FDA label e83acf61-ab8a-43a3-9710-182f0ea309ba

BOXED WARNING SECTION WARNINGS There have been numerous cases of accidental and intentional overdose with propoxpyhene 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 propoxpyhene for patients who are suicidal or have a history of suicidal ideation. The metabolism of propoxpyhene 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 propoxpyhene plasma levels. Patients receiving propoxpyhene 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).

WARNINGS Risk of Overdose 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. Respiratory Depression Respiratory depression is the chief hazard from all opioid agonist preparations. Respiratory depression occurs most frequently in elderly or debilitated patients, usually following large initial doses in non-tolerant patients, or when opioids are given in conjunction with other agents that depress respiration. Propoxyphene Hydrochloride Capsules should be used with extreme caution in patients with significant chronic obstructive pulmonary disease or cor pulmonale, and in patients having substantially decreased respiratory reserve, hypoxia, hypercapnia, or pre-existing respiratory depression. In such patients, even usual therapeutic doses of Propoxyphene Hydrochloride Capsules may decrease respiratory drive to the point of apnea. In these patients alternative non-opioid analgesics should be considered, and opioids should be employed only under careful medical supervision at the lowest effective dose. Hypotensive Effect Propoxyphene Hydrochloride Capsules, like all opioid analgesics, may cause severe hypotension in an individual whose ability to maintain blood pressure has been compromised by a depleted blood volume, or after concurrent administration with drugs such as phenothiazines or other agents which compromise vasomotor tone. Propoxyphene Hydrochloride Capsules may produce orthostatic hypotension in ambulatory patients. Propoxyphene Hydrochloride Capsules, like all opioid analgesics, should be administered with caution to patients in circulatory shock, since vasodilatation produced by the drug may further reduce cardiac output and blood pressure. 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 Alcohol Patients should be cautioned about the concomitant use of propoxyphene products and alcohol because of potentially serious CNS-additive effects of these agents that can lead to death.

ADVERSE REACTIONS In hospitalized patients, the most frequently reported 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 interaction, drug tolerance, 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 Propoxyphene Hydrochloride Capsules. Propoxyphene therapy has been associated with abnormal liver function tests and, more rarely, with instances of reversible jaundice (including cholestatic jaundice). Subacute painful myopathy has been reported following chronic propoxyphene overdosage. To report SUSPECTED ADVERSE REACTIONS, contact West-ward Pharmaceutical Corp. at 1-877-233-2001, and the FDA at 1-800-1088 or www.fda.gov/medwatch.