Levo-Dromoran (Levorphanol Tartrate) - Drug Interactions, Contraindications, Overdosage

DRUG INTERACTIONS

Use in Ambulatory Patients

Levo-Dromoran has been used in both inpatient and outpatient settings, but both physicians and patients must be aware of the risk of orthostatic hypotension, dizziness and syncope in ambulatory patients.

As with other opioids, the use of Levo-Dromoran may impair mental and/or physical abilities required for the performance of potentially hazardous tasks or for the exercise of normal good judgement and patients and staff should be advised accordingly.

Concurrent use of Levo-Dromoran with central nervous system depressants (eg, alcohol, sedatives, hypnotics, other opioids, barbiturates, tricyclic antidepressants, phenothiazines, tranquilizers, skeletal muscle relaxants and antihistamines) may result in additive central nervous system depressant effects.

Carcinogenesis, Mutagenesis, Impairment of Fertility

No information about the effects of Levo-Dromoran on carcinogenesis, mutagenesis, or fertility is available.

Pregnancy

Teratogenic Effects

Pregnancy Category C. Levo-Dromoran has been shown to be teratogenic in mice when given at a single oral dose of 25 mg/kg. The tested dose caused a near 50% mortality of the mouse embryos. There are no adequate and well-controlled studies in pregnant women. Levo-Dromoran should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects

Babies born to mothers who have been taking opioids regularly prior to delivery may be physically dependent.

A study in rabbits has demonstrated that at doses of 1.5 to 20 mg/kg, Levo-Dromoran administered intravenously crosses the placental barrier and depresses fetal respiration.

OVERDOSAGE

Most reports of overdosage known to the manufacturer and to the FDA involve three clinical situations. These are: 1. the use of larger than recommended doses or too frequent doses, 2. administration of the drug to children or small adults without any reduction in dosage, and 3. the use of the drug in ordinary dosage in patients compromised by concurrent illness.

As with all opioids, overdose can occur due to accidental or intentional misuse of this product, especially in infants and children who may gain access to the drug in the home. Based on its pharmacology, levorphanol overdosage would be expected to produce signs of respiratory depression, cardiovascular failure (especially in predisposed patients) and/or central nervous system depression. Serious overdosage with Levo-Dromoran is characterized by respiratory depression (a decrease in respiratory rate and/or tidal volume, periodic breathing, cyanosis), extreme somnolence progressing to stupor or coma, skeletal muscle flaccidity, cold and clammy skin, constricted pupils, and sometimes bradycardia and hypotension. In severe overdosage, apnea, circulatory collapse, cardiac arrest and death may occur.

Treatment: The specific treatment of suspected levorphanol tartrate overdosage is immediate establishment of an adequate airway and ventilation, followed (if necessary) by intravenous naloxone. The respiratory and cardiac status of the patient should be continuously monitored and appropriate supportive measures instituted, such as oxygen, intravenous fluids and/or vasopressors, if required. Physicians are reminded that the duration of levorphanol action far exceeds the duration of action of naloxone, and repeated dosing with naloxone may be required. Naloxone should be administered cautiously to persons known or suspected to be physically dependent on Levo-Dromoran. In such cases an abrupt and complete reversal of opioid effects may precipitate an acute abstinence syndrome. If necessary to administer naloxone to the physically dependent patient, the antagonist should be administered with extreme care and by titration with smaller than usual doses of the antagonist.

CONTRAINDICATIONS

Levo-Dromoran is contraindicated in patients hypersensitive to levorphanol tartrate.