Viagra Interactions with Protease Inhibitors and "Poppers"
On April 21 Pfizer Pharmaceuticals released results from two interaction studies they conducted between saquinavir and Viagra and ritonavir and Viagra. As a result of these studies Pfizer is making modified dosing recommendations for Viagra when used with saquinavir or ritonavir.
All five approved protease inhibitors are inhibitors of the hepatic cytochrome P450 (CYP) 3A4 isoenzyme. Viagra is primarily metabolized by CYP3A4 and coadministration of Viagra with inhibitors of CYP3A4 inhibitors has been shown to increase Viagra blood concentrations.
Preliminary results show saquinavir increased Viagra maximum plasma concentrations (Cmax) about 140% and area under the concentration curve (AUC) 210%, time to maximum plasma concentration (Tmax) was delayed by three hours, and terminal half-life (T 1/2) was extended by about one hour. Saquinavir pharmacokinetics were unaffected by Viagra. As these results are preliminary adverse events are not available but Viagra can cause dizziness so increased Viagra levels in blood may cause increased dizziness.
Viagra PK During SQV Coadministration-
| ...........................VIAGRA+PLACEBO .......|.......VIAGRA+SAQUINAVIR | ||||
| Parameter | ||||
| Cmax (ng/mL) | ||||
| Tmax (h) | ||||
| AUC (ng h/mL) | ||||
| T1/2 (h) | ||||
In both studies healthy male subjects were randomized to either a treatment or placebo. In the treatment group, baseline Viagra PK were determined for each patient on day one with a single 100 mg Viagra dose. Dosing with either RTV or SQV took place on days 2 thru 8. On day 7, subjects randomly received either a single dose of Viagra or matched placebo, and on day 8 subjects received the alternative to what they received on day 7 (crossover phase). Subjects in the placebo group were dosed as those in the treatment group, except they received a placebo instead of RTV or SQV.
Ritonavir increased Viagra Cmax about 4 fold and AUC about 11 fold. Viagra Tmax was delayed about 3 hours and t 1/2 was extended by about one hour. Ritonavir PK was not affected by Viagra. The most common preliminary adverse events occurring more frequently in the 14 Viagra/ritonavir subjects (as compared to the 14 placebo/ritonavir subjects) were visual*, 7 (vs 0); flushing, 5 (vs 2); headache, 5 (vs 2); and orthostatic hypotension, 4 (vs 0).
| *Abnormal vision is described in the Viagra package insert: mild and transient predominantly color tinge to vision, but also increasedsensitivity to light or blurred vision. |
Viagra PK During Ritonavir Coadministration -
| ................|...........VIAGRA+PLACEBO ......|..... .VIAGRA+RITONAVIR | ||||
| Parameter | ||||
| Cmax (ng/mL) | ||||
| Tmax (h) | ||||
| AUC (ng h/mL) | ||||
| T1/2 (h) | ||||
Of the 5 approved protease inhibitors saquinavir is the least potent inhibitor of CYCYP3A4, and ritonavir is the most potent. Pfizer suggests using these results as a guideline for other protease inhibitors. As stated in the Viagra package insert the recommended dose of Viagra for most patients is 50 mg but Pfizer recommends that a starting dose of 25 mg should be considered in patients receiving concomitant potent CYP3A4 inhibitors such as erythromycin, ketoconazole, and itraconazole. Pfizer recommends in their current official printed information that a maximum single dose of 25 mg of Viagra in a 48 hour period should not be exceeded in patients taking ritonavir with Viagra. Additionally, Pfizer recommends that when taking any other protease inhibitor one should use a starting dose of 25 mg not to be exceeding within 24 hours. If additional information becomes available it will be communicated to you. This dosing should be efficacious is receiving the desired effect of Viagra. If not you should consult with your doctor before changing your dosing.
Poppers
Viagra possesses vasodilatory properties, which result in mild, generally clinically insignificant decreases in blood pressure when taken alone. However, when Viagra is taken with nitrates, the vasodilator actions of nitrates are profoundly amplified, resulting in major hemodynamic compromise and potentially fatal events. The administration of Viagra who are using organic nitrates, either regularly and/or intermittently is CONTRAINDICATED.
Viagra may potentiate the hypertensive effects of inhaled forms of nitrates such as amyl nitrate or nitrate, also known as "poppers", and therefore is CONTRAINDICATED with the use of these substances as well. Poppers act by dilating blood vessels and the concurrent use of poppers and Viagra might result in sudden and marked lowering of blood pressure which can be potentially serious or even fatal.