BARICITINIB
Clinical safety rating: caution
Comprehensive clinical and safety monograph for BARICITINIB (BARICITINIB).
Baricitinib is a Janus kinase (JAK) inhibitor, selectively inhibiting JAK1 and JAK2, thereby modulating the signaling pathway involved in inflammatory responses.
| Metabolism | Primarily metabolized by CYP3A4, with minor contribution from CYP2D6. |
| Excretion | Approximately 75% of the dose is excreted in urine (69% as unchanged drug, 6% as metabolites), and 20% in feces (15% unchanged, 5% metabolites). |
| Half-life | Terminal elimination half-life is approximately 12.5 hours in healthy subjects; allowing once-daily dosing with steady-state reached in 2-3 days. |
| Protein binding | Approximately 50% bound to plasma proteins (primarily albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | Volume of distribution is approximately 58 L (0.76 L/kg for a 70 kg individual), indicating extensive tissue distribution. |
| Bioavailability | Absolute oral bioavailability is approximately 79% (no food effect, can be taken with or without food). |
| Onset of Action | Oral: Onset of clinical effect (reduction in joint pain/swelling) observed within 1 week; maximal effect may take 4-12 weeks. |
| Duration of Action | Duration of action supports once-daily dosing; clinical effects persist for the dosing interval; after discontinuation, effects wane over several days to weeks. |
2 mg orally once daily; may increase to 4 mg once daily if inadequate response.
| Dosage form | TABLET |
| Renal impairment | eGFR 30-60 mL/min: 1 mg once daily; eGFR 15-29 mL/min: 0.5 mg once daily; eGFR <15 mL/min or dialysis: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 1 mg once daily; Child-Pugh C: not recommended. |
| Pediatric use | Not approved for pediatric use. |
| Geriatric use | No dose adjustment required; monitor renal function due to age-related decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for BARICITINIB (BARICITINIB).
| Breastfeeding | Unknown if excreted in human milk; M/P ratio not available. Due to potential for serious adverse reactions, breastfeeding is not recommended during therapy and for 2 weeks after last dose. |
| Teratogenic Risk | Baricitinib is contraindicated in pregnancy. Animal studies show teratogenicity (skeletal and cardiovascular malformations) at exposures 2x MRHD. No human data; embryofetal toxicity risk high in all trimesters. |
| Fetal Monitoring |
■ FDA Black Box Warning
Serious infections, including tuberculosis, invasive fungal infections, bacterial, viral, and opportunistic infections; lymphoma and other malignancies; thrombosis, including deep vein thrombosis and pulmonary embolism.
| Serious Effects |
Hypersensitivity to baricitinib or any excipient; severe hepatic impairment (Child-Pugh C); pregnancy; lactation.
| Precautions | Risk of serious infections; thrombosis; gastrointestinal perforation; laboratory abnormalities (neutropenia, lymphopenia, anemia, elevated liver enzymes, lipid elevations); vaccinations (avoid live vaccines); hypersensitivity reactions. |
| Food/Dietary | No specific food interactions known. May be taken with or without food. Avoid grapefruit juice? No significant interaction reported. Maintain adequate hydration. |
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| Pregnancy test prior to initiation; monthly pregnancy tests for women of childbearing potential. Ultrasound monitoring for fetal growth and anatomy if exposure occurs. Due to immunosuppression, monitor for infections (CBC, LFTs, CRP). |
| Fertility Effects | Baricitinib reduced fertility in male and female rats at exposures equivalent to MRHD. Effects on human fertility unknown; reversible after discontinuation in animal studies. Advise fertility preservation counseling. |
| Clinical Pearls | Monitor for thrombosis (DVT/PE), especially in patients with risk factors. Avoid use with strong OAT3 inhibitors (e.g., probenecid) due to increased baricitinib exposure. Screen for TB and viral hepatitis before initiation. Use with caution in patients with history of diverticulitis (risk of GI perforation). Baseline and periodic lipid monitoring recommended. Not recommended in combination with other JAK inhibitors, biologic DMARDs, or potent immunosuppressants. |
| Patient Advice | Baricitinib may increase risk of serious infections, including TB; notify doctor if fever, cough, or other infection signs occur. · Seek immediate medical care for symptoms of blood clots: sudden chest pain, leg swelling, or shortness of breath. · Report any signs of liver problems: yellowing skin/eyes, dark urine, abdominal pain. · Avoid live vaccines during treatment and for some time after. · Take exactly as prescribed; do not change dose or stop without consulting doctor. |