Propoxyphene

Pronunciation

(proe POKS i feen)

U.S. Brand Names

Darvon®; Darvon-N®

Synonyms

Dextropropoxyphene; Propoxyphene Hydrochloride; Propoxyphene Napsylate

Generic Available

Yes: Capsule

Canadian Brand Names

Darvon-N®; 642® Tablet

Use

Management of mild to moderate pain

Restrictions

C-IV

Pregnancy Risk Factor

C/D (prolonged use)

Pregnancy Implications

Withdrawal symptoms have been reported in the neonate following propoxyphene use during pregnancy. Teratogenic effects have also been noted in case reports. Opioid analgesics are considered pregnancy risk factor D if used for prolonged periods or in large doses near term.

Lactation

Enters breast milk/use caution (AAP rates "compatible")

Contraindications

Hypersensitivity to propoxyphene or any component of the formulation

Warnings/Precautions

When given in excessive doses, either alone or in combination with other CNS depressants, propoxyphene is a major cause of drug-related deaths; do not exceed recommended dosage; give with caution in patients dependent on opiates, substitution may result in acute opiate withdrawal symptoms. Avoid use in severely depressed or suicidal patients. Tolerance or drug dependence may result from extended use. Propoxyphene should be used with caution in patients with renal or hepatic dysfunction or in the elderly; consider dosing adjustment.

Adverse Reactions

Frequency not defined.

Cardiovascular: Hypotension, bundle branch block

Central nervous system: Dizziness, lightheadedness, sedation, paradoxical excitement and insomnia, fatigue, drowsiness, mental depression, hallucinations, paradoxical CNS stimulation, increased intracranial pressure, nervousness, headache, restlessness, malaise, confusion, dysphoria, vertigo

Dermatologic: Rash, urticaria

Endocrine & metabolic: Hypoglycemia, urinary 17-OHCS decreased

Gastrointestinal: Anorexia, stomach cramps, xerostomia, biliary spasm, nausea, vomiting, constipation, paralytic ileus, abdominal pain

Genitourinary: Urination decreased, ureteral spasms

Hepatic: LFTs increased, jaundice

Neuromuscular & skeletal: Weakness

Ocular: Visual disturbances

Respiratory: Dyspnea

Miscellaneous: Psychologic and physical dependence with prolonged use, histamine release, hypersensitivity reaction

Overdosage/Toxicology

Symptoms of overdose include CNS disturbances, respiratory depression, hypotension, pulmonary edema, and seizures. Naloxone, 2 mg I.V. with repeat administration as necessary up to a total of 10 mg, can also be used to reverse toxic effects of the opiate. Charcoal is very effective (>95%) at binding propoxyphene.

Drug Interactions

Inhibits CYP2C8/9 (weak), 2D6 (weak), 3A4 (weak)

Decreased effect with charcoal, cigarette smoking

Increased toxicity: CNS depressants may potentiate pharmacologic effects; propoxyphene may inhibit the metabolism and increase the serum concentrations of carbamazepine, phenobarbital, MAO inhibitors, tricyclic antidepressants, and warfarin

Ethanol/Nutrition/Herb Interactions

Ethanol: Avoid or limit ethanol (may increase CNS depression). Watch for sedation.

Food: May decrease rate of absorption, but may slightly increase bioavailability.

Stability

Store at controlled room temperature of 15°C to 30°C (59°F to 86°F).

Mechanism of Action

Propoxyphene is a weak narcotic analgesic which acts through binding to opiate receptors to inhibit ascending pain pathways. Propoxyphene, as with other narcotic (opiate) analgesics, blocks pain perception in the cerebral cortex by binding to specific receptor molecules (opiate receptors) within the neuronal membranes of synapses. This binding results in a decreased synaptic chemical transmission throughout the CNS thus inhibiting the flow of pain sensations into the higher centers. Mu and kappa are the two subtypes of the opiate receptor which propoxyphene binds to to cause analgesia.

Pharmacodynamics/Kinetics

Onset of action: 0.5-1 hour

Duration: 4-6 hours

Metabolism: Hepatic to active metabolite (norpropoxyphene) and inactive metabolites; first-pass effect

Half-life elimination: Adults: Parent drug: 6-12 hours; Norpropoxyphene: 30-36 hours

Excretion: Urine (primarily as metabolites)

Dosage

Oral:

Children: Doses for children are not well established; doses of the hydrochloride of 2-3 mg/kg/d divided every 6 hours have been used

Adults:

Hydrochloride: 65 mg every 3-4 hours as needed for pain; maximum: 390 mg/day

Napsylate: 100 mg every 4 hours as needed for pain; maximum: 600 mg/day

Elderly:

Hydrochloride: 65 mg every 4-6 hours as needed for pain

Napsylate: 100 mg every 4-6 hours as needed for pain

Dosing adjustment in renal impairment: Serum concentrations of propoxyphene may be increased or elimination may be delayed. Avoid use in Clcr<10 mL/minute. Specific dosing recommendations not available for less severe impairment.

Not dialyzable (0% to 5%)

Dosing adjustment in hepatic impairment: Serum concentrations of propoxyphene may be increased or elimination may be delayed; specific dosing recommendations not available.

