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

Is There a Known Interaction Between Ginseng and Vardenafil?

Vardenafil's label has a full drug interaction section, and ginseng is not in it. The section names nitrates and nitric oxide donors (contraindicated), guanylate cyclase stimulators such as riociguat (contraindicated), alpha-blockers, other antihypertensives, and CYP3A4 inhibitors including ketoconazole, ritonavir, indinavir and erythromycin [1]. NCCIH says Asian ginseng may interact with certain medicines and that some herb-drug pairs interact in harmful ways, without naming vardenafil [3].

The label describes no study that gave ginseng and vardenafil together, so any answer has to be assembled from what each one does on its own.

A note on the names in the title: Levitra (film-coated tablets) and Staxyn (the 10 mg orally disintegrating tablet) are both listed as discontinued in Drugs@FDA, with a federal determination that this was not for safety or effectiveness reasons [5][6]. Current labels cover generic vardenafil film-coated tablets and a generic 10 mg orally disintegrating tablet [1][7]. The orally disintegrating tablet is not interchangeable with the 10 mg film-coated tablet because it gives higher exposure, with Cmax 15% and AUC 44% higher in healthy volunteers [7].

Does Ginseng Change Blood Pressure Enough to Matter?

Vardenafil lowers supine blood pressure by a mean maximum of 7 mmHg systolic and 8 mmHg diastolic compared with placebo, with heart rate up 4 beats per minute, maximal 1 to 4 hours after dosing [1]. That is the effect a supplement would theoretically stack on.

Ginseng alone does not appear to change blood pressure much. A meta-analysis of 17 randomized trials (each 4 weeks or longer) in 1,381 people found no significant effect of ginseng on systolic pressure, diastolic pressure or mean arterial pressure [2]. In a subgroup with diabetes, metabolic syndrome or obesity, the systolic difference was -2.76 mmHg (95% CI -6.40 to 0.87), which was not significant [2]. These trials did not involve vardenafil.

Where vardenafil's label does document additive hypotension is with alpha-blockers. In men with benign prostatic hyperplasia who were stable on tamsulosin 0.4 mg, vardenafil 5 mg taken at the same time lowered standing systolic pressure by 6 mmHg more than placebo (95% CI -9.9 to -2.1), and one man taking terazosin 10 mg had symptomatic hypotension with a standing pressure of 80/60 mmHg [1]. That is a documented interaction; the label documents none for ginseng.

Blood Sugar: The Overlap With the Most Human Data

NCCIH says some evidence suggests Asian ginseng might lower blood sugar levels [3]. In one study of American ginseng (a different species), 3 g taken before a 25 g glucose drink cut the glucose curve by 18% to 22% in 10 nondiabetic volunteers and 9 people with type 2 diabetes [11]. In another trial, 36 people with newly diagnosed type 2 diabetes took ginseng 100 or 200 mg daily for 8 weeks, and fasting blood glucose fell compared with placebo [12].

The evidence is not consistent. NCCIH describes research on ginseng for blood sugar control in diabetes as inconclusive and conflicting [3], and a 30-day trial of 8 g of ginseng root extract per day found no improvement in beta-cell function or insulin sensitivity in overweight or obese people with impaired glucose tolerance or newly diagnosed type 2 diabetes [13].

For someone taking insulin or a sulfonylurea, an added glucose-lowering effect is plausible, although no trial of ginseng with those drugs was found.

Does Ginseng Change How Vardenafil Is Metabolized?

Vardenafil is metabolized mainly by CYP3A4/5 and to a lesser degree by CYP2C9 [1]. That pathway is sensitive. Ketoconazole 200 mg daily raised vardenafil AUC 10-fold and Cmax 4-fold; ritonavir raised AUC 49-fold, Cmax 13-fold and stretched the half-life to 26 hours [1]. The label sets dose caps for those drugs [1].

Ginseng's effect on the same enzymes was small in the studies available. In an open-label crossover study, 14 healthy men took probe drugs before and after 2 weeks of red ginseng. The CYP3A4 probe midazolam gave a geometric mean ratio of 0.824 (90% CI 0.658 to 1.032), which was not significant, and the authors concluded there were no clinically significant interactions for the standard red ginseng product [10]. A companion study of fermented red ginseng in 15 men gave a midazolam ratio of 0.816 (90% CI 0.673 to 0.990) and raised fexofenadine AUC by 32% [14].

These effects are far smaller than those of the CYP3A4 inhibitors the label caps doses for. The studies tested only the specific red ginseng products used in them, not other ginseng products or doses [10][14].

Warfarin, Clotting and Bleeding

NCCIH notes that Asian ginseng may interfere with blood clotting [3]. Human warfarin data are mixed and depend on which species was studied; American ginseng (Panax quinquefolius) is a different plant from Asian ginseng (Panax ginseng) [3].

In a randomized, double-blind trial of 20 healthy volunteers, 2 weeks of American ginseng lowered peak INR by 0.19 compared with placebo (95% CI -0.36 to -0.07, P=0.0012), and peak warfarin level and warfarin AUC also fell [9]. Seven days of Asian ginseng before a single 25 mg warfarin dose in 12 healthy men did not change INR or platelet aggregation [15], although a modeling analysis put S-warfarin clearance 14% higher with Asian ginseng [16]. In 25 patients with heart valve replacements taking warfarin, Korean red ginseng 1 g produced INR changes of -0.16 and -0.14 at weeks 3 and 6, against -0.03 and +0.25 with placebo, with no statistically significant difference [17].

Vardenafil's label reports no pharmacokinetic interaction with warfarin, and vardenafil had no effect on prothrombin time [1]. Whether ginseng weakens warfarin is not established.

What Ginseng Does for Erections on Its Own

Ginseng is not a proven treatment for erectile dysfunction. A Cochrane review of 9 randomized trials in 587 men with mild to moderate ED, all comparing ginseng with placebo for up to 12 weeks, found a difference of 3.52 points on the IIEF erectile function domain (95% CI 1.79 to 5.25) against a minimal important difference of 4, which the authors called trivial [18].

For context, the vardenafil label's North American general-ED trial in 762 men reported IIEF erectile function domain scores at 3 months of 18, 21 and 21 on 5, 10 and 20 mg versus 15 on placebo, with intercourse success (SEP3) of 51%, 64% and 65% versus 32% [1]. These are different trials in different men, not a head-to-head comparison.

The Cochrane review's ginseng difference of 3.52 points is smaller than its 4-point minimal important difference [18].

Side Effects

Ginseng's most common side effect is insomnia [3]. Uncommon reports include severe rash, liver damage and severe allergic reactions [3]. In trials of single-ingredient ginseng products, adverse event rates were similar to placebo, with headache, sleep problems and stomach upset the most frequent complaints; more serious events have been reported in isolated case reports and spontaneous reports, but their cause is difficult to establish [19].

Vardenafil's common reactions in placebo-controlled trials were headache (15% versus 4% on placebo), flushing (11% versus 1%), rhinitis (9% versus 3%), dyspepsia (4% versus 1%) and dizziness (2% versus 1%) [1]. Headache is common with both; flushing is listed for vardenafil.

The groups with the most reason to look closely are men on warfarin, because of the INR data with ginseng [9][17], and men on insulin or a sulfonylurea, because ginseng may lower glucose [3].