KYTRIL
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KYTRIL (KYTRIL).
Selective serotonin 5-HT3 receptor antagonist, blocking serotonin binding at vagal nerve terminals and central nervous system chemoreceptor trigger zone.
| Metabolism | Hepatic metabolism via CYP3A4, CYP1A2, and CYP2D6; also metabolism by flavin-containing monooxygenase. |
| Excretion | Approximately 16% of the dose is excreted unchanged in urine; 44% is eliminated as metabolites (mainly 5-hydroxygranisetron) in urine, and 33% is excreted in feces as metabolites. Renal clearance accounts for about 30% of total clearance. |
| Half-life | Terminal elimination half-life is 5.9 hours in healthy young adults; in cancer patients, it may be prolonged to 10-12 hours. Clinical context: supports twice-daily dosing for chemotherapy-induced nausea and vomiting (CINV) prophylaxis. |
| Protein binding | Approximately 65% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Approximately 3 L/kg (range 2–4 L/kg), indicating extensive extravascular distribution, including into the central nervous system. |
| Bioavailability | Oral: 60% (due to first-pass metabolism); IV: 100%. |
| Onset of Action | IV: 1-3 minutes; oral: 60 minutes (peak antiemetic effect correlates with peak plasma concentrations at 1 hour). |
| Duration of Action | Up to 24 hours. Clinical notes: single IV dose covers acute CINV; for delayed nausea, repeat dosing or alternative agents may be needed. |
2 mg orally once daily or 1 mg intravenously 30 minutes before chemotherapy. For prevention of nausea/vomiting, 2 mg orally 1 hour before chemotherapy or 1 mg IV over 30 seconds.
| Dosage form | SOLUTION |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment. For severe renal impairment (CrCl < 30 mL/min), maximum oral dose is 2 mg once daily; IV dosing not recommended due to lack of data. |
| Liver impairment | Child-Pugh A or B: No adjustment needed. Child-Pugh C: Maximum oral dose 2 mg once daily; IV dosing with caution, consider dose reduction to 0.5 mg IV. |
| Pediatric use | Children 2-16 years: 0.02 mg/kg IV (max 1 mg) or 0.2 mg/kg orally (max 2 mg) 30-60 minutes before chemotherapy; may repeat once after 24 hours if needed. |
| Geriatric use | No specific dose adjustment; use with caution due to potential age-related renal impairment. Monitor for QT prolongation in elderly with cardiac risk factors. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for KYTRIL (KYTRIL).
| Breastfeeding | Excreted in rat milk at levels ~6.6% of maternal plasma; not known if excreted in human milk. M/P ratio unknown. Use with caution, especially in neonates or premature infants. |
| Teratogenic Risk | Pregnancy Category B. No evidence of teratogenicity in animal studies; inadequate human data. First trimester: risk cannot be excluded. Second and third trimesters: no known fetal adverse effects from intermittent use. |
| Fetal Monitoring |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to granisetron or any component of the formulation; concomitant use with apomorphine.
| Precautions | QT interval prolongation (dose-dependent), use with caution in patients with pre-existing cardiac conduction abnormalities, electrolyte disturbances, or those taking other QT-prolonging drugs; caution in patients with subacute intestinal obstruction due to decreased GI motility. |
Loading safety data…
| No specific monitoring required. Monitor for maternal adverse effects (headache, constipation, QT prolongation). Fetal monitoring not indicated except for maternal conditions. |
| Fertility Effects | No reported effects on human fertility. In animal studies, no impairment of fertility at doses up to 9 mg/kg/day. |