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Drug Interactions between fesoterodine and saquinavir

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

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Interactions between your drugs

Major

saquinavir fesoterodine

Applies to: saquinavir and fesoterodine

ADJUST DOSE: Coadministration with potent inhibitors of CYP450 3A4 may increase the plasma concentrations of fesoterodine's active metabolite, 5-hydroxymethyl tolterodine, which is partially metabolized by the isoenzyme. The possibility of prolonged and/or increased pharmacologic effects of fesoterodine should be considered. Because 5-hydroxymethyl tolterodine is also metabolized by CYP450 2D6, the clinical significance of the interaction may be greater in patients who are CYP450 2D6-deficient, or so-called poor metabolizers of CYP450 2D6 (approximately 7% of Caucasians and less than 2% of Asians and individuals of African descent) who may rely more on the 3A4 metabolic pathway for clearance of the drug. In one study, administration of fesoterodine (8 mg single oral dose) with the potent CYP450 3A4 inhibitor ketoconazole (200 mg twice a day for 5 days) increased the mean peak plasma concentration (Cmax) of 5-hydroxymethyl tolterodine by 2.0-fold and its systemic exposure (AUC) by 2.3-fold in 2D6 extensive metabolizers compared to administration without ketoconazole. In 2D6 poor metabolizers, 5-hydroxymethyl tolterodine Cmax increased by 2.1-fold and AUC increased by 2.5-fold during coadministration with ketoconazole. However, Cmax and AUC were 4.5- and 5.7-fold higher, respectively, in poor metabolizers taking ketoconazole compared to extensive metabolizers who were not taking ketoconazole. In another study where subjects were administered fesoterodine with ketoconazole 200 mg once a day for 5 days, the Cmax and AUC of 5-hydroxymethyl tolterodine were increased 2.2-fold in 2D6 extensive metabolizers and 1.5- and 1.9-fold, respectively, in 2D6 poor metabolizers. Cmax and AUC were 3.4- and 4.2-fold higher, respectively, in subjects who were poor metabolizers taking ketoconazole compared to extensive metabolizers who were not taking ketoconazole.

MANAGEMENT: The dosage of fesoterodine should not exceed 4 mg/day when used with potent CYP450 3A4 inhibitors. Close clinical and laboratory monitoring is advised whenever a CYP450 3A4 inhibitor is added to or withdrawn from therapy. Patients should be advised to contact their physician if they experience potential adverse effects of fesoterodine such as irregular heartbeat, blurry vision, difficulty urinating, dry mouth, headache, drowsiness, dizziness, gastrointestinal upset, or constipation. The product labeling for itraconazole (a potent CYP450 3A4 inhibitor) states that concomitant use with fesoterodine is contraindicated in patients with moderate to severe renal or hepatic impairment during and for 2 weeks after treatment with itraconazole. In addition, some authorities consider the coadministration of posaconazole with fesoterodine as contraindicated.

References

  1. "Product Information. Sporonox (itraconazole)." Janssen Pharmaceutica, Titusville, NJ.
  2. (2002) "Product Information. Sporanox (itraconazole)." Janssen Pharmaceuticals
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  4. (2006) "Product Information. Noxafil (posaconazole)." Schering-Plough Corporation
  5. Cerner Multum, Inc. "Australian Product Information."
  6. (2008) "Product Information. Toviaz (fesoterodine)." Pfizer U.S. Pharmaceuticals Group
  7. (2022) "Product Information. Posaconazole (AKM) (posaconazole)." Pharmacor Pty Ltd
  8. (2024) "Product Information. Posaconazole (posaconazole)." Morningside Healthcare Ltd
  9. (2023) "Product Information. Posaconazole (posaconazole)." Eugia US LLC
  10. (2023) "Product Information. Gln-Posaconazole (posaconazole)." Glenmark Pharmaceuticals Canada Inc
View all 10 references

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Drug and food interactions

Moderate

saquinavir food

Applies to: saquinavir

ADJUST DOSING INTERVAL: Food significantly increases the absorption of saquinavir.

MONITOR: Coadministration with grapefruit juice may increase the plasma concentrations of saquinavir. The primary mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. In eight healthy volunteers, ingestion of 400 mL of grapefruit juice prior to administration of a 600 mg dose of saquinavir mesylate increased the area under the plasma concentration-time curve and oral bioavailability of saquinavir by 50% and 100%, respectively, compared to water; however, the increase is not considered clinically relevant. A high degree of intersubject variability in the grapefruit juice effect was also observed. The extent to which this interaction may occur with the saquinavir free base soft gelatin capsule is unknown. However, the saquinavir soft gelatin capsule formulation is no longer commercially available.

MANAGEMENT: Saquinavir mesylate should be taken with meals or within 2 hours after eating to enhance bioavailability. Patients should be advised to avoid the consumption of large amounts of grapefruit and grapefruit juice during saquinavir therapy unless otherwise directed by their doctor, as the interaction is unreliable and subject to a high degree of interpatient variation.

References

  1. (2001) "Product Information. Invirase (saquinavir)." Roche Laboratories
  2. Kupferschmidt HHT, Fattinger KE, Ha HR, Follath F, Krahenbuhl S (1998) "Grapefruit juice enhances the bioavailability of the HIV protease inhibitor saquinavir in man." Br J Clin Pharmacol, 45, p. 355-9
  3. Bailey DG, Malcolm J, Arnold O, Spence JD (1998) "Grapefruit juice-drug interactions." Br J Clin Pharmacol, 46, p. 101-10
  4. Eagling VA, Profit L, Back DJ (1999) "Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-I protease inhibitor saquinavir by grapefruit juice components." Br J Clin Pharmacol, 48, p. 543-52
  5. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  6. Cerner Multum, Inc. "Australian Product Information."
View all 6 references

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Moderate

fesoterodine food

Applies to: fesoterodine

MONITOR: Coadministration with moderate inhibitors of CYP450 3A4 such as grapefruit juice may increase the plasma concentrations of fesoterodine's active metabolite, 5-hydroxymethyl tolterodine, which is partially metabolized by the isoenzyme. The possibility of prolonged and/or increased pharmacologic effects of fesoterodine should be considered. Because 5-hydroxymethyl tolterodine is also metabolized by CYP450 2D6, the clinical significance of the interaction may be greater in patients who are CYP450 2D6-deficient, or so-called poor metabolizers of CYP450 2D6 (approximately 7% of Caucasians and less than 2% of Asians and individuals of African descent) who may rely more on the 3A4 metabolic pathway for clearance of the drug.

MANAGEMENT: Caution is advised if fesoterodine is administered with grapefruit or grapefruit juice. Patients should be advised to notify their physician if they experience potential adverse effects of fesoterodine such as irregular heartbeat, blurry vision, difficulty urinating, dry mouth, headache, drowsiness, dizziness, gastrointestinal upset, or constipation.

References

  1. (2008) "Product Information. Toviaz (fesoterodine)." Pfizer U.S. Pharmaceuticals Group

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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

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.