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Drug Interactions between avapritinib and smallpox and monkeypox vaccine

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

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Interactions between your drugs

Moderate

avapritinib smallpox and monkeypox vaccine

Applies to: avapritinib and smallpox and monkeypox vaccine

MONITOR: Administration of the smallpox and monkeypox vaccine, which contains a live, attenuated, non-replicating strain of orthopoxvirus, to immunosuppressed patients is generally safe but may be associated with a diminished or suboptimal immunologic response due to antibody inhibition. Such patients may include those who have recently received or are receiving immunosuppressive agents, antilymphocyte globulins, alkylating agents, antimetabolites, radiation, some antirheumatic agents, high dosages of corticosteroids or adrenocorticotropic agents (e.g., greater than or equal to 2 mg/kg/day or 20 mg/day of prednisone or equivalent for 14 consecutive days or more), or long-term topical or inhaled corticosteroids.

MANAGEMENT: It is generally advisable to complete recommended vaccinations, including smallpox and monkeypox vaccine, before starting immunosuppressant or antineoplastic treatment. Clinicians should consult public health authorities and thoroughly assess risks versus benefits prior to administering the smallpox and monkeypox vaccine to immunosuppressed individuals. If the decision is made to vaccinate, titer testing by the Centers for Disease Control and Prevention (CDC) might be considered on a case-by-case basis. Because a correlate of protection has not been established and there is no known antibody titer level that will ensure protection, titer results should be interpreted with caution to avoid providing a false sense of security. Additionally, since immunosuppressed patients might be less likely to mount an effective vaccine response, infections may occur even after full vaccination and outcomes could be particularly severe in these patients, especially following exposure to more virulent orthopoxviruses. Therefore, vaccine recipients might consider avoiding high-risk exposures until after completion of immunosuppressive therapies. Regardless of vaccination status, all individuals who work with orthopoxviruses should wear appropriate personal protective equipment.

References

  1. CDC Centers for Disease Control and Prevention (2019) General Best Practice Guidelines for Immunization: Altered Immunocompetence. https://www.cdc.gov/vaccines/hcp/acip-recs/general-recs/immunocompetence.pdf
  2. (2021) "Product Information. Jynneos (smallpox and monkeypox vaccine)." Bavarian Nordic, Inc.
  3. Rao AK, Petersen BW, Whitehill F, et al. (2022) "Use of JYNNEOS (Smallpox and Monkeypox Vaccine, Live, Nonreplicating) for Preexposure Vaccination of Persons at Risk for Occupational Exposure to Orthopoxviruses: Recommendations of the Advisory Committee on Immunization Practices--United States, 2022 ht"
  4. Anonymous. (2022) Updated ATAGI Clinical Guidance on Vaccination Against MPX (Monkeypox) https://www.health.gov.au/sites/default/files/documents/2022/08/atagi-clinical-guidance-on-vaccination-against-monkeypox.pdf
View all 4 references

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Drug and food interactions

Major

avapritinib food

Applies to: avapritinib

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of avapritinib. 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 for other CYP450 3A4 inhibitors. Based on pharmacokinetic modeling, administration of avapritinib (300 mg once daily) in combination with the potent CYP450 3A4 inhibitor itraconazole (200 mg once daily) is predicted to increase avapritinib systemic exposure (AUC) by 600% at steady state, while administration with the moderate CYP450 3A4 inhibitor fluconazole (200 mg once daily) is predicted to increase avapritinib systemic exposure (AUC) by 210% at steady state. 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 exposure to avapritinib may increase the risk and/or severity of serious adverse effects such as intracranial hemorrhage, cognitive impairment, mood disorders, hallucinations, edema, and decreases in hemoglobin, leukocytes, neutrophils, and platelets.

ADJUST DOSING INTERVAL: Food may increase the oral absorption of avapritinib. When avapritinib was administered with a high-calorie, high-fat meal (approximately 909 calories; 58 g carbohydrate, 56 g fat, 43 g protein), avapritinib Cmax and AUC increased by 59% and 29%, respectively, compared to administration in the fasted state.

MANAGEMENT: Avapritinib should be administered on an empty stomach at least 1 hour before or 2 hours after a meal. Patients should avoid consumption of grapefruit and grapefruit juice during treatment with avapritinib.

References

  1. (2020) "Product Information. Ayvakit (avapritinib)." Blueprint Medicines Corporation

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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

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