Akeega

Akeega is used with prednisone to treat BRCA2-mutated (BRCA2m) metastatic castration-sensitive prostate cancer (mCSPC) or metastatic castration-resistant prostate cancer (mCRPC). Akeega contains niraparib and abiraterone acetate and is the first dual-action tablet combining a PARP inhibitor with abiraterone acetate.

Akeega received FDA approval on 11 August, 2023, based on positive results from the randomized, double-blind, placebo-controlled multi-center Phase 3 MAGNITUDE study.

Akeega works by slowing prostate cancer cells' ability to grow and by causing prostate cancer cells to die. Akeega contains two active ingredients niraparib, a highly selective poly (ADP-ribose) polymerase (PARP) inhibitor, and abiraterone acetate, an androgen biosynthesis inhibitor.

Niraparib blocks a protein called PARP, which usually repairs cancer cells to make cancer cells live longer. As niraparib blocks PARP from repairing cancer cells, the cancer cells die.

Abiraterone acetate is an androgen biosynthesis inhibitor. Prostate cancer needs testosterone (male hormone) to grow. Abiraterone works by blocking the body from making testosterone, which can help slow down the growth of the cancer.

Take Akeega exactly as your healthcare provider tells you.

• Take Akeega tablets once daily in combination with prednisone
• Take Akeega on an empty stomach. Do not eat food 2 hours before and 1 hour after taking Akeega as taking it with food may cause more of the medicine to be absorbed by the body than is needed which may cause side effects.
• Swallow tablets whole with water. Do not break, crush, or chew tablets.
• Your healthcare provider may change your dose, temporarily stop, or permanently stop treatment with Akeega if you have certain side effects.
• You should not change or stop taking your prescribed dose of Akeega or prednisone without talking with your healthcare provider first.
• You should start or continue a gonadotropin-releasing hormone (GnRH) analog therapy during your treatment with Akeega unless you have had surgery to lower the amount of testosterone in your body (surgical castration).

If you miss a dose of your tablets, take the dose as soon as possible on the same day. Return to your normal schedule on the following day. Do not take extra tablets to make up for the missed dose.

Akeega may cause serious side effects including:

Bone marrow problems called myelodysplastic syndrome (MDS) or a type of cancer of the blood called acute myeloid leukemia (AML). MDS or AML that may lead to death has happened in people treated with niraparib, one of the active ingredients in Akeega. If you develop MDS or AML, your healthcare provider will stop treatment with this medicine. Symptoms of low blood cell counts (low red blood cells, low white blood cells, and low platelets) are common during treatment with Akeega but can also be a sign of serious bone marrow problems, including MDS and AML. Tell your healthcare provider if you have any of the following symptoms during treatment:

• pale skin
• weakness
• shortness of breath
• feeling tired
• bruising or bleeding more easily
• fever
• frequent infections
• blood in the urine or stool
• weight loss.

Myelosuppression: Your healthcare provider will monitor your blood counts weekly for the first month,every two weeks for the next two months, monthly for the remainder of the first year, then every other month, and as needed.

Tell your healthcare provider about all of your medical conditions, including if you:

• have high blood pressure or heart problems
• have low blood potassium levels
• have liver or kidney problems
• have a history of adrenal problems
• have diabetes
• are receiving any other treatment for prostate cancer.

Pregnancy

Females: Tell your healthcare professional if you are pregnant, become pregnant or plan to become pregnant. Akeega can cause harm to your unborn baby and loss of pregnancy (miscarriage).

Females who are or may become pregnant should handle Akeega tablets with protection, such as gloves.

Males: with female partners who can become pregnant should use effective birth control (contraception) during treatment and for 4 months after the last dose of this medicine.

Akeega 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.

Breastfeeding

Tell your healthcare provider if you are breastfeeding or plan to breastfeed. It is not known if Akeega passes into your breastmilk.

Common side effects

The most common side effects of Akeega are:

• muscle and bone pain
• tiredness
• changes in liver function blood tests
• constipation
• high blood pressure
• nausea
• changes in kidney function tests
• increased potassium level in the blood
• decreased potassium level in the blood
• swelling in your legs or feet
• shortness of breath
• decreased appetite
• vomiting
• dizziness
• Coronavirus disease 2019 (COVID-19)
• headache
• stomach area pain
• bleeding
• urinary tract infection
• cough
• trouble sleeping
• decreased weight
• irregular heartbeat (arrhythmia)
• falls
• fever.

