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DESCRIPTION
Propoxyphene is a semisynthetic opioid analgesic medication.
FORMS AND USES
Propoxyphene is used to treat mild pain syndromes. It is generally considered less potent than codeine.
Propoxyphene Hydrochloride
- The adult dosage of propoxyphene hydrochloride is 65 mg orally every 4 hours.
- Formulations include Darvon (65 mg) and Darvon Compound (propoxyphene 65 mg, aspirin 389 mg, caffeine 32 mg).
- Wygesic (propoxyphene 65mg, acetaminophen 650 mg) is also available.
Propoxyphene Napsylate
- The adult dosage of propoxyphene napsylate is 100 mg orally every 4 hours.
- Formulations include Darvon-N(100 mg), Darvocet N 100 (propoxyphene napsylate 100 mg, acetaminophen 650 mg), and Darvocet N 50 (propoxyphene napsylate 50 mg, acetaminophen 325 mg).
TOXIC DOSE
- Toxic effects have been reported after ingestion of propoxyphene hydrochloride 10 mg/kg.
- Death may occur after ingestion of 20 mg/kg.
PATHOPHYSIOLOGY
- The analgesic effect of propoxyphene is mediated by activation of opioid receptors.
- Propoxyphene and its primary metabolite, norpropoxyphene, are cardiotoxic.
- This effect is thought to be mediated by inhibition of cardiac membrane sodium conduction, producing QRS interval widening and dysrhythmia in overdose.
EPIDEMIOLOGY
- Poisoning is uncommon.
- Toxic effects following exposure are typically moderate.
- Death occurs in patients with severe overdose associated with seizures and cardiac toxicity.
CAUSES
- Toxicity is caused usually by suicidal ingestion
- Child abuse should be considered if the patient is less than 1 year of age; suicide attempt if the patient is over 6 years of age.
DRUG AND DISEASE INTERACTIONS
- Respiratory and CNS depression may be exacerbated by concurrent use of ethanol or sedative-hypnotics, or any other agent causing CNS depression.
- In utero exposure may lead to neonatal withdrawal.
- Geriatric patients with underlying cardiac and renal disease may be predisposed to dysrhythmias.
PREGNANCY AND LACTATION
US FDA Pregnancy Category C. The drug exerts animal teratogenic or embryocidal effects, but there are no controlled studies in women, or no studies are available in either animals or women.
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DIFFERENTIAL DIAGNOSIS
- Toxic causes of respiratory and CNS depression include benzodiazepines, ethanol, barbiturates, numerous sedative-hypnotic drugs, tricyclic antidepressants and others.
- Nontoxic causes include hypoxia, severe electrolyte abnormality, hypoglycemia, intracranial bleed, meningitis, encephalitis, and postictal state, among others.
SIGNS AND SYMPTOMS
Propoxyphene overdose has a presentation similar to that of other opioids, with CNS, respiratory depression, and miosis, but is unique in that seizures and cardiac toxicity also may occur.
Vital Signs
- Bradypnea, bradycardia, and hypotension may occur.
- Hypothermia may occur in comatose individuals.
HEENT
Miosis is common.
Dermatologic
Injection may cause skin necrosis or abscess.
Cardiovascular
- QRS or QT interval prolongation may occur.
- Ventricular dysrhythmias and conduction defects including heart block may occur.
Pulmonary
- Respiratory depression, bradypnea, and hypoventilation may occur.
- Aspiration pneumonia may complicate respiratory depression or seizures.
Gastrointestinal
Nausea, vomiting, anorexia, abdominal pain, and constipation may occur.
Neurologic
Drowsiness, sedation, and coma, as well as confusion, hallucinations, and seizures, may occur in overdose.
Endocrine
Nephrogenic diabetes insipidus is a rare complication of propoxyphene use.
PROCEDURES AND LABORATORY TESTS
Essential Tests
No tests may be needed in asymptomatic patients.
Recommended Tests
- Serum electrolytes, glucose BUN, and creatinine levels are used to assess renal injury and altered mental status.
- Pulse oximetry or arterial blood gases are used for assessment of altered mental status.
- ECG assesses cardiac effects and potential toxicity of combination products; propoxyphene may cause cardiac conduction abnormalities similar to type 1a antidysrhythmics.
- Serum acetaminophen and aspirin levels should be evaluated to detect occult ingestion.
- Urinalysis and serum creatine kinase are used to evaluate comatose patients for rhabdomyolysis.
Not Recommended Tests
Many opiate immunoassays will not detect propoxyphene.
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- Treatment should focus on airway management and immediate treatment of seizures or cardiac toxicity.
- Dose and time of exposure for all substances involved must be determined.
DIRECTING PATIENT COURSE
The health-care provider should call the poison control center when:
- Seizure, ECG abnormality, or other serious effects are present.
- Toxic effects are not consistent with propoxyphene toxicity.
