Can I Take Zinc with Vardenafil (Levitra/Staxyn)?

Print or save as PDFOpens the printable medication review sheet and your print dialog. No sign-up.

Which vardenafil product does this apply to?

Levitra (NDA 021400) was approved on 08/19/2003, and Staxyn, the 10 mg orally disintegrating tablet (NDA 200179), on 06/17/2010. Drugs@FDA now lists every Levitra strength and Staxyn as discontinued, with an FDA determination that the withdrawals were not for safety or effectiveness reasons [3][4]. The prescribing information in current use comes from generic vardenafil: film-coated tablets in 2.5, 5, 10 and 20 mg, and a 10 mg orally disintegrating tablet [1][5].

The two forms are not interchangeable. In healthy volunteers the orally disintegrating tablet gave a 15% higher Cmax and a 44% higher AUC than the 10 mg film-coated tablet [5]. It is placed on the tongue, taken without liquid, about 60 minutes before sexual activity, and limited to one tablet a day [5].

Where vardenafil is handled in the body

Vardenafil is metabolized mainly by CYP3A4/5 and to a lesser degree by CYP2C9 [1]. The label names drugs that raise its levels: ritonavir 600 mg twice daily raised vardenafil 5 mg AUC 49-fold and extended the half-life to 26 hours, ketoconazole 200 mg daily raised AUC 10-fold, and erythromycin 500 mg three times daily raised AUC 4-fold [1]. It sets dose caps for these, for example no more than 2.5 mg in a 72-hour period with ritonavir or cobicistat [1]. The orally disintegrating tablet label says not to use that form with strong or moderate CYP3A4 inhibitors [5].

A film-coated tablet reaches peak blood levels in 30 minutes to 2 hours (median 60 minutes) fasting, and the terminal half-life of vardenafil and its main metabolite M1 is about 4 to 5 hours [1]. The label's list of drugs that change vardenafil exposure includes ketoconazole, indinavir, ritonavir, cobicistat and erythromycin, with a note that grapefruit juice would likely raise exposure. Zinc is not on that list [1].

Zinc and a marker of liver drug metabolism

Zinc has been tested against a marker of liver drug metabolism, though not against vardenafil. In a 1991 study, 7 patients with cirrhosis and zinc deficiency took zinc sulfate 660 mg daily for 30 days; antipyrine clearance fell and antipyrine half-life rose (P<0.05), with no significant change in volume of distribution. The authors concluded that restoring zinc status in these patients impaired hepatic oxidative metabolism of antipyrine [6]. Antipyrine is a test marker of drug metabolism, not vardenafil, and the patients had cirrhosis.

Zinc's own dose limits

Adult zinc RDAs are 8 to 12 mg/day depending on sex and life stage, and the tolerable upper intake level is 40 mg/day [2]. At 50 mg/day or more over weeks, zinc can inhibit copper absorption, reduce immune function and lower HDL cholesterol [2]. Nausea, dizziness, headache, stomach upset, vomiting and loss of appetite are effects of too much zinc [2].

Copper status can fall before plasma copper does. In healthy men, 25 mg of zinc twice daily for 6 weeks lowered erythrocyte Cu,Zn-superoxide dismutase, a copper-status marker, against placebo (P<0.05), while plasma copper and ceruloplasmin activity did not change [7]. A 2026 systematic review of 37 reported cases found anemia in nearly all, usually with neutropenia, low serum copper in every case, and elemental zinc intakes from about 50 mg to over 1,500 mg/day for weeks to years [8].

For a man taking vardenafil, the main documented zinc risk is this copper problem, which builds over weeks at high doses [2][8].

Zinc does have documented absorption interactions, just not with vardenafil

Zinc binds some oral drugs in the gut, and the labels say so. The ciprofloxacin label says to take it at least 2 hours before or 6 hours after products containing zinc [9]; the moxifloxacin label says at least 4 hours before or 8 hours after [10]; the levofloxacin label says at least 2 hours before or 2 hours after a multivitamin containing zinc, noting that chelation is less marked than with other fluoroquinolones [11]. In 7 volunteers, zinc sulfate 45 mg of elemental zinc taken with tetracycline 500 mg cut tetracycline serum levels, AUC and urinary excretion by about 30% (P<0.05); doxycycline 200 mg absorption was not significantly changed [12].

That is what a documented zinc-drug interaction looks like: a named drug, a measured change, a timing rule on the label.

Zinc and testosterone

Vardenafil needs sexual stimulation to work. It inhibits PDE5, the enzyme that breaks down cyclic GMP, and has no effect without stimulation [1].

The zinc-testosterone data come from one small 1996 study [13]. In 4 healthy young men, 20 weeks of dietary zinc restriction dropped serum testosterone from 39.9 to 10.6 nmol/L (P=0.005); in 9 marginally zinc-deficient older men, 3 to 6 months of oral zinc gluconate raised it from 8.3 to 16.0 nmol/L (P=0.02) [13]. The same paper found a correlation between cellular zinc and serum testosterone across 40 men aged 20 to 80 [13]. It measured serum testosterone only, not erections or the effects of taking zinc with vardenafil.

What the vardenafil label does flag

Nitrates and nitric oxide donors in any form are contraindicated, and the label says a suitable time interval for giving nitrates after vardenafil has not been determined [1]. For men stable on an alpha-blocker, the film-coated tablet label gives a 5 mg starting dose, and symptomatic hypotension, for example fainting, can occur with the combination [1]. The orally disintegrating tablet label says not to start that form in patients taking alpha-blockers [5]. Vardenafil 20 mg lowered supine blood pressure by a mean maximum of 7 mmHg systolic and 8 mmHg diastolic against placebo, peaking 1 to 4 hours after the dose [1]. The label says patients with congenital QT prolongation or on Class IA or Class III antiarrhythmics should avoid vardenafil, that an erection lasting more than 4 hours needs immediate medical help, and that patients should stop vardenafil and seek medical attention for sudden loss of vision or hearing [1].

Putting it together

Zinc is not a named vardenafil interaction [1]. Zinc's documented harms are copper-related and dose-dependent: 50 mg/day or more over weeks is the level the NIH flags against a 40 mg/day adult upper limit [2], and case reports run from about 50 mg upward [8]. The only study tying zinc to hepatic drug metabolism used antipyrine in 7 patients with cirrhosis, not vardenafil [6].