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Drug Interactions between irinotecan and nafcillin

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

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Interactions between your drugs

Moderate

nafcillin irinotecan

Applies to: nafcillin and irinotecan

MONITOR: Coadministration with inducers of the CYP450 3A4 isoenzyme may decrease the plasma concentrations of irinotecan and its pharmacologically active metabolite, SN-38. Irinotecan is partially metabolized by CYP450 3A4, and induction of this process results in less of the drug available in the plasma for conversion to SN-38 via carboxylesterases. The interaction has been reported with St. John's wort and the enzyme-inducing anticonvulsants carbamazepine, phenobarbital, and phenytoin. An approximately 40% reduction in SN-38 systemic exposure (AUC) has been reported in the presence of St. John's wort and greater than 60% reductions have been reported in the presence of enzyme-inducing anticonvulsants. However, all of these agents are known to be potent inducers of CYP450 3A4 as well as other enzymatic pathways (e.g., UDP-glucuronosyl transferase, or UGT; carboxylesterases) and drug transporters (e.g., multispecific organic anion transporter, or MRP2; P-glycoprotein) that may be involved in the clearance of irinotecan and/or SN-38. The extent, if any, to which irinotecan may interact with less potent CYP450 3A4 inducers is unknown.

MANAGEMENT: The antitumour activity of irinotecan may be reduced in patients treated with CYP450 3A4 inducers. Pharmacologic response to irinotecan should be monitored more closely whenever a CYP450 3A4 inducer is added to or withdrawn from therapy, and the irinotecan dosage adjusted as necessary.

References (15)
  1. (2001) "Product Information. Camptosar (irinotecan)." Pharmacia and Upjohn
  2. De Bruijn P, De Jonge MJ, Mathijssen RH, Sparreboom A, Verweij J (2002) Modulation of irinotecan(CPT-11)metabolism by St. John's wort in cancer patients. http:aacr02.agora.com/planner/displayabstract.asp?presentationid=2603
  3. Murry DJ, Cherrick I, Salama V, et al. (2002) "Influence of phenytoin on the disposition of irinotecan: a case report." J Pediatr Hematol Oncol, 24, p. 130-3
  4. Mathijssen RH, Verweij J, De Bruijn P, Loos WJ, Sparreboom A (2002) "Effects of St. John's Wort on Irinotecan Metabolism." J Natl Cancer Inst, 94, p. 1247-9
  5. Kuhn JG (2002) "Influence of anticonvulsants on the metabolism and elimination of irinotecan. A North American Brain Tumor Consortium preliminary report." Oncology (Williston Park, 16(8 Suppl 7), p. 33-40
  6. Friedman HS, Petros WP, Friedman AH, et al. (1999) "Irinotecan therapy in adults with recurrent or progressive malignant glioma." J Clin Oncol, 17, p. 1516-25
  7. Santos A, Zanetta S, Cresteil T, et al. (2000) "Metabolism of irinotecan (CPT-11) by CYP3A4 and CYP3A5 in humans." Clin Cancer Res, 6, p. 2012-20
  8. Yonemori K, Takeda Y, Toyota E, Kobayashi N, Kudo K (2004) "Potential interactions between irinotecan and rifampin in a patient with small-cell lung cancer." Int J Clin Oncol, 9, p. 206-9
  9. Innocenti F, Undevia SD, Ramirez J, et al. (2004) "A phase I trial of pharmacologic modulation of irinotecan with cyclosporine and phenobarbital." Clin Pharmacol Ther, 76, p. 490-502
  10. Di YM, Li CG, Xue CC, Zhou SF (2008) "Clinical drugs that interact with St. John's wort and implication in drug development." Curr Pharm Des, 14, p. 1723-42
  11. Crews KR, Stewart CF, Jones-Wallace D, et al. (2002) "Altered irinotecan pharmacokinetics in pediatric high-grade glioma patients receiving enzyme-inducing anticonvulsant therapy." Clin Cancer Res, 8, p. 2202-9
  12. Radomski KM, Gajjar AJ, Kirstein MN, et al. (2000) "Irinotecan clearance is increased by concomitant administration of enzyme inducers in a patient with glioblastoma multiforme." Pharmacotherapy, 20, p. 353
  13. Minami H, Lad TE, Nicholas MK, Vokes EE, Ratain MJ (1999) "Pharmacokinetics and pharmacodynamics of 9-aminocamptothecin infused over 72 hours in phase II studies." Clin Cancer Res, 5, p. 1325-30
  14. Zamboni WC, Gajjar AJ, Heideman RL, et al. (1998) "Phenytoin alters the disposition of topotecan and N-desmethyl topotecan in a patient with medulloblastoma." Clin Cancer Res, 4, p. 783-9
  15. (2015) "Product Information. Onivyde (irinotecan liposomal)." Merrimack Pharmaceuticals

Drug and food interactions

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

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