Side effects of Viagra and sildenafil

viagraSildenafil is the medical name for the active ingredient in Viagra tablets, used to treat erectile dysfunction. Viagra and sildenafil are medically the same. Pfizer was the first drug company to manufacture sildenafil. Pfizer held the exclusive license to market sildenafil in the UK up until the summer of 2013 and marketed and continue to market their sildenafil under the brand name Viagra. Since summer 2013 various other drug companies now supply licensed sildenafil legally in the UK. They usually market it under its medical name ‘sildenafil’, or sometimes somewhat misleadingly, under the name ‘generic Viagra’, or brand names, such as Teva sildenafil, Sandoz, or Mylan (see brands of sildenafil).

A generic medicine is one which is identical to a branded medicine but NOT marketed under the original brand name. If a generic medicine does not have a UK license, it is illegal to sell it in the UK, and may be a fake.

It is a confusing area, but essentially, if men stick to buying their erectile dysfunction treatments from UK regulated websites, they can be confident that whether they buy Viagra or sildenafil, they will get medically identical UK licensed medicine. Buying ‘sildenafil’ rather than ‘Viagra’ is likely to be very much cheaper.

General advice

A medical history and physical examination should be undertaken to diagnose erectile dysfunction and determine potential underlying causes, before pharmacological treatment is considered. Online assessments do not entirely replace face-to-face erectile dysfunction consultations with GPs.

Most men take Viagra/sildenafil in a situation where they expect sexual stimulation and in which they expect to have intercourse. They have usually previously experienced unsatisfactory erections. 40% of men or more will have some degree of impotence at some time in their lives, the proportion increasing with age. If sexual stimulation does not occur within 4 to 6 hours of taking Viagra/sildenafil, the effects of the tablets simply wears-off.

Men taking Viagra/sildenafil for the first time should usually start with the middle dose of one 50mg tablet. They should be prepared to sit or lie down in the rare event that there is a significant drop in blood pressure and they feel dizzy or light-headed. A fairly large proportion, more than 1 in 100, of men taking Viagra/sildenafil notice a bluish or yellowish discolouration of their vision. This is not in itself a cause for concern, and usually does not interfere with normal activity. It wears off after a few hours. Other side-effects are listed in the table at the bottom of the page and are repeated in the ‘patient information leaflets’ supplied with the medication – see link below.

In the rare event of serious side effects men should seek immediate medical advice. This applies particularly to chest pains (possibly cardiac), loss of vision, and prolonged and painful erection (4 hours or more). Prolonged painful erections are known medically as ‘priapism’, and if left untreated, can damage the penis.

Men who take Viagra/sildenafil in combination with recreational drugs, particularly amyl nitrate (poppers) or cocaine, but also others, are at significant risk of more serious side-effects. Men who take Viagra/sildenafil whilst they are intoxicated risk not only increased side effects, but also increase their chances of catching sexually transmitted diseases, through a lack of caution (see beware club drugs and Viagra).

Viagra/sildenafil side-effects, interactions and cautions

As Viagra and sildenafil are medically the same, they have the same side-effects and interact with other medicines in the same way. The same cautions apply to their supply.

Easy to read guidance is provided by manufacturers and supplied with the tablets: ‘Patient information Leaflet’ of Viagra.

If in doubt about a medicine, ask your GP or pharmacist or one of the online clinics who supply it.

Summary of common side effects of Viagra/sildenafil

Viagra/sildenafil is remarkably well tolerated and free from significant side effects in the vast majority of men who take it. Listed below are the most common side effects:

  • Headache (very common)
  • Dizziness
  • Visual colour distortions (blue vision), visual disturbance, blurred vision
  • Flushing, hot flushes
  • Nasal congestion
  • Nausea, Dyspepsia (indigestion)

See full list of adverse reactions (below).

Viagra/sildenafil is a ‘PDE5 inhibitor‘, but also affects other PDE isozymes, such as PDE6 (an enzyme in the retina) which can lead to visual disturbance (for fuller list see table 1 in compare PDE5 inhibitors).

