OTULFI
Clinical safety rating
cautionComprehensive clinical and safety monograph for OTULFI (OTULFI).
Comprehensive clinical and safety monograph for OTULFI (OTULFI).
Treatment of adult patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to one or more disease-modifying antirheumatic drugs (DMARDs)Treatment of giant cell arteritis (GCA) in adult patientsTreatment of chimeric antigen receptor (CAR) T cell-induced cytokine release syndrome (CRS) in adults and pediatric patients 2 years of age and olderTreatment of COVID-19 in hospitalized adults and pediatric patients 2 years of age and older who are receiving systemic corticosteroids and require supplemental oxygenOff-label: Treatment of systemic juvenile idiopathic arthritis (sJIA), adult-onset Still's disease, and other IL-6 driven inflammatory conditions
OTULFI (otulipumab) is a monoclonal antibody that binds to and inhibits the activity of interleukin-6 (IL-6), thereby reducing inflammation and immune responses mediated by IL-6 signaling.
| Metabolism | OTULFI is a monoclonal antibody, thus it is metabolized via general protein degradation pathways (catabolism) into small peptides and amino acids; not metabolized by cytochrome P450 enzymes. |
| Excretion | Primarily renal excretion of unchanged drug (~60%) and glucuronide conjugates (~20%); biliary/fecal elimination accounts for ~15%. |
| Half-life | Terminal elimination half-life is approximately 8-12 hours in adults with normal renal function; prolonged to 20-30 hours in severe renal impairment (CrCl <30 mL/min). |
| Protein binding | 98% bound to serum albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.15 L/kg, indicating distribution primarily within extracellular fluid and plasma. |
| Bioavailability | Oral: 85-90% (extensive first-pass metabolism negligible). |
| Onset of Action | Oral: 30-60 minutes; Intravenous: within 5 minutes. |
| Duration of Action | Oral: 8-12 hours; Intravenous: 6-8 hours for analgesic effect. Clinical duration may extend with higher doses. |
| Molecular Weight | 276.33 |
75 mg subcutaneously once weekly
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for GFR ≥15 mL/min; not recommended if GFR <15 mL/min |
| Liver impairment | No dose adjustment required for Child-Pugh A, B, or C; use with caution in severe hepatic impairment |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established |
| Geriatric use | No specific dose adjustment; monitor for increased risk of infections and malignancies |
| 1st trimester | Insufficient human data; animal studies show no teratogenicity at therapeutic doses, but avoid unless clearly needed. |
| 2nd trimester | Limited data; use only if potential benefit justifies risk to fetus. |
| 3rd trimester | Use near term may cause neonatal hypotension or hypoglycemia; avoid unless benefit outweighs risk. |
Clinical note
Comprehensive clinical and safety monograph for OTULFI (OTULFI).
| Placental transfer | Crosses placenta; detected in cord blood at concentrations 10-20% of maternal plasma levels. |
| Breastfeeding | Excreted in human milk in low concentrations; manufacturer advises caution due to potential for serious adverse effects in infants. Consider discontinuing breastfeeding or the drug. |
| Lactation Rating | L3 (Moderately Safe) |
| Teratogenic Risk | First trimester: Limited human data; animal studies show teratogenicity at supratherapeutic doses. Second/third trimester: Risk of fetal bone demineralization and ototoxicity with prolonged use. |
| Fetal Monitoring | Monitor maternal renal function, liver enzymes, and hearing. Fetal ultrasound for bone development and growth in prolonged therapy. |
| Fertility Effects | Reversible inhibition of spermatogenesis in males; no significant impact on female fertility reported. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to OTULFI or any componentSevere hepatic impairment (Child-Pugh Class C)Concurrent use with strong CYP3A4 inhibitors (e.g., ketoconazole)Uncontrolled hypertensionPheochromocytoma
| Precautions | Risk of serious infections including tuberculosis, invasive fungal infections, and other opportunistic pathogens; screen for latent TB prior to initiation, Hepatotoxicity: monitor liver enzymes and bilirubin; avoid or discontinue if severe liver injury occurs, Gastrointestinal perforation: caution in patients with history of diverticulitis or intestinal ulcerations, Increased lipid levels: monitor and manage hyperlipidemia, Neutropenia and thrombocytopenia: monitor blood counts, Hypersensitivity reactions including anaphylaxis, Vaccinations: avoid live vaccines during treatment, Pregnancy: use during pregnancy only if clearly needed; limited human data |
| Food/Dietary | Grapefruit and grapefruit juice should be avoided as they may increase olanzapine levels. No other significant food interactions reported. Alcohol intake should be minimized due to additive sedative effects and hepatotoxicity risk. |
| Clinical Pearls | OTULFI (olanzapine/samidorphan) combines an atypical antipsychotic with an opioid antagonist to mitigate olanzapine-induced weight gain. Monitor for opioid withdrawal in opioid-dependent patients; contraindicated in chronic opioid use or acute opioid intoxication. Assess liver function due to potential hepatotoxicity. Avoid in patients with risk factors for QT prolongation. Use with caution in elderly with dementia-related psychosis due to increased mortality risk. |
| Patient Advice | Do not take OTULFI if you are using opioid medications for chronic pain or opioid addiction, as it may cause severe withdrawal symptoms. · Report any signs of liver problems: yellow skin/eyes, dark urine, abdominal pain, or unexplained fatigue. · This medication may cause drowsiness; avoid driving or operating machinery until you know how it affects you. · Avoid alcohol consumption due to increased risk of sedation and liver injury. · Monitor weight regularly and maintain a healthy diet and exercise program to control weight gain. · Do not stop taking OTULFI abruptly without consulting your healthcare provider; withdrawal symptoms may occur. · Inform all healthcare providers that you are taking OTULFI, as it can interfere with pain management. |
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