CAPRELSA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for CAPRELSA (CAPRELSA).
Inhibits multiple receptor tyrosine kinases involved in tumor angiogenesis and oncogenesis, including VEGFR2, EGFR, and RET.
| Metabolism | Primarily metabolized by CYP3A4, with minor contributions from FMO1 and FMO3. |
| Excretion | Primarily fecal (approximately 75% of administered dose, mainly as unchanged drug and metabolites); renal excretion accounts for about 25% (less than 1% unchanged). |
| Half-life | Terminal half-life approximately 90 hours (range 30–150 hours), supporting once-daily dosing; steady-state achieved by day 15. |
| Protein binding | Highly protein bound (>99.9%) primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution (Vd) is approximately 160 L (2.3 L/kg for a 70 kg patient), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is approximately 50% (range 30–80%) after a 300 mg dose. |
| Onset of Action | Time to clinical effect is not well-defined; maximal plasma concentrations achieved 2–6 hours post-dose. |
| Duration of Action | Sustained inhibition of RET kinase; duration corresponds to dosing interval with continuous daily administration. |
| Action Class | Protein synthesis inhibitors |
300 mg orally once daily, with or without food.
| Dosage form | TABLET |
| Renal impairment | For moderate renal impairment (CrCl 30-50 mL/min): reduce dose to 200 mg once daily. For severe renal impairment (CrCl <30 mL/min): 200 mg once daily with close monitoring; not recommended if CrCl <15 mL/min. |
| Liver impairment | Child-Pugh Class B: reduce dose to 200 mg once daily. Child-Pugh Class C: not recommended. |
| Pediatric use | Safety and efficacy not established; no recommended pediatric dosing. |
| Geriatric use | No specific dose adjustment required; monitor renal function due to age-related decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for CAPRELSA (CAPRELSA).
| Breastfeeding | No data on vandetanib in human milk. Animal studies show excretion into milk. Due to potential for serious adverse reactions in the breastfed infant (e.g., growth retardation, developmental delay), advise women not to breastfeed during treatment and for at least 4 months after the last dose. M/P ratio is unknown. |
| Teratogenic Risk | CAPRELSA (vandetanib) is contraindicated in pregnancy. Based on its mechanism of action (VEGF receptor inhibitor), there is a risk of fetal harm. Animal studies show teratogenicity, including fetal malformations and growth retardation, at exposures below the human dose. First trimester exposure carries highest risk for major congenital anomalies. Second and third trimester exposure may cause fetal renal impairment, oligohydramnios, and placental insufficiency. |
■ FDA Black Box Warning
QT interval prolongation, Torsades de Pointes, and sudden death have been reported. Caprelsa should not be used in patients with hypocalcemia, hypokalemia, hypomagnesemia, or long QT syndrome.
| Serious Effects |
["Congenital long QT syndrome","Hypocalcemia, hypokalemia, or hypomagnesemia (must be corrected prior to initiation)"]
| Precautions | ["QT prolongation and arrhythmias: Monitor electrolytes and ECG; correct electrolyte abnormalities before initiating.","Hypothyroidism: Monitor TSH levels; thyroid hormone replacement may be needed.","Hypertension: Monitor blood pressure and manage with antihypertensives.","Hemorrhage: Serious bleeding events have occurred; discontinue for severe bleeding.","Wound healing impairment: Interrupt therapy for at least 3 weeks prior to elective surgery.","Diarrhea: Manage with antidiarrheal agents and fluid/electrolyte replacement."] |
| Food/Dietary | Avoid grapefruit, grapefruit juice, and Seville oranges as they inhibit CYP3A4 and may increase vandetanib exposure. CAPRELSA should be taken at least 1 hour before or 2 hours after a meal to minimize food effect on absorption. No specific restrictions with other foods. |
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| Fetal Monitoring | Monitor maternal blood pressure for hypertension (common, up to 33%). Assess for proteinuria. Perform serial fetal ultrasound for growth restriction, oligohydramnios (due to VEGF inhibition). Monitor maternal ECG for QTc prolongation (vandetanib prolongs QTc). Check electrolytes (potassium, magnesium, calcium) regularly. Monitor thyroid function (TSH) due to hypothyroidism risk. |
| Fertility Effects | Vandetanib may impair fertility. In animal studies, decreased fertility and testicular degeneration were observed. Human data are limited but may include amenorrhea or ovarian failure. Pre-treatment counseling on fertility preservation (sperm or oocyte cryopreservation) is recommended. |
| Clinical Pearls | CAPRELSA (vandetanib) is a once-daily oral VEGF and EGFR inhibitor with significant QT prolongation risk; obtain baseline ECG and monitor QTc at 4 and 8 weeks post-initiation, then every 3 months. Avoid in patients with QTc > 480 ms. Administer at least 1 hour before or 2 hours after meals to reduce variability. Dose reduction for moderate hepatic impairment (Child-Pugh B) but avoid in severe (Child-Pugh C). Concurrent use of strong CYP3A4 inducers (e.g., rifampin) decreases exposure; avoid combination or adjust dose. |
| Patient Advice | Take CAPRELSA at the same time each day, at least 1 hour before or 2 hours after a meal. · Do not crush or split tablets; swallow whole with water. · Avoid grapefruit, grapefruit juice, and Seville oranges during treatment. · Report any signs of irregular heartbeat, fainting, or dizziness immediately. · Use effective contraception during and for at least 8 months after stopping treatment. · Avoid sun exposure; use sunscreen and protective clothing as photosensitivity is common. · Do not take any new medications, including OTC or herbal products, without consulting your doctor. · Monitor for diarrhea, hypertension, rash, and fatigue; report if severe. |