Alecensa

Before taking alectinib,

• tell your doctor and pharmacist if you are allergic to alectinib, any other medications, or any of the ingredients in alectinib capsules. Ask your pharmacist for a list of the ingredients.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention any of the following: medications to treat high blood pressure or heart problems. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor if you have or have ever had liver disease, lung or breathing problems, or a slow or irregular heartbeat.
• tell your doctor if you are pregnant or plan to become pregnant, or if you plan to father a child. You should not become pregnant while you are taking alectinib. If you are a female, you should use a reliable method of birth control while taking alectinib and for at least 1 week after your final dose. If you are a male, you and your female partner should use effective birth control while you are taking alectinib and for 3 months after your final dose. If you or your partner becomes pregnant while taking alectinib call your doctor immediately. Alectinib may harm the fetus.
• tell your doctor if you are breast-feeding. You should not breast-feed while taking alectinib and for 1 week after your last dose.
• plan to avoid unnecessary or prolonged exposure to sunlight (including sunlamps and tanning beds) and to wear protective clothing, sunglasses, and a sunscreen that has a sun protection factor (SPF) of at least 50 while taking alectininb and for at least 7 days after your last dose. Alectinib may make your skin sensitive to sunlight.

Unless your doctor tells you otherwise, continue your normal diet.

Alecensa is a prescription medication used to treat a certain type of advanced lung cancer. Alecensa belongs to a group of drugs called kinase inhibitors. These work by blocking the activity of the ALK (gene mutation) protein to prevent cancer cells from growing and spreading.

This medication comes in capsule (by mouth) form and is taken twice a day with food.

Common side effects of Alecensa include tiredness, constipation, and swelling in the hands, feet, ankles, and eyelids.

Avoid exposure to sunlight or tanning beds during treatment and for at least 7 days after your last dose of alectinib. This medicine can make you sunburn more easily. Wear protective clothing and use sunscreen and lip balm (SPF 50 or higher) when you are outdoors.

No clinically important interactions identified to date.1

Metabolized to major active M4 metabolite by CYP3A4.1 In vitro, M4, but not alectinib, is a substrate of P-glycoprotein (P-gp); neither alectinib nor M4 is a substrate of breast cancer resistance protein (BCRP), organic anion transport protein (OATP) 1B1, or OATP1B3.1

In vitro, alectinib and M4 do not inhibit CYP isoenzymes 1A2, 2B6, 2C9, 2C19, or 2D6.1 In vitro, alectinib does not inhibit OATP1B1 or OATP1B3, organic anion transporter (OAT) 1 and OAT3, or organic cation transporter (OCT) 2.1

Alectinib and M4 inhibit P-gp and BCRP in vitro.1

Drugs Associated with Bradycardia

Possible increased risk of bradycardia.1 If clinically important bradycardia occurs, discontinue or adjust dosage of the concomitant drug, if possible.1 (See Bradycardia under Dosage and Administration.)

Specific Drugs

• It is used to treat lung cancer.

Pregnancy

Risk Summary

Based on 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-times 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 (AUC0-24h,ss) in humans treated with alectinib 600 mg BID) 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 AUC0-24h,ss in humans treated with alectinib 600 mg BID). Doses greater than or equal to 9 mg/kg/day (approximately 2.7-fold the estimated human AUC0-24h,ss in humans treated with alectinib 600 mg BID), 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.

Lactation

Risk Summary

There are no data on the presence of alectinib or its metabolites in human milk, the effects of alectinib on the breast-fed infant, or its effects on milk production. Because of the potential for serious adverse reactions in breast-fed infants from alectinib, advise a lactating woman not to breastfeed during treatment with Alecensa and for 1 week after the final dose.

Females and Males of Reproductive Potential

Contraception

Females

Alecensa can cause fetal harm when administered to a pregnant woman. Advise females of reproductive potential to use effective contraception during treatment with Alecensa and for 1 week after the final dose [see Use in Specific Populations (8.1)].

Males

Based on genotoxicity findings, advise males with female partners of reproductive potential to use effective contraception during treatment with Alecensa and for 3 months following the final dose [see Non Clinical Toxicology (13.1)].

Pediatric Use

The safety and effectiveness of Alecensa in pediatric patients have not been established.

