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Drug Interactions between midostaurin and nafcillin

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

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Interactions between your drugs

Moderate

nafcillin midostaurin

Applies to: nafcillin and midostaurin

MONITOR: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of midostaurin and its active metabolites, which are all substrates of the isoenzyme. When a single 50 mg dose of midostaurin was administered to healthy volunteers on day 9 of treatment with the potent CYP450 3A4 inducer rifampin (600 mg daily for 14 days), midostaurin systemic exposure (AUC) decreased by 96% compared to administration with placebo. The AUC of the two active metabolites, CGP62221 and CGP52421, decreased by 92% and 59%, respectively. It is not known to what extent midostaurin may interact with weak and moderate CYP450 3A4 inducers.

MANAGEMENT: The potential for diminished pharmacologic effects of midostaurin should be considered during coadministration with CYP450 3A4 inducers. Alternative treatments may be required if an interaction is suspected.

References (2)
  1. Dutreix C, Munarini F, Lorenzo S, Roesel J, Wang Y (2013) "Investigation into CYP3A4-mediated drug-drug interactions on midostaurin in healthy volunteers." Cancer Chemother Pharmacol, 72, p. 1223-34
  2. (2017) "Product Information. Rydapt (midostaurin)." Novartis Pharmaceuticals

Drug and food interactions

Major

midostaurin food

Applies to: midostaurin

GENERALLY AVOID: Grapefruit juice may significantly increase the plasma concentrations of midostaurin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. 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. Ketoconazole, a potent CYP450 3A4 inhibitor, has been shown to increase midostaurin systemic exposure (AUC) by greater than 10-fold in healthy volunteers. Increased exposure to midostaurin may increase the risk of adverse effects such as nausea, vomiting, diarrhea, edema, hyperglycemia, hyperuricemia, QT prolongation, neutropenia, lymphopenia, thrombocytopenia, and anemia.

ADJUST DOSING INTERVAL: Food enhances the oral bioavailability of midostaurin. Relative to fasting conditions, midostaurin systemic exposure (AUC) increased by approximately 1.2-fold when administered with a standard meal (457 calories; 50 g fat, 21 g proteins, 18 g carbohydrates) and 1.6-fold when administered with a high-fat meal (1007 calories; 66 g fat, 32 g proteins, 64 g carbohydrates), while midostaurin peak plasma concentration (Cmax ) decreased by 20% and 27%, respectively.

MANAGEMENT: The manufacturer recommends taking midostaurin with food. Midostaurin was administered with food in clinical trials. Patients should avoid consumption of grapefruit and grapefruit juice during treatment with midostaurin.

References (1)
  1. (2017) "Product Information. Rydapt (midostaurin)." Novartis Pharmaceuticals
Moderate

nafcillin food

Applies to: nafcillin

ADJUST DOSING INTERVAL: Certain penicillins may exhibit reduced gastrointestinal absorption in the presence of food. The therapeutic effect of the antimicrobial may be reduced.

MANAGEMENT: The interacting penicillin should be administered one hour before or two hours after meals. Penicillin V and amoxicillin are not affected by food and may be given without regard to meals.

References (6)
  1. Neu HC (1974) "Antimicrobial activity and human pharmacology of amoxicillin." J Infect Dis, 129, s123-31
  2. Welling PG, Huang H, Koch PA, Madsen PO (1977) "Bioavailability of ampicillin and amoxicillin in fasted and nonfasted subjects." J Pharm Sci, 66, p. 549-52
  3. McCarthy CG, Finland M (1960) "Absorption and excretion of four penicillins." N Engl J Med, 263, p. 315-26
  4. Cronk GA, Wheatley WB, Fellers GF, Albright H (1960) "The relationship of food intake to the absorption of potassium alpha-phenoxyethyl penicillin and potassium phenoxymethyl penicillin from the gastrointestinal tract." Am J Med Sci, 240, p. 219-25
  5. Klein JO, Sabath LD, Finland M (1963) "Laboratory studies on oxacillin. I: in vitro activity against staphylococci and some other bacterial pathogens. II: absorption and urinary excretion in normal young." Am J Med Sci, 245, p. 399-411
  6. Neuvonen PJ, Elonen E, Pentikainen PJ (1977) "Comparative effect of food on absorption of ampicillin and pivampicillin." J Int Med Res, 5, p. 71-6

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.

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