Propoxyphene

Generic Name: Propoxyphene hydrochloride
Dosage Form: Capsules

Propoxyphene Description

Propoxyphene hydrochloride is an odorless, white crystalline powder with a bitter taste. It is freely soluble in water. Chemically, it is (2S,3R)‑(+)‑4‑(Dimethylamino)‑3‑methyl-1,2‑ diphenyl‑2‑butanol propionate (ester) hydrochloride, which can be represented by the following structural formula:

C22H29NO2 HCl M.W. 375.94

Each capsule, for oral administration, contains 65 mg Propoxyphene hydrochloride. Propoxyphene Hydrochloride Capsules contain the inactive ingredients corn starch, gelatin, lactose monohydrate, magnesium stearate, titanium dioxide, FD&C yellow #6, and D&C red #33.

Propoxyphene - Clinical Pharmacology

Propoxyphene is a centrally acting narcotic analgesic agent. Equimolar doses of Propoxyphene hydrochloride or napsylate provides similar plasma concentrations. Following administration of 65, 130, or 195 mg of Propoxyphene hydrochloride, the bioavailability of Propoxyphene is equivalent to that of 100, 200, or 300 mg respectively of Propoxyphene napsylate. Peak plasma concentrations of Propoxyphene are reached in 2 to 2 ½ hours. After a 65 mg oral dose of Propoxyphene hydrochloride, peak plasma levels of 0.05 to 0.1 mcg/mL are achieved.

Repeated doses of Propoxyphene at 6 hour intervals lead to increasing plasma concentrations, with a plateau after the ninth dose at 48 hours.

Propoxyphene is metabolized in the liver to yield norPropoxyphene. Propoxyphene has a half‑life of 6 to 12 hours, whereas that of norPropoxyphene is 30 to 36 hours.

NorPropoxyphene has substantially less central‑nervous‑system‑depressant effect than Propoxyphene, but a greater local anesthetic effect, which is similar to that of amitriptyline and antiarrhythmic agents, such as lidocaine and quinidine.

In animal studies in which Propoxyphene and norPropoxyphene were continuously infused in large amounts, intracardiac conduction time (P‑R and QRS intervals) was prolonged. Any intracardiac conduction delay attributable to high concentrations of norPropoxyphene may be of relatively long duration.

Actions

Propoxyphene is a mild narcotic analgesic structurally related to methadone. The potency of Propoxyphene hydrochloride is from two‑thirds to equal that of codeine.

Indications and Usage for Propoxyphene

This product is indicated for the relief of mild to moderate pain.

Contraindications

Hypersensitivity to Propoxyphene.

Precautions

General

Propoxyphene should be administered with caution to patients with hepatic or renal impairment since higher serum concentrations or delayed elimination may occur.

Drug Interactions

The CNS depressant effect of Propoxyphene is additive with that of other CNS depressants, including alcohol.

As is the case with many medicinal agents, Propoxyphene may slow the metabolism of a concomitantly administered drug. Should this occur, the higher serum concentrations of that drug may result in increased pharmacologic or adverse effects of that drug. Such occurrences have been reported when Propoxyphene was administered to patients on antidepressants, anticonvulsants, or warfarin‑like drugs. Severe neurologic signs, including coma, have occurred with concurrent use of carbamazepine.

Usage in Pregnancy

Safe use in pregnancy has not been established relative to possible adverse effects on fetal development. Instances of withdrawal symptoms in the neonate have been reported following usage during pregnancy. Therefore, Propoxyphene should not be used in pregnant women unless, in the judgement of the physician, the potential benefits outweigh the possible hazards.

Usage in Nursing Mothers

Low levels of Propoxyphene have been detected in human milk. In postpartum studies involving nursing mothers who were given Propoxyphene, no adverse effects were noted in infants receiving mother"s milk.

Pediatric Use

Propoxyphene is not recommended for use in pediatric patients, because documented clinical experience has been insufficient to establish safety and a suitable dosage regimen in the pediatric age group.

Usage in the Elderly

The rate of Propoxyphene metabolism may be reduced in some patients. Increased dosing interval should be considered.

A Patient Information Sheet is available for this product. See text following “How Supplied” section below.

Adverse Reactions

In a survey conducted in hospitalized patients, less than 1% of patients taking Propoxyphene hydrochloride at recommended doses experienced side effects. The most frequently reported were dizziness, sedation, nausea, and vomiting. Some of the adverse reactions may be alleviated if the patient lies down.

Other adverse reactions include constipation, abdominal pain, skin rashes, lightheadedness, headache, weakness, euphoria, dysphoria, and minor visual disturbances.

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 occurred following chronic Propoxyphene overdosage.

Propoxyphene Dosage and Administration

This product is given orally. The usual dosage is 65 mg every four hours as needed for pain. The maximum recommended dose of Propoxyphene hydrochloride is 390 mg per day.

