Alectinib Capsules

ALECENSA is indicated for the 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. This indication is approved under accelerated approval based on tumor response rate and duration of response [see Clinical Studies]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

The following adverse reactions are discussed in greater detail in other sections of the label:

• Hepatotoxicity [see WARNINGS AND PRECAUTIONS]
• Interstitial Lung Disease (ILD)/Pneumonitis [see WARNINGS AND PRECAUTIONS]
• Bradycardia [see WARNINGS AND PRECAUTIONS]
• Severe Myalgia and Creatine Phosphokinase (CPK) Elevation [see WARNINGS AND PRECAUTIONS]
• Embryo-Fetal Toxicity [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The safety of ALECENSA was evaluated in 253 patients with ALK-positive non-small cell lung cancer (NSCLC) treated with ALECENSA 600 mg orally twice daily in two clinical trials, Studies 1 and 2. The median duration of exposure to ALECENSA was 9.3 months. One hundred sixty-nine patients (67%) were exposed to ALECENSA for more than 6 months, and 100 patients (40%) for more than one year. The population characteristics were: median age 53 years, age less than 65 (86%), female (55%), White (74%), Asian (18%), NSCLC adenocarcinoma histology (96%), never or former smoker (98%), ECOG Performance Status (PS) 0 or 1 (91%), and prior chemotherapy treatment (78%).

Serious adverse reactions occurred in 19% of patients; the most frequently reported serious adverse reactions were pulmonary embolism (1.2%), dyspnea (1.2%), and hyperbilirubinemia (1.2%). Fatal adverse reactions occurred in 2.8% of patients and included hemorrhage (0.8%), intestinal perforation (0.4%), dyspnea (0.4%), pulmonary embolism (0.4%), and endocarditis (0.4%). Permanent discontinuation of ALECENSA for adverse reactions occurred in 6% of patients. The most frequent adverse reactions that led to permanent discontinuation were hyperbilirubinemia (1.6%), increased ALT levels (1.6%), and increased AST levels (1.2%). Overall, 23% of patients initiating treatment at the recommended dose required at least one dose reduction. The median time to first dose reduction was 48 days. The most frequent adverse reactions that led to dose reductions or interruptions were elevations in bilirubin (6%), CPK (4.3%), ALT (4.0%), and AST (2.8%), and vomiting (2.8%).

Table 3 summarizes adverse reactions in Studies 1 and 2.

Table 3: Adverse Reactions in ≥ 10% (All Grades) or ≥ 2% (Grade 3-4) of Patients in Studies 1 and 2

Photosensitivity occurred in 9.9% of patients exposed to ALECENSA in Studies 1 and 2. Patients were advised to avoid sun exposure and to use broad-spectrum sunscreen. The incidence of Grade 2 photosensitivity was 0.4%; the remaining events were Grade 1 in severity.

Table 4 summarizes laboratory abnormalities of ALECENSA in Studies 1 and 2.

Table 4: Laboratory Abnormalities Occurring in ≥ 20% of Patients in Studies 1 and 2

No experience with overdose is available. There is no specific antidote for overdose with ALECENSA. Alectinib and its major active metabolite M4 are > 99% bound to plasma proteins; therefore, hemodialysis is likely to be ineffective in the treatment of overdose.

ALECENSA®
(a-le-sen'-sah)
(alectinib) Capsules

What is the most important information I should know about ALECENSA?

ALECENSA may cause serious side effects, including:

• Liver problems (hepatotoxicity). ALECENSA may cause liver injury. Your healthcare provider will do blood tests at least every 2 weeks for the first 2 months and as needed during treatment with ALECENSA. Tell your healthcare provider right away if you get any of the following signs and symptoms:
  • feeling tired
  • itchy skin
  • feeling less hungry than usual
  • nausea or vomiting
  • yellowing of your skin or the whites of your eyes
  • pain on the right side of your stomach area
  • dark urine
  • bleeding or bruising more easily than normal
• Lung problems. ALECENSA may cause severe or life-threatening swelling (inflammation) of the lungs during treatment. Symptoms may be similar to those symptoms from lung cancer. Tell your healthcare provider right away if you have any new or worsening symptoms, including trouble breathing, shortness of breath, cough, or fever.
• Slow heartbeat (bradycardia). ALECENSA may cause very slow heartbeats that can be severe. Your healthcare provider will check your heart rate and blood pressure during treatment with ALECENSA. Tell your healthcare provider right away if you feel dizzy, lightheaded, or faint during treatment with ALECENSA. Tell your healthcare provider if you take any heart or blood pressure medicines.
• Muscle pain, tenderness, and weakness (myalgia). Muscle problems are common with ALECENSA and can be severe. Your healthcare provider will do blood tests at least every 2 weeks for the first month and as needed during treatment with ALECENSA. Tell your healthcare provider right away if you get new or worsening signs and symptoms of muscle problems, including unexplained muscle pain or muscle pain that does not go away, tenderness, or weakness.

