On November 19, 2010, Xanodyne announced a voluntary withdrawal of propoxyphene-containing preparations (Darvon®, Darvocet®) from the US market. The withdrawal was requested by FDA following review of new data on cardiac risk. (See Cardiac Effects under Cautions.) FDA requested that manufacturers of generic propoxyphene-containing preparations also voluntarily withdraw these preparations from the US market.
[Posted 01/13/2011] ISSUE: FDA notified healthcare professionals that it has asked drug manufacturers to limit the strength of acetaminophen in prescription drug products, predominantly combinations of acetaminophen and opioids, to 325 mg per tablet, capsule, or other dosage unit, making these products safer for patients. This action will help to reduce the risk of severe liver injury and allergic reactions associated with acetaminophen. A Boxed Warning highlighting the potential for severe liver injury and a Warning highlighting the potential for allergic reactions (swelling of the face, mouth, and throat, difficulty breathing, itching, or rash) will be added to the label of all prescription drug products that contain acetaminophen.
BACKGROUND: Acetaminophen, one of the most commonly used drugs in the United States, is widely and effectively used in both prescription and over-the-counter (OTC) products to reduce pain and fever. Examples of prescription products that contain acetaminophen include hydrocodone with acetaminophen (Vicodin, Lortab), and oxycodone with acetaminophen (Tylox, Percocet). OTC products containing acetaminophen (e.g., Tylenol) are not affected by this action. Information about the potential for liver injury is already required on the label for OTC products containing acetaminophen. FDA is continuing to evaluate ways to reduce the risk of acetaminophen related liver injury from OTC products. No drug shortages are expected, because the 3-year implementation period should permit adequate time for necessary reformulations.
RECOMMENDATION: Healthcare professionals were reminded to advise patients not to exceed the acetaminophen maximum total daily dose (4 grams/day), and not to drink alcohol while taking acetaminophen-containing medications.
Healthcare professionals were encouraged to inform patients that there is no immediate danger to patients who take these combination pain medications, and patients should continue to take them as directed by their health care provider. The Drug Safety Communication provides additional information for healthcare professionals, information for patients, a data summary and a list of all affected products. For more information visit the FDA website at: [Web] and [Web].
REMS:
FDA approved a REMS for propoxyphene to ensure that the benefits of a drug outweigh the risks. The REMS may apply to one or more preparations of propoxyphene and consists of the following: medication guide. See the FDA REMS page ([Web]) or the ASHP REMS Resource Center ([Web]).
Pending revision, the material in this section should be considered in light of more recently available information in the MEDWATCH notification at the beginning of this monograph.
Pain
Relief of mild to moderate pain. Therapy in combination with acetaminophen or aspirin or with aspirin and caffeine may result in greater analgesia; however, some studies have shown no difference in analgesia.
Dosage and Administration
Administration
Oral Administration
Administer orally.
Dosage
Pending revision, the material in this section should be considered in light of more recently available information in the MEDWATCH notification at the beginning of this monograph.
Available as propoxyphene hydrochloride and propoxyphene napsylate; dosage expressed in terms of the salt.
Propoxyphene napsylate 100 mg is equivalent to propoxyphene hydrochloride 65 mg.
Adults
Pain
Oral
Propoxyphene hydrochloride: Usual dosage is 65 mg every 4 hours as needed. Doses <65 mg have questionable efficacy.
Propoxyphene napsylate: Usual dosage is 100 mg every 4 hours as needed.
Prescribing Limits
Adults
Pain
Oral
Propoxyphene hydrochloride: Maximum 390 mg daily.
Propoxyphene napsylate: Maximum 600 mg daily.
Special Populations
Hepatic Impairment
Consider dosage reduction.
Renal Impairment
Consider dosage reduction.
Geriatric Patients
Consider increase in dosing interval.
Cautions
Contraindications
Known hypersensitivity to propoxyphene or any ingredient in the formulation.
Pending revision, the material in this section should be considered in light of more recently available information in the MEDWATCH notification at the beginning of this monograph.
Opiate Withdrawal
Caution in patients dependent on opiates. Will not support morphine dependence; sudden substitution of usual propoxyphene dosage for opiates may result in acute opiate withdrawal symptoms. Avoid withdrawal symptoms by gradually reducing dosage of prior opiate as propoxyphene is substituted.
Abuse Potential
Possible tolerance, psychologic dependence, and physical dependence. Dependence liability is qualitatively similar to that of codeine, but quantitatively less.
CNS Depression
Performance of activities requiring mental alertness and physical coordination may be impaired.
