Erleada (apalutamide)

Erleada is a prescription medicine used for the treatment of prostate cancer:

• that has spread to other parts of the body and still responds to a medical or surgical treatment that lowers testosterone, OR
• that has not spread to other parts of the body and no longer responds to a medical or surgical treatment that lowers testosterone.

It is not known if Erleada is safe and effective in females.

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

Erleada may cause serious side effects including:

• Heart Disease. Blockage of the arteries in the heart that can lead to death has happened in some people during treatment with Erleada. Your healthcare provider will monitor you for signs and symptoms of heart problems during your treatment with Erleada. Call your healthcare provider or go to the nearest emergency room right away if you get chest pain or discomfort at rest or with activity, or shortness of breath during your treatment with Erleada.
• Fractures and falls. Erleada treatment can cause bones and muscles to weaken and may increase your risk for falls and fractures. Falls and fractures have happened in people during treatment with Erleada. Your healthcare provider will monitor your risks for falls and fractures during treatment with Erleada.
• Seizure. Treatment with Erleada may increase your risk of having a seizure. You should avoid activities where a sudden loss of consciousness could cause serious harm to yourself or others. Tell your healthcare provider right away if you have a loss of consciousness or seizure. Your healthcare provider will stop Erleada if you have a seizure during treatment.

The most common side effects of Erleada include:

• feeling very tired
• joint pain
• rash. Tell your healthcare provider if you get a rash.
• decreased appetite
• fall
• weight loss
• hypertension
• hot flash
• diarrhea
• fracture

Erleada may cause fertility problems in males, which may affect the ability to father children. Talk to your healthcare provider if you have concerns about fertility. Do not donate sperm during treatment with Erleada and for 3 months after the last dose of Erleada.

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

These are not all the possible side effects of Erleada.

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

Recommended Dosage

• The recommended dose of Erleada is 240 mg (four 60 mg tablets) administered orally once daily. Swallow the tablets whole. Erleada can be taken with or without food.
• Patients should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had a bilateral orchiectomy.

Dose Modification

• If a patient experiences a greater than or equal to Grade 3 toxicity or an intolerable side effect, hold dosing until symptoms improve to less than or equal to Grade 1 or original grade, then resume at the same dose or a reduced dose (180 mg or 120 mg), if warranted.

Alternate Method Of Administration

For patients who have difficulty swallowing tablets whole, the recommended dose of Erleada tablets may be mixed in applesauce.

1. Mix whole Erleada tablets in 4 ounces (120 mL) of applesauce by stirring. Do not crush the tablets.
2. Wait 15 minutes, stir the mixture.
3. Wait another 15 minutes, stir the mixture until tablets are dispersed (well mixed with no chunks remaining).
4. Using a spoon, swallow the mixture right away.
5. Rinse the container with 2 ounces (60 mL) of water and immediately drink the contents. Repeat the rinse with 2 ounces (60 mL) of water a second time to ensure the whole dose is taken.

Consume the mixture within one hour of preparation. Do not store Erleada that is mixed with applesauce.

Effect Of Other Drugs On Erleada

Strong CYP2C8 Or CYP3A4 Inhibitors

• Co-administration of a strong CYP2C8 or CYP3A4 inhibitor is predicted to increase the steady-state exposure of the active moieties (sum of unbound apalutamide plus the potency-adjusted unbound N-desmethyl-apalutamide).
• No initial dose adjustment is necessary however, reduce the Erleada dose based on tolerability.
• Mild or moderate inhibitors of CYP2C8 or CYP3A4 are not expected to affect the exposure of apalutamide.

Effect Of Erleada On Other Drugs

CYP3A4, CYP2C9, CYP2C19 And UGT Substrates

• Erleada is a strong inducer of CYP3A4 and CYP2C19, and a weak inducer of CYP2C9 in humans.
• Concomitant use of Erleada with medications that are primarily metabolized by CYP3A4, CYP2C19, or CYP2C9 can result in lower exposure to these medications.
• Substitution for these medications is recommended when possible or evaluate for loss of activity if medication is continued.
• Concomitant administration of Erleada with medications that are substrates of UDP-glucuronosyl transferase (UGT) can result in decreased exposure.
• Use caution if substrates of UGT must be co-administered with Erleada and evaluate for loss of activity.

P-gp, BCRP Or OATP1B1 Substrates

• Apalutamide was shown to be a weak inducer of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and organic anion transporting polypeptide 1B1 (OATP1B1) clinically.
• At steady-state, apalutamide reduced the plasma exposure to fexofenadine (a P-gp substrate) and rosuvastatin (a BCRP/OATP1B1 substrate).
• Concomitant use of Erleada with medications that are substrates of P-gp, BCRP, or OATP1B1 can result in lower exposure of these medications.
• Use caution if substrates of P-gp, BCRP or OATP1B1 must be co-administered with Erleada and evaluate for loss of activity if medication is continued.

• The safety and efficacy of Erleada have not been established in females.
• Based on its mechanism of action, Erleada can cause fetal harm and loss of pregnancy.
• There are no human data on the use of Erleada in pregnant women.
• Erleada is not indicated for use in females, so animal embryo-fetal developmental toxicology studies were not conducted with apalutamide.
• The safety and efficacy of Erleada have not been established in females.
• There are no data on the presence of apalutamide or its metabolites in human milk, the effect on the breastfed child, or the effect on milk production.