Administration

Should be administered with glass of water on an empty stomach. Food may decrease rate of absorption, but may slightly increase bioavailability.

Monitoring Parameters

Pain relief, respiratory and mental status, blood pressure

Reference Range

Therapeutic: Ranges published vary between laboratories and may not correlate with clinical effect

Therapeutic concentration: 0.1-0.4 mcg/mL (SI: 0.3-1.2 mol/L)

Toxic: >0.5 mcg/mL (SI: >1.5 mol/L)

Test Interactions

False-positive methadone test

Dietary Considerations

May administer with food if gastrointestinal distress occurs.

Patient Education

Take as directed; do not take a larger dose or more often than prescribed. Do not use alcohol, other prescription or OTC sedatives, tranquilizers, antihistamines, or pain medications without consulting prescriber. May cause dizziness, drowsiness, or impaired judgment; avoid driving or engaging in tasks requiring alertness until response to drug is known. If you experience vomiting or loss of appetite, frequent mouth care, small, frequent meals, chewing gum, or sucking lozenges may help. Increased fluid intake, exercise, fiber in diet may help with constipation (if unresolved consult prescriber). Report unresolved nausea or vomiting, respiratory difficulty or shortness of breath, or unusual weakness. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant.

Nursing Implications

Monitor pain relief, respiratory and mental status, blood pressure, excessive sedation

Additional Information

100 mg of napsylate = 65 mg of hydrochloride

Propoxyphene hydrochloride: Darvon®

Propoxyphene napsylate: Darvon-N®

Anesthesia and Critical Care Concerns/Other Considerations

Equivalent dosing: 100 mg of napsylate = 65 mg of hydrochloride

Dental Health: Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Xerostomia (normal salivary flow resumes upon discontinuation).

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

Dizziness, drowsiness, insomnia, and paradoxical excitement are common; may cause nervousness, restlessness, confusion; may rarely cause depression or hallucinations

Mental Health: Effects on Psychiatric Treatment

Concurrent use with psychotropics may produce additive sedation as well as increase their serum levels; monitor for altered clinical response or preferably, use a different analgesic

Dosage Forms

Capsule, as hydrochloride (Darvon®): 65 mg

Tablet, as napsylate (Darvon-N®): 100 mg

References

"American Academy of Pediatrics Committee on Drugs. The Transfer of Drugs and Other Chemicals Into Human Milk,"Pediatrics, 2001, 108(3):776-89.

"Drugs for Pain,"Med Lett Drugs Ther, 2000, 42(1085):73-8.

Ferrell BA, "Pain Management in Elderly People,"J Am Geriatr Soc, 1991, 39(1):64-73.

Finkle BS, "Self-Poisoning With Dextropropoxyphene and Dextropropoxyphene Compounds: The USA Experience,"Hum Toxicol, 1984, 3(Suppl):115-34.

Hasday JD and Weintraub M, "Propoxyphene in Children With Iatrogenic Morphine Dependence,"Am J Dis Child, 1983, 137(8):745-8.

Lawson AA and Northridge DB, "Dextropropoxyphene Overdose. Epidemiology, Clinical Presentation, and Management,"Med Toxicol Adverse Drug Exp, 1987, 2(6):430-44.

Miller RR, "Propoxyphene: A Review,"Am J Hosp Pharm, 1977, 34(4):413-23.

Mokhlesi B, Leikin JB, Murray P, et al, "Adult Toxicology in Critical Care: Part II: Specific Poisonings,"Chest, 2003, 123(3):897-922.

Proudfoot AT, "Clinical Features and Management of Distalgesic Overdose,"Hum Toxicol, 1984, 3(Suppl):85-94.

Rathmell JP, Viscomi CM, and Ashburn MA, "Management of Nonobstetric Pain During Pregnancy and Lactation,"Anesth Analg, 1997, 85(5):1074-87.

Stork CM, Redd JT, Fine K, et al, "Propoxyphene-Induced Wide QRS Complex Dysrhythmia Responsive to Sodium Bicarbonate - A Case Report,"J Toxicol Clin Toxicol, 1995, 33(2):179-83.

Tennant FS Jr, "Complications of Propoxyphene Abuse,"Arch Intern Med, 1973, 132(2):191-4.

Wetli CV and Bednarczyk LR, "Deaths Related to Propoxyphene Overdose: A Ten Year Assessment,"South Med J, 1980, 73(9):1205-9.

International Brand Names

Abalgin® (DK, FI); Acrogesico® (EC); Darvon® (ES); Darvon-N® (CA); Darvon N® (RO); Deprancol® (ES); Depronal® (BE, LU, NL); Dexofen® (SE); Dextropropoxifen "Dak"® (DK); Dextropropoxifeno Bouzen® (AR); Distalgesic® (IE, SE); Doloxene® (AU, DK, GB, IE, NZ, SE, ZA); Lentadol® (AR); Liberen® (IT); Parvodex® (IN); Proxifen® (EC); Romidon® (GR); 642® Tablet (CA); Zideron® (GR)