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Drug Interactions between Akeega and venetoclax

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Moderate

abiraterone venetoclax

Applies to: Akeega (abiraterone / niraparib) and venetoclax

MONITOR: Coadministration with inhibitors of CYP450 3A4 may increase the plasma concentrations of venetoclax, which is a substrate of the isoenzyme. In a study of 11 previously treated non-Hodgkin lymphoma patients, when the potent CYP450 3A4 inhibitor, P-glycoprotein (P-gp) inhibitor and breast cancer resistance protein (BCRP) inhibitor ketoconazole (400 mg daily for 7 days) was coadministered with venetoclax (50 mg single dose), venetoclax peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 2.3-fold and 6.4-fold, respectively. Likewise, concomitant use of the P-gp and potent CYP450 3A4 inhibitor posaconazole (300 mg) with venetoclax 50 mg or 100 mg daily for 7 days increased the venetoclax Cmax by 1.61-fold and 1.86-fold, respectively, and AUC by 1.9-fold and 2.44-fold, respectively, compared with venetoclax (400 mg daily) alone. Clinical data exploring the use of venetoclax with less potent CYP450 3A4 inhibitors are not available. However, physiologically-based pharmacokinetic modeling estimates that the moderate CYP450 3A4 inhibitors diltiazem and erythromycin may increase the AUC of venetoclax by between 2- to 4.9-fold, while the weak CYP450 3A4 inhibitors fluoxetine and fluvoxamine appear to have no significant effect on its Cmax or AUC. Increased venetoclax exposure may potentiate the risk of tumor lysis syndrome, particularly at initiation of therapy and during the dosage ramp-up phase, as well as other adverse effects such as diarrhea, nausea, vomiting, neutropenia, anemia, and thrombocytopenia.

MANAGEMENT: Caution is advised when venetoclax is used with inhibitors of CYP450 3A4. Close clinical and laboratory monitoring for the development of tumor lysis syndrome and myelosuppression is recommended following the addition of a CYP450 3A4 inhibitor. If signs or symptoms of venetoclax-related adverse effects develop, the dosage should be modified as per the manufacturer's recommendations.

References (8)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2016) "Product Information. Venclexta (venetoclax)." AbbVie US LLC
  4. (2022) "Product Information. Venclexta (venetoclax)." AbbVie US LLC
  5. (2023) "Product Information. Venclexta (venetoclax)." AbbVie Pty Ltd
  6. (2024) "Product Information. Venclyxto (venetoclax)." AbbVie Ltd
  7. (2022) "Product Information. Venclexta (venetoclax)." AbbVie Corporation
  8. Freise K.J, Shebley M, Salem A.H (2017) "Quantitative prediction of the effect of CYP3A inhibitors and inducers on venetoclax pharmacokinetics using a physiologically based pharmacokinetic model" J Clin Pharmacol, 57, p. 796-804

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Moderate

venetoclax niraparib

Applies to: venetoclax and Akeega (abiraterone / niraparib)

MONITOR: The concomitant use of myelosuppressive, immunosuppressive, or cytotoxic agents may potentiate and/or prolong the bone marrow toxicity associated with niraparib. Thrombocytopenia, anemia, neutropenia, and/or pancytopenia have all been observed with niraparib during clinical trials, especially during the initial phase of treatment. Additionally, myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) have been reported in patients treated with niraparib. Some cases were fatal, and the duration of therapy with niraparib in patients who developed MDS/AML varied from less than 1 month to approximately 6 years. All patients had previous chemotherapy with platinum agents and/or other DNA-damaging agents, including radiotherapy.

MANAGEMENT: Caution is advised if niraparib is prescribed with other myelosuppressive, immunosuppressive, or cytotoxic agents. Do not start niraparib until patients have recovered from hematological toxicity caused by previous chemotherapy (Grade 1 or less). Complete blood counts should be monitored as recommended in the product labeling and any relevant institutional protocols. Recommendations for dose adjustments as well as treatment interruption and discontinuation can also be found in the product labeling for serious hematologic adverse reactions. If hematological toxicities have not resolved within 4 weeks after interruption, discontinue niraparib and refer the patient to a hematologist for further investigations, including bone marrow analysis and blood sample for cytogenetics. If MDS/AML is confirmed, discontinue niraparib. Patients should be advised to contact their physician if they experience pale skin, weakness, fatigue, fever, weight loss, infections, shortness of breath, unusual bleeding or bruising, or blood in urine or stool.

References (7)
  1. (2023) "Product Information. Akeega (abiraterone-niraparib)." Janssen Biotech, Inc.
  2. (2023) "Product Information. Zejula (niraparib)." GlaxoSmithKline
  3. (2023) "Product Information. Zejula (niraparib)." GlaxoSmithKline Inc
  4. (2023) "Product Information. Akeega (abiraterone-niraparib)." Janssen Inc
  5. (2023) "Product Information. Zejula (niraparib)." GlaxoSmithKline Australia Pty Ltd
  6. (2023) "Product Information. Zejula (niraparib)." GlaxoSmithKline UK Ltd
  7. (2024) "Product Information. Vyvgart (efgartigimod alfa)." Argenx UK Ltd

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Drug and food interactions

Major

venetoclax food

Applies to: venetoclax

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of venetoclax. Relative to fasting conditions, venetoclax systemic exposure (AUC) increased by approximately 3.4-fold when administered with a low-fat meal (approximately 512 kilocalories, 25% calories from fat) and by 5.1- to 5.3-fold when administered with a high-fat meal (approximately 753 kilocalories, 55% calories from fat).

