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Drug Interactions between paliperidone and st. john's wort

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

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Interactions between your drugs

Major

St. John's wort paliperidone

Applies to: st. john's wort 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 (5)
  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

Drug and food interactions

Moderate

St. John's wort food

Applies to: st. john's wort

GENERALLY AVOID: An isolated case report suggests that foods containing large amounts of tyramine may precipitate a hypertensive crisis in patients treated with St. John's wort. The mechanism of interaction is unknown, as St. John's wort is not thought to possess monoamine oxidase (MAO) inhibiting activity at concentrations achieved in vivo. The case patient was a 41-year-old man who had been taking St. John's wort for seven days prior to presentation at the emergency room with confusion and disorientation. The patient recalled last eating aged cheese and having a glass of red wine approximately 10 hours prior to admission. No other cause of delirium or hypertension could be identified. In addition, alcohol may potentiate some of the pharmacologic effects of St. John's wort. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Until further information is available, patients treated with St. John's wort should consider avoiding consumption of protein foods in which aging or breakdown of protein is used to increase flavor. These foods include cheese (particularly strong, aged or processed cheeses), sour cream, wine (particularly red wine), champagne, beer, pickled herring, anchovies, caviar, shrimp paste, liver (particularly chicken liver), dry sausage, figs, raisins, bananas, avocados, chocolate, soy sauce, bean curd, yogurt, papaya products, meat tenderizers, fava beans, protein extracts, and dietary supplements. Caffeine may also precipitate hypertensive crisis so its intake should be minimized as well. Patients should also be advised to avoid or limit consumption of alcohol.

References (1)
  1. Patel S, Robinson R, Burk M (2002) "Hypertensive crisis associated with St. John's Wort." Am J Med, 112, p. 507-8
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)
  1. (2007) "Product Information. Invega (paliperidone)." Janssen Pharmaceuticals

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.


Report options

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.