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Drug Interactions between avapritinib and smallpox vaccine

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

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Interactions between your drugs

Major

smallpox vaccine avapritinib

Applies to: smallpox vaccine and avapritinib

CONTRAINDICATED: The administration of live smallpox virus vaccine during immunosuppressant or intense antineoplastic therapy may be associated with a risk of disseminated infection due to enhanced replication of vaccine virus in the presence of diminished immune competence. Patients may be immunosuppressed if they have recently received or are receiving alkylating agents, antimetabolites, radiation, some antirheumatic agents, high dosages of corticosteroids or adrenocorticotropic agents, or long-term topical or inhaled corticosteroids. These patients may also have increased adverse reactions and decreased or suboptimal immunologic response to vaccines. Cases of generalized vaccinia and progressive vaccinia have been reported in HIV patients who received the smallpox vaccine.

MANAGEMENT: Routine, nonemergency smallpox vaccination is contraindicated in patients receiving immunosuppressive therapy or cancer chemotherapy. Vaccination should be deferred until after such therapy is discontinued for at least 3 months in most cases. A longer waiting period may be necessary following treatment with agents that have a prolonged elimination half-life (e.g., leflunomide, teriflunomide). In patients who have recently been vaccinated, such therapy should not be initiated for at least 2 weeks (may be longer in some cases; refer to individual product labeling). Household contacts of immunosuppressed patients should also not be vaccinated. However, there are no absolute contraindications to vaccination if a high-risk exposure has occurred. In an outbreak emergency, smallpox vaccine is recommended for all persons, regardless of medical conditions. The risk for experiencing serious complications from the vaccine should be weighed against the risk of acquiring a potentially fatal smallpox infection.

References

  1. CDC. Centers for Disease Control and Prevention/ (1993) "Recommendations of the advisory committtee on immunization practices (ACIP): use of vaccines and immune globulins in persons with altered immunocompetence." MMWR Morb Mortal Wkly Rep, 42(RR-04), p. 1-18
  2. CDC. Centers for Disease Control and Prevention (2002) Smallpox vaccination clinic guide. Logistical considerations and guidance for state and local planning for emergency, large-scale, voluntary administration of smallpox vaccine in response to a smallpox outbreak. http://www.bt.cdc.gov/agents/smallpox/vac
  3. (2002) "Product Information. Dryvax (smallpox vaccine)." Wyeth-Ayerst Laboratories
  4. Cerner Multum, Inc. "Australian Product Information."
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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