LEVORPHANOL TARTRATE
Clinical safety rating
cautionComprehensive clinical and safety monograph for LEVORPHANOL TARTRATE (LEVORPHANOL TARTRATE).
Levorphanol is a potent opioid analgesic that acts as a mu-opioid receptor agonist. It also has NMDA receptor antagonist activity, inhibits norepinephrine and serotonin reuptake, and acts as a sigma receptor agonist, contributing to its analgesic effects and reduced tolerance development.
| Metabolism | Primarily hepatic via glucuronidation and N-demethylation; CYP450 involvement not fully characterized. |
| Excretion | Renal: approximately 30% as unchanged drug and 50% as glucuronide conjugates; fecal: 20% via biliary excretion. |
| Half-life | 11-16 hours; extended in hepatic impairment (up to 30 hours). |
| Protein binding | Approximately 50% bound to albumin. |
| Volume of Distribution | 10-15 L/kg; extensive tissue distribution. |
| Bioavailability | Oral: 50-70% (first-pass effect); intravenous: 100%. |
| Onset of Action | Intravenous: 2-5 minutes; subcutaneous/intramuscular: 10-30 minutes; oral: 30-60 minutes. |
| Duration of Action | Analgesia: 4-6 hours (all routes); respiratory depression may persist longer. |
| Molecular Weight | 443.5 |
2 mg orally every 6-8 hours as needed for pain; for opioid-tolerant patients, doses up to 4 mg orally every 6-8 hours may be used. Parenterally: 1-2 mg subcutaneously or intramuscularly every 6-8 hours; may be given intravenously at 0.5-1 mg every 6-8 hours.
| Dosage form | TABLET |
| Renal impairment | CrCl 10-50 mL/min: Administer 75% of usual dose at extended intervals (e.g., every 12 hours). CrCl <10 mL/min: Administer 50% of usual dose at extended intervals (e.g., every 12-24 hours). For patients on dialysis, use with caution and reduce dose; not well-studied. |
| Liver impairment | Child-Pugh Class A: No adjustment needed. Child-Pugh Class B: Reduce dose by 50% and administer at extended intervals (e.g., every 12 hours). Child-Pugh Class C: Avoid use; if necessary, reduce dose by 75% and monitor closely. |
| Pediatric use | Not recommended for use in pediatric patients due to lack of safety and efficacy data; use in children under 18 years is generally avoided. For palliative care in older children, consult specialist. |
| Geriatric use | Start at 50% of the usual adult dose (e.g., 1 mg orally every 6-8 hours) due to increased sensitivity and reduced clearance; titrate carefully with close monitoring for respiratory depression and constipation. |
| 1st trimester | Associated with congenital malformations (e.g., neural tube defects) in early pregnancy; avoid unless clearly needed. |
| 2nd trimester | May cause fetal opioid dependence and growth restriction; use only if benefits outweigh risks. |
| 3rd trimester | Risk of neonatal opioid withdrawal syndrome (NOWS) and respiratory depression; use during labor may cause respiratory depression in neonate. |
Clinical note
Comprehensive clinical and safety monograph for LEVORPHANOL TARTRATE (LEVORPHANOL TARTRATE).
| Placental transfer | Crosses the placenta rapidly; concentrations in fetal plasma may exceed maternal levels. |
| Breastfeeding | Levorpahol accumulates in breast milk; monitor infant for respiratory depression and sedation. Use with caution, especially in neonates or premature infants. |
| Lactation Rating | L4 (Possibly Hazardous) - limited data suggest risk of adverse effects in nursing infants. |
| Teratogenic Risk | Levorphanol is an opioid agonist; limited data in pregnancy. First trimester: potential for neural tube defects based on animal studies; human risk unclear. Second/third trimesters: risk of fetal opioid dependence, preterm labor, and intrauterine growth restriction. Use only if benefit outweighs risk. |
| Fetal Monitoring | Monitor maternal respiratory rate, level of sedation, and signs of opioid withdrawal. Fetal monitoring: nonstress test or biophysical profile if near term; assess for fetal growth restriction. Neonatal monitoring: observe for neonatal abstinence syndrome (NAS) after prolonged exposure. |
| Fertility Effects | Opioid use may disrupt hypothalamic-pituitary-gonadal axis leading to amenorrhea, anovulation, and reduced fertility in females; males may experience reduced libido and erectile dysfunction. Effects are reversible upon discontinuation. |
■ FDA Black Box Warning
Risk of addiction, abuse, and misuse; life-threatening respiratory depression; accidental ingestion; neonatal opioid withdrawal syndrome; risks from concomitant use with benzodiazepines or other CNS depressants.
| Serious Effects |
Known hypersensitivity to levorpahol or any componentSignificant respiratory depressionAcute or severe bronchial asthmaParalytic ileusMonoamine oxidase inhibitor (MAOI) use within 14 days
| Precautions | Respiratory depression: potentially fatal, especially at initiation and dose escalation, Adrenal insufficiency, Severe hypotension, Seizures, Serotonin syndrome, Risks from concomitant CNS depressants, Impaired mental or physical abilities |
| Food/Dietary | Avoid grapefruit juice as it may increase levorphenol levels via CYP3A4 inhibition. High-fat meals may delay absorption but not overall extent. Alcohol must be avoided due to additive CNS depression. |
| Clinical Pearls | Levorphanol is a potent mu-opioid agonist with a long half-life (12-16 hours) and active metabolites; avoid use in opioid-naive patients due to risk of respiratory depression. It has NMDA antagonist activity, which may provide benefit in neuropathic pain but also contributes to psychotomimetic effects. Equianalgesic dose: 2 mg oral levorphenol ≈ 10 mg morphine. Accumulation occurs with repeated dosing; monitor for sedation and respiratory depression. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · Avoid alcohol and other CNS depressants (e.g., benzodiazepines, sedatives) as they increase risk of severe drowsiness and breathing problems. · Do not drive or operate heavy machinery until you know how levorphenol affects you. · Do not stop abruptly; withdrawal symptoms may occur. Taper under medical supervision. · Constipation is common; increase fluid and fiber intake, and consider stool softeners. · Store securely out of reach of others, as misuse can cause overdose and death. · Report any difficulty breathing, severe drowsiness, or confusion immediately. |
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