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Drug Interactions between PCE Dispertab and tofacitinib

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

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Interactions between your drugs

Moderate

erythromycin tofacitinib

Applies to: PCE Dispertab (erythromycin) and tofacitinib

ADJUST DOSE: Coadministration with one or more medications that may result in both moderate inhibition of CYP450 3A4 and potent inhibition of CYP450 2C19 may significantly increase the plasma concentrations of tofacitinib, which is primarily metabolized by the former isoenzyme with minor contribution from the latter. In study subjects, administration with the moderate CYP450 3A4 and potent CYP450 2C19 inhibitor fluconazole increased tofacitinib peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 27% and 79%, respectively, compared to administration of tofacitinib alone. Side effects including lymphopenia, neutropenia, anemia, serious infections, and hyperlipidemia may be increased.

MANAGEMENT: The dosage of tofacitinib should be reduced by 50% when used concomitantly with one or more medications that may result in both moderate inhibition of CYP450 3A4 and potent inhibition of CYP450 2C19. For example, the dose for patients receiving 10 mg twice daily should be reduced to 5 mg twice daily and the dose for patients receiving 5 mg twice daily should be reduced to 5 mg once daily. For patients receiving 11 mg once daily of the extended-release formulation, the dose should be reduced to 5 mg once daily of the immediate-release formulation. The dose for patients receiving 3.2 mg twice daily should be reduced to 3.2 mg once daily and the dose for patients receiving 4 mg twice daily should be reduced to 4 mg once daily. Moderate inhibitors of CYP450 3A4 include amiodarone, aprepitant, ciprofloxacin, crizotinib, darunavir, dalfopristin-quinupristin, diltiazem, dronedarone, erythromycin, fluconazole, fusidic acid, grapefruit juice, imatinib, isavuconazonium, netupitant, and verapamil. Potent inhibitors of CYP450 2C19 include fluconazole, fluvoxamine, esomeprazole, lansoprazole, and omeprazole. Inhibitors of CYP450 2C19 alone are unlikely to substantially alter the pharmacokinetics of tofacitinib.

References (3)
  1. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  2. Cerner Multum, Inc. "Australian Product Information."
  3. (2012) "Product Information. Xeljanz (tofacitinib)." Pfizer U.S. Pharmaceuticals Group

Drug and food interactions

Moderate

erythromycin food

Applies to: PCE Dispertab (erythromycin)

ADJUST DOSING INTERVAL: Food may variably affect the bioavailability of different oral formulations and salt forms of erythromycin. The individual product package labeling should be consulted regarding the appropriate time of administration in relation to food ingestion. Grapefruit juice may increase the plasma concentrations of orally administered erythromycin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In an open-label, crossover study consisting of six healthy subjects, the coadministration with double-strength grapefruit juice increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of a single dose of erythromycin (400 mg) by 52% and 49%, respectively, compared to water. The half-life was not affected. The clinical significance of this potential interaction is unknown.

MANAGEMENT: In general, optimal serum levels are achieved when erythromycin is taken in the fasting state, one-half to two hours before meals. However, some erythromycin products may be taken without regard to meals.

References (7)
  1. Welling PG, Huang H, Hewitt PF, Lyons LL (1978) "Bioavailability of erythromycin stearate: influence of food and fluid volume." J Pharm Sci, 67, p. 764-6
  2. Welling PG, Elliott RL, Pitterle ME, et al. (1979) "Plasma levels following single and repeated doses of erythromycin estolate and erythromycin stearate." J Pharm Sci, 68, p. 150-5
  3. Welling PG (1977) "Influence of food and diet on gastrointestinal drug absorption: a review." J Pharmacokinet Biopharm, 5, p. 291-334
  4. Coyne TC, Shum S, Chun AH, Jeansonne L, Shirkey HC (1978) "Bioavailability of erythromycin ethylsuccinate in pediatric patients." J Clin Pharmacol, 18, p. 194-202
  5. Malmborg AS (1979) "Effect of food on absorption of erythromycin. A study of two derivatives, the stearate and the base." J Antimicrob Chemother, 5, p. 591-9
  6. Randinitis EJ, Sedman AJ, Welling PG, Kinkel AW (1989) "Effect of a high-fat meal on the bioavailability of a polymer-coated erythromycin particle tablet formulation." J Clin Pharmacol, 29, p. 79-84
  7. Kanazawa S, Ohkubo T, Sugawara K (2001) "The effects of grapefruit juice on the pharmacokinetics of erythromycin." Eur J Clin Pharmacol, 56, p. 799-803
Moderate

tofacitinib food

Applies to: tofacitinib

MONITOR: Grapefruit juice may increase the plasma concentrations of tofacitinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The extent and clinical significance are unknown. Moreover, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability.

MANAGEMENT: Until more information is available, some authorities recommend avoiding consumption of grapefruit juice during tofacitinib therapy (Canada). Patients receiving tofacitinib therapy who ingest grapefruits or grapefruit juice should be monitored for adverse effects and undue fluctuations in plasma drug levels.

References (1)
  1. (2024) "Product Information. Xeljanz (tofacitinib)." Pfizer Canada ULC
Minor

erythromycin food

Applies to: PCE Dispertab (erythromycin)

Ethanol, when combined with erythromycin, may delay absorption and therefore the clinical effects of the antibiotic. The mechanism appears to be due to slowed gastric emptying by ethanol. Data is available only for erythromycin ethylsuccinate. Patients should be advised to avoid ethanol while taking erythromycin salts.

References (1)
  1. Morasso MI, Chavez J, Gai MN, Arancibia A (1990) "Influence of alcohol consumption on erythromycin ethylsuccinate kinetics." Int J Clin Pharmacol, 28, p. 426-9

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.