Consideration should be given to a reduced total daily dosage in patients with hepatic or renal impairment.

MANAGEMENT OF OVERDOSAGE

In all cases of suspected overdosage, call your regional Poison Control Center to obtain the most up‑to‑date information about the treatment of overdosage. This recommendation is made because, in general, information regarding the treatment of overdosage may change more rapidly than do package inserts.

Initial consideration should be given to the management of the CNS effects of Propoxyphene overdosage. Resuscitative measures should be initiated promptly.

Symptoms of Propoxyphene Overdosage

The manifestations of acute overdosage with Propoxyphene are those of narcotic overdosage. The patient is usually somnolent but may be stuporous or comatose and convulsing. Respiratory depression is characteristic. The ventilatory rate and/or tidal volume is decreased, which results in cyanosis and hypoxia. Pupils, initially pinpoint, may become dilated as hypoxia increases. Cheyne‑Stokes respiration and apnea may occur. Blood pressure and heart rate are usually normal initially, but blood pressure falls and cardiac performance deteriorates, which ultimately results in pulmonary edema and circulatory collapse, unless the respiratory depression is corrected and adequate ventilation is restored promptly. Cardiac arrhythmias and conduction delay may be present. A combined respiratory‑metabolic acidosis occurs owing to retained CO2 (hypercapnia) and to lactic acid formed during anaerobic glycolysis. Acidosis may be severe if large amounts of salicylates have also been ingested. Death may occur.

Treatment of Propoxyphene Overdosage

Attention should be directed first to establishing a patent airway and to restoring ventilation. Mechanically assisted ventilation with or without oxygen, may be required, and positive pressure respiration may be desirable if pulmonary edema is present. The narcotic antagonist naloxone will markedly reduce the degree of respiratory depression, and 0.4 to 2 mg should be administered promptly, preferably intravenously. If the desired degree of counteraction with improvement in respiratory functions is not obtained, naloxone should be repeated at 2 to 3 minute intervals. The duration of action of the antagonist may be brief. If no response is observed after 10 mg of naloxone have been administered, the diagnosis of Propoxyphene toxicity should be questioned. Naloxone may also be administered by continuous intravenous infusion.

Treatment of Propoxyphene Overdosage in Children

The usual initial dose of naloxone in children is 0.01 mg/kg body weight given intravenously. If this dose does not result in the desired degree of clinical improvement, a subsequent increased dose of 0.1 mg/kg body weight may be administered. If an IV route of administration is not available, naloxone may be administered IM or subcutaneously in divided doses. If necessary, naloxone can be diluted with sterile water for injection.

Blood gases, pH, and electrolytes should be monitored in order that acidosis and any electrolyte disturbance present may be corrected promptly. Acidosis, hypoxia, and generalized CNS depression predispose to the development of cardiac arrhythmias. Ventricular fibrillation or cardiac arrest may occur and necessitate the full complement of cardiopulmonary resuscitation (CPR) measures. Respiratory acidosis rapidly subsides as ventilation is restored and hypercapnia eliminated, but lactic acidosis may require intravenous bicarbonate for prompt correction.

Electrocardiographic monitoring is essential. Prompt correction of hypoxia, acidosis and electrolyte disturbance (when present) will help prevent these cardiac complications and will increase the effectiveness of agents administered to restore normal cardiac function.

In addition to the use of a narcotic antagonist, the patient may require careful titration with an anticonvulsant to control convulsions. Analeptic drugs (for example, caffeine or amphetamine) should not be used because of their tendency to precipitate convulsions.

General supportive measures, in addition to oxygen, include, when necessary, intravenous fluids, vasopressor‑inotropic compounds, and when infection is likely, anti‑infective agents. Gastric lavage may be useful, and activated charcoal can adsorb a significant amount of ingested Propoxyphene. Dialysis is of little value in poisoning due to Propoxyphene. Efforts should be made to determine whether other agents, such as alcohol, barbiturates, tranquilizers, or other CNS depressants, were also ingested, since these increase CNS depression as well as cause specific toxic effects.

How is Propoxyphene Supplied

Propoxyphene hydrochloride capsules, 65 mg, available in bottles of 100, 500, and 1000. The #3 pink capsule is imprinted "93"‑"741".

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

Dispense contents with a child-resistant closure (as required) and in a tight, light‑resistant container as defined in the USP/NF.

PATIENT INFORMATION SHEET

YOUR PRESCRIPTION FOR A Propoxyphene PRODUCT

Summary

Products containing Propoxyphene are used to relieve pain.

LIMIT YOUR INTAKE OF ALCOHOL WHILE TAKING THIS DRUG. Make sure your doctor knows if you are taking tranquilizers, sleep aids, antidepressants, antihistamines, or any other drugs that make you sleepy. Combining Propoxyphene with alcohol or these drugs in excessive doses is dangerous.

