AKEEGA FILM-COATED TABLETS 100MG/500MG [SIN17110P]

Product Info

AKEEGA FILM-COATED TABLETS 100MG/500MG

[SIN17110P]

Indication

AKEEGA®, the combination of niraparib and abiraterone acetate with prednisone or prednisolone, is indicated as treatment for adults with metastatic castration-resistant prostate cancer (mCRPC) and BReast CAncer (BRCA) gene mutations (germline and/or somatic), in whom chemotherapy is not clinically indicated.

Dosage and Administration

AKEEGA® is a dual action combination of niraparib, a PARP inhibitor, and abiraterone acetate, a CYP17 inhibitor.

When considering the use of AKEEGA®, positive BRCA status must be established using a validated test method (see Pharmacodynamic effects – Clinical studies – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Dosage

The recommended dosage of AKEEGA® is 200 mg niraparib/1000 mg abiraterone acetate (two 100 mg/500 mg tablets), as a single daily dose at approximately the same time every day. AKEEGA® must be taken on an empty stomach. AKEEGA® must be taken at least two hours after eating and food must not be eaten for at least one hour after taking AKEEGA®. The tablets must be swallowed whole with water (see Pharmacokinetic Properties – Absorption – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Dosage of prednisone or prednisolone

AKEEGA® is used with 10 mg prednisone or prednisolone daily.

Missed dose(s)

If a dose of either AKEEGA®, prednisone or prednisolone is missed, it should be taken as soon as possible on the same day with a return to the normal schedule the following day. Extra tablets must not be taken to make up for the missed dose.

Treatment withdrawal

Treatment should be continued until disease progression or unacceptable toxicity.

Dose modification

Non-hematologic adverse reactions
For patients who develop Grade ≥ 3 non-hematologic adverse reactions, treatment should be interrupted and appropriate medical management should be instituted (see Warnings and Precautions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). Treatment with AKEEGA® should not be reinitiated until symptoms of the toxicity have resolved to Grade 1 or baseline. If a patient was on a reduced dose of AKEEGA® (100mg/1000mg), AKEEGA® must be discontinued for a Grade ≥ 3 treatment-related adverse reaction lasting more than 28 days.

Hematologic adverse reactions
For patients who develop a ≥ Grade 3 or intolerable hematological toxicity, dosing with AKEEGA® should be interrupted rather than discontinued, and supportive management considered. Permanently discontinue AKEEGA® if hematological toxicity has not returned to acceptable levels within 28 days of the dose interruption period. The dose adjustment recommendations for thrombocytopenia and neutropenia are listed in Table 1.

Further dosing with AKEEGA® may be resumed only when toxicity due to thrombocytopenia and neutropenia is improved to Grade 1 or resolved to baseline. If warranted, treatment may resume at a lower strength of AKEEGA® 50 mg/500 mg (2 tablets). For the most common adverse reactions, see Adverse Reactions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

For Grade ≥ 3 anemia, AKEEGA® should be interrupted and supportive management provided until recovered to Grade ≤2. Dose reduction (two 50 mg/500 mg tablets) should be considered if anemia persists based on clinical judgment. The dose adjustment recommendations for anemia are listed in Table 2.

Recommended monitoring

Complete blood counts should be obtained prior to starting treatment, weekly for the first month, every two weeks for the next two months, followed by monthly monitoring for the first year and then every other month for the remainder of treatment to monitor for clinically significant changes in any hematologic parameter (see Warnings and Precautions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Serum aminotransferases and total bilirubin should be measured prior to starting treatment, every two weeks for the first three months of treatment and monthly thereafter for the first year and then every other month for the duration of treatment (see Warnings and Precautions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). When starting the lower strength dose (two tablets) after dose interruption, liver function should be monitored every two weeks for six weeks due to risk of increased abiraterone exposure (see Pharmacokinetic Properties – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information), before resuming regular monitoring.

Serum potassium should be monitored monthly for the first year and then every other month for the duration of treatment (see Warnings and Precautions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information). In patients with pre-existing hypokalemia or those that develop hypokalemia whilst being treated with AKEEGA®, consider maintaining the patient’s potassium level at ≥ 4.0 mM.

Blood pressure monitoring should occur weekly for the first two months, monthly for the first year and then every other month for the duration of treatment. Fluid retention (weight gain, peripheral edema) and other signs and symptoms of congestive heart failure should be monitored every two weeks for three months, then monthly thereafter, and abnormalities corrected (see Warnings and Precautions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Special populations

Pediatrics (17 years of age and younger)

The safety and effectiveness of AKEEGA® in children have not been evaluated.

There is no relevant use of AKEEGA® in pediatric patients aged 17 years and younger.

Elderly (65 years of age and older)

No dose adjustment is necessary for elderly patients (see Pharmacodynamic Properties – Clinical studies and Pharmacokinetic Properties – Special populations – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Hepatic impairment

AKEEGA® must not be used in patients with moderate to severe hepatic impairment (see Pharmacokinetic Properties – Special populations – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Hepatotoxicity

For patients who develop ≥ Grade 3 hepatotoxicity (alanine aminotransferase [ALT] increases or aspartate aminotransferase [AST] increases above 5 times the upper limit of normal [ULN]) or total bilirubin increases above 3 times the ULN, treatment with AKEEGA® should be interrupted and liver function closely monitored (see Warnings and Precautions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

If patients develop severe hepatotoxicity (ALT or AST 20 times the ULN) while on AKEEGA®, treatment should be permanently discontinued.

Permanently discontinue AKEEGA® for patients who develop a concurrent elevation of ALT greater than 3 times ULN and total bilirubin greater than 2 times ULN in the absence of biliary obstruction or other causes responsible for the concurrent elevation (see Warnings and Precautions – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Renal impairment

No dosage adjustment is necessary for patients with mild to moderate renal impairment. AKEEGA® should be used with caution in patients with severe renal impairment (see Pharmacokinetic Properties – Special populations – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Administration

The tablets must be taken as a single dose, once daily on an empty stomach. AKEEGA® must be taken at least two hours after eating and food must not be eaten for at least one hour after taking AKEEGA®. AKEEGA® tablets must be swallowed whole with water. Do not break, crush, or chew tablets.

Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in Pharmaceutical Information – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information.

Women who are or may become pregnant (see Pregnancy, Breast-feeding and Fertility – Pregnancy – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).

Moderate or severe hepatic impairment (see Dosage and Administration, Warnings and Precautions and Pharmacokinetic Properties – Special populations – please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information).