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Drug Interactions between Adcirca and conivaptan

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

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Interactions between your drugs

Moderate

tadalafil conivaptan

Applies to: Adcirca (tadalafil) and conivaptan

GENERALLY AVOID: Coadministration with conivaptan may significantly increase the plasma concentrations of phosphodiesterase-5 (PDE5) inhibitors. The mechanism is conivaptan inhibition of CYP450 3A4, the isoenzyme responsible for the metabolic clearance of these agents. Although the interaction has not been specifically studied, high plasma levels of PDE5 inhibitors (e.g., due to high doses or interaction with other potent 3A4 inhibitors such as protease inhibitors) have been associated with increased PDE5 adverse effects such as headache, flushing, dyspepsia, rhinitis, visual disturbances, hypotension, and even death. In pharmacokinetic studies with other drugs that are primarily metabolized by CYP450 3A4 such as midazolam, simvastatin, and amlodipine, conivaptan has increased systemic exposure (AUC) by 2- to 3-fold.

MANAGEMENT: Use of PDE5 inhibitors should preferably be avoided in patients treated with conivaptan. Patients currently using PDE5 inhibitors should consider an interruption during administration of conivaptan, and allow an appropriate amount of time following completion of conivaptan therapy before resuming these medications.

References

  1. Nandwani R, Gourlay Y (1999) "Possible interaction between sildenafil and HIV combination therapy." Lancet, 353, p. 840
  2. Hall MCS, Ahmad S (1999) "Interaction between sildenafil and HIV-1 combination therapy." Lancet, 353, p. 2071-2
  3. Merry C, Barry MG, Ryan M, Tjia JF, Hennessy M, Eagling VA, Mulcahy F, Back DJ (1999) "Interaction of sildenafil and indinavir when co-administered to HIV-positive patients." AIDS, 13, f101-7
  4. Warrington JS, Shader RI, vonMoltke LL, Greenblatt DJ (2000) "In vitro biotransformation of sildenafil (Viagra): Identification of human cytochromes and potential drug interactions." Drug Metab Disposition, 28, p. 392-7
  5. Hyland R, Roe GH, Jones BC, Smith DA (2001) "Identification of the cytochrome P450 enzymes involved in the N-demethylation of sildenafil." Br J Clin Pharmaacol, 51, p. 239-48
  6. (2006) "Product Information. Vaprisol (conivaptan)." Cumberland Pharmaceuticals Inc
View all 6 references

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Drug and food interactions

Moderate

tadalafil food

Applies to: Adcirca (tadalafil)

GENERALLY AVOID: Additive hypotensive effects may occur when phosphodiesterase-5 (PDE5) inhibitors such as tadalafil are used with alcohol, as both are mild systemic vasodilators. In clinical pharmacology studies, more subjects administered alcohol at a dose of 0.7 g/kg (equivalent to approximately 6 ounces of 80-proof vodka in an 80-kg male; consumed within 10 minutes in study subjects, providing blood alcohol levels of 0.08%) in combination with tadalafil 10 or 20 mg single doses had clinically significant decreases in blood pressure than with alcohol alone. There were reports of postural dizziness, and orthostatic hypotension was observed in some. When tadalafil 20 mg was administered with alcohol at a lower dose of 0.6 g/kg (equivalent to approximately 4 ounces of 80-proof vodka in an 80-kg male), orthostatic hypotension was not observed, dizziness occurred with similar frequency relative to alcohol alone, and the hypotensive effects of alcohol were not potentiated. Neither tadalafil nor alcohol affected the plasma concentrations of the other.

GENERALLY AVOID: Coadministration with grapefruit juice is likely to increase the plasma concentrations of tadalafil, which is primarily metabolized by CYP450 3A4. However, the interaction has not been studied. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit.

MANAGEMENT: Patients taking tadalafil should avoid consuming large amounts of alcohol (for example, 5 units or more), which may increase the potential for orthostatic signs and symptoms including increase in heart rate, decrease in standing blood pressure, dizziness, and headache. It may also be appropriate to avoid consuming large amounts of grapefruit juice.

References

  1. (2003) "Product Information. Cialis (tadalafil)." Lilly, Eli and Company
  2. (2009) "Product Information. Adcirca (tadalafil)." United Therapeutics Corporation

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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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