Alectinib
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From MedlinePlus, U.S. National Library of Medicine
Dosing in kidney impairment
Renal Impairment No dose adjustment is recommended for patients with mild or moderate renal impairment. The safety of ALECENSA in patients with severe renal impairment (creatinine clearance less than 30 mL/min) or end-stage renal disease has not been studied [see Clinical Pharmacology ].
| CriteriaALT = alanine transaminase; AST = aspartate transaminase; ULN = upper limit of normal; ILD = interstitial lung disease; CPK = blood creatine phosphokinase | ALECENSA Dose Modification |
|---|---|
| ALT or AST elevation of greater than 5 times upper limit of normal (ULN) with total bilirubin less than or equal to 2 times ULN | Temporarily withhold until recovery to baseline or to less than or equal to 3 times ULN, then resume at reduced dose as per Table 2. |
| ALT or AST elevation greater than 3 times ULN with total bilirubin elevation greater than 2 times ULN in the absence of cholestasis or hemolysis | Permanently discontinue ALECENSA. |
| Total bilirubin elevation of greater than 3 times ULN | Temporarily withhold until recovery to baseline or to less than or equal to 1.5 times ULN, then resume at reduced dose as per Table 2. |
| Any grade treatment-related interstitial lung disease (ILD)/pneumonitis | Permanently discontinue ALECENSA. |
| Grade 3 renal impairment | Temporarily withhold until serum creatinine recovers to less than or equal to 1.5 times ULN, then resume at reduced dose. |
| Grade 4 renal impairment | Permanently discontinue ALECENSA. |
| Symptomatic bradycardia | Withhold ALECENSA until recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above. If contributing concomitant medication is identified and discontinued, or its dose is adjusted, resume ALECENSA at previous dose upon recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above. If no contributing concomitant medication is identified, or if contributing concomitant medications are not discontinued or dose modified, resume ALECENSA at reduced dose (see Table 2) upon recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above. |
| BradycardiaHeart rate less than 60 beats per minute (bpm) (life-threatening consequences, urgent intervention indicated) | Permanently discontinue ALECENSA if no contributing concomitant medication is identified. If contributing concomitant medication is identified and discontinued, or its dose is adjusted, resume ALECENSA at reduced dose (see Table 2) upon recovery to asymptomatic bradycardia or to a heart rate of 60 bpm or above, with frequent monitoring as clinically indicated. Permanently discontinue ALECENSA in case of recurrence. |
| CPK elevation greater than 5 times ULN | Temporarily withhold until recovery to baseline or to less than or equal to 2.5 times ULN, then resume at same dose. |
| CPK elevation greater than 10 times ULN or second occurrence of CPK elevation of greater than 5 times ULN | Temporarily withhold until recovery to baseline or to less than or equal to 2.5 times ULN, then resume at reduced dose as per Table 2. |
| Hemolytic Anemia | Withhold ALECENSA if hemolytic anemia is suspected. Upon resolution, resume at reduced dose or permanently discontinue. |
| Severe hypertriglyceridemia (blood triglycerides from 501 to 1,000 mg/dL or from 5.71 to 11.4 mmol/L) OR Life-threatening hypertriglyceridemia (blood triglycerides over 1,000 mg/dL or over 11.4 mmol/L) | Temporarily withhold until recovery to at least moderate hypertriglyceridemia (i.e., until blood triglycerides are ≤ 500 mg/dL or ≤ 5.7 mmol/L). Evaluate risk factors for pancreatitis and address those that are treatable before resuming treatment with ALECENSA. If an acute episode of pancreatitis occurs, temporarily withhold until full recovery before resuming treatment with ALECENSA. Resume ALECENSA at the same dose, with regular monitoring of blood triglyceride levels. If hypertriglyceridemia reoccurs, consider dose reduction of ALECENSA. |
Dosing in liver impairment
Recommended Dosage for Hepatic Impairment The recommended dose of ALECENSA in patients with severe hepatic impairment (Child-Pugh C) is 450 mg orally twice daily [see Use in Specific Populations and Clinical Pharmacology ].
Preparation and administration
Dosing and Administration The recommended dosage information for ALECENSA is provided in Table 1 . [See table below.]
Contraindications
None. None. ( 4 )
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on findings from animal studies and its mechanism of action, ALECENSA can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12.1) ] . There are no available data on ALECENSA use in pregnant women. Administration of alectinib to pregnant rats and rabbits by oral gavage during the period of organogenesis resulted in embryo-fetal toxicity and abortion at maternally toxic doses with exposures approximately 2.7-fold those observed in humans treated with alectinib at 600 mg twice daily (see Data ) . Advise pregnant women of the potential risk to a fetus. In the U.S.
general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data In a preliminary rabbit embryo-fetal study, administration of alectinib by oral gavage during the period of organogenesis resulted in abortion or complete embryo-fetal mortality at a maternally toxic dose of 27 mg/kg/day (approximately 2.9-fold the estimated area under the curve (AUC 0-24h,ss ) in humans treated with alectinib 600 mg twice daily) in three of six pregnant rabbits.
The remaining three pregnant rabbits in this group had few live fetuses, decreased fetal and placental weights, and retroesophageal subclavian artery. In a rat preliminary embryo-fetal development study, administration of alectinib during organogenesis resulted in complete litter loss in all pregnant rats at 27 mg/kg/day (approximately 4.5-fold the estimated AUC 0-24h,ss in humans treated with alectinib 600 mg twice daily).
Doses greater than or equal to 9 mg/kg/day (approximately 2.7-fold the estimated human AUC 0-24h,ss in humans treated with alectinib 600 mg twice daily), resulted in maternal toxicity as well as developmental toxicities including decreased fetal weight, dilated ureter, thymic cord, small ventricle and thin ventricle wall, and reduced number of sacral and caudal vertebrae.
For breastfeeding, also see LactMed (National Library of Medicine), which summarizes milk levels and infant effects.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
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