JESDUVROQ
Clinical safety rating: caution
Comprehensive clinical and safety monograph for JESDUVROQ (JESDUVROQ).
JESDUVROQ is a small molecule inhibitor of cyclin-dependent kinase 4 (CDK4) and CDK6, blocking retinoblastoma protein phosphorylation and inducing G1 cell cycle arrest.
| Metabolism | Primarily metabolized by CYP3A4. Minor contributions from CYP3A5 and SULT2A1. |
| Excretion | Primarily renal elimination (70-80% unchanged drug) via glomerular filtration and active tubular secretion; biliary/fecal excretion accounts for 15-20% as metabolites, with less than 5% unchanged in feces. |
| Half-life | Terminal elimination half-life is 12-15 hours in patients with normal renal function (CrCl >90 mL/min). Half-life increases with renal impairment (up to >30 hours in end-stage renal disease), requiring dose adjustment. |
| Protein binding | 92-96% bound to serum albumin (primarily) and alpha-1-acid glycoprotein. Binding is concentration-independent over therapeutic range. |
| Volume of Distribution | 0.8-1.2 L/kg, indicating extensive distribution into total body water and tissue binding. Not confined to plasma or extracellular fluid. |
| Bioavailability | Oral bioavailability is 75-85% (taken on an empty stomach); food reduces absorption by 20-30%. Intravenous bioavailability is 100%. |
| Onset of Action | Oral: 1-2 hours (peak plasma concentration); Intravenous: within 5-10 minutes (immediate therapeutic effect). |
| Duration of Action | Duration is 12-24 hours per dose, depending on renal function and dose. Steady-state achieved after 3-5 days. Twice-daily dosing is recommended to maintain therapeutic levels. |
IV: 10 mg/kg every 4 weeks, infused over 60 minutes.
| Dosage form | TABLET |
| Renal impairment | eGFR 30-59 mL/min: 7.5 mg/kg every 4 weeks; eGFR 15-29 mL/min: 5 mg/kg every 4 weeks; eGFR <15 mL/min or dialysis: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 7.5 mg/kg every 4 weeks; Child-Pugh C: not recommended. |
| Pediatric use | Age ≥2 years: 10 mg/kg every 4 weeks IV, max 1000 mg; age <2 years: safety not established. |
| Geriatric use | No adjustment for age alone; monitor renal function and adjust per renal guidelines. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for JESDUVROQ (JESDUVROQ).
| Breastfeeding | Not recommended during breastfeeding; M/P ratio unknown. Excreted in rat milk. Potential for serious adverse reactions in nursing infants. |
| Teratogenic Risk | First trimester: Potential for fetal malformations (limited human data; animal studies show teratogenicity at supratherapeutic doses). Second and third trimesters: Risk of fetal toxicity (e.g., low birth weight, neurodevelopmental effects) based on drug mechanism. |
| Fetal Monitoring |
■ FDA Black Box Warning
None.
| Serious Effects |
["Severe hypersensitivity to JESDUVROQ or any of its excipients","Concomitant use with strong CYP3A4 inducers"]
| Precautions | ["Interstitial lung disease/pneumonitis","Severe cutaneous adverse reactions (SCARs) including Stevens-Johnson syndrome and toxic epidermal necrolysis","Hepatotoxicity","Neutropenia","Embryo-fetal toxicity"] |
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| Monitor maternal liver function, renal function, and complete blood count monthly. Fetal ultrasound for growth and anatomy at 18-20 weeks and repeat at 32 weeks. Assess for signs of perinatal depression or neurobehavioral effects postpartum. |
| Fertility Effects | Animal studies show reduced fertility in males and females at clinically relevant doses. Human data insufficient to determine impact on spermatogenesis or ovulation. |