Akeega may cause serious side effects

Bone marrow problems called myelodysplastic syndrome (MDS), myelosuppression, or a type of cancer of the blood called acute myeloid leukemia (AML). See 'Important Information below for more details.

Low blood potassium levels (hypokalemia), fluid retention (edema), high blood pressure (hypertension) and heart problems. Tell your healthcare provider if you have any of the following symptoms

• dizziness
• fast or irregular heartbeats
• feel faint or lightheaded
• headache
• confusion
• muscle weakness
• pain in your legs
• swelling in your hands, ankles, legs or feet

Liver problems. Severe liver problems, liver failure, and death have happened in people treated with abiraterone acetate, one of the active ingredients in Akeega. Tell your healthcare provider right away if you develop any symptoms of liver problems, including:

• yellowing of the skin or eyes
• darkening of the urine
• severe nausea or vomiting.

Adrenal problems. Adrenal problems may happen if you stop taking prednisone, get an infection, or are under stress. Tell your healthcare provider right away if you develop any symptoms of adrenal problems, including:

• feeling tired
• weakness
• feeling dizzy or lightheaded
• nausea or vomiting
• weight loss

Low blood sugar (hypoglycemia). Akeega may cause low blood sugar in people taking medicines for diabetes. Severe low blood sugar has happened in people who take certain medicines for diabetes and were treated with abiraterone acetate, one of the active ingredients in Akeega. You and your healthcare provider should check your blood sugar levels during treatment and after you stop treatment with Akeega. Your healthcare provider may need to change the dose of your diabetes medicine to reduce your risk of low blood sugar. Tell your healthcare provider right away if you have any of the following signs or symptoms of low blood sugar, including:

• headache
• drowsiness
• weakness
• dizziness
• confusion
• irritability
• hunger
• fast heartbeat
• sweating
• feeling jittery.

Increased risk of bone fracture and death when abiraterone acetate, one of the active ingredient in this medicine, and prednisone or prednisolone is used in combination with a type of radiation called Radium 223 (Ra-223) dichloride. You should not receive treatment with Ra-223 dichloride for at least 5 days after your last dose of Akeega with prednisone. Tell your healthcare provider about any other treatments you are taking for prostate cancer.

Posterior Reversible Encephalopathy Syndrome (PRES). PRES is a condition that affects the brain and may happen during treatment with Akeega. If you have headache, vision changes, confusion, or seizure with or without high blood pressure, please contact your healthcare provider.

Fertility problems in males this medicine 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.

These are not all the possible side effects of Akeega. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Dose of Akeega for BRCA2m mCSPC

• Akeega 200 mg/1000 mg orally once daily in combination with prednisone 5 mg daily

Dose of Akeega for BRCA2m mCRPC

• Akeega 200 mg/1000 mg orally once daily in combination with prednisone 10 mg daily
• Patients receiving Akeega should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had a bilateral orchiectomy.

Sometimes it is not safe to use certain medicines at the same time. Some drugs can affect your blood levels of other drugs you use. Tell your doctor about all your current medicines and any medicine you start or stop using.

You should not take the group of medicines called strong CYP3A4 inducers with Akeega. Examples of strong CYP3A4 inducers including apalutamide, carbamazepine, enzalutamide, ivosidenib, lumacaftor and ivacaftor, mitotane, phenytoin, rifampin, and St. John’s wort.

You should not take the group of medicines called CYP2D6 Substrates with Akeega, if a small change in concentration of your medicine may lead to serious toxicities. If alternative treatments cannot be used, consider a dose reduction of the concomitant CYP2D6 substrate.

Not all possible interactions are listed here.

Store between 68°F to 77°F (20°C to 25°C).

Manufactured for: Janssen Biotech, Inc., Horsham, PA 19044, USA.

Active ingredients: niraparib tosylate and abiraterone acetate.

Inactive ingredients:

Core tablet: colloidal anhydrous silica, crospovidone, hypromellose, lactose monohydrate, magnesium stearate, silicified microcrystalline cellulose, sodium lauryl sulfate.

Film-coating of 50 mg/500 mg tablets: iron oxide black, iron oxide red, iron oxide yellow, sodium lauryl sulphate, glycerol monocaprylocaprate, polyvinyl alcohol, talc, and titanium dioxide.

Film-coating of 100 mg/500 mg tablets: iron oxide red, iron oxide yellow, sodium lauryl sulphate, glycerol monocaprylocaprate, polyvinyl alcohol, talc, and titanium dioxide.

Akeega is available as:

• 50 mg niraparib/500 mg abiraterone acetate tablet
• 100 mg niraparib/500 mg abiraterone acetate tablet