Animal Data

Juvenile animal studies have not been conducted using alectinib. In general toxicology studies, treatment of rats with doses of alectinib resulting in exposures greater than or equal to approximately 4.5 times those in humans treated with alectinib at 600 mg twice daily resulted in changes in the growing teeth and bones. Findings in teeth included discoloration and changes in tooth size along with histopathological disarrangement of the ameloblast and odontoblast layers. There were also decreases in the trabecular bone and increased osteoclast activity in the femur and sternum.

Geriatric Use

Clinical studies of Alecensa did not include sufficient number of subjects aged 65 and older to determine whether they respond differently from younger subjects.

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 (12.3)].

Hepatic Impairment

No dose adjustment is recommended for patients with mild hepatic impairment (total bilirubin less than or equal to upper limit of normal (ULN) and aspartate transaminase (AST) greater than ULN or total bilirubin greater than 1.0 to 1.5 times ULN and any AST). The safety of Alecensa in patients with moderate or severe hepatic impairment has not been studied [see Clinical Pharmacology (12.3)].

Alecensa (alectinib) is a kinase inhibitor for oral administration. The molecular formula for alectinib is C30H34N4O2 ∙ HCl. The molecular weight is 482.62 g/mol (free base form) and 519.08 g/mol (hydrochloride salt). Alectinib is described chemically as 9-ethyl-6, 6-dimethyl-8-[4-(morpholin-4-yl)piperidin-1-yl]-11-oxo-6, 11-dihydro-5H-benzo[b]carbazole-3-carbonitrile hydrochloride. The chemical structure of alectinib is shown below:

Alectinib HCl is a white to yellow white powder or powder with lumps with a pKa of 7.05 (base).

Alecensa is supplied as hard capsules containing 150 mg of alectinib (equivalent to 161.33 mg alectinib HCl) and the following inactive ingredients: lactose monohydrate, hydroxypropylcellulose, sodium lauryl sulfate, magnesium stearate, and carboxymethylcellulose calcium. The capsule shell contains hypromellose, carrageenan, potassium chloride, titanium dioxide, corn starch, and carnauba wax. The printing ink contains red iron oxide (E172), yellow iron oxide (E172), FD&C Blue No. 2 aluminum lake (E132), carnauba wax, white shellac, and glyceryl monooleate.

Advise the patient to read the FDA-approved patient labeling (Patient Information).  

Inform patients of the following:

Hepatotoxicity

Inform patients of the signs and symptoms of bilirubin and hepatic transaminase elevations. Advise patients to contact their healthcare provider immediately for signs or symptoms of bilirubin and hepatic transaminase elevations [see Warnings and Precautions (5.1)].

Interstitial Lung Disease (ILD)/Pneumonitis

Inform patients of the risks of severe ILD/pneumonitis. Advise patients to contact their healthcare provider immediately to report new or worsening respiratory symptoms [see Warnings and Precautions (5.2)].

Bradycardia

Inform patients that symptoms of bradycardia including dizziness, lightheadedness, and syncope can occur while taking Alecensa. Advise patients to contact their healthcare provider to report these symptoms and to inform their healthcare provider about the use of any heart or blood pressure medications [see Warnings and Precautions (5.3)].

Severe Myalgia/CPK elevation

Inform patients of signs and symptoms of myalgia, including unexplained and/or persistent muscle pain, tenderness, or weakness. Advise patients to contact their healthcare provider immediately to report new or worsening symptoms of muscle pain or weakness [see Warnings and Precautions (5.4)].

Photosensitivity

Inform patients of the signs and symptoms of photosensitivity. Advise patients to avoid prolonged sun exposure while taking Alecensa and for at least 7 days after study drug discontinuation and to use proper protection from the sun. Advise patients to use a broad spectrum ultraviolet A (UVA)/ultraviolet B (UVB) sunscreen and lip balm (SPF ≥50) to help protect against potential sunburn [see Adverse Reactions (6.1)].

Embryo-Fetal Toxicity

Alecensa can cause fetal harm if taken during pregnancy. Advise a pregnant woman of the potential risk to a fetus [see Warnings and Precautions (5.5) and Use in Specific Populations (8.1, 8.3)].

Advise females of reproductive potential to use effective contraception during treatment with Alecensa and for at least 1 week after the last dose of Alecensa. Advise patients to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions (5.5) and Use in Specific Populations (8.1, 8.3)].

Advise male patients with female partners of reproductive potential to use effective contraception during treatment with Alecensa and for 3 months after the last dose [see Use in Specific Populations (8.3) and Nonclinical Toxicology (13.1)].

Lactation

Advise women not to breastfeed during treatment with Alecensa and for one week after the last dose [see Use in Specific Populations (8.2)].

