LEVO-DROMORAN
Clinical safety rating
cautionComprehensive clinical and safety monograph for LEVO-DROMORAN (LEVO-DROMORAN).
Levo-dromoran (levorphanol) is a potent opioid agonist primarily at mu-opioid receptors, with additional agonist activity at kappa and delta opioid receptors. It also acts as an NMDA receptor antagonist and inhibits serotonin and norepinephrine reuptake, contributing to its analgesic effects.
| Metabolism | Primarily hepatic via glucuronidation (UGT2B7) and N-demethylation (CYP3A4). Active metabolite: norlevorphanol. |
| Excretion | Primarily renal (approximately 60% as unchanged drug and metabolites); biliary/fecal elimination accounts for about 30%. |
| Half-life | Terminal elimination half-life is 15-30 hours (mean 22 hours) in adults; prolonged in hepatic or renal impairment, requiring dose adjustment. |
| Protein binding | Approximately 60-70% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 3-5 L/kg, indicating extensive tissue distribution beyond plasma volume. |
| Bioavailability | Oral bioavailability is about 40-60% due to first-pass metabolism; rectal bioavailability is approximately 50-70%. |
| Onset of Action | Oral: 30-60 minutes; Subcutaneous: 10-15 minutes; Intravenous: 5-10 minutes. Effects peak at 1-2 hours orally. |
| Duration of Action | Oral: 6-8 hours; Parenteral: 4-6 hours. Duration may be prolonged in elderly or debilitated patients due to reduced clearance. |
| Molecular Weight | 370.5 |
2 mg orally every 6-8 hours as needed for pain; 2-4 mg intramuscularly or subcutaneously every 6-8 hours; intravenous administration: 1-2 mg slowly (over 2-3 minutes) every 6-8 hours.
| Dosage form | TABLET |
| Renal impairment | For GFR 30-50 mL/min: administer every 8-12 hours; GFR 10-29 mL/min: administer every 12-18 hours; GFR <10 mL/min: administer every 24 hours or consider alternative. |
| Liver impairment | Child-Pugh Class A (mild): no adjustment necessary; Child-Pugh Class B (moderate): reduce dose by 25-50%; Child-Pugh Class C (severe): avoid use or reduce dose by 75% with extended dosing interval. |
| Pediatric use | Oral: 0.04-0.08 mg/kg/dose every 6-8 hours; Parenteral: 0.02-0.04 mg/kg/dose every 6-8 hours. Maximum single dose: 2 mg. Not recommended for children under 6 months. |
| Geriatric use | Initiate at 25-50% of adult dose (e.g., 1 mg orally every 6-8 hours) due to increased sensitivity and renal clearance decline; titrate cautiously. |
| 1st trimester | Limited human data; animal studies show increased risk of neural tube defects. Use only if benefit outweighs risk. |
| 2nd trimester | May cause fetal dependence; use only if clearly needed. |
| 3rd trimester | Risk of neonatal respiratory depression, withdrawal syndrome, and altered fetal heart rate. Avoid prolonged use near term. |
Clinical note
Comprehensive clinical and safety monograph for LEVO-DROMORAN (LEVO-DROMORAN).
| Placental transfer | Crosses the placenta; detected in fetal plasma at concentrations approximately 50% of maternal levels. |
| Breastfeeding | Excreted into breast milk in low concentrations; monitor infant for sedation and respiratory depression. American Academy of Pediatrics considers compatible with caution. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Limited human data; animal studies show no evidence of teratogenicity at clinically relevant doses. Second and third trimesters: Chronic use may cause neonatal opioid withdrawal syndrome (NOWS) and respiratory depression at birth. Avoid prolonged use. |
| Fetal Monitoring | Monitor maternal respiratory rate, sedation level, and fetal heart rate patterns during labor. Assess neonatal for signs of opioid withdrawal (e.g., irritability, poor feeding) for 48-72 hours after birth. |
| Fertility Effects | May impair fertility in both males and females via hormonal alterations (e.g., reduced libido, erectile dysfunction, menstrual irregularities). 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 |
Hypersensitivity to levorphanol or any componentAcute or severe bronchial asthmaRespiratory depression in the absence of resuscitative equipmentSuspected surgical abdomen (until diagnosis confirmed)MAO inhibitor use within 14 days
| Precautions | Risk of respiratory depression, hypotension, bradycardia, increased intracranial pressure, seizures, serotonin syndrome, adrenal insufficiency, severe hypotension, and opioid-induced hyperalgesia. Avoid abrupt discontinuation. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase levorphanol levels. Alcohol and any foods that cause CNS depression should be avoided. Maintenance of adequate hydration and fiber intake is recommended to mitigate constipation. |
| Clinical Pearls | LEVO-DROMORAN (levorphanol) is a potent opioid agonist with NMDA antagonism, making it effective for neuropathic pain. It has a long half-life (12-16 hours) requiring careful dosing intervals to avoid accumulation. Monitor for respiratory depression, especially in elderly or opioid-naïve patients. It should not be used in patients with severe respiratory insufficiency or asthma. Due to its high potency, start at lower doses and titrate slowly. Beware of QT prolongation; obtain baseline ECG. Avoid concomitant use with MAOIs. |
| Patient Advice | Take exactly as prescribed; do not increase dose or frequency without consulting your doctor. · This medication can cause dizziness, drowsiness, or confusion; avoid driving or operating heavy machinery. · Do not consume alcohol or other CNS depressants (e.g., benzodiazepines) while taking this drug. · Constipation is common; increase fluid intake, fiber, and consider stool softeners. · Do not stop abruptly; withdrawal symptoms may occur. Taper under medical supervision. · Store securely away from children and pets. Dispose of unused medication via drug take-back programs. · Seek emergency care if you experience difficulty breathing, severe drowsiness, or fainting. |
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