Darvon ® (Propoxyphene Hydrochloride, USP) 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 accompanying structural formula. Its molecular weight is 375.94.

Each Pulvule contains 65 mg (172.9 µmol) propoxyphene hydrochloride. It also contains D & C Red No. 33, F D & C Yellow No. 6, gelatin, magnesium stearate, silicone, starch, titanium dioxide, and other inactive ingredients.

For the relief of mild to moderate pain.

Darvon is given orally. The usual dosage is 65 mg propoxyphene hydrochloride every 4 hours as needed for pain. The maximum recommended dose of propoxyphene hydrochloride is 390 mg/day.

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

Darvon ® Pulvules ® are available in:
65 mg capsules with opaque pink body and cap, imprinted with the script "Darvon" on the body, in edible black ink.

They are available as follows:

Bottles of 100                                        NDC 66479-510-10

Storage: Store at 20º to 25º C (68º to 77º F ) [see USP Controlled Room Temperature]

© 2006
Marketed by: Xanodyne Pharmaceuticals Inc., Newport, KY 41071
REV. 02-2006
FDA rev date: 8/1/2002

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 these adverse reactions may be alleviated if the patient lies down.

Other adverse reactions include constipation, abdominal pain, skin rashes, lightheadedness, headache, weakness, euphoria, dysphoria, hallucinations, 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.

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.

Drug Dependence-Propoxyphene, when taken in higher-than-recommended doses over long periods of time, can produce drug dependence characterized by psychic dependence and, less frequently, physical dependence and tolerance. Propoxyphene will only partially suppress the withdrawal syndrome in individuals physically dependent on morphine or other narcotics. The abuse liability of propoxyphene is qualitatively similar to that of codeine although quantitatively less, and propoxyphene should be prescribed with the same degree of caution appropriate to the use of codeine.

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.

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

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 judgment 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.

Usage in Pediatric Patients-Safety and effectiveness in pediatric patients have not been established.

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.

In all cases of suspected overdosage, call your regional Poison Control Center to obtain the most up-to-date information about the treatment of overdose. 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 CO 2 (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 Pediatric Patients-The usual initial dose of naloxone in pediatric patients 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.

Hypersensitivity to propoxyphene.

Propoxyphene is a centrally acting narcotic analgesic agent. Equimolar doses of propoxyphene hydrochloride or napsylate provide 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 1/2 hours. After a 65-mg oral dose of propoxyphene hydrochloride, peak plasma levels of 0.05 to 0.1 µg/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 (PR 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.

YOUR PRESCRIPTION FOR A DARVON®
(PROPOXYPHENE) PRODUCT

Summary

Products containing Darvon 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 not 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 Darvon

Products containing Darvon are used for the relief of mild to moderate pain. Products that contain Darvon plus aspirin or acetaminophen are prescribed for the relief of pain or pain associated with fever.

Before Taking Darvon

Make sure your doctor knows if you have ever had an allergic reaction to propoxyphene, aspirin, or acetaminophen. Some forms of propoxyphene products contain aspirin to help relieve the pain. Your doctor should be advised if you have a history of ulcers or if you are taking an anticoagulant ("blood thinner"). The aspirin may irritate the stomach lining and may cause bleeding, particularly if an ulcer is present. Also, bleeding may occur if you are taking an anticoagulant. In a small group of people, aspirin may cause an asthma attack. If you are one of these people, be sure your drug does not contain aspirin.

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

Also, due to the possible association between aspirin and Reye Syndrome, those propoxyphene products containing aspirin should not be given to children, including teenagers, with chicken pox or flu unless prescribed by a physician. The following propoxyphene product contains aspirin:
Darvon ® Compound-65 (Propoxyphene Hydrochloride, Aspirin, and Caffeine, USP)

How to Take Darvon

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 Darvon, 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.

If the propoxyphene product contains acetaminophen, the overdosage symptoms include nausea, vomiting, lack of appetite, and abdominal pain. Liver damage may occur.

When the propoxyphene product contains aspirin, symptoms of taking too much of the drug are headache, dizziness, ringing in the ears, difficulty in hearing, dim vision, confusion, drowsiness, sweating, thirst, rapid breathing, nausea, vomiting, and, occasionally, diarrhea.

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 THE PEDIATRIC POPULATION.

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.

Darvon, Darvon-N, Darvocet-N and Darvocet are registered trademarks of Xanodyne Pharmaceuticals Inc.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

PROPOXYPHENE - ORAL

(pro-POX-ee-feen)

COMMON BRAND NAME(S): Darvon, Darvon-N

WARNING: Propoxyphene has caused death when taken in large doses, either alone or with alcohol/drugs that can cause drowsiness (e.g., antidepressants, sedatives, muscle relaxants). Do not take this medication more often or use a larger dose than prescribed. Limit alcoholic beverages. Before taking this medication, tell your doctor or pharmacist of all the medications you may use.

USES: This medication is used to treat mild-to-moderate pain. It acts on certain centers in the brain to give you pain relief. This medication is a narcotic pain reliever (opiate-type).

HOW TO USE: Read the Patient Information Leaflet provided by your pharmacist before you start using propoxyphene and each time you get a refill. If you have any questions, consult your doctor or pharmacist.

Take this medication by mouth with or without food, usually every 4 hours or as directed by your doctor. Do not take more than 6 tablets/capsules in a 24-hour period. If you have nausea, you may take this drug with food. Also, consult your doctor or pharmacist about other ways to decrease nausea (e.g., antihistamines, lying down for 1-2 hours with as little head movement as possible).