- Coingestant, drug interaction, or underlying disease presents an unusual problem.
The patient should be referred to a health-care facility when:
- Attempted suicide or homicide is possible.
- Patient or caregiver seems unreliable.
- Any toxic effects develop.
- Coingestant, drug interaction, or underlying disease presents an unusual problem.
Admission Considerations
Inpatient management is warranted for patients who develop cardiac conduction abnormality, seizure, or persistent CNS or respiratory depression.
DECONTAMINATION
Out of Hospital
Emesis should not be induced because CNS depression may develop rapidly.
In Hospital
- Gastric lavage should be performed in pediatric (tube size 24-32 French) or adult (tube size 36-42 French) patients presenting within 1 hour of a large ingestion or if serious effects are present.
- One dose of activated charcoal (1-2 g/kg) should be administered without a cathartic if a substantial ingestion has occurred within the previous few hours.
- Multiple-dose activated charcoal increases propoxyphene elimination but is not recommended due to potential for complications and lack of effect on duration of toxicity.
ANTIDOTES
Naloxone is used as an antidote.
- Indications: altered mental status of undetermined etiology (naloxone often does not effectively treat cardiac effects or respiratory depression).
- Absolute contraindications: none.
- Method of administration
- Adult or pediatric dose of 2.0 to 10.0 mg should be administered in 2.0-mg increments.
- Cumulative dose of 10.0 to 20.0 mg may be needed for propoxyphene.
- If only partial response is achieved, influence of another agent should be suspected.
- Potential adverse effects
- Naxolone may induce withdrawal syndrome.
- Reversal of opioid effects may unmask another underlying toxicity such as cocaine.
ADJUNCTIVE TREATMENT
Hypotension
- Hypotension related to bradycardia is corrected by atropine; an infusion of 10 to 20 ml/kg 0.9% saline also should be started and the patient placed in the Trendelenburg position.
- Further fluid therapy should be guided by central pressure monitoring to avoid volume overload.
- A vasopressor can be added, if needed.
Seizures
- Patency of airway must be ensured.
- A benzodiazepine should be administered for initial control.
- If seizures persist or recur, another anticonvulsant such as phenobarbital should be added.
Ventricular Dysrhythmia or Conduction Abnormality
- Seizures should be controlled rapidly and acidemia corrected.
- If QRS widening or dysrhythmia persists, sodium bicarbonate 1 to 2 mEq/kg intravenous bolus should be administered to increase the arterial pH to 7.45 to 7.55 and to narrow the complex width.
- An arterial pH of 7.55 should not be exceeded.
- Bretylium may be administered, 5 mg/kg over 1 minute; if unsuccessful, then a dose of 10 mg/kg over 1 minute should be administered and repeated as necessary for a total dose of 30 mg/kg.
Not Recommended Therapies
Procainamide, quinidine, and other type 1a antidysrhythmics should be avoided.
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PATIENT MONITORING
- Respiratory and cardiac parameters should be monitored continuously in all patients.
- Electroencephalographic (EEG) monitoring may be needed in patients with seizures that have been intubated and paralyzed.
EXPECTED COURSE AND PROGNOSIS
- Toxicity usually develops within hours and resolves over 24 hours.
- CNS depression following massive doses may require a longer recovery period.
- Possible complications include end-organ injury from hypotension or seizures.
DISCHARGE CRITERIA/INSTRUCTIONS
- From the emergency department
- Asymptomatic patients with a normal ECG may be discharged following decontamination, 6 hours of observation, and psychiatric evaluation, if needed.
- Patients receiving naloxone should be asymptomatic for 6 hours following naloxone administration before discharge.
- From the hospital. Patients may be discharged after resolution of toxic effects and psychiatric evaluation, if needed.
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DIAGNOSIS
Many products containing propoxyphene also contain acetaminophen or aspirin, and these coingestants may be overlooked.
TREATMENT
- Naloxone should not be used to treat cardiac conduction abnormalities.
- Large amounts of naloxone may be required to reverse the effects of propoxyphene intoxication causing hypotension or seizures.
- Due to short duration of action of naloxone, propoxyphene toxicity is likely to recur following naloxone administration.
Section Outline:
ICD-9-CM 965.0Poisoning by analgesics, antipyretics, and antirheumatics: opiates and related drugs.
See Also: SECTION II, Hypotension, Seizures, and Ventricular Dysrhythmias chapters; SECTION III, Naloxone chapter; and SECTION IV, Acetaminophen and Salicylate chapters.
RECOMMENDED READING
POISINDEX Editorial Staff. Propoxyphene. In: Rumack BH, Sayre NK, Gelman CR, eds. POISINDEX system. Englewood, CO: Micromedex, Inc. (edition expires November 30, 1997).
Author: Lada Kokan
Reviewer: Katherine M. Hurlbut