accidental and intentional overdose with propoxyphene products either alone or in combination with other CNS depressants, including alcohol. Fatalities within the first hour of overdosage are not uncommon. Many of the propoxyphene-related deaths have occurred in patients with previous histories of emotional disturbances or suicidal ideation/attempts and/or concomitant administration of sedatives, tranquilizers, muscle relaxants, antidepressants, or other CNS-depressant drugs. Do not prescribe propoxyphene for patients who are suicidal or have a history of suicidal ideation. The metabolism of propoxyphene may be altered by strong CYP3A4 inhibitors (such as ritonavir, ketoconazole, itraconazole, troleandomycin, clarithromycin, nelfinavir, nefazadone, amiodarone, amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, and verapamil) leading to enhanced propoxyphene plasma levels. Patients receiving propoxyphene and any CYP3A4 inhibitor should be carefully monitored for an extended period of time and dosage adjustments should be made if warranted (see CLINICAL PHARMACOLOGY – Drug Interactions , and WARNINGS, PRECAUTIONS and DOSAGE AND ADMINISTRATION for further information).

Head Injury and Increased Intracranial Pressure The respiratory depressant effects of narcotics and their capacity to elevate cerebrospinal fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions or a pre-existing increase in intracranial pressure. Furthermore, narcotics produce adverse reactions which may obscure the clinical course of patients with head injuries.

Drug Interactions The concomitant use of propoxyphene and CNS depressants, including alcohol, can result in potentially serious adverse events including death. Because of its added depressant effects, propoxyphene should be prescribed with caution for those patients whose medical condition requires the concomitant administration of sedatives, tranquilizers, muscle relaxants, antidepressants, or other CNS-depressant drugs.

Usage in Ambulatory Patients Propoxyphene may impair the mental and/or physical abilities required for the performance of potentially hazardous tasks, such as driving a car or operating machinery. The patient should be cautioned accordingly.

Use with Other Acetaminophen-Containing Agents Due to the potential for acetaminophen hepatotoxicity at doses higher than the recommended dose, propoxyphene napsylate and acetaminophen tablets should not be used concomitantly with other acetaminophen-containing products.

ADVERSE REACTIONS During clinical trials, the most frequently reported adverse reactions were dizziness, sedation, nausea, and vomiting. Other adverse reactions include constipation, abdominal pain, skin rashes, lightheadedness, headache, weakness, euphoria, dysphoria, hallucinations, and minor visual disturbances. The most frequently reported postmarketing adverse events have included completed suicide, accidental and intentional overdose, drug dependence, cardiac arrest, coma, drug ineffective, drug toxicity, nausea, respiratory arrest, cardio-respiratory arrest, death, vomiting, dizziness, convulsion, confusional state, and diarrhea. Additional adverse experiences reported through postmarketing surveillance include: Cardiac disorders: arrhythmia, bradycardia, cardiac/respiratory arrest, congestive arrest, congestive heart failure (CHF), tachycardia, myocardial infarction (MI) Eye disorder: eye swelling, vision blurred General disorder and administration site conditions: drug ineffective, drug interaction, drug tolerance, influenza type illness, drug withdrawal syndrome Gastrointestinal disorder: gastrointestinal bleed, acute pancreatitis Hepatobiliary disorder: hepatic steatosis, hepatomegaly, hepatocellular injury Immune system disorder: hypersensitivity Injury poisoning and procedural complications: drug toxicity, hip fracture, multiple drug overdose, narcotic overdose Investigations: blood pressure decreased, heart rate elevated/abnormal Metabolism and nutrition disorder: metabolic acidosis Nervous system disorder: ataxia, coma, dizziness, somnolence, syncope Psychiatric: abnormal behavior, confusional state, hallucinations, mental status change Respiratory, thoracic, and mediastinal disorders: respiratory depression, dyspnoea Skin and subcutaneous tissue disorder: rash, itch Liver dysfunction has been reported in association with both active components of propoxyphene napsylate and acetaminophen tablets. Propoxyphene therapy has been associated with abnormal liver function tests and, more rarely, with instances of reversible jaundice (including cholestatic jaundice). Hepatic necrosis may result from acute overdose of acetaminophen (see OVERDOSAGE ). In chronic ethanol abusers, this has been reported rarely with short-term use of acetaminophen dosages of 2.5 to 10 g/day. Fatalities have occurred. There have also been postmarketing reports of renal papillary necrosis associated with chronic acetaminophen use, particularly when the dosage is greater than recommended and when combined with aspirin. Subacute painful myopathy has been reported following chronic propoxyphene overdosage.