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Drug Interactions between adalimumab and avapritinib

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

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Interactions between your drugs

Major

adalimumab avapritinib

Applies to: adalimumab and avapritinib

MONITOR CLOSELY: The use of tumor necrosis factor (TNF) blockers with other immunosuppressive or myelosuppressive agents may increase the risk of infections. Serious infections and sepsis, including fatalities, have been reported with the use of TNF blockers, particularly in patients on concomitant immunosuppressive therapy. Agents that may be significantly myelo- or immunosuppressive include antineoplastic agents, radiation, zidovudine, linezolid, some antirheumatic agents, high dosages of corticosteroids or adrenocorticotropic agents (greater than 10 mg/day to 1 mg/kg/day, whichever is less, of prednisone or equivalent for more than 2 weeks), and long-term topical or inhaled corticosteroids. Concomitant use of TNF blockers with other immunosuppressants such as azathioprine or mercaptopurine may also increase the risk of a rare and often fatal cancer of white blood cells known as hepatosplenic T-Cell lymphoma (HSTCL), which has primarily been reported in adolescent and young adult males receiving treatment for Crohn's disease or ulcerative colitis. Cases of HSTCL have also occurred during use of these agents alone. Because individuals with rheumatoid arthritis, Crohn's disease, ankylosing spondylitis, psoriatic arthritis, or plaque psoriasis may be more likely to develop lymphoma than the general population, it is difficult to assess the added risk of TNF blockers, azathioprine, and/or mercaptopurine.

MANAGEMENT: Patients receiving a TNF blocker alone or with other immunosuppressive or myelosuppressive agents should be monitored closely for the development of infections. TNF blocker therapy should be discontinued if a serious infection or sepsis occurs. Close monitoring for signs and symptoms of HSTCL (e.g., splenomegaly, hepatomegaly, abdominal pain, persistent fever, night sweats, weight loss) is also recommended during use of TNF blockers, particularly in combination with other immunosuppressants such as azathioprine and mercaptopurine.

References

  1. (2001) "Product Information. Remicade (infliximab)." Centocor Inc
  2. (2001) "Product Information. Enbrel (etanercept)." Wyeth-Ayerst Laboratories
  3. (2003) "Product Information. Humira (adalimumab)." Abbott Pharmaceutical
  4. (2008) "Product Information. Cimzia (certolizumab)." UCB Pharma Inc
  5. (2009) "Product Information. Simponi (golimumab)." Centocor Inc
  6. FDA. U.S. Food and Drug Administration (2012) FDA Drug Safety Communication: Drug labels for the Tumor Necrosis Factor-alpha (TNFa) blockers now include warnings about infection with Legionella and Listeria bacteria. http://www.fda.gov/Drugs/DrugSafety/ucm270849.htm
View all 6 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.

See also

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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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