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

What is known about the pair?

Glycine has been tested against one medicine in a controlled setting: clozapine. In 19 treatment-resistant patients on clozapine 400 to 1,200 mg/day, glycine 30 g/day for 12 weeks did not reduce symptoms, while patients on clozapine alone had a 35% fall in positive symptoms; the authors suggested glycine may interfere with clozapine's effect [4]. A separate placebo-controlled trial of 30 adults added glycine 60 g/day for 8 weeks and found no significant change in symptoms or thinking, and no clinically significant worsening [5]. Both used doses far above supplement doses.

Beyond that, no human interaction studies of glycine with other common drugs, including blood pressure, diabetes or hormone medicines, were found [1].

What does the vardenafil label list as interactions?

The label for the generic vardenafil film-coated tablet runs through nitrates, guanylate cyclase stimulators, alpha-blockers, antihypertensives, alcohol and CYP3A4 inhibitors, and notes no pharmacokinetic interaction with warfarin, digoxin, glyburide, a magnesium-aluminum hydroxide antacid, ranitidine or cimetidine [2]. Glycine is not named in that section.

Nitrates and riociguat are contraindicated

Nitrates and nitric oxide donors in any form are contraindicated, and the label says a suitable time interval for giving a nitrate after vardenafil has not been determined [2]. In 18 healthy men given vardenafil 20 mg before sublingual nitroglycerin 0.4 mg, extra blood pressure effects appeared when vardenafil was taken 1 or 4 hours before and heart rate effects at 1, 4 and 8 hours, but not when it was taken 24 hours before; the combination remains contraindicated [2]. Guanylate cyclase stimulators such as riociguat are also contraindicated because of added hypotension [2].

Alpha-blockers and blood pressure medicines

In men with BPH who were stable on an alpha-blocker, vardenafil 5 mg taken at the same time gave placebo-subtracted standing systolic changes of -6 mmHg (95% CI -9.9 to -2.1) with tamsulosin 0.4 mg and -3 mmHg with terazosin 5 or 10 mg; one man on terazosin 10 mg had symptomatic hypotension with a standing pressure of 80/60 mmHg [2]. A 6-hour gap between doses did not remove the effect with tamsulosin (-4 mmHg standing) [2]. With slow-release nifedipine 30 or 60 mg daily, vardenafil 20 mg added a mean supine reduction of 6/5 mmHg versus placebo, without changing either drug's levels [2].

CYP3A4 inhibitors

Vardenafil is metabolized mainly by CYP3A4/5 and to a lesser degree by CYP2C9 [2]. Ketoconazole 200 mg daily raised vardenafil 5 mg exposure (AUC) 10-fold and peak concentration 4-fold; ritonavir 600 mg twice daily raised AUC 49-fold, peak 13-fold and stretched the half-life to 26 hours; erythromycin 500 mg three times daily raised AUC 4-fold and peak 3-fold [2]. The label's dose caps are: no more than 2.5 mg in 72 hours with ritonavir or cobicistat; 2.5 mg in 24 hours with indinavir, saquinavir, atazanavir, clarithromycin, ketoconazole 400 mg or itraconazole 400 mg; and 5 mg in 24 hours with ketoconazole 200 mg, itraconazole 200 mg or erythromycin [2]. Grapefruit juice was not studied, but the label says it would likely increase vardenafil exposure [2].

Alcohol

Vardenafil 20 mg did not potentiate the blood-pressure-lowering effect of alcohol 0.5 g/kg over a 4-hour observation period, and neither substance changed the other's plasma levels [2].

What do the glycine studies actually show?

Glycine is a non-essential amino acid sold over the counter as a dietary supplement [7].

In a sleep study, healthy volunteers whose sleep was cut by about 25% for three nights took 3 g of glycine or placebo before bed: fatigue on a visual analog scale fell, sleepiness tended to fall, psychomotor vigilance improved, and plasma melatonin was unchanged [1]. That was a study of short sleep restriction, not an insomnia treatment trial [1].

Other human doses on record are 2.4, 4.8 or 7.2 g/day of glycine plus N-acetylcysteine (GlyNAC, 1:1) for 2 weeks in 114 healthy older adults, and 30 to 60 g/day in the schizophrenia trials [3][4][5]. GlyNAC was described as safe and well tolerated in both the 24-person 16-week trial and the 114-person dose trial, though neither report gives a side-effect list for glycine alone [9][3]. These are study doses, not recommended doses.

Does the form of vardenafil change anything?

Drugs@FDA lists all Levitra strengths and Staxyn as discontinued, so the current prescription products are generic vardenafil tablets and generic vardenafil orally disintegrating tablets [10][11][12]. The orally disintegrating tablet exists only as 10 mg and is not interchangeable with the 10 mg film-coated tablet because it gives higher exposure: peak concentration 15% and AUC 44% higher in healthy volunteers [6]. Its label is stricter than the tablet label: it says not to use it with strong or moderate CYP3A4 inhibitors such as ketoconazole, itraconazole, ritonavir, clarithromycin or erythromycin, and not in moderate or severe hepatic impairment [6].

What does the vardenafil label say to watch for?

The label says an erection lasting more than 4 hours needs immediate medical help, and painful erections over 6 hours are priapism that can cause permanent loss of potency if untreated [2]. Sudden loss of vision in one or both eyes may be non-arteritic anterior ischemic optic neuropathy, and the label says to stop vardenafil and seek medical attention; the same applies to sudden hearing loss [2]. The label advises avoiding vardenafil in people with congenital QT prolongation or those taking Class IA or Class III antiarrhythmics, and urges caution with a history of QT prolongation or other QT-prolonging medicines [2]. Vardenafil is not recommended for men whose sexual activity is inadvisable for cardiac reasons, or with a resting systolic pressure below 90 mmHg or uncontrolled hypertension above 170/110 mmHg [2].

Bottom line

The interaction concerns the vardenafil label does name are nitrates and riociguat (contraindicated), alpha-blockers and antihypertensives (additive blood pressure lowering) and CYP3A4 inhibitors (large rises in vardenafil exposure) [2]. Glycine is not among them.