Administration

Instruct patients to take Alecensa twice a day. Advise patients to take Alecensa with food and to swallow Alecensa capsules whole [see Dosage and Administration (2.1)].

Missed Dose

Advise patients that if a dose of Alecensa is missed or if the patient vomits after taking a dose of Alecensa, patients should be advised not to take an extra dose, but to take the next dose at the regular time [see Dosage and Administration (2.1)].

Distributed by:
Genentech USA, Inc.
A Member of the Roche Group
1 DNA Way
South San Francisco, CA 94080-4990

Alecensa® is a registered trademark of Chugai Pharmaceutical Co., Ltd., Tokyo, Japan
©2015 Genentech, Inc. All rights reserved.

Representative sample of labeling (see the HOW SUPPLIED section for complete listing):

NDC 50242-130-01

Alecensa®
(alectinib)
capsules

150 mg

Each capsule contains 150 mg of alectinib
(equivalent to 161.33 mg alectinib HCl).

Rx only

240 capsules
Genentech

10164046

Alecensa can cause serious side effects. Call your doctor at once if you have: severe dizziness, very slow heartbeats, new or worsening breathing problems, upper stomach pain, dark urine, clay-colored stools, or jaundice (yellowing of the skin or eyes); or unexplained muscle pain, tenderness, or weakness.

Alecensa is usually taken twice per day. Follow all directions on your prescription label. Your doctor may occasionally change your dose to make sure you get the best results. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Before you start treatment, your doctor may perform tests to make sure Alecensa is the best treatment for your type of lung cancer.

Alecensa works best if you take it with food.

Do not crush, chew, dissolve, or open an Alecensa capsule. Swallow it whole.

If you vomit shortly after taking an Alecensa capsule, do not take another one. Wait until your next scheduled dose and take the regular amount of medicine at that time.

While using Alecensa, your heart rate and blood pressure will need to be checked often. You will also need frequent blood tests to check your liver function. Your cancer treatments may be delayed based on the results of these tests.

Read all patient information, medication guides, and instruction sheets provided to you. Ask your doctor or pharmacist if you have any questions.

Store at room temperature away from moisture, heat, and light.

Avoid exposure to sunlight or tanning beds during treatment and for at least 7 days after your last dose. Alecensa can make you sunburn more easily. Wear protective clothing and use sunscreen and lip balm (SPF 50 or higher) when you are outdoors.

Applies to alectinib: oral capsule

Hematologic

Very common (10% or more): Anemia (56%), lymphopenia (22%)[Ref]

Hepatic

Very common (10% or more): Increased AST (51%), increased alkaline phosphatase (47%), hyperbilirubinemia (39%), increased ALT (34%)[Ref]

Musculoskeletal

Very common (10% or more): Increased CPK (43%), myalgia/musculoskeletal pain (29%), back pain (12%)[Ref]

Other

Very common (10% or more): Fatigue/asthenia (41%), edema (30%)[Ref]

The following types of edema were reported: peripheral, generalized, eyelid, and periorbital.[Ref]

Metabolic

Very common (10% or more): Hyperglycemia (36%), hypocalcemia (32%), hypokalemia (29%), hypophosphatemia (21%), hyponatremia (20%), increased weight (11%)[Ref]

Gastrointestinal

Very common (10% or more): Constipation (34%), nausea (18%), diarrhea (16%), vomiting (12%)[Ref]

Renal

Very common (10% or more): Increased creatinine (28%)[Ref]

Dermatologic

Very common (10% or more): Rash (18%)
Common (1% to 10%): Photosensitivity[Ref]

Reported cases of rash included acneiform dermatitis, erythema, and different types of rash (macular, papular, maculopapular, generalized, and pruritic).[Ref]

Nervous system

Very common (10% or more): Headache (17%)[Ref]

Respiratory

Very common (10% or more): Cough (19%), dyspnea (16%)
Uncommon (0.1% to 1%): Interstitial lung disease[Ref]

Ocular

Reported cases of vision disorder included blurred vision, vitreous floaters, visual impairment, reduced visual acuity, asthenopia, and diplopia.[Ref]

Very common (10% or more): Vision disorder (10%)[Ref]

Cardiovascular

Common (1% to 10%): Bradycardia[Ref]

General

In 253 patients with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) who received this drug (600 mg orally twice a day) for a median duration of 9.3 months, serious (19%) and fatal (2.8%) adverse reactions occurred.[Ref]

Some side effects of Alecensa may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.