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

Vardenafil is a prescription PDE5 inhibitor sold for erectile dysfunction. Drugs@FDA lists all Levitra strengths and Staxyn as discontinued. Generic vardenafil film-coated tablets and orally disintegrating tablets are listed as prescription products [5][6][1][2][9]; the label details below come from the current generic film-coated tablet and orally disintegrating tablet labels [1][2].

Creatine is a compound the body makes from glycine, arginine and methionine and also gets from meat and fish, and it is sold over the counter as a dietary supplement [7]. A Drugs@FDA search returns no approved drug application with creatine as the active ingredient [7][8].

Is there a direct interaction between creatine and vardenafil?

Creatine is not named in either vardenafil label's drug-interaction section [1][2]. A missing label entry is not the same as shown to be safe.

Vardenafil is metabolized primarily by CYP3A4/5 and to a lesser degree by CYP2C9; the label attributes ritonavir's 49-fold rise in vardenafil AUC to blockade of that hepatic metabolism, and it sets dose caps when strong or moderate CYP3A4 inhibitors are taken with the film-coated tablet [1]. Creatine is a different case: the body turns it into creatinine, the waste product that standard kidney blood tests measure [3][4].

Why creatinine comes up at all

Creatinine is what standard kidney blood tests measure, and it is the number creatine moves.

Pooled randomized trials put the average rise at 0.13 mg/dL (95% CI 0.07 to 0.18; 19 RCTs plus one crossover study) and 0.14 mg/dL (95% CI 0.05 to 0.22; 26 studies, 1,036 healthy adults and people with chronic kidney disease) [3][4]. In the 26-study analysis, GFR estimated from creatinine fell by 10.75 mL/min (95% CI -17.48 to -4.02), while GFR measured by Cr-EDTA clearance did not change (+5.89 mL/min, 95% CI -0.30 to 12.08), and urea, albuminuria and proteinuria were unchanged [4]. The authors read the pattern as altered creatinine metabolism rather than kidney injury [4]. A creatinine-based eGFR can therefore under-read kidney function in someone taking creatine, so whoever orders the kidney tests needs to know about the supplement [4].

What the filtration trials found

Trials that measured filtration directly, or used cystatin C (a marker not made from creatine), found no fall.

• Resistance-trained adults on a high-protein diet took creatine 20 g/day for 5 days then 5 g/day for 12 weeks: 51Cr-EDTA clearance went from 101.42 to 108.78 mL/min/1.73 m2 on creatine versus 103.29 to 106.68 on placebo (group-by-time p=0.64) [11].
• Adults with type 2 diabetes took creatine for 12 weeks alongside exercise: 51Cr-EDTA clearance was 90.4 to 96.1 on creatine versus 97.9 to 96.4 on placebo (p=0.58), with proteinuria and albuminuria unchanged [12].
• Eighteen healthy sedentary men took about 10 g/day for 3 months with aerobic training: cystatin C fell from 0.82 to 0.71 mg/L on creatine and from 0.88 to 0.75 on placebo, so there was no sign of reduced filtration [13].
• Ninety-eight college football players were followed for up to 21 months (open label, about 5 g/day after a 5-day load of 15.75 g/day), with no significant group differences across a broad blood and urine panel that included renal markers [14].

One case report describes a 24-year-old weightlifter who developed biopsy-proven acute interstitial nephritis while taking creatine plus several other supplements and recovered fully after stopping all of them; creatine cannot be singled out from that case [15].

If kidney function is already reduced

Few creatine trials enrolled people with kidney disease: the type 2 diabetes trial above, and a hemodialysis subgroup within the 26-study analysis, in which serum creatinine rose while urea fell [4][12]. Long-term safety in advanced kidney disease is not established by those data [4].

What the vardenafil labels do list as interactions

For contrast, the interactions the labels treat as real are nitrates in any form (contraindicated, and the label says a suitable time interval for giving a nitrate after vardenafil has not been determined) and guanylate cyclase stimulators such as riociguat (contraindicated) [1][2].

Alpha-blockers and CYP3A4 inhibitors are handled differently by form. The film-coated tablet label gives a 5 mg starting dose in men stable on an alpha-blocker, and caps the dose with certain CYP3A4 inhibitors: no more than 5 mg in 24 hours with ketoconazole 200 mg daily, itraconazole 200 mg daily or erythromycin, and no more than 2.5 mg in 24 hours with indinavir, saquinavir, atazanavir, clarithromycin, ketoconazole 400 mg daily or itraconazole 400 mg daily [1]. The orally disintegrating tablet label says not to start that form in patients taking alpha-blockers and not to use it with moderate or strong CYP3A4 inhibitors [2]. Grapefruit juice was not studied but would likely raise vardenafil exposure, in the film-coated tablet label's words [1].

Creatine kinase is not creatinine

The vardenafil label's adverse-reaction table lists increased creatine kinase in 2% of men on vardenafil versus 1% on placebo [1]. That is a muscle enzyme, a different measurement from creatinine, the breakdown product of creatine that kidney tests read [3]. Similar names, separate tests.

Doses and timing

Typical adult protocols studied for creatine are 20 g/day of creatine monohydrate in four 5 g portions for 5 to 7 days followed by 3 to 5 g/day, or about 3 to 6 g/day for 3 to 4 weeks with no loading phase [7]; these are study protocols, not prescriptions. The International Society of Sports Nutrition position stand calls short- and long-term supplementation (up to 30 g/day for 5 years) safe and well tolerated in healthy people and some patient groups, though that is a society position rather than a regulator's finding [16]. The consistent side effect is weight gain from water retention, about 1 to 2 kg in a month with strength training [7].

Vardenafil film-coated tablets are usually started at 10 mg about 60 minutes before sexual activity, adjusted between 5 and 20 mg, at most once a day, with or without food [1]. Creatine is taken daily in the protocols studied. Neither vardenafil label gives a creatine-specific timing instruction [1][2].