Concurrent use of other CNS depressants may potentiate CNS depression. (See Specific Drugs under Interactions.)
Acute Toxicity
Pending revision, the material in this section should be considered in light of more recently available information in the MEDWATCH notification at the beginning of this monograph.
Propoxyphene preparations alone or in combination with other CNS depressants (e.g., alcohol) are a major cause of drug-related deaths; usually related to intentional overdose, but may be accidental. (See Contraindications under Cautions.)
General Precautions
Fixed-Combination Products
When used in fixed combination with other drugs, consider the cautions, precautions, and contraindications associated with the other drug(s).
Specific Populations
Pregnancy
Category C (category D, if used for prolonged periods).
Manufacturer states that safe use during pregnancy has not been established. Cases of withdrawal symptoms in neonates reported following use during pregnancy. Use during pregnancy only when potential benefits outweigh possible risks to fetus.
Lactation
Distributed into milk in low concentrations. Use with caution; however, in postpartum studies involving nursing women who received propoxyphene, no adverse effects observed in breast-fed infants.
Pediatric Use
Safety and efficacy not established.
Geriatric Use
Potential for reduced rate of propoxyphene metabolism. (See Geriatric Patients under Dosage and Administration.)
Hepatic Impairment
Use with caution; serum concentrations of the drug may be increased or elimination may be delayed. (See Hepatic Impairment under Dosage and Administration.)
Renal Impairment
Use with caution; serum concentrations of the drug may be increased or elimination may be delayed. (See Renal Impairment under Dosage and Administration.)
Absorbed principally in the upper small intestine following oral administration. Peak plasma concentrations usually achieved within 2–2.5 hours (propoxyphene hydrochloride) or 3 hours (propoxyphene napsylate).
In large doses, the napsylate salt appears to be absorbed more gradually than the hydrochloride salt.
Equimolar doses of propoxyphene hydrochloride or napsylate provide similar plasma concentrations.
Distribution
Extent
Distributed into CSF. Assumed to cross the placenta; however, placental fluid and fetal blood concentrations have not been determined. Distributed into milk in low concentrations.
Elimination
Metabolism
Metabolized mainly in the liver.
Approximately 25% of a dose is metabolized to norpropoxyphene (which has less CNS depressant activity than propoxyphene but greater local anesthetic effect).
Elimination Route
Propoxyphene and norpropoxyphene are excreted unchanged in urine.
Half-life
Propoxyphene: 6–12 hours.
Norpropoxyphene: 30–36 hours.
Stability
Storage
Oral
Capsules and Tablets
Tight, light resistant container at 15–30 °C.
Actions
Mild analgesic effects at usual dosages.
No antipyretic action and little or no antitussive activity. Norpropoxyphene has a local anesthetic effect.
Advice to Patients
Pending revision, the material in this section should be considered in light of more recently available information in the MEDWATCH notification at the beginning of this monograph.
Potential for drug to impair mental alertness or physical coordination; use caution when driving or operating machinery until effects on individual are known.
Importance of taking exactly as prescribed; do not exceed recommended dosage.
Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, and alcohol consumption. Importance of limiting alcohol intake.
Importance of women informing their clinicians if they are or plan to become pregnant or plan to breast-feed.
Importance of informing patients of other important precautionary information. (See Cautions.)
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Subject to control under the Federal Controlled Substances Act of 1970 as schedule IV (C-IV) drugs.
Propoxyphene Hydrochloride
Routes
Dosage Forms
Strengths
Brand Names
Manufacturer
Oral
Capsules
65 mg*
Darvon® Pulvules® ( C-IV)
Lilly
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Propoxyphene Napsylate
Routes
Dosage Forms
Strengths
Brand Names
Manufacturer
Oral
Tablets, film-coated
100 mg
Darvon-N® ( C-IV)
aaiPharma
Propoxyphene Napsylate Combinations
Routes
Dosage Forms
Strengths
Brand Names
Manufacturer
Oral
Tablets, film-coated
50 mg with Acetaminophen 325 mg*
Darvocet-N® 50 ( C-IV)
aaiPharma
100 mg with Acetaminophen 500 mg
Darvocet A500® ( C-IV)
aaiPharma
100 mg with Acetaminophen 650 mg*
Darvocet-N® 100 ( C-IV)
aaiPharma
Propocet® 100 ( C-IV)
Teva
* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name
Comparative Pricing
This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 09/2009. For the most current and up-to-date pricing information, please visit www.drugstore.com. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.
Remember, keep this and all other medicines out of the reach of children,
never share your medicines with others, and use this medication only for the indication prescribed.