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Drug Interactions between fosphenytoin and Sulfimycin

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

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Interactions between your drugs

Moderate

erythromycin fosphenytoin

Applies to: Sulfimycin (erythromycin / sulfisoxazole) and fosphenytoin

MONITOR: Coadministration with phenytoin may reduce the plasma concentrations and antimicrobial efficacy of erythromycin and other macrolide antibiotics. The mechanism is induction of CYP450 3A metabolism by phenytoin. Additionally, plasma concentrations of phenytoin may be increased. One study has suggested that the pharmacokinetic disposition of phenytoin is not significantly altered in patients receiving erythromycin. However, occasional large changes in phenytoin clearance were noted in some patients.

MANAGEMENT: If concomitant use is medically necessary, caution and monitoring for altered efficacy and safety of both medications is recommended.

References

  1. Bachmann K, Schwartz JI, Forney RB Jr, Jauregui L (1984) "Single dose phenytoin clearance during erythromycin treatment." Res Commun Chem Pathol Pharmacol, 46, p. 207-17
  2. Milne RW, Coulthard K, Nation RL, et al. (1988) "Lack of effect of erythromycin on the pharmacokinetics of single oral doses of phenytoin." Br J Clin Pharmacol, 26, p. 330-3
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  4. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  5. Cerner Multum, Inc. "Australian Product Information."
View all 5 references

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Moderate

sulfiSOXAZOLE fosphenytoin

Applies to: Sulfimycin (erythromycin / sulfisoxazole) and fosphenytoin

MONITOR: Some sulfonamides may inhibit the hepatic metabolism of hydantoins. Serum hydantoin levels and risk of toxicity may be increased. Data are available for sulfadiazine, sulfaphenazole, and sulfamethizole.

MANAGEMENT: Monitoring for clinical and laboratory evidence of altered efficacy and safety is recommended. Hydantoin dosage adjustments or an alternate antimicrobial may be required if an interaction is suspected. Patients should be advised to notify their physician if they experience symptoms of hydantoin toxicity (e.g., drowsiness, visual disturbances, change in mental status, seizures, nausea, or ataxia).

References

  1. Lumholtz B, Siersbaek-Nielsen K, Skovsted L, Kampmann J, Hansen JM (1975) "Sulfamethizole-induced inhibition of diphenylhydantoin, tolbutamide, and warfarin metabolism." Clin Pharmacol Ther, 17, p. 731-4
  2. Hansen JM, Kampmann JP, Siersback-Nielsen K, et al. (1979) "The effect of different sulfonamides on phenytoin metabolism in man." Acta Med Scand Suppl, 624, p. 106-10

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Drug and food interactions

Moderate

erythromycin food

Applies to: Sulfimycin (erythromycin / sulfisoxazole)

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

  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
View all 7 references

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Minor

erythromycin food

Applies to: Sulfimycin (erythromycin / sulfisoxazole)

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. 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

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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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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