OTULFI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OTULFI (OTULFI).
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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for OTULFI (OTULFI).
| Breastfeeding | Excreted in breast milk; M/P ratio unknown. Caution advised due to potential for bone and auditory toxicity in nursing infants. |
| 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. |
■ FDA Black Box Warning
None
| Serious Effects |
["Known hypersensitivity to otulipumab or any excipients","Active severe infections","Not recommended for use in patients with active hepatic impairment or elevated liver enzymes >5 times ULN"]
| 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"] |
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| Fertility Effects | Reversible inhibition of spermatogenesis in males; no significant impact on female fertility reported. |