Alecensa

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.

Avoid exposure to sunlight or tanning beds. Alectinib can make you sunburn more easily. Wear protective clothing and use sunscreen and lip balm (SPF 50 or higher) when you are outdoors.

Other drugs may interact with alectinib, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Alectinib comes as a capsule to take by mouth. It is usually taken with food twice daily. Take alectinib at around the same times every day. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take alectinib exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.

Swallow the capsules whole; do not open or dissolve them.

If you vomit after you take alectinib, do not immediately take another dose. Continue your regular dosing schedule.

Your doctor may temporarily or permanently stop your treatment or decrease your dose if you experience certain side effects of alectinib. Tell your doctor how you are feeling during your treatment. Continue to take alectinib even if you feel well. Do not stop taking alectinib without talking to your doctor.

Ask your pharmacist or doctor for a copy of the manufacturer's information for the patient.

• Genentech, Inc.

Tell your doctor if you are breastfeeding or plan to breastfeed. 

It is not known if Alecensa crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, it is recommended that women do not breastfeed while they are taking Alecensa and for 1 week after completing treatment with Alecensa. Talk to your healthcare provider about the best way to feed your baby during this time.

If you take too much Alecensa, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If Alecensa is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

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.

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;

• 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. Use effective birth control to prevent pregnancy while you are using this medicine 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.

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

Other drugs may interact with alectinib, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell each of your health care providers about all medicines you use now and any medicine you start or stop using.

Antineoplastic agent; an inhibitor of several receptor tyrosine kinases, including anaplastic lymphoma kinase (ALK).1 6 8 9 11

Non-small Cell Lung Cancer (NSCLC)

Treatment of ALK-positive metastatic NSCLC in patients following failure (secondary to resistance or intolerance) of prior crizotinib therapy1 2 3 (designated an orphan drug by FDA for this use).4

Accelerated approval based on tumor response rate and duration of response; continued approval may be contingent on verification and description of clinical benefit in confirmatory studies.1

About 3–7% of patients with NSCLC have ALK-positive disease; such patients typically are nonsmokers or light smokers, and often have adenocarcinoma.6 7 8 9 10 11

Long-term therapeutic potential of crizotinib (another ALK inhibitor) is limited by eventual development of secondary resistance and development and/or progression of brain metastases (because of poor distribution of crizotinib into CSF).2 3 6 7 8 9 11 12 13 (See Actions.) Responses to alectinib in patients with crizotinib-refractory ALK-positive metastatic NSCLC have included objective CNS responses.1 2 3

• Inhibits receptor tyrosine kinases ALK and ret proto-oncogene (RET).1 6 8 9 11 13

• Inhibits ALK phosphorylation and ALK-mediated activation of the downstream signaling proteins signal transducer and activator of transcription 3 (STAT3) and AKT serine/threonine kinase.1

• Activating mutations or translocations of the ALK gene identified in several malignancies and can result in the expression of oncogenic fusion proteins (e.g., echinoderm microtubule-associated protein-like 4 [EML4]-ALK).6 7 8 9 10 11 Formation of ALK fusion proteins results in activation and dysregulation of the gene's expression and signaling, which can contribute to increased cell proliferation and survival in tumors expressing these proteins.9 10 11

• ALK rearrangements identified in approximately 3–7% of patients with NSCLC.6 7 8 9 10

• Clinical resistance to crizotinib attributed to several possible mechanisms, including acquired resistance mutations of ALK, amplification of gene expression, and activation of alternate signaling pathways.7 8 9 11 CNS is a common site of disease progression in crizotinib-treated patients because of poor distribution of crizotinib into CSF.2 6 8 9 11 12 13

• Alectinib is approximately fivefold more potent than crizotinib against ALK in vitro.3

• Exhibits dose-dependent antitumor activity and increased survival in mice bearing NSCLC tumor xenografts expressing EML4-ALK, including several with demonstrated resistance to crizotinib.1 6 7 Active against several crizotinib-resistant ALK mutations (e.g., L1196M, C1156Y, G1269A, F1174L).1 6 8 9

• Demonstrates antitumor activity and increased survival in mice bearing intracranial ALK-positive NSCLC tumor xenografts.1 6 13 Demonstrated antitumor activity in patients with crizotinib-resistant ALK-positive NSCLC with baseline CNS metastases.1 8 12 13

• Importance of reading the manufacturer's patient information.1

• Importance of taking alectinib exactly as prescribed and of not altering the dosage or discontinuing therapy unless advised to do so by clinician.1 Importance of swallowing alectinib capsules whole with food and not dissolving or opening the capsules.1