See “What are the possible side effects of ALECENSA?” for more information about side effects.

What is ALECENSA?

ALECENSA is a prescription medicine used to treat people with non-small cell lung cancer (NSCLC) that.

• has a certain type of abnormal anaplastic lymphoma kinase (ALK) gene, and
• has spread to other parts of your body, and
• who have taken the medicine crizotinib, but their NSCLC worsened or they cannot tolerate taking crizotinib.

It is not known if ALECENSA is safe and effective in children.

Before you take ALECENSA, tell your healthcare provider about all of your medical conditions, including if you:

• have liver problems
• have lung or breathing problems
• have a slow heartbeat
• are pregnant or plan to become pregnant. ALECENSA can harm your unborn baby. Tell your healthcare provider right away if you become pregnant during treatment with ALECENSA or think you may be pregnant.
  • Females who are able to become pregnant should use effective birth control during treatment with ALECENSA and for 1 week after the final dose of ALECENSA.
  • Males who have female partners that are able to become pregnant should use effective birth control during treatment with ALECENSA and for 3 months after the final dose of ALECENSA.
• are breastfeeding or plan to breastfeed. It is not known if ALECENSA passes into your breast milk. Do not breastfeed during treatment with ALECENSA and for 1 week after the final dose of ALECENSA. Talk to your healthcare provider about the best way to feed your baby during this time.

Tell your healthcare provider about all the medicines you take, including prescription medicines, over-the-counter medicines, vitamins, or herbal supplements.

How should I take ALECENSA?

• Take ALECENSA exactly as your healthcare provider tells you to take it. Do not change your dose or stop taking ALECENSA unless your healthcare provider tells you to.
• Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with ALECENSA if you have side effects.
• Take ALECENSA 2 times a day.
• Take ALECENSA with food.
• Swallow ALECENSA capsules whole. Do not open or dissolve the capsule contents.
• If you miss a dose of ALECENSA, do not take the missed dose. Take your next dose at your regular time.
• If you vomit after taking a dose of ALECENSA, do not take an extra dose. Take your next dose at your regular time.

What should I avoid while taking ALECENSA?

• Avoid spending time in the sunlight during treatment with ALECENSA and for 7 days after the final dose of ALECENSA. You may burn more easily and get severe sunburns. Use sunscreen and lip balm with a SPF 50 or greater to help protect against sunburn.

What are the possible side effects of ALECENSA?

ALECENSA may cause serious side effects, including:

• See “What is the most important information I should know about ALECENSA?”

The most common side effects of ALECENSA include:

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

These are not all of the possible side effects of ALECENSA. For more information, ask your healthcare provider or pharmacist.

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

How should I store ALECENSA?

• Do not store ALECENSA at temperatures above 86°F (30°C).
• Store ALECENSA capsules in the original container.
• Keep ALECENSA capsules dry and away from light.

Keep ALECENSA and all medicines out of the reach of children.

General information about the safe and effective use of ALECENSA.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use ALECENSA for a condition for which it was not prescribed. Do not give ALECENSA to other people, even if they have the same symptoms you have. It may harm them. You can ask your healthcare provider or pharmacist for more information about ALECENSA that is written for health professionals.

What are the ingredients in ALECENSA?

Active ingredient: alectinib

Inactive ingredients: lactose monohydrate, hydroxypropylcellulose, sodium lauryl sulfate, magnesium stearate and carboxymethylcellulose calcium. Capsule shell contains: hypromellose, carrageenan, potassium chloride, titanium dioxide, corn starch, and carnauba wax. 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.

• Cancer