Use care while driving a car or using machines until you see how the drug affects you because Propoxyphene can make you sleepy. Do no take more of the drug than your doctor prescribed. Dependence has occurred when patients have taken Propoxyphene for a long period of time at doses greater than recommended.

The rest of this leaflet gives you more information about Propoxyphene. Please read it and keep it for future use.

Uses of Propoxyphene

Products containing Propoxyphene are used for the relief of mild to moderate pain.

Before Taking Propoxyphene

Make sure your doctor knows if you have ever had an allergic reaction to Propoxyphene.

The effect of Propoxyphene in children under 12 has not been studied. Therefore, use of the drug in this age group is not recommended.

How to Take Propoxyphene

Follow your doctor’s directions exactly. Do not increase the amount you take without your doctor’s approval. If you miss a dose of the drug, do not take twice as much the next time.

Pregnancy

Do not take Propoxyphene during pregnancy unless your doctor knows you are pregnant and specifically recommends its use. Cases of temporary dependence in the newborn have occurred when the mother has taken Propoxyphene consistently in the weeks before delivery. As a general principle, no drug should be taken during pregnancy unless it is clearly necessary.

General Cautions

Heavy use of alcohol with Propoxyphene is hazardous and may lead to overdosage symptoms (see Overdose below). THEREFORE, LIMIT YOUR INTAKE OF ALCOHOL WHILE TAKING Propoxyphene.

Combinations of excessive doses of Propoxyphene, alcohol, and tranquilizers are dangerous. Make sure your doctor knows if you are taking tranquilizers, sleep aids, antidepressant drugs, antihistamines, or any other drugs that make you sleepy. The use of these drugs with Propoxyphene increases their sedative effects and may lead to overdosage symptoms, including death (see Overdose below).

Propoxyphene may cause drowsiness or impair your mental and/or physical abilities; therefore, use caution when driving a vehicle or operating dangerous machinery. DO NOT perform any hazardous task until you have seen your response to this drug.

Propoxyphene may increase the concentration in the body of medications, such as anticoagulants (“blood thinners”), antidepressants, or drugs used for epilepsy. The result may be excessive or adverse effects of these medications. Make sure your doctor knows if you are taking any of these medications.

Dependence

You can become dependent on Propoxyphene if you take it in higher than recommended doses over a long period of time. Dependence is a feeling of need for the drug and a feeling that you cannot perform normally without it.

Overdose

An overdose of Propoxyphene, alone or in combination with other drugs, including alcohol, may cause weakness, difficulty in breathing, confusion, anxiety, and more severe drowsiness and dizziness. Extreme overdosage may lead to unconsciousness and death.

In any suspected overdosage situation, contact your doctor or nearest hospital emergency room. GET EMERGENCY HELP IMMEDIATELY.

KEEP THIS DRUG AND ALL DRUGS OUT OF THE REACH OF CHILDREN.

Possible Side Effects

When Propoxyphene is taken as directed, side effects are infrequent. Among those reported are drowsiness, dizziness, nausea, and vomiting. If these effects occur, it may help if you lie down and rest.

Less frequently reported side effects are constipation, abdominal pain, skin rashes, lightheadedness, headache, weakness, hallucinations, minor visual disturbances, and feelings of elation or discomfort.

If side effects occur and concern you, contact your doctor.

Other Information

The safe and effective use of Propoxyphene depends on your taking it exactly as directed. This drug has been prescribed specifically for you and your present condition. Do not give this drug to others who may have similar symptoms. Do not use it for any other reason.

If you would like more information about Propoxyphene, ask your doctor or pharmacist. They have a more technical leaflet (professional labeling) you may read.

Manufactured By:

TEVA PHARMACEUTICALS USA

Sellersville, PA 18960

Rev. N 7/2004

Propoxyphene Hydrochloride (Propoxyphene Hydrochloride)

PRODUCT INFO Product Code 0093-0741 Dosage Form CAPSULE Route Of Administration ORAL DEA Schedule

INGREDIENTS Name (Active Moiety) Type Strength Propoxyphene hydrochloride (Propoxyphene) Active 65 MILLIGRAM  In 1 CAPSULE corn starch Inactive   gelatin Inactive   lactose monohydrate Inactive   magnesium stearate Inactive   titanium dioxide Inactive   FD&C yellow #6 Inactive   D&C red #33 Inactive

IMPRINT INFORMATION Characteristic Appearance Characteristic Appearance Color PINK Score 1 Shape CAPSULE Symbol false Imprint Code 93;741 Coating false Size 16mm

PACKAGING # NDC Package Description Multilevel Packaging 1 0093-0741-01 100 CAPSULE In 1 BOTTLE None 2 0093-0741-05 500 CAPSULE In 1 BOTTLE None 3 0093-0741-10 1000 CAPSULE In 1 BOTTLE None

Revised: 10/2006