Special Warning : אזהרת שימוש

4.4   Special warnings and precautions for use

Interstitial lung disease (ILD)/pneumonitis
Cases of ILD/pneumonitis have been reported in clinical trials with Alecensa (see section 4.8).
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 section 4.2).

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 section 4.8). 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 3 times the ULN and total bilirubin greater than or equal 2 times the ULN, with normal alkaline phosphatase, occurred in one 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. Thereafter, monitoring should be performed periodically, since events may occur later than 3 months, with more frequent testing in patients who develop aminotransferase and bilirubin elevations. Based on the severity of the adverse drug reaction, Alecensa should be withheld and resumed at a reduced dose, or permanently discontinued as described in Table 2 (see section 4.2).

Severe myalgia and creatine phosphokinase (CPK) elevation
Myalgia or musculoskeletal pain was reported in patients in pivotal trials with Alecensa, including Grade 3 events (see section 4.8).

Elevations of CPK occurred in pivotal trials with Alecensa, including Grade 3 events (see section 4.8).
Median time to Grade ≥ 3 CPK elevation was 15 days across clinical trials (BO40336, BO28984, NP28761, NP28673).

Patients should be advised to report any unexplained muscle pain, tenderness, or weakness. CPK levels should be assessed 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, Alecensa should be withheld, then resumed or dose reduced (see section 4.2).

Bradycardia
Symptomatic bradycardia can occur with Alecensa (see section 4.8). Heart rate and blood pressure should be monitored as clinically indicated. Dose modification is not required in case of asymptomatic bradycardia (see section 4.2). If patients experience symptomatic bradycardia or life-threatening events, concomitant medicinal products known to cause bradycardia, as well as anti-hypertensive medicinal products should be evaluated and Alecensa treatment should be adjusted as described in Table 2 (see sections 4.2 and 4.5, ‘P-gp substrates’ and ‘BCRP substrates’).

Haemolytic anaemia
Haemolytic anaemia has been reported with Alecensa (see section 4.8). If haemoglobin concentration is below 10 g/dL and haemolytic anaemia is suspected, Alecensa should be withheld and appropriate laboratory testing should be initiated. If haemolytic anaemia is confirmed, Alecensa should be resumed at a reduced dose upon resolution as described in Table 2 (see section 4.2).

Gastrointestinal perforation
Cases of gastrointestinal perforations have been reported in patients at increased risk (e.g., history of diverticulitis, metastases to the gastrointestinal tract, concomitant use of medicinal product with a recognized risk of gastrointestinal perforation) treated with alectinib. Discontinuation of Alecensa in patients who develop gastrointestinal perforation should be considered. Patients should be informed of the signs and symptoms of gastrointestinal perforations and advised to consult rapidly in case of occurrence.

Photosensitivity
Photosensitivity to sunlight has been reported with Alecensa administration (see section 4.8). 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 (sun protection factor [SPF] ≥50) to help protect against potential sunburn.

Women of child-bearing potential
Alecensa may cause foetal harm when administered to a pregnant woman. Female patients of child-bearing potential receiving Alecensa, must use highly effective contraceptive methods during treatment and for at least 3 months following the last dose of Alecensa (see sections 4.5, 4.6 and 5.3).
Lactose intolerance
This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, a congenital lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

Sodium content
This medicinal product contains 48 mg sodium per daily dose (1200 mg), equivalent to 2.4% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

Effects on Driving

4.7   Effects on ability to drive and use machines

Alecensa has minor influence on the ability to drive and use machines. Caution should be exercised when driving or operating machines as patients may experience symptomatic bradycardia (e.g., syncope, dizziness, hypotension) or vision disorders while taking Alecensa (see section 4.8).