The dosage is based on your medical condition and response to therapy. Pain medications work best if they are used as the first signs of pain occur. If you wait until the pain has worsened, the medication may not work as well.

You may also take long-acting narcotic medications or use narcotic patches for ongoing pain if so directed by your doctor. In that case, this medication might be used for sudden (breakthrough) pain only as needed. Also follow your doctor's or pharmacist's instructions for safely using non-narcotic pain relievers (e.g., naproxen, ibuprofen). Ask your doctor or pharmacist if you have any questions.

This medication may cause dependence, especially if it has been used regularly for an extended time or if it has been used in high doses. In such cases, withdrawal reactions (e.g., restlessness, watery eyes, runny nose) may occur if you suddenly stop this drug. To prevent withdrawal reactions when stopping extended, regular treatment with this drug, gradually reduce the dosage as directed. Consult your doctor or pharmacist for more details, and report any withdrawal reactions immediately.

Though very unlikely, abnormal drug-seeking behavior (addiction) is possible with this medication. To lessen the risk of becoming addicted, do not increase your dose, take it more frequently, or take it for a longer time than prescribed. Properly stop the medication when so directed.

When used for an extended period, this medication may not work as well and may require different dosing. Talk with your doctor if this medication stops working well.

Inform your doctor if your pain persists or worsens.

SIDE EFFECTS: Nausea, vomiting, constipation, lightheadedness, dizziness, drowsiness, abdominal pain, or headache may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.

To prevent constipation, maintain a diet adequate in fiber, drink plenty of water, and exercise. If you become constipated while using this drug, consult your pharmacist for help in selecting a laxative (e.g., stimulant-type with stool softener).

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: slow/shallow breathing, mental/mood changes, vision changes, dark urine, yellowing eyes/skin, persistent nausea/vomiting, severe stomach/abdominal pain.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any of the following symptoms of a serious allergic reaction: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking propoxyphene, tell your doctor or pharmacist if you are allergic to it; or to other narcotic pain medications (e.g., methadone, morphine) or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: personal or family history of regular use/abuse of drugs/alcohol, thoughts of suicide or history of suicide attempt, intoxication with medications that depress the nervous system or your breathing (CNS/respiratory depressants such as alcohol or tranquilizers/sedatives), infectious diarrhea.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: brain disorders (e.g., seizures, head injury, tumor, increased intracranial pressure), heart problems (e.g., irregular heartbeat), lung diseases (e.g., chronic obstructive pulmonary disease-COPD, hypoxia, hypercapnia), disease of the pancreas (e.g., pancreatitis), mental/mood disorders (e.g., toxic psychosis, depression), a certain spinal problem (kyphoscoliosis), gallbladder disease, kidney disease, liver disease, adrenal gland problem (e.g., Addison's disease), difficulty urinating (e.g., due to enlarged prostate or urethral stricture), underactive thyroid (hypothyroidism), intestinal diseases (e.g., colitis), recent bowel/abdominal surgery.

This drug may make you dizzy or drowsy. Use caution while driving, using machinery, or taking part in any other activity that requires alertness. Limit alcoholic beverages because they may increase the risk of this drug's side effects.

To lower your risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

Caution is advised when using this drug in the elderly because they may be more sensitive to its effects.

During pregnancy, this medication should be used only when clearly needed. Using it for long periods or in high doses near the expected delivery date is not recommended because of possible harm to the unborn baby. Discuss the risks and benefits with your doctor. Infants born to mothers who have used this medication for an extended time may have withdrawal symptoms such as irritability, abnormal/persistent crying, vomiting, or diarrhea. Tell your doctor immediately if you notice any of these symptoms in your newborn.

This medication passes into breast milk. Though there have been no reports of harm to nursing infants, consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.

This drug should not be used with the following medication because a very serious interaction may occur: naltrexone.

If you are currently using this medication listed above, tell your doctor or pharmacist before starting propoxyphene.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: "blood thinners" (e.g., warfarin), carbamazepine, cimetidine, MAO inhibitors (e.g., furazolidone, isocarboxazid, linezolid, moclobemide, phenelzine, procarbazine, rasagiline, selegiline, tranylcypromine), other medications for pain (e.g., pentazocine, nalbuphine), ritonavir, tipranavir, tricyclic antidepressants (e.g., doxepin).

Tell your doctor or pharmacist if you also take drugs that cause drowsiness such as: certain antihistamines (e.g., diphenhydramine), anti-seizure drugs (e.g., phenytoin), medicine for sleep or anxiety (e.g., alprazolam, diazepam, zolpidem), muscle relaxants, narcotic pain relievers (e.g., codeine), psychiatric medicines (e.g., chlorpromazine, risperidone, amitriptyline, trazodone).

Check the labels on all your medicines (e.g., cough-and-cold products) because they may contain drowsiness-causing ingredients. Ask your pharmacist about using those products safely.

This medication may interfere with certain laboratory tests (including amylase and lipase levels), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents should call the US National Poison Hotline at 1-800-222-1222. Canada residents should call a provincial poison control center. Symptoms of overdose may include: slow breathing, slow/irregular heartbeat, loss of consciousness, muscle pain, seizures.

NOTES: Do not share this medication with others. It is against the law.

This medication has been prescribed for your current condition only. Do not use it later for another condition unless told to do so by your doctor. A different medication may be necessary in that case.

MISSED DOSE: If you take this medication regularly and you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature at 77 degrees F (25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.