‘Summary of product characteristics’

More detailed information taken from ‘Summary of Product Characteristics’ of Viagra (the drug license document, data provided by manufacturers for product licensing) is copied below under the following headings (correct as of October 2016):

  • Cardiovascular risk factors
  • Viagra and the effect of nitrates
  • Priapism
  • Interactions with other treatments for erectile dysfunction
  • Effects on vision
  • Alpha-blockers
  • Effect on bleeding
  • Women
  • Interaction with other medicinal products
  • Effects of sildenafil on other medicinal products
  • Fertility, pregnancy and breast feeding
  • Effects on ability to drive and use machines
  • Undesirable effects (side-effects)
  • Summary of the safety profile
  • Tabulated list of adverse reactions

Cardiovascular risk factors

Prior to initiating any treatment for erectile dysfunction, physicians should consider the cardiovascular status of their patients, since there is a degree of cardiac risk associated with sexual activity. Sildenafil has vasodilator properties, resulting in mild and transient decreases in blood pressure. Prior to prescribing sildenafil, physicians should carefully consider whether their patients with certain underlying conditions could be adversely affected by such vasodilatory effects, especially in combination with sexual activity. Patients with increased susceptibility to vasodilators include those with left ventricular outflow obstruction (e.g., aortic stenosis, hypertrophic obstructive cardiomyopathy), or those with the rare syndrome of multiple system atrophy manifesting as severely impaired autonomic control of blood pressure.

Viagra and the effect of nitrates

Serious cardiovascular events, including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, cerebrovascular haemorrhage, transient ischaemic attack, hypertension and hypotension have been reported post-marketing in temporal association with the use of VIAGRA. Most, but not all, of these patients had pre-existing cardiovascular risk factors. Many events were reported to occur during or shortly after sexual intercourse and a few were reported to occur shortly after the use of VIAGRA without sexual activity. It is not possible to determine whether these events are related directly to these factors or to other factors.

Priapism

Agents for the treatment of erectile dysfunction, including sildenafil, should be used with caution in patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis, or Peyronie’s disease), or in patients who have conditions which may predispose them to priapism (such as sickle cell anaemia, multiple myeloma, or leukaemia).

Interactions with other treatments for erectile dysfunction

The safety and efficacy of combinations of sildenafil with other treatments for erectile dysfunction have not been studied. Therefore the use of such combinations is not recommended.

Effects on vision

Cases of visual defects have been reported spontaneously in connection with the intake of sildenafil and other PDE5 inhibitors. Cases of non-arteritic anterior ischaemic optic neuropathy, a rare condition, have been reported spontaneously and in an observational study in connection with the intake of sildenafil and other PDE5 inhibitors. Patients should be advised that in the event of any sudden visual defect, they should stop taking VIAGRA and consult a physician immediately.

Alpha-blockers

Caution is advised when sildenafil is administered to patients taking an alpha-blocker, as the co-administration may lead to symptomatic hypotension in a few susceptible individuals. This is most likely to occur within 4 hours post sildenafil dosing. In order to minimise the potential for developing postural hypotension, patients should be hemodynamically stable on alpha-blocker therapy prior to initiating sildenafil treatment. Initiation of sildenafil at a dose of 25mg should be considered. In addition, physicians should advise patients what to do in the event of postural hypotensive symptoms.

Effect on bleeding

Studies with human platelets indicate that sildenafil potentiates the antiaggregatory effect of sodium nitroprusside in vitro. There is no safety information on the administration of sildenafil to patients with bleeding disorders or active peptic ulceration. Therefore sildenafil should be administered to these patients only after careful benefit-risk assessment.

The film coating of the tablet contains lactose. VIAGRA should not be administered to men with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption.

Women

VIAGRA is not indicated for use by women.

Interaction with other medicinal products

Population pharmacokinetic analysis of clinical trial data indicated a reduction in sildenafil clearance when co-administered with CYP3A4 inhibitors (such as ketoconazole, erythromycin, cimetidine). Although no increased incidence of adverse events was observed in these patients, when sildenafil is administered concomitantly with CYP3A4 inhibitors, a starting dose of 25mg should be considered.

Co-administration of the HIV protease inhibitor ritonavir, which is a highly potent P450 inhibitor, at steady state (500mg twice daily) with sildenafil (100mg single dose) resulted in a 300% (4-fold) increase in sildenafil Cmax and a 1,000% (11-fold) increase in sildenafil plasma AUC. At 24 hours, the plasma levels of sildenafil were still approximately 200ng/mL, compared to approximately 5ng/mL when sildenafil was administered alone. This is consistent with ritonavir’s marked effects on a broad range of P450 substrates. Sildenafil had no effect on ritonavir pharmacokinetics. Based on these pharmacokinetic results co-administration of sildenafil with ritonavir is not advised (see section 4.4) and in any event the maximum dose of sildenafil should under no circumstances exceed 25 mg within 48 hours.

