Skip to main content

Drug Interactions between Di-Phen and mefloquine

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

Edit list (add/remove drugs)

Interactions between your drugs

Major

phenytoin mefloquine

Applies to: Di-Phen (phenytoin) and mefloquine

GENERALLY AVOID: Mefloquine may increase the risk of seizures and decrease the effectiveness of anticonvulsant drugs in patients with epilepsy. The use of mefloquine alone and in combination with other related antimalarial agents (e.g., quinine, quinidine, chloroquine) has been associated with convulsions in some patients. Coadministration of mefloquine with certain anticonvulsant medications may also result in reduced seizure control by lowering the plasma levels of the anticonvulsant. In one case report, a patient with a seizure disorder previously well controlled on valproic acid and carbamazepine experienced several seizure episodes after taking mefloquine (250 mg weekly) for malaria prophylaxis. A subsequent kinetics study performed on the patient revealed a significant reduction in sodium valproate half-life (5.65 hours vs. reported normal of 8 to 20 hours) and no change in carbamazepine half-life. The author suggested that mefloquine be administered to epileptic patients with caution, particularly if being treated with sodium valproate. Additional clinical data with other antiepileptics are unavailable.

MANAGEMENT: According to the product labeling, mefloquine may precipitate convulsions in patients with a history of seizure disorder and should not be used for malaria prophylaxis in such patients. If mefloquine administration is required for curative treatment of malaria, anticonvulsant blood levels should be closely monitored and the anticonvulsant dosage adjusted accordingly as needed. Patients should be advised to notify their physician if they experience a loss of seizure control.

MONITOR CLOSELY: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of mefloquine, which is primarily metabolized by the isoenzyme. In seven healthy, nonsmoking male volunteers, administration of a single 500 mg oral dose of mefloquine on day 7 of treatment with the potent CYP450 3A4 inducer rifampin (600 mg orally once daily on days 1 through 7, followed by 600 mg twice weekly on days 8 through 56) decreased mean mefloquine peak plasma concentration (Cmax) and systemic exposure (AUC) by 19% and 68%, respectively, compared to mefloquine administered alone. The mean elimination half-life of mefloquine was also decreased by 63% (from 305 to 113 hours) in the presence of rifampin, while mean apparent oral clearance increased by 281%.

MANAGEMENT: The possibility of diminished antimalarial efficacy should be considered when mefloquine is used in combination with potent CYP450 3A4 inducers. Alternative agents with minimal or less enzyme induction potential are recommended when possible to avoid the risk of therapeutic failure, particularly in the treatment of acute malaria infections.

References

  1. Singh K, Shanks GD, Wilde H (1991) "Seizures after mefloquine." Ann Intern Med, 114, p. 994
  2. Weinke T, Trautmann M, Held T, et al. (1991) "Neuropsychiatric side effects after the use of mefloquine." Am J Trop Med Hyg, 45, p. 86-91
  3. Bem JL, Kerr L, Stuerchler D (1992) "Mefloquine prophylaxis: an overview of spontaneous reports of severe psychiatric reactions and convulsions." J Trop Med Hyg, 95, p. 167-79
  4. Jallon P (1988) "Use of mefloquine in epileptic patients." J Neurol Neurosurg Psychiatry, 51, p. 732
  5. (2021) "Product Information. Mefloquine Hydrochloride (mefloquine)." Hikma USA (formerly West-Ward Pharmaceutical Corporation)
  6. Ries S, Pohlmanneden B (1993) "Seizures during malaria prophylaxis with mefloquine." Dtsch Med Wochenschr, 118, p. 1911-2
  7. Ruff TA, Sherwen SJ, Donnan GA (1994) "Seizure associated with mefloquine for malaria prophylaxis." Med J Aust, 161, p. 453
  8. Pous E, Gascon J, Obach J, Corachan M (1995) "Mefloquine-induced grand mal seizure during malaria chemoprophylaxis in a non-epileptic subject." Trans R Soc Trop Med Hyg, 89, p. 434
  9. Potasman I, Juven Y, Weller B, Schwartz E (2002) "Does mefloquine prophylaxis affect electroencephalographic patterns?" Am J Med, 112, p. 147-9
  10. Jimenez-Huete A, Gil-Nagel A, Franch O (2002) "Multifocal myoclonus associated with mefloquine chemoprophylaxis." Clin Neuropharmacol, 25, p. 243
  11. Ridtitid W, Wongnawa M, Mahatthanatrakul W, Chaipol P, Sunbhanich M (2000) "Effect of rifampin on plasma concentrations of mefloquine in healthy volunteers." J Pharm Pharmacol, 52, p. 1265-9
  12. (2022) "Product Information. Lariam (mefloquine)." Pharmaco Australia Ltd
  13. (2017) "Product Information. Mefloquine (mefloquine)." AA Pharma Inc
  14. (2022) "Product Information. Lariam (mefloquine)." Neon Healthcare Ltd
View all 14 references

Switch to consumer interaction data

Drug and food interactions

Moderate

phenytoin food

Applies to: Di-Phen (phenytoin)

ADJUST DOSING INTERVAL: Phenytoin bioavailability may decrease to subtherapeutic levels when the suspension is given concomitantly with enteral feedings. The mechanism may be related to phenytoin binding to substances in the enteral formula (e.g., calcium, protein) and/or binding to the tube lumen. Data have been conflicting and some studies have reported no changes in phenytoin levels, while others have reported significant reductions.

