Alectinib

Alectinib is a cancer medicine that interferes with the growth and spread of cancer cells in the body.

Alectinib is used to treat non-small cell lung cancer that has spread to other parts of the body. Alectinib is usually given after another medicine has been tried without success.

Alectinib was approved by the US Food and Drug Administration (FDA) on an "accelerated" basis. In clinical studies, tumors responded to this medicine. However, further studies are needed to determine if this medicine can lengthen survival time.

Alectinib may also be used for purposes not listed in this medication guide.

Alectinib 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).

You should not use alectinib if you are allergic to it.

To make sure alectinib is safe for you, tell your doctor if you have:

• liver disease;
• slow heartbeats or other heart rhythm disorder;
• a personal or family history of Long QT syndrome;
• kidney disease; or
• a condition for which you take heart or blood pressure medicine.

Do not use alectinib if you are pregnant. It could harm the unborn baby. Tell your doctor if you become pregnant during treatment. Use effective birth control while you are using this medication and for at least 1 week after your last dose.

• If you are a man, use effective birth control if your sexual partner is able to get pregnant. An unborn baby can be harmed if a man fathers the child while he is taking alectinib. Keep using birth control for at least 3 months after your treatment ends.
• Tell your doctor right away if a pregnancy occurs while either the mother or the father is taking alectinib.

It is not known whether alectinib passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are using alectinib and for at least 1 week after your last dose.

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

Alectinib 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.

Alectinib works best if you take it with food.

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

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

While using alectinib, 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.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Alectinib is used to treat a certain type of non-small-cell lung cancer (NSCLC) that has spread to other parts of the body in people who were not treated successfully with crizotinib (Xalkori) or who cannot take crizotinib. Alectinib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps slow or stop the spread of cancer cells.

Serious side effects have been reported with alectinib. See the "Drug Precautions" section.

Common side effects of alectinib include the following:

• tiredness
• constipation
• swelling in the hands, feet, ankles, and eyelids

This is not a complete list of alectinib side effects. Ask your doctor or pharmacist for more information.

Tell your doctor if you have any side effect that bothers you or that does not go away.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Take alectinib exactly as prescribed.

Alectinib comes in capsule form and is taken twice daily, with food.

Do not open or dissolve the contents of the capsule. Swallow alectinib capsules whole.

If you miss a dose of alectinib, do not take your missed dose. Take your next dose at the scheduled time.

If you vomit after taking a dose of alectinib, do not take an extra dose. Take your next dose at your regular time.

Usual Adult Dose for Non-Small Cell Lung Cancer:

600 mg orally twice a day

Duration of Therapy: Until disease progression or unacceptable toxicity

Comments: This drug should be taken with food.

Use: Treatment of patients with anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib.

In the U.S.

• Alecensa

Available Dosage Forms:

• Capsule

Therapeutic Class: Antineoplastic Agent

Pharmacologic Class: Tyrosine Kinase Inhibitor

It is very important that your doctor check your progress at regular visits to make sure alectinib is working properly. Blood tests may be needed to check for unwanted effects.

Using alectinib while you are pregnant can harm your unborn baby. It may also cause birth defects if the father is using it when his sexual partner becomes pregnant. Women should use effective birth control during treatment and for at least 1 week after the last dose. Men with sexual partners should use effective birth control during treatment and for at least 3 months after the last dose. If you think a pregnancy has occurred with alectinib, tell your doctor right away.

Check with your doctor right away if you have pain or tenderness in the upper stomach, pale stools, dark urine, loss of appetite, nausea, vomiting, or yellow eyes or skin. These could be symptoms of a serious liver problem.

alectinib may cause swelling of the lungs (pneumonitis) or interstitial lung disease. These are life-threatening conditions and require immediate medical attention. The symptoms may be similar to those for lung cancer. Check with your doctor right away if you have a new or worsening cough, fever, shortness of breath, or trouble breathing.

Bradycardia (slow heartbeat) may occur while you are using alectinib. Tell your doctor right away if you have chest pain or discomfort, lightheadedness, dizziness, or fainting, or a slow or uneven heartbeat.

Tell your doctor right away if you have unexplained muscle pain, tenderness, or weakness after taking alectinib. These may be symptoms of a serious muscle problem.

alectinib may make your skin more sensitive to sunlight. Use a sunscreen and protective clothing when you are outdoors. Avoid sunlamps and tanning beds.

• It is used to treat lung cancer.

Non-small cell lung cancer, metastatic: Treatment of patients with anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib.

There are no contraindications listed in the manufacturer’s US labeling.

Canadian labeling: Known hypersensitivity to alectinib or any component of the formulation.

Non-small cell lung cancer (NSCLC), metastatic (ALK-positive): Oral: 600 mg twice daily; continue until disease progression or unacceptable toxicity (Ou 2016)

Missed doses: If a dose is missed or if vomiting occurs, take the next dose at the regularly scheduled time.

Store at ≤30°C (86°F); store in original container to protect from light and moisture.

Bradycardia-Causing Agents: May enhance the bradycardic effect of other Bradycardia-Causing Agents. Monitor therapy

Bretylium: May enhance the bradycardic effect of Bradycardia-Causing Agents. Bretylium may also enhance atrioventricular (AV) blockade in patients receiving AV blocking agents. Monitor therapy

Ceritinib: Bradycardia-Causing Agents may enhance the bradycardic effect of Ceritinib. Management: If this combination cannot be avoided, monitor patients for evidence of symptomatic bradycardia, and closely monitor blood pressure and heart rate during therapy. Avoid combination

Ivabradine: Bradycardia-Causing Agents may enhance the bradycardic effect of Ivabradine. Monitor therapy

Lacosamide: Bradycardia-Causing Agents may enhance the AV-blocking effect of Lacosamide. Monitor therapy

Ruxolitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Management: Ruxolitinib Canadian product labeling recommends avoiding use with bradycardia-causing agents to the extent possible. Monitor therapy

Tofacitinib: May enhance the bradycardic effect of Bradycardia-Causing Agents. Monitor therapy

Pregnancy

Based on animal studies and its mechanism of action, can cause fetal harm when administered to a pregnant woman There are no available data on use in humans during pregnancy

Animal data

• Administration 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 BID

Contraception

• Females: Use effective contraception during treatment and for 1 week after the final dose
• Males: Use effective contraception during treatment and for 3 months following the final dose

Lactation

Unknown if distributed in human breast milk

Because of the potential for serious adverse reactions in breastfed infants from alectinib, advise a lactating woman not to breastfeed during treatment and for 1 week after the final dose

Pregnancy Categories

A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA:Information not available.

Commonly reported side effects of alectinib include: cough, dyspnea, increased creatine phosphokinase, increased serum aspartate aminotransferase, musculoskeletal pain, and myalgia. Other side effects include: bradycardia, and increased serum bilirubin. See below for a comprehensive list of adverse effects.

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