Co-administration of the HIV protease inhibitor saquinavir, a CYP3A4 inhibitor, at steady state (1200mg three times a day) with sildenafil (100mg single dose) resulted in a 140% increase in sildenafil Cmax and a 210% increase in sildenafil AUC. Sildenafil had no effect on saquinavir pharmacokinetics (see section 4.2). Stronger CYP3A4 inhibitors such as ketoconazole and itraconazole would be expected to have greater effects.

When a single 100mg dose of sildenafil was administered with erythromycin, a moderate CYP3A4 inhibitor, at steady state (500mg twice daily for 5 days), there was a 182% increase in sildenafil systemic exposure (AUC). In normal healthy male volunteers, there was no evidence of an effect of azithromycin (500mg daily for 3 days) on the AUC, Cmax, tmax, elimination rate constant, or subsequent half-life of sildenafil or its principal circulating metabolite. Cimetidine (800mg), a cytochrome P450 inhibitor and non-specific CYP3A4 inhibitor, caused a 56% increase in plasma sildenafil concentrations when co-administered with sildenafil (50 mg) to healthy volunteers.

Grapefruit juice is a weak inhibitor of CYP3A4 gut wall metabolism and may give rise to modest increases in plasma levels of sildenafil.

Single doses of antacid (magnesium hydroxide/aluminium hydroxide) did not affect the bioavailability of sildenafil.

Although specific interaction studies were not conducted for all medicinal products, population pharmacokinetic analysis showed no effect of concomitant treatment on sildenafil pharmacokinetics when grouped as CYP2C9 inhibitors (such as tolbutamide, warfarin, phenytoin), CYP2D6 inhibitors (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and related diuretics, loop and potassium sparing diuretics, angiotensin converting enzyme inhibitors, calcium channel blockers, beta-adrenoreceptor antagonists or inducers of CYP450 metabolism (such as rifampicin, barbiturates). In a study of healthy male volunteers, co-administration of the endothelin antagonist, bosentan, (an inducer of CYP3A4 [moderate], CYP2C9 and possibly of CYP2C19) at steady state (125mg twice a day) with sildenafil at steady state (80 mg three times a day) resulted in 62.6% and 55.4% decrease in sildenafil AUC and Cmax, respectively. Therefore, concomitant administration of strong CYP3A4 inducers, such as rifampin, is expected to cause greater decreases in plasma concentrations of sildenafil.

Nicorandil is a hybrid of potassium channel activator and nitrate. Due to the nitrate component it has the potential to result in a serious interaction with sildenafil.

Effects of sildenafil on other medicinal products

Consistent with its known effects on the nitric oxide/cGMP pathway, sildenafil was shown to potentiate the hypotensive effects of nitrates, and its co-administration with nitric oxide donors or nitrates in any form is therefore contraindicated.

Concomitant administration of sildenafil to patients taking alpha-blocker therapy may lead to symptomatic hypotension in a few susceptible individuals. This is most likely to occur within 4 hours post sildenafil dosing. In three specific drug-drug interaction studies, the alpha-blocker doxazosin (4mg and 8mg) and sildenafil (25mg, 50mg, or 100mg) were administered simultaneously to patients with benign prostatic hyperplasia (BPH) stabilized on doxazosin therapy. In these study populations, mean additional reductions of supine blood pressure of 7/7mmHg, 9/5mmHg, and 8/4mmHg, and mean additional reductions of standing blood pressure of 6/6mmHg, 11/4mmHg, and 4/5mmHg, respectively, were observed. When sildenafil and doxazosin were administered simultaneously to patients stabilized on doxazosin therapy, there were infrequent reports of patients who experienced symptomatic postural hypotension. These reports included dizziness and light-headedness, but not syncope.

No significant interactions were shown when sildenafil (50mg) was co-administered with tolbutamide (250mg) or warfarin (40mg), both of which are metabolised by CYP2C9.

