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Drug Interactions between gepirone and Tofranil

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

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Interactions between your drugs

Major

imipramine gepirone

Applies to: Tofranil (imipramine) and gepirone

Consumer information for this interaction is not currently available.

MONITOR CLOSELY: Concomitant use of the selective 5-HT1A receptor agonist gepirone with agents that possess or enhance serotonergic activity may potentiate the risk of a potentially life-threatening condition called serotonin syndrome. The exact mechanism by which serotonin syndrome occurs may differ based on the agent(s) involved. It is thought to result from the hyperstimulation of postsynaptic 5-HT receptors and while postsynaptic 5-HT1A and 5-HT2A receptors are usually implicated, it is more likely that no single receptor is solely responsible.

MONITOR CLOSELY: Gepirone can cause prolongation of the QTc interval (QT interval corrected for heart rate). Coadministration with other agents that can prolong the QTc interval may result in additive effects and increased risk of ventricular arrhythmias. When immediate release gepirone (100 mg per day) was evaluated in a thorough QT study, the largest mean increase in baseline- and placebo-corrected QTc interval was 18.4 ms on Day 1 and 16.1 ms on Day 7. However, the exposure in this study was 2-fold the exposure of the maximum recommended dose of gepirone extended-release. Clinical data examining the QT prolonging effects of gepirone at recommended dosages are not available. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors including, but not limited to cardiac disease, uncontrolled hypothyroidism, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation may vary depending on the dosage(s) and specific drug(s) involved.

MANAGEMENT: If coadministration of gepirone with other agents that both prolong the QT interval and possess or enhance serotonergic activity is required, patients should have more frequent electrocardiograms (ECGs) than normally recommended and be monitored closely for and counseled about the signs and symptoms of serotonin syndrome (e.g., altered mental status, hypertension, restlessness, myoclonus, hyperthermia, hyperreflexia, diaphoresis, shivering, and tremor) as well as prolonged QT interval (irregular heartbeat, dizziness, lightheadedness, fainting). Additionally, the dose of gepirone should not be escalated if the patient develops a QTcF (QT corrected for heart rate by Fridericia's cube root formula) greater than 450 msec during treatment.

References

  1. US Food and Drug Administration (FDA) "FDA Drug Safety Communication: FDA warns about several safety issues with opioid pain medicines; requires label changes. https://www.fda.gov/downloads/Drugs/DrugSafety/UCM491302.pdf" (2018):
  2. "Product Information. Exxua (gepirone)." Mission Pharmacal Company 1 (2023):
  3. Scotton WJ, Hill LJ, Williams AC, Barnes NM "Serotonin syndrome: pathophysiology, clinical features, management, and potential future directions." Int J Tryptophan Res 12 (2019): 1178646919873925
  4. Foong AL, Grindrod KA, Patel T, Kellar J "Demystifying serotonin syndrome (or serotonin toxicity)." Can Fam Physician 64 (2018): 720-7
View all 4 references

Drug and food interactions

Moderate

gepirone food

Applies to: gepirone

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Grapefruit and/or grapefruit juice may increase the plasma concentrations and effects of gepirone. The proposed mechanism is inhibition of CYP450 3A4 mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. The interaction has not been studied with grapefruit juice, but has been reported for other CYP450 3A4 inhibitors. For example, when subjects who were at steady state on the strong CYP450 3A4 inhibitor ketoconazole (200 mg twice daily) received a single dose of gepirone (36.3 mg), the maximum plasma concentration (Cmax) and systemic exposure (AUC) of gepirone increased by approximately 5-fold. Similarly, when subjects who were at steady state on the moderate CYP450 3A4 inhibitor verapamil (80 mg three times daily) received a single dose of gepirone (18.2 mg), the maximum plasma concentration (Cmax) and systemic exposure (AUC) of gepirone increased by approximately 2.6-fold. In general, the effects of grapefruit products are concentration-, dose-, and preparation-dependent and can vary widely among both brands and individual patients. Some preparations have demonstrated strong CYP450 3A4 inhibition, while others have demonstrated moderate inhibition.

ADJUST DOSING INTERVAL: Food enhances the bioavailability of gepirone and its major active metabolites (3'-OH-gepirone and 1-PP). The magnitude of the effect is dependent on the fat content of the meal, but the systemic exposure of gepirone and its major metabolites was consistently higher under fed conditions as compared to the fasted state. The peak plasma concentration (Cmax) of gepirone after intake of a low-fat (about 200 calorie) breakfast was 27% higher, after a medium-fat (about 500 calorie) breakfast was 55% higher, and after a high-fat (about 850 calorie) breakfast was 62% higher than the Cmax achieved in the fasted state. Likewise, the systemic exposure (AUC) of gepirone was about 14% higher after a low-fat breakfast, 22% higher after a medium-fat breakfast, and 32% to 37% higher after a high-fat breakfast when compared to the AUC achieved in the fasted state. The effect of varying amounts of fat on the AUC and Cmax of 3'-OH-gepirone and 1-PP were similar to that of gepirone.

MANAGEMENT: Coadministration of gepirone with grapefruit products should be avoided. If grapefruit juice is consumed, monitoring for adverse effects (e.g., QT prolongation, serotonin syndrome, dizziness, nausea, insomnia, abdominal pain, and/or dyspepsia) should be considered. Gepirone should be taken orally with food at the approximately the same time each day. Tablets should be swallowed whole.

References

  1. "Product Information. Exxua (gepirone)." Mission Pharmacal Company 1 (2023):
  2. FDA. U.S. Food and Drug Administration "Grapefruit juice and some drugs don't mix. https://www.fda.gov/consumers/consumer-updates/grapefruit-juice-and-some-drugs-dont-mix" (2024):
  3. Chen M, Zhou S, Fabriaga E, Zhang P, Zhou Q "Food-drug interactions precipitated by fruit juices other than grapefruit juice: an update review. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9326888/" (2024):
  4. Kiani J, Imam SZ "Medicinal importance of grapefruit juice and its interaction with various drugs. https://nutritionj.biomedcentral.com/articles/10.1186/1475-2891-6-33" (2024):
View all 4 references
Moderate

imipramine food

Applies to: Tofranil (imipramine)

Ask your doctor before using imipramine together with ethanol, this can alter the effects of imipramine and cause increased side effects. Call the doctor if you experience uneven heartbeats, extreme drowsiness, confusion, agitation, vomiting, blurred vision, sweating, muscle stiffness, feeling light-headed, and seizures. You should be warned not to exceed recommended dosages, to avoid alcohol, and to avoid activities requiring mental alertness. If your doctor prescribes these medications together, you may need a dose adjustment to safely take this combination. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

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Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Antidepressants

Therapeutic duplication

The recommended maximum number of medicines in the 'antidepressants' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'antidepressants' category:

  • gepirone
  • Tofranil (imipramine)

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

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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