OLUMIANT
Clinical safety rating: caution
Comprehensive clinical and safety monograph for OLUMIANT (OLUMIANT).
Janus kinase (JAK) inhibitor; selectively inhibits JAK1 and JAK2, modulating cytokine signaling involved in inflammation.
| Metabolism | Primarily metabolized by CYP3A4, with minor contributions from CYP2C19 and CYP2D6. |
| Excretion | Approximately 70% excreted renally as unchanged drug, with about 20% as inactive metabolites; fecal excretion accounts for <10%. |
| Half-life | Terminal half-life is approximately 12.5 hours in healthy subjects, supporting once-daily dosing. |
| Protein binding | ~52% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 0.4 L/kg, indicating distribution mainly in extracellular fluid. |
| Bioavailability | Oral bioavailability is approximately 76% under fasting conditions; no significant food effect. |
| Onset of Action | Clinical improvement (e.g., reduction in joint pain/swelling) may be observed as early as 1 week after starting oral therapy; maximal effect typically by 12 weeks. |
| Duration of Action | Pharmacodynamic effects (e.g., JAK-STAT inhibition) persist over the 24-hour dosing interval; clinical effects wane if doses are missed; steady state achieved by ~3 days. |
| Molecular Weight | 371.42 |
| Action Class | Janus kinase inhibitors |
2 mg orally once daily; may increase to 4 mg once daily based on clinical response.
| Dosage form | TABLET |
| Renal impairment | eGFR 30-60 mL/min/1.73m2: 2 mg once daily. eGFR 15-29 mL/min/1.73m2: 2 mg every other day. eGFR <15 mL/min/1.73m2 or on dialysis: not recommended. |
| Liver impairment | Child-Pugh Class A: 2 mg once daily. Child-Pugh Class B: 2 mg once daily (use with caution). Child-Pugh Class C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment required; monitor for adverse effects given higher risk of infections and malignancies. |
| 1st trimester | Limited human data; animal studies show developmental toxicity (skeletal malformations, decreased fetal weight) at exposures similar to human therapeutic doses. Avoid use unless benefit outweighs risk. |
| 2nd trimester | Limited human data; animal studies show developmental toxicity. Avoid use unless benefit outweighs risk. |
| 3rd trimester | Limited human data; animal studies show developmental toxicity. Avoid use unless benefit outweighs risk, particularly near term due to potential effects on neonatal immune system. |
Clinical note
Comprehensive clinical and safety monograph for OLUMIANT (OLUMIANT).
| Placental transfer | Baricitinib is a small molecule (MW 371.4 Da) with moderate protein binding (~50-60%), suggesting potential placental transfer. In animal studies, baricitinib crossed the placenta and achieved fetal concentrations similar to maternal plasma concentrations. |
| Breastfeeding |
■ FDA Black Box Warning
Increased risk of serious infections, including tuberculosis (TB), invasive fungal infections, bacterial, viral, and other opportunistic pathogens. Malignancies including lymphoma and other solid tumors have been observed. Thrombosis, including deep vein thrombosis (DVT) and pulmonary embolism (PE), has occurred. Increased all-cause mortality, especially in rheumatoid arthritis patients >50 years with at least one cardiovascular risk factor. Major adverse cardiovascular events (MACE) such as cardiovascular death, myocardial infarction, and stroke were observed.
| Serious Effects |
Hypersensitivity to baricitinib or any excipientsSevere hepatic impairment (Child-Pugh Class C)
| Precautions | Serious infections: monitor for signs/symptoms; discontinue if infection develops., Thrombosis: use with caution in patients with risk factors; discontinue if symptoms occur., Malignancy: periodic skin exams; avoid in patients with known malignancy unless treated., Cardiovascular risk: increased MACE and mortality; avoid in patients >50 with at least one CV risk factor., Gastrointestinal perforations: monitor for symptoms., Laboratory abnormalities: monitor neutrophils, lymphocytes, hemoglobin, liver enzymes, and lipids., Vaccinations: update immunizations before therapy; avoid live vaccines during treatment., Hypersensitivity: angioedema and urticaria reported; discontinue if serious reaction occurs. |
Loading safety data…
| No data on presence in human milk; based on molecular weight and high protein binding, excretion is likely minimal but unknown. In animal studies, baricitinib was detected in milk of lactating rats. Due to potential for serious adverse reactions in nursing infants, breastfeeding is not recommended during treatment and for at least 4 days after the last dose. |
| Lactation Rating | L4 - Possibly Hazardous |
| Teratogenic Risk | In animal studies, baricitinib was embryotoxic and teratogenic at exposures higher than human therapeutic doses. In pregnant women, inadequate data. Use is not recommended during pregnancy. First trimester: potential for structural anomalies; second and third trimesters: risk of low fetal weight and possibly impaired immune development. |
| Fetal Monitoring | Monitor for maternal infections, hematologic parameters (CBC with differential), liver function tests, and lipid profile. In case of accidental pregnancy exposure, perform fetal ultrasound to assess for anomalies and monitor growth. |
| Fertility Effects | In animal studies, no adverse effects on male or female fertility were observed. Human data are insufficient. Baricitinib may impair fertility in females due to hormonal effects; consider impact on ovulation and menstruation. |
| Food/Dietary | No specific food interactions. Take with or without food. Grapefruit and grapefruit juice have no known interaction. Avoid alcohol due to potential liver effects. |
| Clinical Pearls | Baricitinib (Olumiant) is a JAK1/JAK2 inhibitor used for moderate-to-severe rheumatoid arthritis (RA) and COVID-19. Monitor for thrombosis, especially in patients with risk factors; avoid in patients with a history of DVT/PE. Screen for TB and viral hepatitis before initiation. Do not use with other JAK inhibitors or biologic DMARDs. Dose adjust for renal impairment (CrCl 30-60 mL/min: 2 mg daily; CrCl <30: not recommended). Baseline and periodic lipid monitoring recommended. |
| Patient Advice | Take Olumiant exactly as prescribed, usually once daily with or without food. · Do not take if you have an active infection; report fever, chills, or cough immediately. · Olumiant may increase the risk of blood clots; seek immediate medical help for sudden leg pain/swelling or chest pain/shortness of breath. · Avoid live vaccines while on Olumiant; update vaccinations before starting therapy. · Use effective contraception during treatment and for 4 weeks after stopping, as Olumiant may harm a fetus. · Store at room temperature away from moisture and heat. |