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Drug Interactions between Invirase and Uroplus DS

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

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Interactions between your drugs

Minor

sulfamethoxazole saquinavir

Applies to: Uroplus DS (sulfamethoxazole / trimethoprim) and Invirase (saquinavir)

Limited data suggest that sulfamethoxazole-trimethoprim (SMX-TMP) may rarely prolong the QT interval of the electrocardiogram. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. There have been isolated reports of QT prolongation and ventricular arrhythmias occurring in patients treated with SMX-TMP intravenously. However, a causal relationship has not been established, and the risk of clinically significant QT prolongation is unlikely at recommended dosages of SMX-TMP. 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 such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s). Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References

  1. Wiener I, Rubin D, Martinez E, et al. (1981) "QT prolongation and paroxysmal ventricular tachycardia occurring during fever following trimethoprim-sulfamethoxazole administration." Mt Sinai J Med, 48, p. 53-5
  2. Crouch MA, Limon L, Cassano AT (2003) "Clinical relevance and management of drug-related QT interval prolongation." Pharmacotherapy, 23, p. 881-908
  3. Lopez JA, Harold JG, Rosenthal MC, Oseran DS, Schapira JN, Peter T (1987) "QT prolongation and torsades de pointes after administration of trimethoprin-sulfamethoxazole." Am J Cardiol, 59, p. 376-7
  4. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  5. Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
  6. Cerner Multum, Inc. "Australian Product Information."
  7. Darpo B (2001) "Spectrum of drugs prolonging QT interval and the incidence of torsades de pointes." Eur Heart J Suppl, 3(Suppl K), K70-80
View all 7 references

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Drug and food interactions

Moderate

saquinavir food

Applies to: Invirase (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

sulfamethoxazole food

Applies to: Uroplus DS (sulfamethoxazole / trimethoprim)

MONITOR: Two cases have been reported in which patients on sulfamethoxazole-trimethoprim therapy, after consuming beer, reported flushing, heart palpitations, dyspnea, headache, and nausea (disulfiram - alcohol type reactions). First-generation sulfonylureas have been reported to cause facial flushing when administered with alcohol by inhibiting acetaldehyde dehydrogenase and subsequently causing acetaldehyde accumulation. Since sulfamethoxazole is chemically related to first-generation sulfonylureas, a disulfiram-like reaction with products containing sulfamethoxazole is theoretically possible. However, pharmacokinetic/pharmacodynamic data are lacking and in addition, the two reported cases cannot be clearly attributed to the concomitant use of sulfamethoxazole-trimethoprim and alcohol.

MANAGEMENT: Patients should be alerted to the potential for this interaction and although the risk for this interaction is minimal, caution is recommended while taking sulfamethoxazole-trimethoprim concomitantly with alcohol.

References

  1. Heelon MW, White M (1998) "Disulfiram-cotrimoxazole reaction." Pharmacotherapy, 18, p. 869-70
  2. Mergenhagen KA, Wattengel BA, Skelly MK, Clark CM, Russo TA (2020) "Fact versus fiction: a review of the evidence behind alcohol and antibiotic interactions." Antimicrob Agents Chemother, 64, e02167-19

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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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