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Drug Interactions between Di-Phen and praziquantel

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

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Interactions between your drugs

Major

phenytoin praziquantel

Applies to: Di-Phen (phenytoin) and praziquantel

CONTRAINDICATED: Coadministration with potent inducers of CYP450 3A4 may significantly decrease the plasma concentrations of praziquantel, which is a substrate of the isoenzyme. In a crossover study with a 2-week washout period, plasma praziquantel concentrations were undetectable in 7 out of 10 subjects who ingested a single 40 mg/kg dose of praziquantel following pretreatment with the potent CYP450 3A4 inducer, rifampin, given at 600 mg daily for 5 days. When the same dose of praziquantel was administered two weeks after discontinuation of rifampin, the mean praziquantel peak plasma concentration (Cmax) and systemic exposure (AUC) were only 35% and 23% lower, respectively, than when praziquantel was given alone. The oral bioavailability of praziquantel has also been shown to decrease significantly in patients treated with carbamazepine or phenytoin, both of which are known potent CYP450 3A4 inducers. In one study, maximum plasma praziquantel concentrations in epileptic patients receiving stable carbamazepine (n=10) and phenytoin (n=10) therapy were 8% and 24%, respectively, of those observed in control subjects following administration of a single 25 mg oral dose of praziquantel.

MANAGEMENT: Concomitant use of praziquantel with potent CYP450 3A4 inducers is considered contraindicated because therapeutically effective blood levels of praziquantel may not be achieved.

References

  1. Bittencourt PR, Gracia CM, Martins R, et al. "Phenytoin and carbamazepine decrease oral bioavailability of praziquantel." Neurology 42 (1992): 492-6
  2. "Product Information. Biltricide (praziquantel)." Bayer PROD (2001):
  3. Ridtitid W, Wongnawa M, Mahatthanatrakul W, Punyo J, Sunbhanich M "Rifampin markedly decreases plasma concentrations of praziquantel in healthy volunteers." Clin Pharmacol Ther 72 (2002): 505-13
  4. Cerner Multum, Inc. "Australian Product Information." O 0
View all 4 references

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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 "Effect of short- and long-term alcohol use on phenytoin kinetics in chronic alcoholics." Clin Pharmacol Ther 30 (1981): 390-7
  2. Holtz L, Milton J, Sturek JK "Compatibility of medications with enteral feedings." JPEN J Parenter Enteral Nutr 11 (1987): 183-6
  3. Sellers EM, Holloway MR "Drug kinetics and alcohol ingestion." Clin Pharmacokinet 3 (1978): 440-52
  4. "Product Information. Dilantin (phenytoin)." Parke-Davis PROD (2001):
  5. Doak KK, Haas CE, Dunnigan KJ, et al. "Bioavailability of phenytoin acid and phenytoin sodium with enteral feedings." Pharmacotherapy 18 (1998): 637-45
  6. Rodman DP, Stevenson TL, Ray TR "Phenytoin malabsorption after jejunostomy tube delivery." Pharmacotherapy 15 (1995): 801-5
  7. Au Yeung SC, Ensom MH "Phenytoin and enteral feedings: does evidence support an interaction?" Ann Pharmacother 34 (2000): 896-905
  8. Ozuna J, Friel P "Effect of enteral tube feeding on serum phenytoin levels." J Neurosurg Nurs 16 (1984): 289-91
  9. Faraji B, Yu PP "Serum phenytoin levels of patients on gastrostomy tube feeding." J Neurosci Nurs 30 (1998): 55-9
  10. Marvel ME, Bertino JS "Comparative effects of an elemental and a complex enteral feeding formulation on the absorption of phenytoin suspension." JPEN J Parenter Enteral Nutr 15 (1991): 316-8
  11. Fleisher D, Sheth N, Kou JH "Phenytoin interaction with enteral feedings administered through nasogastric tubes." JPEN J Parenter Enteral Nutr 14 (1990): 513-6
  12. Haley CJ, Nelson J "Phenytoin-enteral feeding interaction." DICP 23 (1989): 796-8
  13. Guidry JR, Eastwood TF, Curry SC "Phenytoin absorption in volunteers receiving selected enteral feedings." West J Med 150 (1989): 659-61
  14. Krueger KA, Garnett WR, Comstock TJ, Fitzsimmons WE, Karnes HT, Pellock JM "Effect of two administration schedules of an enteral nutrient formula on phenytoin bioavailability." Epilepsia 28 (1987): 706-12
  15. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  16. Cerner Multum, Inc. "Australian Product Information." O 0
View all 16 references

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Moderate

praziquantel food

Applies to: praziquantel

ADJUST DOSING INTERVAL: Administration with food increases the oral bioavailability of praziquantel. The mechanism has not been described. In nine healthy volunteers, administration of praziquantel (1800 mg single oral dose) following a high-fat meal increased the mean praziquantel peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) by 243% and 180%, respectively, compared to administration under fasting conditions. Administration with a high-carbohydrate meal increased these values by 515% and 271%, respectively, compared to fasting. Overall, the relative bioavailability was increased by a factor of 2.72 and 3.98 with the high-fat and high-carbohydrate meals, respectively. The time to reach peak concentration (Tmax) and elimination half-life (T1/2) were not significantly altered.

Coadministration with grapefruit juice may increase the oral bioavailability of praziquantel. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruit. In 18 healthy volunteers, administration of praziquantel (1800 mg single oral dose) with 250 mL of commercially squeezed grapefruit juice resulted in increases in the mean praziquantel Cmax and AUC of 63% and 90%, respectively, compared to administration with water. The Tmax and T1/2 were not significantly altered. The pharmacokinetics of praziquantel were subject to a high degree of interpatient variability with and without grapefruit juice.

MANAGEMENT: To ensure maximal oral absorption, praziquantel should be administered with meals. Administration with grapefruit juice may further increase pharmacologic effects of praziquantel, including adverse effects such dizziness, abdominal discomfort, and nausea.

References

  1. Castro N, Jung H, Medina R, Gonzalez-Esquivel D, Lopez M, Sotelo J "Interaction between grapefruit juice and praziquantel in humans." Antimicrob Agents Chemother 46 (2002): 1614-6
  2. Castro N, Medina R, Sotelo J, Jung H "Bioavailability of praziquantel increases with concomitant administration of food." Antimicrob Agents Chemother 44 (2000): 2903-4

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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.

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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.

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