ALECENSA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ALECENSA (ALECENSA).
Alectinib is a selective, potent inhibitor of anaplastic lymphoma kinase (ALK) and RET. It inhibits ALK phosphorylation and downstream signaling pathways (STAT3, PI3K/AKT, and MAPK) in ALK-positive cancers.
| Metabolism | Primarily metabolized by CYP3A4 to a major active metabolite (M4). Minor contributions from CYP3A5 and CYP2C8. |
| Excretion | Primarily fecal (84.3%) as unchanged drug and metabolites; renal excretion accounts for <1%. |
| Half-life | Terminal elimination half-life is approximately 22 hours; supports once-daily dosing. |
| Protein binding | 99.4% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 5.4 L/kg (range 4.2-8.2 L/kg), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability is 37% under fasting conditions; increased to 2.6-fold with a high-fat meal. |
| Onset of Action | Not well-defined; clinical response observed within 4-6 weeks of continuous oral therapy. |
| Duration of Action | Sustained ALK inhibition over 24 hours with once-daily dosing; continuous treatment required for disease control. |
| Molecular Weight | 483.58 |
600 mg orally twice daily with food.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose to 450 mg twice daily. Child-Pugh C: Not recommended. |
| Pediatric use | Safety and efficacy not established; no approved pediatric dosing. |
| Geriatric use | No specific dose adjustments; monitor for adverse reactions due to potential age-related declines in organ function. |
| 1st trimester | There are no adequate and well-controlled studies in pregnant women. Based on its mechanism of action, Alecensa can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. |
| 2nd trimester | Same as first trimester. Animal studies show embryotoxicity and teratogenicity at maternal exposures lower than human exposure at the recommended dose. |
| 3rd trimester | Same as first and second trimesters. There is no specific additional risk for third trimester beyond general fetal harm. |
Clinical note
Comprehensive clinical and safety monograph for ALECENSA (ALECENSA).
| Placental transfer | Alecensa is expected to cross the placenta due to its molecular weight and mechanism of action. Animal studies confirm placental transfer with evidence of fetal toxicity. |
| Breastfeeding | It is not known whether Alecensa 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, advise women not to breastfeed during treatment and for 1 week after the last dose. |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
Hypersensitivity to alectinib or any excipients
| Precautions | Hepatotoxicity: Elevations in AST, ALT, and bilirubin; monitor LFTs., Interstitial lung disease (ILD)/pneumonitis: Withhold for suspected ILD; discontinue if confirmed., Bradycardia: Monitor heart rate and blood pressure., Myalgia: Grade ≥3 creatine phosphokinase elevation; monitor CPK., Hemolytic anemia: If Coombs-positive hemolytic anemia occurs, withhold and consider discontinuation., Embryo-fetal toxicity: Can cause fetal harm; advise contraception. |
| Food/Dietary | Take with food to enhance absorption. Avoid grapefruit, grapefruit juice, and Seville oranges as they may increase alectinib exposure. No other significant food interactions reported. |
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| Lactation Rating | L5 (Contraindicated) |
| Teratogenic Risk | Based on its mechanism of action (ALK inhibitor) and animal studies, alectinib is teratogenic. In pregnant rats, embryofetal toxicities including malformations and fetal death were observed at exposures below human clinical exposure. There are no adequate human data. First trimester exposure carries highest risk for major congenital anomalies; second and third trimester exposure may cause fetal growth impairment and CNS effects. |
| Fetal Monitoring | Monitor complete blood counts, liver function tests (ALT, AST, bilirubin), creatine phosphokinase, serum creatinine, and pulmonary function (for interstitial lung disease). Perform pregnancy test before initiation in women of reproductive potential. Fetal ultrasound monitoring for growth and anatomy if exposed during pregnancy. |
| Fertility Effects | In animal studies, alectinib caused testicular toxicity and impaired male fertility. No formal female fertility studies; however, based on mechanism and animal findings, potential for impaired fertility in both males and females. Consider fertility preservation options. |
| Clinical Pearls | Alectinib (Alecensa) is a potent CNS-penetrant ALK inhibitor. Monitor for bradycardia, hepatotoxicity, and pneumonitis. Coadministration with strong CYP3A4 inducers reduces alectinib exposure; avoid concurrent use. Dose reduction may be needed for severe hepatic impairment. Alectinib can cause myalgia and increased creatine kinase; check CK levels if symptomatic. |
| Patient Advice | Take Alecensa exactly as prescribed, with food to improve absorption. · Do not crush or break the capsules; swallow whole. · Avoid grapefruit, grapefruit juice, and Seville oranges while taking Alecensa. · Report symptoms like severe tiredness, dizziness, fainting (bradycardia), or yellowing of skin/eyes (liver problems) immediately. · Tell your doctor about all medications, including over-the-counter and herbal supplements, as many interact with Alecensa. · Do not stop taking Alecensa without consulting your doctor, even if you feel well. |