Alecensa

/ Roche

The recommended dose of Alectinib is 600 mg (four 150 mg capsules) taken twice daily with food (total daily dose of 1200 mg).
Duration of treatment: Treatment with Alectinib should be continued until disease progression or unacceptable toxicity.
Delayed or missed doses: If a planned dose of Alectinib is missed, patients can make up that dose unless the next dose is due within 6 hours. Patients should not take two doses at the same time to make up for a missed dose. If vomiting occurs after taking a dose of Alectinib, patients should take the next dose at the scheduled time.
Dose adjustments: Management of adverse events may require dose reduction, temporary interruption, or discontinuation of treatment with Alectinib. The dose of Alectinib should be reduced in steps of 150 mg twice daily based on tolerability. Alectinib treatment should be permanently discontinued if patients are unable to tolerate the 300 mg twice daily dose.
Dose reduction schedule: Starting dose: 600 mg twice daily. First dose reduction: 450 mg twice daily. Second dose reduction: 300 mg twice daily.
For dose modification advice for specified adverse drug reactions: See prescribing information for full details.

Treatment of patients with ALK positive, locally advanced or metastatic non-small cell lung cancer (NSCLC) who progressed on or are intolerant to crizotinib. Alectinib as monotherapy is indicated for the first-line treatment of adult patients with anaplastic lymphoma kinase (ALK)-positive advanced non-small cell lung cancer.

Hypersensitivity to alectinib or to any of the excipients.

Interstitial lung disease (ILD)/pneumonitis: Cases of ILD/pneumonitis have been reported in clinical trials with Alectinib. 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.
Hepatotoxicity: Elevations in alanine aminotransferase (ALT) and aspartate aminotransferase (AST) greater than 5 times the ULN as well as bilirubin elevations of more than 3 times the ULN occurred in patients in pivotal clinical trials with Alectinib. 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, Alectinib should be withheld and resumed at a reduced dose, or permanently discontinued.
Severe myalgia and creatine phosphokinase (CPK) elevation: Myalgia or musculoskeletal pain was reported in patients in pivotal trials with Alectinib, including Grade 3 events. Elevations of CPK occurred in pivotal trials with Alectinib, including Grade 3 events.
Bradycardia: Symptomatic bradycardia can occur with Alectinib. Heart rate and blood pressure should be monitored as clinically indicated. Dose modification is not required in case of asymptomatic bradycardia. 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 Alectinib treatment should be adjusted accordingly.
Photosensitivity: Photosensitivity to sunlight has been reported with Alectinib administration. Patients should be advised to avoid prolonged sun exposure while taking Alectinib, 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.
Women of child-bearing potential: Alectinib may cause foetal harm when administered to a pregnant woman. Female patients of child-bearing potential receiving Alectinib, must use highly effective contraceptive methods during treatment and for at least 3 months following the last dose of Alectinib.
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: The recommended daily dose (1200 mg) of Alectinib contains 2.1 mmol (or 48 mg) sodium. To be taken into consideration by patients on a controlled sodium diet.
See prescribing information for full details.

Constipation, oedema (peripheral, oedema, generalised oedema, eyelid oedema, periorbital oedema, face oedema and localised oedema), myalgia.
See prescribing information for full details.

Effects of other medicinal products on alectinib: Based on in vitro data, CYP3A4 is the primary enzyme mediating the metabolism of both alectinib and its major active metabolite M4, and CYP3A contributes to 40%  50% of total hepatic metabolism.
CYP3A inhibitors: Co-administration of multiple oral doses of 400 mg posaconazole twice daily, a strong CYP3A inhibitor, with a single oral dose of 300 mg alectinib increased alectinib exposure Cmax and AUCinf by 1.18 and 1.75-fold respectively, and reduced M4 Cmax and AUCinf by 71% and 25% respectively.
Medicinal products that increase gastric pH: Multiple doses of esomeprazole, a proton pump inhibitor, 40 mg once daily, demonstrated no clinically relevant effect on the combined exposure of alectinib and M4. Therefore, no dose adjustments are required when Alecensa is co-administered with proton pump inhibitors or other medicinal products which raise gastric pH (e.g. H2 receptor antagonists or antacids).
Effect of transporters on alectinib disposition M4 is a substrate of P-gp. As alectinib inhibits P-gp, it is not expected that co-medication with P-gp inhibitors has a relevant effect on M4 exposure.
Effect of transporters on alectinib disposition: M4 is a substrate of P-gp. As alectinib inhibits P-gp, it is not expected that co-medication with P-gp inhibitors has a relevant effect on M4 exposure.
Effects of alectinib on other medicinal products:
P-gp substrates: In vitro, alectinib and its major active metabolite M4 are inhibitors of the efflux transporter P-glycoprotein (P-gp). Therefore, alectinib and M4 may have the potential to increase plasma concentrations of co-administered substrates of P-gp. When Alecensa is co-administered with P-gp substrates (e.g., digoxin, dabigatran etexilate, topotecan, sirolimus, everolimus, nilotinib and lapatinib), appropriate monitoring is recommended.
BCRP substrates: In vitro, alectinib and M4 are inhibitors of the efflux transporter Breast Cancer Resistance Protein (BCRP). Therefore, alectinib and M4 may have the potential to increase plasma concentrations of co-administered substrates of BCRP. When Alecensa is co-administered with BCRP substrates (e.g., methotrexate, mitoxantrone, topotecan and lapatinib), appropriate monitoring is recommended.
CYP substrates: In vitro, alectinib and M4 show weak time-dependent inhibition of CYP3A4, and alectinib exhibits a weak induction potential of CYP3A4 and CYP2B6 at clinical concentrations. Multiple doses of 600 mg alectinib had no influence on the exposure of midazolam (2 mg), a sensitive CYP3A substrate. Therefore, no dose adjustment is required for co-administered CYP3A substrates. A risk for induction of CYP2B6 and PXR regulated enzymes apart from CYP3A4 cannot be completely excluded. The effectiveness of concomitant administration of oral contraceptives may be reduced.
See prescribing information for full details.

Pregnancy: Women of childbearing potential/contraception. Women of childbearing potential must be advised to avoid pregnancy while on Alectinib. Female patients of child-bearing potential receiving Alectinib must use highly effective contraceptive methods during treatment and for at least 3 months following the last dose of Alectinib. There are no or limited amount of data from the use of Alectinib in pregnant women. Based on its mechanism of action, Alectinib may cause fetal harm when administered to a pregnant woman. Studies in animals have shown reproductive toxicity
Lactation: It is unknown whether alectinib and its metabolites are excreted in human milk. A risk to the newborn/infant cannot be excluded. Mothers should be advised against breast-feeding while receiving Alectinib.
See prescribing information for full details.

Patients who experience overdose should be closely supervised and general supportive care instituted. There is no specific antidote for overdose with Alectinib.

Lactose: contains lactose.
Storage: Do not store above 30°C. Store in the original container to protect from light and moisture.
Shelf life: after first opening: 12 months.