Sildenafil (50 mg) did not potentiate the increase in bleeding time caused by acetyl salicylic acid (150mg).

Sildenafil (50 mg) did not potentiate the hypotensive effects of alcohol in healthy volunteers with mean maximum blood alcohol levels of 80mg/dl.

Pooling of the following classes of antihypertensive medication; diuretics, beta-blockers, ACE inhibitors, angiotensin II antagonists, antihypertensive medicinal products (vasodilator and centrally-acting), adrenergic neurone blockers, calcium channel blockers and alpha-adrenoceptor blockers, showed no difference in the side effect profile in patients taking sildenafil compared to placebo treatment. In a specific interaction study, where sildenafil (100mg) was co-administered with amlodipine in hypertensive patients, there was an additional reduction on supine systolic blood pressure of 8mmHg. The corresponding additional reduction in supine diastolic blood pressure was 7mmHg. These additional blood pressure reductions were of a similar magnitude to those seen when sildenafil was administered alone to healthy volunteers.

Sildenafil (100mg) did not affect the steady state pharmacokinetics of the HIV protease inhibitors, saquinavir and ritonavir, both of which are CYP3A4 substrates.

Fertility, pregnancy, and lactation

VIAGRA is not indicated for use by women.

There are no adequate and well-controlled studies in pregnant or breast-feeding women.

No relevant adverse effects were found in reproduction studies in rats and rabbits following oral administration of sildenafil.

There was no effect on sperm motility or morphology after single 100mg oral doses of sildenafil in healthy volunteers.

Effects on ability to drive and use machines

No studies on the effects on the ability to drive and use machines have been performed.

As dizziness and altered vision were reported in clinical trials with sildenafil, patients should be aware of how they react to VIAGRA, before driving or operating machinery.

Undesirable effects (side-effects)

The safety profile of Viagra/sildenafil is based on 9,570 patients in 74 double blind placebo-controlled clinical studies.

Adverse reactions from post-marketing surveillance has been gathered covering an estimated period >10 years. Because not all adverse reactions are reported to the Marketing Authorisation Holder and included in the safety database, the frequencies of these reactions cannot be reliably determined.

Tabulated list of adverse reactions

In the table below all medically important adverse reactions, which occurred in clinical trials at an incidence greater than placebo are listed by system organ class and frequency (very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to, 1/1,000).

In addition, the frequency of medically important adverse reactions reported from post-marketing experience is included as not known.

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Medically important adverse reactions reported at an incidence greater than placebo in controlled clinical studies and medically important adverse reactions reported through post-marketing surveillance.
System Organ ClassAdverse Reaction
Immune system disorders
RareHypersensitivity reactions
Nervous system disorders
Very commonHeadache
CommonDizziness
UncommonSomnolence, Hypoaesthesia
RareCerebrovascular accident, Syncope
Not knownTransient ischaemic attack, Seizure, Seizure recurrence
Eye disorders
CommonVisual disorders, Visual colour distortion
UncommonConjunctival disorders, Eye disorders, Lacrimation disorders, Other eye disorders
Not knownNon-arteritic anterior ischaemic optic neuropathy (NAION), Retinal vascular occlusion, Visual field defect.
Ear and labyrinth disorders
UncommonVertigo, Tinnitus
RareSudden decrease or loss of hearing
Cardiac disorders
UncommonPalpitations, Tachycardia
RareMyocardial infarction, Atrial fibrillation
UnknownVentricular arrhythmia, Unstable angina, Sudden cardiac death
Vascular disorders
CommonFlushing
RareHypertension, Hypotension
Respiratory, thoracic and mediastinal disorders
CommonNasal congestion
RareEpistaxis
Gastrointestinal disorders
CommonDyspepsia
UncommonVomiting, Nausea, Dry mouth
Skin, subcutaneous and soft tissue disorders
UncommonSkin rash
Not KnownStevens Johnson Syndrome (SJS), Toxic Epidermal Necrolysis (TEN)
Musculoskeletal and connective tissue disorders
UncommonMyalgia
Renal and urinary disorders
UncommonHaematuria
Reproductive system and breast disorders
UncommonHaematospermia, Penile haemorrhage
Not knownPriapism, Prolonged erection
General disorders and administration site conditions
UncommonChest pain, Fatigue
Investigations
UncommonHeart rate increased

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