MONITOR: Acute consumption of alcohol may increase plasma phenytoin levels. Chronic consumption of alcohol may decrease plasma phenytoin levels. The mechanism of this interaction is related to induction of phenytoin metabolism by ethanol during chronic administration. Other hydantoin derivatives may be similarly affected by ethanol.

MANAGEMENT: Some experts have recommended interrupting the feeding for 2 hours before and after the phenytoin dose, giving the phenytoin suspension diluted in water, and flushing the tube with water after administration; however, this method may not entirely avoid the interaction and is not always clinically feasible. Patients should be closely monitored for clinical and laboratory evidence of altered phenytoin efficacy and levels upon initiation and discontinuation of enteral feedings. Dosage adjustments or intravenous administration may be required until therapeutic serum levels are obtained. In addition, patients receiving phenytoin therapy should be warned about the interaction between phenytoin and ethanol and they should be advised to notify their physician if they experience worsening of seizure control or symptoms of toxicity, including drowsiness, visual disturbances, change in mental status, nausea, or ataxia.

References

  1. Sandor P, Sellers EM, Dumbrell M, Khouw V (1981) "Effect of short- and long-term alcohol use on phenytoin kinetics in chronic alcoholics." Clin Pharmacol Ther, 30, p. 390-7
  2. Holtz L, Milton J, Sturek JK (1987) "Compatibility of medications with enteral feedings." JPEN J Parenter Enteral Nutr, 11, p. 183-6
  3. Sellers EM, Holloway MR (1978) "Drug kinetics and alcohol ingestion." Clin Pharmacokinet, 3, p. 440-52
  4. (2001) "Product Information. Dilantin (phenytoin)." Parke-Davis
  5. Doak KK, Haas CE, Dunnigan KJ, et al. (1998) "Bioavailability of phenytoin acid and phenytoin sodium with enteral feedings." Pharmacotherapy, 18, p. 637-45
  6. Rodman DP, Stevenson TL, Ray TR (1995) "Phenytoin malabsorption after jejunostomy tube delivery." Pharmacotherapy, 15, p. 801-5
  7. Au Yeung SC, Ensom MH (2000) "Phenytoin and enteral feedings: does evidence support an interaction?" Ann Pharmacother, 34, p. 896-905
  8. Ozuna J, Friel P (1984) "Effect of enteral tube feeding on serum phenytoin levels." J Neurosurg Nurs, 16, p. 289-91
  9. Faraji B, Yu PP (1998) "Serum phenytoin levels of patients on gastrostomy tube feeding." J Neurosci Nurs, 30, p. 55-9
  10. Marvel ME, Bertino JS (1991) "Comparative effects of an elemental and a complex enteral feeding formulation on the absorption of phenytoin suspension." JPEN J Parenter Enteral Nutr, 15, p. 316-8
  11. Fleisher D, Sheth N, Kou JH (1990) "Phenytoin interaction with enteral feedings administered through nasogastric tubes." JPEN J Parenter Enteral Nutr, 14, p. 513-6
  12. Haley CJ, Nelson J (1989) "Phenytoin-enteral feeding interaction." DICP, 23, p. 796-8
  13. Guidry JR, Eastwood TF, Curry SC (1989) "Phenytoin absorption in volunteers receiving selected enteral feedings." West J Med, 150, p. 659-61
  14. Krueger KA, Garnett WR, Comstock TJ, Fitzsimmons WE, Karnes HT, Pellock JM (1987) "Effect of two administration schedules of an enteral nutrient formula on phenytoin bioavailability." Epilepsia, 28, p. 706-12
  15. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  16. Cerner Multum, Inc. "Australian Product Information."
View all 16 references

Switch to consumer interaction data

Moderate

mefloquine food

Applies to: mefloquine

ADJUST DOSING INTERVAL: Food enhances the oral absorption and bioavailability of mefloquine. The proposed mechanism is increased drug solubility in the presence of food. In 20 healthy volunteers, administration of a single 750 mg oral dose of mefloquine 30 minutes following a high-fat meal increased the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of mefloquine by 73% and 40%, respectively, compared to administration in the fasting state. The Cmax and AUC of the carboxylic acid metabolite were also increased by 35% and 33%, respectively, compared to fasting. In addition, the time to reach peak plasma concentration (Tmax) of mefloquine was significantly shorter after food intake (17 hours) than in the fasting state (36 hours). There was no difference in the elimination half-life of mefloquine and metabolite, or the Tmax for the metabolite.

MANAGEMENT: To ensure maximal oral absorption, mefloquine should be administered immediately after a meal with at least 8 ounces of water.

References

  1. (2021) "Product Information. Mefloquine Hydrochloride (mefloquine)." Hikma USA (formerly West-Ward Pharmaceutical Corporation)
  2. Schmidt LE, Dalhoff K (2002) "Food-drug interactions." Drugs, 62, p. 1481-502

Switch to consumer interaction data

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

Report options

Loading...
QR code containing a link to this page

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.

Medical Disclaimer