Alecensa Special Precautions

General: Interstitial lung disease (ILD)/Pneumonitis: Cases of ILD/pneumonitis have been reported in clinical trials with Alecensa (see Adverse Reactions). Patients should be monitored for pulmonary symptoms indicative of pneumonitis. Alecensa should be immediately interrupted in patients diagnosed with ILD/pneumonitis and should be permanently discontinued if no other potential causes of ILD/pneumonitis have been identified (see Dosage & Administration).
Hepatotoxicity: Elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) greater than 5 times the upper limit of normal (ULN) as well as bilirubin elevations of more than 3 times the ULN occurred in patients in pivotal clinical trials with Alecensa (see Adverse Reactions). The majority of these events occurred during the first 3 months of treatment. In the pivotal Alecensa clinical trials it was reported that three patients with Grade 3-4 AST/ALT elevations had drug induced liver injury. Concurrent elevations in ALT or AST greater than or equal to three times the ULN and total bilirubin greater than or equal to two times the ULN, with normal alkaline phosphatase, occurred in 1 patient treated in Alecensa clinical trials.
Liver function, including ALT, AST, and total bilirubin should be monitored at baseline and then every 2 weeks during the first 3 months of treatment, and then periodically, since events may occur later than 3 months, with more frequent testing in patients who develop transaminase and bilirubin elevations. Based on the severity of the adverse drug reaction, withhold Alecensa and resume at a reduced dose, or permanently discontinue Alecensa as described in Table 5 (see Dosage & Administration).
Severe Myalgia and Creatine Phosphokinase (CPK) elevation: Myalgia or musculoskeletal pain was reported in patients in pivotal trials with Alecensa, including Grade 3 events.
Elevations of CPK occurred in pivotal trials with Alecensa, including Grade 3 events. Median time to Grade 3 CPK elevation was 14 days in the pivotal phase II trials (NP28761, NP28673). Median time to Grade 3 CPK elevation was 27.5 days in the pivotal phase III clinical trial (BO28984) (see Adverse Reactions).
Advise patients to report any unexplained muscle pain, tenderness, or weakness. Assess CPK levels every two weeks for the first month of treatment and as clinically indicated in patients reporting symptoms. Based on the severity of the CPK elevation, withhold Alecensa, then resume or reduce dose (see Dosage & Administration).
Bradycardia: Symptomatic bradycardia can occur with Alecensa (see Adverse Reactions). Heart rate and blood pressure should be monitored as clinically indicated. Dose modification is not required in case of asymptomatic bradycardia (see Dosage & Administration). If patients experience symptomatic bradycardia or life-threatening events, concomitant medications known to cause bradycardia, as well as anti-hypertensive medications should be evaluated and Alecensa treatment should be adjusted as described in Table 5 (see Dosage & Administration and Interactions).
Photosensitivity: Photosensitivity to sunlight has been reported with Alecensa administration (see Adverse Reactions). Patients should be advised to avoid prolonged sun exposure while taking Alecensa and for at least 7 days after discontinuation of treatment. Patients should also be advised to use a broad spectrum Ultraviolet A (UVA)/ Ultraviolet B (UVB) sun screen and lip balm (SPF ≥50) to help protect against potential sunburn.
Embryo-fetal toxicity: Alecensa may cause fetal harm when administered to a pregnant woman. When administrated to pregnant rats and rabbits, alectinib caused embryo-fetal toxicity. Female patients of child-bearing potential, or women of child-bearing potential who are partners of male patients receiving Alecensa, must use highly effective contraceptive methods during treatment and for at least 3 months following the last dose of Alecensa. (See Use in Pregnancy & Lactation.)
Drug Abuse and Dependence: Not applicable.
Effects on the Ability to Drive and Use Machines: No studies on the effects on the ability to drive and to use machines have been performed.
Renal Impairment: See Dosage & Administration and Pharmacology: Pharmacokinetics: Special Populations under Actions.
Hepatic Impairment: See Dosage & Administration and Pharmacology: Pharmacokinetics: Special Populations under Actions.
Contraception: Female patients of child-bearing potential, or women of child-bearing potential who are partners of male patients receiving Alecensa, must use highly effective contraceptive methods during treatment and for at least 3 months following the last dose of Alecensa.
Use in Children: The safety and efficacy of Alecensa in paediatric patients below the age of 18 years have not been established.
Use in Elderly: See Dosage & Administration and Pharmacology: Pharmacokinetics: Special Populations under Actions).