COSELA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for COSELA (COSELA).
Selective inhibitor of cyclin-dependent kinase 4 and 6 (CDK4/6), preventing phosphorylation of retinoblastoma protein and inducing G1 cell cycle arrest.
| Metabolism | Primarily metabolized by CYP3A4 and to a minor extent by CYP3A5. |
| Excretion | Primarily hepatic metabolism with <5% excreted unchanged renally. Fecal excretion accounts for approximately 80% of total clearance, with biliary elimination playing a major role. |
| Half-life | Terminal elimination half-life is approximately 3.5 hours in patients with normal hepatic function. This short half-life supports once-daily dosing but requires continuous exposure for sustained CDK4/6 inhibition. |
| Protein binding | 97% bound to human plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 2.1 L/kg (range 1.5–2.7 L/kg), indicating extensive extravascular distribution beyond plasma volume. |
| Bioavailability | Oral bioavailability is approximately 30% (range 23–37%) with high interpatient variability. Administration with a high-fat meal reduces absorption and is not recommended. |
| Onset of Action | Oral administration: Clinical effect (tumor cytostasis) begins within 1–2 days based on pharmacodynamic markers (phospho-Rb inhibition). Maximal effect on cell cycle arrest observed within 1 week. |
| Duration of Action | Pharmacodynamic effects (CDK4/6 inhibition) persist for approximately 24–48 hours after a single dose due to slow dissociation from target enzymes. Clinical duration of action necessitates daily dosing for continuous cell cycle blockade. |
900 mg/m2 (not to exceed 1400 mg) intravenously over 30 minutes on days 1, 8, and 15 of each 28-day cycle.
| Dosage form | POWDER |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl 30-89 mL/min). Insufficient data for severe renal impairment (CrCl <30 mL/min) or ESRD; use with caution. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). For moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment, not recommended due to lack of data. |
| Pediatric use | Safety and efficacy in pediatric patients have not been established. |
| Geriatric use | No specific dose adjustments recommended for geriatric patients. Clinical studies included patients aged ≥65 years; no overall differences in safety or efficacy observed. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for COSELA (COSELA).
| Breastfeeding | No data on the presence of COSELA in human milk, effects on the breastfed infant, or milk production. Because of the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with COSELA and for at least 3 weeks after the last dose. M/P ratio not determined. |
| Teratogenic Risk | Pregnancy category D. Based on its mechanism of action (CDK4/6 inhibitor) and animal studies, COSELA can cause fetal harm when administered to a pregnant woman. In pregnant rats, daily doses ≥10 mg/kg (approximately 0.3 times the human exposure at the recommended dose) caused embryofetal mortality, reduced fetal body weights, and fetal skeletal abnormalities. Advise pregnant women of the potential risk to the fetus. Verify pregnancy status in females of reproductive potential prior to initiating therapy. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Concomitant use with strong CYP3A4 inducers or inhibitors."]
| Precautions | ["Neutropenia: Monitor complete blood counts; may require dose interruption or reduction.","Thrombocytopenia and anemia.","Embryo-fetal toxicity: Can cause fetal harm; advise females of reproductive potential to use effective contraception."] |
| Food/Dietary | Avoid grapefruit and grapefruit juice, Seville oranges, and pomelos due to potential CYP3A4 inhibition. No other specific food restrictions. |
| Clinical Pearls |
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| Fetal Monitoring | Monitor complete blood counts (CBC) prior to start of therapy and at the beginning of each cycle, as well as on Day 15 of the first 2 cycles, or as clinically indicated. Monitor liver function tests (AST, ALT, bilirubin) and renal function (serum creatinine) periodically. Assess for signs of infection, bleeding, or anemia. In pregnant patients, perform serial ultrasounds to assess fetal growth and anatomy, considering the potential for fetal harm. |
| Fertility Effects | Based on animal studies, COSELA may impair fertility in males and females of reproductive potential. In male rats, testicular degeneration and reduced sperm motility were observed at doses ≥10 mg/kg (approximately 0.3 times human exposure). In female rats, irregular estrus cycles and reduced corpora lutea were observed at doses ≥30 mg/kg (approximately 0.9 times human exposure). The effects on human fertility are unknown. |
| COSELA (trilaciclib) is a cyclin-dependent kinase 4/6 inhibitor indicated to reduce the incidence of chemotherapy-induced myelosuppression in extensive-stage small cell lung cancer patients receiving platinum/etoposide or topotecan. Administer as a 30-minute IV infusion within 4 hours before chemotherapy. Monitor absolute neutrophil count recovery and transfusion needs. No dose adjustment for mild-to-moderate hepatic impairment; avoid in severe impairment. Contraindicated with strong CYP3A4 inducers; reduce dose with moderate CYP3A4 inducers and strong CYP3A4 inhibitors. |
| Patient Advice | COSELA is given before chemotherapy to help protect your bone marrow from damage. · You will receive this medication as an IV infusion over 30 minutes. · Common side effects include fatigue, nausea, and low blood cell counts; report any signs of infection or unusual bleeding. · Avoid grapefruit and Seville oranges during treatment as they may affect drug levels. · Tell your healthcare provider about all medications you take, including herbal supplements. |