Sildenafil Viagra: controindicazioni ed avvertenze

Contraindications and warnings for use

Before starting treatment with sildenafil, it is recommended to undergo a physical medical examination and a thorough medical history in order to correctly diagnose any erectile dysfunction and determine the possible physiological and psychological causes that may underlie the disease. In addition, medical examinations of cardiovascular conditions should be performed on patients who intend to start treatment of erectile dysfunction with sildenafil, also because there is a percentage risk of cardiac events associated with sexual activity. Therefore, before prescribing sildenafil to patients with certain cardiovascular conditions, physicians should ensure that the vasodilatory effects of the drug do not adversely affect the health of the patients.

Another experience that confirms the theory that sexual activity can act as a negative and worsening factor on a person’s cardiovascular condition was the marketing phase of sildenafil (Viagra), during which serious side effects on the cardiovascular system were reported in association with the intake of the drug. Another unclear experience, which occurred during the marketing phase of sildenafil, concerns the serious cardiovascular events associated with the use of the drug. Cardiovascular events such as angina pectoris intermedia, ventricular arrhythmias, myocardial infarction, cerebrovascular haemorrhage, transient ischaemic attack and hypertension have been reported in patients taking sildenafil. It should be emphasized that most of these patients were already suffering from a compromised cardiovascular condition. Many of these events occurred during sexual activity or in any case immediately after sexual intercourse, confirming that the sexual factor can have a worsening effect on cardiovascular conditions. In some cases, however, such side effects have occurred soon after taking sildenafil in the absence of sexual activity. Therefore, it is not yet very clear whether these cardiovascular events are directly related to the above factors or not.

In vitro studies in human platelets show that sildenafil increases the antiplatelet effect of sodium nitroprusside; Therefore, the administration of sildenafil in patients suffering from pathologies with bleeding disorders should be done with particular caution and only after appropriate medical investigations on the risk-benefit ratio for the patient.

It is also recommended to take great care when administering sildenafil for the treatment of erectile dysfunction in patients suffering from anatomical deformities of the penis, such as cavernous fibrosis or angulation, and also in patients who have conditions that may predispose them to priapism, such as sickle cell anemia.

Interactions of Viagra with Other Medications

Sildenafil, like most drugs, is metabolized by the cytochrome P450 (CYP450) enzyme group, more precisely by two isoenzymes CYP3A4 and CYP2C9. From clinical studies on the pharmacokinetic analysis of sildenafil, it has been noted that CYP3A4 inhibitors – such as ketoconazole or erythromycin – cause a reduction in sildenafil clearance. Although no side effects associated with increased sildenafil activity have been observed in patients given CYP3A4 inhibitors together with sildenafil, it is advisable to use the lowest dose of sildenafil in these cases, i.e. 25 mg. Ritonavir, which is an HIV protease inhibitor and a highly specific inhibitor of the CYP450 enzyme group, was administered together with the maximum dose, i.e., 100 mg, of sildenafil; This experiment resulted in a 300% increase in the maximum plasma concentration of sildenafil and a 1,000% increase in the plasma bioavailability of sildenafil. At 24 hours after administration of the two drugs, plasma levels of sildenafil were still about 200 ng/ml, 40 times greater than the approximately 5 ng/ml measured when sildenafil is administered in the absence of other drugs. These data are an expression of the marked inhibitory effects of ritonavir on a wide range of CYP450 substrates. From this study it was noted that sildenafil did not alter the pharmacokinetics of ritonavir. Based on these pharmacokinetic findings, administration of sildenafil concomitantly with ritonavir is not recommended; If such administration is necessary, it is recommended to stagger the time of intake of the two drugs and not to exceed the maximum dose of 25 mg of sildenafil over a 48-hour period.

Saquinavir, which belongs to the same family as ritonavir, i.e. an HIV protease inhibitor and CYP3A4 inhibitor, was also administered together with the maximum dose of 100 mg sildenafil; The researchers observed a 140% increase in the maximum plasma concentration of sildenafil and a 210% increase in the plasma bioavailability of sildenafil. Sildenafil, on the other hand, did not alter the pharmacokinetics of saquinavir in any way. Also from these studies, more potent CYP3A4 inhibitors, such as ketoconazole and itraconazole, can be expected to have even greater side effects. When a single 100 mg dose of sildenafil was administered together with erythromycin, which is a specific inhibitor of CYP3A4, a 182% increase in the plasma bioavailability of sildenafil was observed. Administration of azithromycin together with sildenafil in some healthy male volunteers did not manifest any undesirable effects on either the bioavailability, maximum plasma concentration or elimination constant or half-life of sildenafil or its major circulating metabolite. Concomitant administration of cimetidine, which is a cytochrome P450 inhibitor and non-specific CYP3A4 inhibitor, and sildenafil in healthy volunteers resulted in a 56% increase in sildenafil plasma concentrations. Therefore, even in this case, it is recommended to pay attention to the concomitant administration of the two drugs, staggering – if necessary – their intake.

Although no specific interaction studies have been conducted with all medicinal products, the pharmacokinetic analysis performed in the population showed no effect on the pharmacokinetics of sildenafil following concomitant administration with CYP2C9 inhibitors, such as warfarin or phenytoin; CYP2D6 inhibitors, such as tricycle antidepressants, thiazide and similar diuretics, loop diuretics and potassium sparers; angiotensin-converting enzyme inhibitors and calcium channel blockers. However, sildenafil can also alter the pharmacokinetics of other drugs if it is given at the same time as them. Concomitant administration of sildenafil in patients receiving alpha-blocker therapy, for example, may cause symptomatic hypotension in some patients, particularly at the highest sildenafil dosages, i.e. 50 or 100 mg. However, there are no data on interactions between sildenafil and non-specific phosphodiesterase inhibitors, such as theophylline or dipyridamole. Analysis of data from clinical trials of the following classes of antihypertensive drugs showed no difference in the pharmacokinetic profile between patients taking sildenafil and those receiving placebo: diuretics, beta-blockers, ACE inhibitors, angiotensin II antagonists, centrally acting vasodilators, calcium channel blockers and alpha-adrenergic blockers. During a specific interaction study, in which a 100 mg dose of sildenafil was administered together with amlodipine in patients suffering from arterial hypertension, the additional reduction in supine systolic blood pressure was 8 mmHg. The corresponding additional reduction in supine diastolic blood pressure was 7 mmHg. These additional blood pressure reductions were comparable to those seen when sildenafil was administered as the only drug under therapy in healthy volunteers. However, it is recommended that special care be taken when administering sildenafil together with other drugs, especially if they are antihypertensive or antiarrhythmic drugs.

Pregnancy and lactation

First of all, it should be noted that sildenafil is not approved for use by women. Be that as it may, if for some particular reason it must be used, especially during pregnancy, it is recommended that you consult your doctor beforehand to discuss the risk-benefit ratio that the administration of sildenafil may cause. Sildenafil has been shown in animal studies to cause no teratogenic or foetotoxic effects, even though it is administered at doses about 40 times higher than those used in human therapy. However, there are no clinical data on the effects of sildenafil in pregnant women, and it is not known whether or not the drug is secreted in breast milk.