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Drug Interactions between paliperidone and Phenytek

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

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Major

phenytoin paliperidone

Applies to: Phenytek (phenytoin) and paliperidone

ADJUST DOSE: Coadministration with dual potent inducers of CYP450 3A4 and P-glycoprotein (P-gp) may decrease the plasma concentrations of paliperidone. In vitro studies suggest that CYP450 2D6 and 3A4 are involved in paliperidone metabolism. However, in vivo data indicate that these isoenzymes play a limited role in the overall elimination of paliperidone and contribute to only a small fraction of total body clearance. Approximately 60% of a paliperidone dose is excreted unchanged in the urine, which may involve active tubular secretion mediated by P-gp efflux transporter. When paliperidone 6 mg (extended-release) once daily was coadministered with the potent CYP450 3A4 and P-gp inducer carbamazepine at a dosage of 200 mg twice daily, mean steady-state paliperidone peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by approximately 37%. The decrease in AUC was largely caused by a 35% increase in renal clearance of paliperidone, which may be attributable to induction of P-gp in renal proximal tubules by carbamazepine. In general, P-gp induction may take 2 to 3 weeks to reach steady state following initiation of an inducer and a similar length of time to wear off following withdrawal of the inducer. Injectable paliperidone has not been studied in combination with carbamazepine or other dual CYP450 3A4/P-gp inducers. In a retrospective study using data from a therapeutic drug monitoring database, the dose-adjusted serum concentrations of paliperidone were reportedly more than 50% lower in three patients who were taking carbamazepine compared to the general study population.

MANAGEMENT: When paliperidone is administered orally, the prescribing information recommends re-evaluating the dosage and increasing if necessary following the addition of a dual potent CYP450 3A4 and P-gp inducer. For patients receiving extended-release injectable formulations of paliperidone, concomitant use of potent inducers should be avoided. If coadministration is required, consideration should be given to use of oral extended-release paliperidone. Changes in efficacy and safety should be carefully monitored with any dosage adjustment. Upon discontinuation of the inducer, paliperidone dosage should be reassessed and readjusted accordingly based on clinical response. The prescribing information for individual paliperidone products should be consulted for specific recommendations regarding concomitant use with potent CYP450 3A4 inducers.

References

  1. (2022) "Product Information. Invega (paliperidone)." Janssen Pharmaceuticals, SUPPL-39
  2. (2021) "Product Information. Invega Hafyera (paliperidone)." Janssen Pharmaceuticals
  3. (2022) "Product Information. Invega Sustenna (paliperidone)." Janssen Pharmaceuticals
  4. (2022) "Product Information. Invega Trinza (paliperidone)." Janssen Pharmaceuticals
  5. Helland A, Spigset O (2017) "Serum concentrations of paliperidone after administration of the long-acting injectable formulation." Ther Drug Monit, 39, p. 659-62
View all 5 references

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Drug and food interactions

Moderate

phenytoin food

Applies to: Phenytek (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

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Moderate

paliperidone food

Applies to: paliperidone

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of paliperidone. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

Administration with food may increase the bioavailability of paliperidone from the extended release tablets. In healthy ambulatory subjects, administration of a 12 mg paliperidone extended release tablet with a standard high-fat/high-caloric meal resulted in 60% and 54% increases, respectively, in the mean peak plasma concentration (Cmax) and area under the concentration-time curve (AUC) of paliperidone compared to administration under fasting conditions. The clinical significance of these changes is unknown.

MANAGEMENT: Patients receiving paliperidone should be advised to avoid the consumption of alcohol. Since clinical trials establishing the safety and efficacy of paliperidone were carried out without regard to the timing of meals, presumably paliperidone may be administered with or without food.

References

  1. (2007) "Product Information. Invega (paliperidone)." Janssen Pharmaceuticals

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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.

Further information

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