ORLAAM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ORLAAM (ORLAAM).
Mu-opioid receptor agonist; produces analgesia and CNS depression by mimicking endogenous opioids.
| Metabolism | Hepatic via CYP3A4; major metabolite is noracetylmethadol (active). |
| Excretion | Primarily renal (approximately 50-60% as unchanged drug and metabolites), with biliary/fecal elimination accounting for about 20-30%. The remainder is metabolized and eliminated via other routes. |
| Half-life | Terminal elimination half-life is approximately 30-60 hours (mean ~45 hours) in normal renal function. Due to this long half-life, steady-state is reached in 7-10 days, and the drug accumulates with repeated dosing, providing prolonged opioid effects. Half-life is significantly prolonged in renal impairment. |
| Protein binding | Approximately 70-80% bound to plasma proteins, primarily to alpha-1-acid glycoprotein. Binding is saturable and concentration-dependent. |
| Volume of Distribution | Vd ~ 5-10 L/kg (large volume due to extensive tissue binding; indicates distribution into total body water and extensive tissue uptake, including brain, lungs, and liver). |
| Bioavailability | Oral: approximately 40-60% (due to extensive first-pass metabolism). Bioavailability is increased in hepatic impairment. Not administered via other routes clinically (IV/IM are investigational). |
| Onset of Action | Oral: 30-60 minutes (slow onset due to hepatic first-pass metabolism; oral bioavailability is limited). Peak effect occurs at 3-6 hours. Intravenous: 5-10 minutes; Intramuscular: 10-20 minutes. |
| Duration of Action | Oral: 24-48 hours (long duration due to slow metabolism; single oral dose provides opioid effects for over 24 hours). Intravenous/Intramuscular: 8-12 hours for analgesic effect, but opioid effects may persist longer. Note: ORLAAM is not approved for acute pain due to slow onset and long duration. |
| Molecular Weight | 353.5 |
Initial: 20-40 mg orally every 48-72 hours; maintenance: 80-120 mg orally every 72 hours; maximum single dose: 150 mg. Use only under direct medical supervision in opioid-tolerant patients.
| Dosage form | CONCENTRATE |
| Renal impairment | No specific guideline available; caution with GFR <30 mL/min; consider dose reduction or extended interval due to potential accumulation. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use or use extreme caution with 50-75% dose reduction and extended interval. |
| Pediatric use | Not recommended for use in pediatric patients due to high risk of respiratory depression and lack of safety data. |
| Geriatric use | Start at lower end of dosing range (20-30 mg every 48-72 hours); increase dose cautiously due to increased sensitivity and risk of adverse effects; monitor renal and hepatic function. |
| 1st trimester | Avoid use during first trimester due to risk of congenital malformations and neonatal opioid withdrawal syndrome. |
| 2nd trimester | Use only if clearly needed; monitor for preterm labor and fetal growth restriction. |
| 3rd trimester | Use may cause neonatal opioid withdrawal syndrome; avoid near term unless necessary. |
Clinical note
Comprehensive clinical and safety monograph for ORLAAM (ORLAAM).
| Placental transfer | Orlaam crosses the placenta; detected in fetal plasma at concentrations approximately 50% of maternal levels. |
| Breastfeeding | Orlaam is excreted in breast milk; use during breastfeeding is not recommended due to potential for infant sedation and respiratory depression. If used, monitor infant for signs of opioid intoxication. |
■ FDA Black Box Warning
Respiratory depression; risk of life-threatening respiratory depression, especially during initiation and dose titration.
| Serious Effects |
Hypersensitivity to levomethadyl acetate or any componentsSevere respiratory depressionAcute or severe bronchial asthmaParalytic ileusConcurrent use with MAO inhibitors or within 14 days
| Precautions | QT prolongation; risk of torsades de pointes. Respiratory depression. Abuse potential. Neonatal withdrawal syndrome if used during pregnancy. Concomitant use with benzodiazepines or other CNS depressants increases risk of profound sedation and respiratory depression. |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase ORLAAM levels and risk of toxicity. High-fat meals may increase absorption; take consistently with or without food. Alcohol and tyramine-rich foods (e.g., aged cheeses, cured meats) are contraindicated due to risk of hypertensive crisis from monoamine oxidase inhibition-like effects. |
Loading safety data…
| Lactation Rating |
| L4 (possibly hazardous) |
| Teratogenic Risk | FDA Pregnancy Category C. First trimester: Limited data; potential risk of neural tube defects based on animal studies. Second/third trimesters: May cause opioid withdrawal in fetus and neonatal abstinence syndrome (NAS) after prolonged use. No evidence of major malformations from human data. |
| Fetal Monitoring | Monitor maternal vital signs, respiratory rate, and sedation level. Fetal assessment includes non-stress test and biophysical profile after 24 weeks if chronic use. Monitor for signs of preterm labor and intrauterine growth restriction. Assess newborn for NAS using Finnegan scoring. |
| Fertility Effects | May cause menstrual irregularities and reduce fertility due to opioid-induced hyperprolactinemia and hypothalamic-pituitary-gonadal axis suppression. Reversible upon discontinuation. |
| Clinical Pearls | ORLAAM (levomethadyl acetate) is a long-acting opioid agonist used for maintenance therapy in opioid dependence. Due to its long half-life (2-4 days), dosing is typically thrice weekly but carries risk of cumulative toxicity. ECG monitoring is essential because it prolongs the QTc interval; avoid in patients with baseline QTc >500 ms. ORLAAM is a Schedule II controlled substance and must be dispensed directly by the clinic. It is contraindicated in patients with opioid hypersensitivity, severe respiratory depression, or acute asthma. |
| Patient Advice | Take ORLAAM exactly as prescribed; never adjust dose or frequency yourself. · Do not drink alcohol or use other central nervous system depressants (e.g., benzodiazepines, other opioids) while on ORLAAM; this can cause severe respiratory depression or death. · Inform your healthcare provider of all other medications, including over-the-counter and herbal products, due to risk of serious interactions. · ORLAAM can cause dizziness or drowsiness; avoid driving or operating machinery until you know how it affects you. · Seek immediate medical attention if you experience signs of QTc prolongation: fainting, palpitations, or seizures. · Never share ORLAAM with another person; it is intended only for you. · Store ORLAAM in a secure location out of reach of children and pets. · Gradual withdrawal under medical supervision is necessary to avoid severe withdrawal symptoms. · Attend all follow-up appointments for monitoring of ECG, liver function, and overall treatment response. |