Viagra and Bupropion Interaction: Can You Take Them Together?

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What each label says

The Viagra label's drug interactions section covers nitrates (contraindicated), alpha-blockers, amlodipine, ritonavir and other CYP3A4 inhibitors, and alcohol [1]. Bupropion is not among them.

The Contrave label (naltrexone plus bupropion) is the bupropion-containing label used here. Its interaction highlights cover monoamine oxidase inhibitors, drugs metabolized by CYP2D6, digoxin, CYP2B6 inhibitors and inducers, drugs that lower the seizure threshold, levodopa and amantadine, and false-positive amphetamine urine tests [2].

Does bupropion change how sildenafil is broken down?

The Viagra label says sildenafil is cleared mainly by CYP3A4, with CYP2C9 a minor route [1]. Bupropion's documented enzyme effect sits elsewhere: the Contrave label says bupropion inhibits CYP2D6 and can raise concentrations of CYP2D6 substrates [2]. With Contrave (32 mg naltrexone with 360 mg bupropion a day), metoprolol AUC rose about 4-fold and Cmax about 2-fold. The label notes that similar increases in CYP2D6 substrate exposure have been seen with bupropion alone alongside desipramine or venlafaxine [2].

For scale, the Viagra label documents what a strong metabolic interaction looks like in numbers. Ritonavir raised sildenafil AUC 11-fold, saquinavir raised Cmax 140% and AUC 210%, and erythromycin raised Cmax 160% and AUC 182%. For erythromycin and strong CYP3A4 inhibitors the label says to consider a 25 mg starting dose [1].

What happens to blood pressure?

Single 100 mg doses of sildenafil lowered supine blood pressure in healthy volunteers by a mean maximum of about 8.4/5.5 mmHg, and the fall was not dose-related between 25 and 100 mg [1]. With amlodipine 5 or 10 mg in hypertensive patients, sildenafil 100 mg produced a further mean fall of 8/7 mmHg [1]. With alpha-blockers the Viagra label advises caution, a stable alpha-blocker dose before sildenafil starts, and a 25 mg sildenafil starting dose [1].

Bupropion can raise blood pressure [2]. The Contrave label warns that blood pressure and heart rate can rise during treatment, that the risk may be greater during the first three months, and to monitor blood pressure and heart rate in all patients, especially those with cardiac or cerebrovascular disease [2]. The blood-pressure data in the Viagra label are for sildenafil with amlodipine and alpha-blockers, not with bupropion [1].

What about seizure risk?

Bupropion's seizure risk is dose-related: about 0.1% (1 in 1,000) with sustained-release bupropion up to 300 mg/day and about 0.4% (13 of 3,200) with immediate-release bupropion at 300 to 450 mg/day [3]. Seizure disorder is a contraindication on bupropion-containing labels [2]. The Contrave label asks for extreme caution when bupropion is combined with other drugs that lower the seizure threshold, such as antipsychotics, antidepressants, theophylline and systemic corticosteroids, with low initial doses and gradual increases [2].

Dosing under the Viagra label

For most men the label dose is 50 mg taken as needed about 1 hour before sexual activity, anywhere from 30 minutes to 4 hours beforehand, no more than once a day. It may be raised to 100 mg or lowered to 25 mg depending on effect and tolerance [1]. The label says to consider a 25 mg starting dose for people over 65, with hepatic impairment such as cirrhosis, with creatinine clearance below 30 mL/min, or taking strong CYP3A4 inhibitors (ketoconazole, itraconazole, saquinavir) or erythromycin. It also says to start at 25 mg when beginning Viagra while stable on an alpha-blocker. With ritonavir the label limits the dose to 25 mg in 48 hours [1]. Bupropion is not one of the drugs named in those dose-adjustment instructions [1].

Bupropion and sexual function

Bupropion does not inhibit serotonin reuptake [3]. Two identically designed 8-week double-blind trials in adults with major depressive disorder and normal sexual function compared bupropion XL 300 to 450 mg/day, escitalopram 10 to 20 mg/day and placebo. Pooled arm sizes were 276, 281 and 273 [4]. Orgasm dysfunction at week 8 was reported by 15% on bupropion XL, 30% on escitalopram and 9% on placebo; bupropion XL did not differ significantly from placebo (P of 0.067 or higher) [4]. Worsened sexual functioning at the end of treatment was reported by 20%, 36% and 15% respectively [4].