• If a dose is missed or if vomiting occurs after taking a dose, importance of taking the next dose at the regularly scheduled time; do not take the missed dose or take an extra dose to replace the vomited dose.1

• Risk of hepatotoxicity; importance of liver function test monitoring.1 Importance of immediately informing clinician if manifestations suggestive of hepatotoxicity (e.g., fatigue, anorexia, nausea, vomiting, right upper quadrant pain, jaundice, dark urine, generalized pruritus, unusual bleeding or bruising) occur.1

• Risk of severe or fatal ILD/pneumonitis.1 Symptoms may be similar to those of lung cancer.1 Importance of immediately informing clinician if any new or worsening pulmonary symptoms (e.g., dyspnea, shortness of breath, cough, fever) occur.1

• Risk of bradycardia.1 Importance of immediately informing clinician if dizziness, lightheadedness, or faintness occurs.1

• Risk of muscle problems or myalgia; importance of CK monitoring.1 Importance of promptly informing clinician if any unexplained or persistent muscle pain, tenderness, or weakness occurs.1

• Risk of photosensitivity.1 Importance of avoiding prolonged sun exposure during therapy and for ≥7 days after drug discontinuance and of using a broad-spectrum sunscreen and lip balm (minimum SPF of 50).1

• Risk of fetal harm.1 Advise women of childbearing potential to use effective methods of contraception during therapy and for ≥1 week after drug discontinuance.1 Advise men who are partners of such women to use adequate methods of contraception during therapy and for ≥3 months after drug discontinuance.1

• Importance of women informing their clinicians if they are or plan to become pregnant.1 If pregnancy occurs, advise patient of potential fetal risk.1

• Importance of advising women to avoid breast-feeding during therapy and for ≥1 week after drug discontinuance.1

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs (e.g., cardiac or hypotensive agents) and dietary or herbal supplements, as well as any concomitant illnesses (e.g., hepatic impairment).1

• Importance of informing patients of other important precautionary information.1 (See Cautions.)

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Chest pain or discomfort
• cough
• difficulty with moving
• joint pain
• lightheadedness, dizziness, or fainting
• muscle aching or cramping
• muscle pains or stiffness
• shortness of breath
• slow or irregular heartbeat
• swollen joints
• unusual tiredness

• Abdominal pain or tenderness
• clay colored stools
• dark urine
• decreased appetite
• fever
• headache
• itching or skin rash
• loss of appetite
• nausea and vomiting
• swelling of the feet or lower legs
• yellow eyes or skin

• Difficult breathing
• fever

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Back pain
• bloating or swelling of the face, arms, hands, lower legs, or feet
• blurred vision
• difficulty having a bowel movement (stool)
• double vision
• lack or loss of strength
• rapid weight gain
• rash with flat lesions or small raised lesions on the skin
• seeing double
• seeing floating dark spots or material before the eyes
• swelling around the eyes
• tingling of the hands or feet
• unusual weight gain or loss
• vision changes

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

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

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
• Signs of liver problems like dark urine, feeling tired, not hungry, upset stomach or stomach pain, light-colored stools, throwing up, or yellow skin or eyes.
• Signs of lung or breathing problems like shortness of breath or other trouble breathing, cough, or fever.
• Signs of high blood sugar like confusion, feeling sleepy, more thirst, more hungry, passing urine more often, flushing, fast breathing, or breath that smells like fruit.
• Signs of electrolyte problems like mood changes, confusion, muscle pain or weakness, a heartbeat that does not feel normal, seizures, not hungry, or very bad upset stomach or throwing up.
• Slow heartbeat.
• Dizziness or passing out.
• Muscle pain or weakness.
• Swelling.
• Change in eyesight.
• Feeling very tired or weak.

None.

Contraindications

None

Cautions

Elevated liver enzymes reported; monitor liver function tests, including ALT, AST, and total bilirubin, q2weeks during the first 2 months of treatment, then periodically during treatment, with more frequent testing in patients who develop transaminase and bilirubin elevations (see Dosage Modifications)

Interstitial lung disease (ILD) and pneumonitis reported; promptly investigate any patient who presents with worsening respiratory symptoms (eg, dyspnea, cough, fever) and immediately withhold treatment in patients diagnosed with ILD/pneumonitis (see Dosage Modifications)

Symptomatic bradycardia may occur; monitor heart rate and blood pressure regularly (see Dosage Modifications)

Severe myalgia and elevated CPK reported; advise patients to report any unexplained muscle pain, tenderness, or weakness; assess CPK levels q2weeks for the first month of treatment and as clinically indicated in patients reporting symptoms (see Dosage Modifications)

Based on findings from animal studies and its mechanism of action, alectinib can cause fetal harm when administered to pregnant women (see Pregnancy)