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Viagra and Grapefruit Juice -- Not a Good Mix

By Sean R. Hosein

February 12, 2002

The original formulation of the protease inhibitor saquinavir -- Invirase -- became available in North America around the mid-1990s. However, Invirase was poorly absorbed. The manufacturer suggested that taking Invirase with concentrated grapefruit juice would enhance the absorption of this drug. This effect occurs because grapefruit juice contains compounds that impair the activity of certain enzymes in the intestine -- enzymes that help break down Invirase.

A few years later, doctors began to use another protease inhibitor, ritonavir (Norvir), in combination with Invirase. Ritonavir is much more effective than grapefruit juice at inhibiting enzymes in the intestine and liver. Examples of other drugs affected by grapefruit juice include the following:

Now it appears that grapefruit juice can also affect the absorption of the popular erectile dysfunction drug Viagra (Sildenafil). Because erectile dysfunction is common in some males with HIV/AIDS, we report on the interaction between grapefruit juice and Viagra.

Study Details

Researchers in Köln, Germany, conducted a study using 24 healthy, HIV negative male subjects whose average age was 29 years. The men received a glass of grapefruit juice on an empty stomach and then one hour later another glass of grapefruit juice with Viagra 50 mg. Blood samples were collected over the next 24 hours. A week later the experiment was repeated with water being substituted for grapefruit juice.


Researchers found that the absorption of Viagra increased by 23% when taken with grapefruit juice instead of water. Grapefruit juice also delayed the absorption of Viagra. This latter point is important because Viagra is supposed to be taken one hour before sex, and taking the drug with grapefruit juice may result in disappointment for some users of Viagra.

The grapefruit juice used in this study was white juice and supplied by Döhler-Euro Citrus NBI, GmbH. Other brands, types and doses of grapefruit juice may have different effects. The researchers suggest that the combination of Viagra and grapefruit juice be "avoided."

Men who use protease inhibitors are usually prescribed less-than-normal doses of Viagra because protease inhibitors can raise levels of Viagra several times greater than normal, which can cause dangerous side effects. Therefore, men who use protease inhibitors and Viagra may wish to also avoid taking Viagra with grapefruit juice.


  1. Jetter A., Kinzig-Schippers M., Walchner-Bonjean M., et al. Effects of grapefruit juice on the pharmacokinetics of sildenafil. Clinical Pharmacology and Therapeutics 2002; 71:21-29.
  2. Hyland R., Roe E. G., Jones B. C. and Smith D. A. Identification of the cytochrome P450 enzymes involved in the N-demethylation of sildenafil. British Journal of Clinical Pharmacology 2001; 51(3):239-248.
  3. Muirhead G. J., Wulff M. B., Fielding A., et al. Pharmacokinetic interactions between sildenafil and saquinavir/ritonavir. British Journal of Clinical Pharmacology 2000; 50(2):99-107.

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