KEMEYA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KEMEYA (KEMEYA).
Selective inhibitor of Janus kinase 1 (JAK1), modulating the JAK-STAT signaling pathway to reduce pro-inflammatory cytokine production.
| Metabolism | Primarily metabolized by CYP3A4 and to a lesser extent by CYP2C19. Forms inactive metabolites. |
| Excretion | Renal: ~70% as unchanged drug; Fecal: ~20% as metabolites; Biliary: <10% |
| Half-life | Terminal elimination half-life: 12-15 hours; Clinical context: allows twice-daily dosing; prolonged in renal impairment (up to 24-30 hours in CrCl <30 mL/min) |
| Protein binding | High: ~95% bound to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | Vd: 3-5 L/kg; indicates extensive tissue distribution |
| Bioavailability | Oral: 80-90% |
| Onset of Action | Oral: 2-4 hours to peak effect; Intravenous: within 30 minutes |
| Duration of Action | 24-48 hours for analgesic effect; sustained with hepatic impairment |
KEMEYA (zoledronic acid) 5 mg intravenously once yearly for osteoporosis. For Paget disease, 5 mg intravenously as a single dose.
| Dosage form | TABLET |
| Renal impairment | Contraindicated if CrCl <35 mL/min; for osteoporosis, not recommended if CrCl <35 mL/min. No dose adjustment needed for CrCl >=35 mL/min. |
| Liver impairment | No specific dose adjustment required for hepatic impairment; caution in severe hepatic impairment due to limited data. |
| Pediatric use | Safety and efficacy not established in children; no approved pediatric dosing. |
| Geriatric use | No specific dose adjustment for elderly; monitor renal function as age-related decline in CrCl may necessitate avoidance if CrCl <35 mL/min. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for KEMEYA (KEMEYA).
| Breastfeeding | It is not known whether KEMEYA is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from KEMEYA, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. The milk-to-plasma (M/P) ratio has not been determined for KEMEYA. |
| Teratogenic Risk | KEMEYA is contraindicated in pregnancy. Based on animal studies and its mechanism of action, KEMEYA may cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Teratogenic effects have been observed in animal reproduction studies at doses below the recommended human dose. In particular, exposure during the first trimester is associated with major congenital malformations, including neural tube defects, craniofacial abnormalities, and cardiovascular defects. During the second and third trimesters, fetal growth restriction and oligohydramnios may occur. |
■ FDA Black Box Warning
WARNING: SERIOUS INFECTIONS, MORTALITY, MALIGNANCY, AND THROMBOSIS. Patients treated with KEMEYA are at increased risk for developing serious infections that may lead to hospitalization or death. Most patients who developed these infections were taking concomitant immunosuppressants. If a serious infection develops, interrupt KEMEYA until the infection is controlled. Reported infections include active tuberculosis, invasive fungal infections, and infections due to opportunistic pathogens. Malignancies, including lymphoma, have been observed. Thrombosis, including deep vein thrombosis, pulmonary embolism, and arterial thrombosis, have been reported. Consider risks vs benefits before initiating therapy.
| Serious Effects |
["Hypersensitivity to the active substance or any excipients.","Active serious infections, including localized infections.","Known active tuberculosis.","Severe hepatic impairment (Child-Pugh C).","Pregnancy (based on animal studies showing fetal harm)."]
| Precautions | ["Risk of serious infections, including tuberculosis and invasive fungal infections.","Avoid use in patients with active infections.","Monitor for signs and symptoms of infection during treatment.","Risk of thrombosis: Use with caution in patients with risk factors for thrombosis.","Risk of malignancy, particularly lymphoma.","Hepatotoxicity: Monitor liver enzymes regularly.","Cytopenias: Monitor complete blood counts at baseline and periodically.","Gastrointestinal perforations have been reported; monitor for abdominal pain."] |
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| Fetal Monitoring | For women of reproductive potential, pregnancy testing should be performed prior to initiating KEMEYA. Effective contraception must be used during treatment and for at least 1 month after the last dose. For pregnant patients inadvertently exposed, ultrasound monitoring for fetal malformations and growth assessment is recommended, as well as monitoring of amniotic fluid volume. Maternal monitoring includes liver function tests, renal function, and blood counts at baseline and periodically during treatment. |
| Fertility Effects | Based on animal studies, KEMEYA may impair fertility in females and males. In female rats, decreased fertility and increased preimplantation loss were observed at clinically relevant doses. In male rats, testicular degeneration and reduced sperm counts were noted. These effects may be reversible upon discontinuation of the drug. Human data on fertility effects are not available. |