CIBINQO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CIBINQO (CIBINQO).
CIBINQO (abrocitinib) is a Janus kinase (JAK) inhibitor. It selectively inhibits JAK1, which modulates cytokine signaling involved in inflammatory pathways, including interleukin (IL)-4, IL-13, IL-31, and interferon-gamma, reducing the inflammatory response in atopic dermatitis.
| Metabolism | Metabolized primarily by CYP2C9 and to a lesser extent by CYP3A4. Two major metabolites: M1 (active, 5-fold less potent) and M2 (inactive). |
| Excretion | Primarily excreted via feces (69%) and urine (20%) after oral administration. Renal elimination accounts for <1% of unchanged drug. Biliary excretion is the major route for metabolites. |
| Half-life | Terminal elimination half-life is approximately 4-6 hours in healthy subjects, supporting twice-daily dosing. No significant accumulation after multiple doses. |
| Protein binding | Approximately 85-90% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 200 L (2.9 L/kg), indicating extensive tissue distribution beyond plasma volume. |
| Bioavailability | Absolute oral bioavailability is approximately 10-20% due to first-pass metabolism. Bioavailability is dose-proportional over the therapeutic range. |
| Onset of Action | Oral administration: Clinical effect (improvement in pruritus) observed within 2 weeks; maximal effect achieved by 4-6 weeks. |
| Duration of Action | Duration of action per dose corresponds to half-life, requiring twice-daily dosing to maintain therapeutic levels. Continuous treatment is needed for sustained response. |
| Molecular Weight | 380.4 |
100 mg orally once daily, with or without food.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²). Not recommended for severe renal impairment (eGFR <30 mL/min/1.73 m²) or ESRD. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: 50 mg orally once daily. Child-Pugh C: Not recommended. |
| Pediatric use | Safety and efficacy in pediatric patients (<12 years) have not been established; no approved pediatric dosing. |
| Geriatric use | No specific dose adjustment recommended based on age alone; monitor renal function closely as elderly patients may have reduced renal clearance. |
| 1st trimester | Limited human data; animal studies show embryotoxicity and malformations at exposures similar to clinical doses. Avoid use unless no alternative. |
| 2nd trimester | Limited human data; animal studies show fetotoxicity. Use only if maternal benefit justifies potential fetal risk. |
| 3rd trimester | Limited human data; may cause neonatal immunosuppression. Consider risk-benefit. |
Clinical note
Comprehensive clinical and safety monograph for CIBINQO (CIBINQO).
| Placental transfer | Expected to cross placenta based on molecular weight and animal studies showing fetal exposure. |
| Breastfeeding | Cibinqo is excreted in animal milk; no human data. Due to potential for serious adverse reactions in nursing infants, advise breastfeeding discontinuation or avoid drug. |
■ FDA Black Box Warning
WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, MAJOR ADVERSE CARDIOVASCULAR EVENTS, AND THROMBOSIS. Serious infections including tuberculosis, bacterial, invasive fungal, viral, and opportunistic infections have been reported; some fatal. Patients should be tested for latent TB before initiation; if positive, treated prior to use. Increased rate of all-cause mortality including sudden cardiovascular death. Lymphoma and other malignancies have been observed. Major adverse cardiovascular events (MACE) including myocardial infarction and stroke occurred in patients with risk factors. Thrombosis including deep vein thrombosis, pulmonary embolism, and arterial thrombosis reported.
| Serious Effects |
Hypersensitivity to abrocitinib or any excipientSevere hepatic impairment (Child-Pugh C)
| Precautions | Serious infections; viral reactivation (herpes zoster, hepatitis B); hypersensitivity reactions; thrombocytopenia; lipid elevations; liver enzyme elevations; vaccination with live vaccines not recommended; increased risk of malignancies; gastrointestinal perforation; avoid use in patients with severe hepatic impairment. |
| Food/Dietary |
Loading safety data…
| Lactation Rating |
| L4 (possibly hazardous) |
| Teratogenic Risk | Abrocitinib is contraindicated in pregnancy. Animal studies show teratogenicity at exposures below human exposure at the recommended dose. First trimester: high risk of major congenital malformations. Second and third trimesters: risk of fetal growth restriction and potential effects on immune development. |
| Fetal Monitoring | Pregnancy test prior to initiation. Monthly pregnancy tests during therapy. Use effective contraception during treatment and for 1 week after last dose. No specific fetal monitoring required if pregnancy occurs; refer to teratology specialist. |
| Fertility Effects | Animal studies show reduced fertility in males and females at clinically relevant exposures. Reversible after discontinuation. Human data lacking. May impair spermatogenesis and ovulation. |
| No specific food interactions have been reported. Grapefruit juice does not affect abrocitinib pharmacokinetics. However, avoid alcohol as it may exacerbate hepatotoxicity. |
| Clinical Pearls | CIBINQO (abrocitinib) is a Janus kinase 1 (JAK1) selective inhibitor approved for moderate-to-severe atopic dermatitis. Monitor for serious infections, thrombosis, and laboratory abnormalities (CBC, LFTs, lipids) at baseline and periodically. Avoid use in patients with severe hepatic impairment or with strong CYP2C19/CYP2C9 inhibitors. Dose reduction to 100 mg daily recommended in patients with moderate renal impairment (eGFR 30-59 mL/min) or in those on strong CYP2C19 inhibitors. Not recommended in combination with other JAK inhibitors or biologic immunomodulators. |
| Patient Advice | Take CIBINQO exactly as prescribed once daily with or without food. Do not crush, cut, or chew the tablet. · Do not use if you have a serious infection or active tuberculosis. Notify your doctor immediately if you develop fever, sweats, or other signs of infection. · CIBINQO may increase your risk of blood clots, heart attack, stroke, and cancer. Report any sudden chest pain, leg swelling, or shortness of breath. · Avoid live vaccines during treatment and for 4 weeks after stopping CIBINQO. Update routine immunizations before starting. · Tell your doctor about all medications you take, especially blood thinners, antifungal agents (e.g., fluconazole), or anti-seizure drugs. · Do not take CIBINQO if you are pregnant, planning to become pregnant, or breastfeeding. Use effective contraception during treatment and for 1 month after the last dose. |