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of venetoclax, which is metabolized by the CYP450 3A4 isoenzyme. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but has been reported with potent CYP450 3A4 inhibitors. In a study of 11 previously treated non-Hodgkin lymphoma patients, when the potent CYP450 3A4 inhibitor, P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) inhibitor ketoconazole (400 mg daily for 7 days) was coadministered with venetoclax (50 mg single dose), venetoclax peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 2.3-fold and 6.4-fold, respectively. Physiologically based pharmacokinetic modeling estimates that the moderate CYP450 3A4 inhibitors diltiazem and erythromycin may increase the Cmax and AUC of venetoclax by between 1.4- to 2- fold and 2- to 4.9-fold, respectively, while the weak CYP450 3A4 inhibitors fluoxetine and fluvoxamine appear to have no significant effect on its Cmax or AUC. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased venetoclax exposure may potentiate the risk of tumor lysis syndrome, particularly at initiation of therapy and during the dosage ramp-up phase, as well as other adverse effects such as diarrhea, nausea, vomiting, neutropenia, anemia, and thrombocytopenia.

MANAGEMENT: Venetoclax should be administered with a meal and water at approximately the same time each day. Patients should avoid consumption of grapefruit products, Seville oranges, and starfruit during treatment with venetoclax.

References (6)
  1. (2016) "Product Information. Venclexta (venetoclax)." AbbVie US LLC
  2. (2022) "Product Information. Venclexta (venetoclax)." AbbVie US LLC
  3. (2023) "Product Information. Venclexta (venetoclax)." AbbVie Pty Ltd
  4. (2024) "Product Information. Venclyxto (venetoclax)." AbbVie Ltd
  5. (2022) "Product Information. Venclexta (venetoclax)." AbbVie Corporation
  6. Freise K.J, Shebley M, Salem A.H (2017) "Quantitative prediction of the effect of CYP3A inhibitors and inducers on venetoclax pharmacokinetics using a physiologically based pharmacokinetic model" J Clin Pharmacol, 57, p. 796-804

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Moderate

abiraterone food

Applies to: Akeega (abiraterone / niraparib)

ADJUST DOSING INTERVAL: Food may significantly increase the oral bioavailability of some formulations of abiraterone acetate. Compared to administration in the fasted state, abiraterone peak plasma concentration (Cmax) and systemic exposure (AUC) were approximately 7- and 5-fold higher, respectively, when a single dose of abiraterone acetate was administered with a low-fat meal (7% fat; 300 calories) and approximately 17- and 10-fold higher, respectively, when it was administered with a high-fat meal (57% fat; 825 calories). Given the normal variation in the content and composition of meals, taking abiraterone acetate with meals has the potential to result in increased and highly variable exposures. The safety of these increased exposures during multiple dosing has not been assessed. However, the abiraterone acetate 125 mg tablet, commonly marketed as Yonsa, was found to have an approximately 6.5-fold higher Cmax and 4.4-fold higher AUC when a single dose of 500 mg (4 tablets) was administered with a high-fat meal (56% - 60% fat, 900 - 1000 calories) compared to overnight fasting in healthy volunteers. These differences were not considered clinically significant for this formulation.

MANAGEMENT: Some formulations of abiraterone acetate must be taken on an empty stomach. No food should be consumed for at least two hours before and one hour after the abiraterone acetate dose. However, the abiraterone acetate 125 mg tablet, commonly marketed as Yonsa, can be taken with or without food. The manufacturer's product labeling should be consulted for specific guidance.

References (9)
  1. (2011) "Product Information. Zytiga (abiraterone)." Centocor Inc
  2. (2023) "Product Information. Akeega (abiraterone-niraparib)." Janssen Biotech, Inc.
  3. (2023) "Product Information. Akeega (abiraterone-niraparib)." Janssen Inc
  4. (2021) "Product Information. Zytiga (abiraterone)." Janssen Biotech, Inc.
  5. (2022) "Product Information. Yonsa (abiraterone)." Sun Pharmaceutical Industries
  6. (2023) "Product Information. Apo-Abiraterone (abiraterone)." Apotex Inc
  7. (2021) "Product Information. Zytiga (abiraterone)." Janssen-Cilag Pty Ltd
  8. (2023) "Product Information. Abiraterone (abiraterone)." Wockhardt UK Ltd
  9. (2023) "Product Information. Yonsa Mpred (abiraterone-methylprednisolone)." Sun Pharma ANZ Pty Ltd

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Therapeutic duplication warnings

No warnings were found for your selected drugs.

Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.


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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.