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Drug Interactions between avanafil and Cardura

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

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Interactions between your drugs

Moderate

doxazosin avanafil

Applies to: Cardura (doxazosin) and avanafil

ADJUST DOSE: Avanafil may potentiate the hypotensive effect of alpha blockers, resulting in symptomatic hypotension in some patients. Avanafil inhibits phosphodiesterase-5-mediated degradation of cyclic guanosine monophosphate (cGMP), which in vascular smooth muscles can cause peripheral vasodilation that may be additive with that induced by alpha blockers. In 24 healthy male subjects taking doxazosin 8 mg daily for 11 days, administration of a single 200 mg dose of avanafil resulted in potentially clinically significant augmentation of the blood pressure lowering effect of doxazosin in some subjects. Specifically, seven subjects given avanafil had either a standing systolic blood pressure (SBP) or diastolic blood pressure (DBP) of less than 85 mmHg or 45 mmHg, respectively, and/or a decrease from baseline of greater than 30 mmHg for standing SBP or 20 mmHg for standing DBP, compared to one such subject when given placebo. In another cohort of 24 healthy male subjects given tamsulosin 0.4 mg daily for 11 days, 5 subjects experienced potentially clinically significant absolute values and/or changes from baseline in standing SBP or DBP after administration of a single 200 mg dose of avanafil, whereas only one subject did so after receiving placebo. The placebo-subtracted mean maximum decreases from baseline in standing and supine SBP with avanafil 200 mg was -2.5 and -6.0, respectively, in the doxazosin cohort and -3.6 and -3.1, respectively, in the tamsulosin cohort. There were no severe adverse events related to hypotension and no cases of syncope reported in study subjects.

MANAGEMENT: Caution is advised if avanafil is used in combination with alpha blockers. Patients who demonstrate hemodynamic instability on alpha blocker therapy alone are at increased risk of symptomatic hypotension with concomitant use of avanafil. Therefore, patients should be stable on alpha blocker therapy prior to initiating avanafil, and avanafil should be initiated at the lowest recommended dosage of 50 mg. In those patients already on an optimized dosage of avanafil, alpha blocker therapy should be initiated at the lowest dosage. The safety of avanafil in combination with alpha blockers may also be affected by other variables such as intravascular volume depletion and use of other antihypertensive medications.

References

  1. (2012) "Product Information. Stendra (avanafil)." Vivus Inc

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Drug and food interactions

Moderate

avanafil food

Applies to: avanafil

GENERALLY AVOID: Additive hypotensive effects may occur when phosphodiesterase-5 (PDE5) inhibitors 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. Administration of avanafil 200 mg with alcohol at a dose of 0.5 g/kg (equivalent to approximately 3 ounces of 80-proof vodka in a 70-kg male; consumed within 15 minutes in study subjects, providing blood alcohol levels of 0.057%) resulted in additional maximum supine systolic/diastolic blood pressure decreases of 3.5/4.5 mm Hg and additional maximum pulse rate increase of 9.3 bpm compared to alcohol alone, but did not cause orthostatic hypotension or dizziness. The plasma concentrations of alcohol were not affected. Sildenafil 50 mg and vardenafil 20 mg reportedly did not potentiate the hypotensive effect of alcohol in healthy volunteers with mean maximum blood alcohol levels of 0.08% and in healthy volunteers administered alcohol at a dose of 0.5 g/kg, respectively. Alcohol and vardenafil plasma levels were not altered when dosed simultaneously.

GENERALLY AVOID: Coadministration with grapefruit juice is likely to increase the plasma concentrations of avanafil, 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 avanafil should avoid consuming large amounts of alcohol, 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. Some authorities advise that grapefruit juice should be avoided within 24 hours prior to taking avanafil.

References

  1. (2001) "Product Information. Viagra (sildenafil)." Pfizer U.S. Pharmaceuticals
  2. (2003) "Product Information. Levitra (vardenafil)." Bayer
  3. (2003) "Product Information. Cialis (tadalafil)." Lilly, Eli and Company
  4. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  5. (2012) "Product Information. Stendra (avanafil)." Vivus Inc
View all 5 references

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Moderate

doxazosin food

Applies to: Cardura (doxazosin)

GENERALLY AVOID: The concurrent use of ethanol and alpha-1 adrenergic blockers may cause increased hypotensive effects. Patients with aldehyde dehydrogenase deficiencies (primarily Asians) may be at a higher risk of this interaction. The mechanism has not been determined. Data exist for prazosin and other alpha adrenergic blockers are expected to interact also. In addition, any patients taking alpha adrenergic blockers may experience excessive orthostatic hypotension with ethanol ingestion, due to ethanol's unopposed vasodilatory effects in the presence of alpha adrenergic blockade.

MANAGEMENT: Patients who develop a flushing reaction after ethanol ingestion (indicates a possible aldehyde dehydrogenase deficiency) should be advised to avoid ethanol or limit their intake. All patients should be warned about the possibility of orthostatic hypotension with concurrent ethanol use.

References

  1. Kawano Y, Abe H, Kojima S, Takishita S, Omae T (2000) "Interaction of alcohol and an a1-blocker on ambulatory blood pressure in patients with essential hypertension." Am J Hypertens, 13, p. 307-12
  2. (2002) "Product Information. Xatral (alfuzosin)." Sanofi-Synthelabo Canada Inc

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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.