Viagra® odt

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT VIAGRA® ODT (VIAGRA® ODT)

Composition:

Active substance: sildenafil;

1 tablet contains 70.225 mg of sildenafil citrate, equivalent to 50 mg of sildenafil;

Excipients: Ludiflash (mannitol (E 421), crospovidone, polyvinyl acetate, povidone), sodium croscarmellose, microcrystalline cellulose, colloidal silicon dioxide (hydrophobic), sucralose (E 955), indigo carmine aluminum lake 30–36% (E 132), sweet taste enhancer, special natural component, lemon flavor, magnesium stearate.

Pharmaceutical form. Orodispersible tablets.

Main physicochemical properties: blue diamond-shaped tablets with "V50" engraved on one side and no engraving on the other.

Pharmacotherapeutic group. Agents used in erectile dysfunction. Sildenafil. ATC code G04BE03.

Pharmacological Properties

Pharmacodynamics

Mechanism of action. Sildenafil is an orally administered drug intended for the treatment of erectile dysfunction. During sexual stimulation, the drug restores impaired erectile function by enhancing blood flow to the penis.

The physiological mechanism underlying erection involves the release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. Released NO activates the enzyme guanylate cyclase, which stimulates an increase in the level of cyclic guanosine monophosphate (cGMP), leading in turn to relaxation of the smooth muscle of the corpus cavernosum and promoting blood inflow.

Sildenafil is a potent and selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum, where PDE5 is responsible for cGMP breakdown. The effect of sildenafil on erection is peripheral. Sildenafil does not directly cause relaxation of isolated human corpus cavernosum tissue, but strongly potentiates the relaxing effect of NO on this tissue. When the NO/cGMP metabolic pathway is activated during sexual stimulation, sildenafil's inhibition of PDE5 leads to increased cGMP levels in the corpus cavernosum. Thus, for sildenafil to produce the desired pharmacological effect, sexual stimulation is required.

Effect on pharmacodynamics. In vitro studies have shown that sildenafil is selective for PDE5, which actively participates in the process of erection. The effect of sildenafil on PDE5 is more potent than its effect on other known phosphodiesterases. This effect is 10 times more potent than its effect on PDE6, which is involved in phototransduction in the retina. At maximum recommended doses, sildenafil's selectivity for PDE5 exceeds its selectivity for PDE1 by 80-fold, is 700-fold higher than for PDE2, PDE3, PDE4, PDE7, PDE8, PDE9, PDE10, and PDE11. In particular, sildenafil's selectivity for PDE5 exceeds its selectivity for PDE3—the cAMP-specific phosphodiesterase isoform involved in regulating cardiac contractility—by 4000-fold.

Pharmacokinetics

Absorption. Sildenafil is rapidly absorbed. Maximum plasma concentration is reached within 30–120 minutes (with a median of 60 minutes) after oral administration on an empty stomach. The mean absolute bioavailability after oral administration is 41% (ranging from 25% to 63%). Within the recommended dose range (25 to 100 mg), AUC and Cmax values of sildenafil increase proportionally with dose.

When sildenafil is taken with food, the extent of absorption is reduced, with a mean delay in Tmax by 60 minutes and a mean reduction in Cmax by 29%.

Distribution. The mean steady-state volume of distribution (Vd) is 105 liters, indicating extensive tissue distribution. After a single 100 mg oral dose, the mean peak total plasma concentration of sildenafil is approximately 440 ng/mL (coefficient of variation 40%). Since binding of sildenafil and its major N-desmethyl metabolite to plasma proteins reaches 96%, the mean peak free plasma concentration of sildenafil is about 18 ng/mL (38 nmol). The degree of protein binding is independent of total sildenafil concentrations.

In healthy volunteers who received a single 100 mg dose of sildenafil, less than 0.0002% (mean 188 ng) of the administered dose was detected in semen 90 minutes after administration.

Biotransformation. Sildenafil is metabolized primarily by hepatic microsomal isoenzymes CYP3A4 (major pathway) and CYP2C9 (minor pathway). The major circulating metabolite is formed via N-demethylation of sildenafil. The metabolite's selectivity for PDE5 is comparable to that of sildenafil, and its activity against PDE5 is approximately 50% of the parent compound. Plasma concentrations of this metabolite are about 40% of sildenafil plasma concentrations. The N-desmethyl metabolite undergoes further metabolism, and its elimination half-life is approximately 4 hours.

Elimination. Total clearance of sildenafil is 41 L/h, resulting in an elimination half-life of 3–5 hours. Following both oral and intravenous administration, sildenafil is excreted primarily as metabolites in feces (approximately 80% of the orally administered dose) and to a lesser extent in urine (approximately 13% of the orally administered dose).

Pharmacokinetics in special patient populations

Elderly patients. In healthy elderly volunteers (aged 65 years and older), reduced clearance of sildenafil was observed, resulting in approximately 90% higher plasma concentrations of sildenafil and its active N-desmethyl metabolite compared to younger healthy volunteers (aged 18–45 years). Due to age-related differences in plasma protein binding, the corresponding increase in free sildenafil plasma concentration was approximately 40%.

Renal impairment. In volunteers with mild to moderate renal impairment (creatinine clearance 30–80 mL/min), the pharmacokinetics of sildenafil remained unchanged after a single 50 mg oral dose. Mean AUC and Cmax of the N-desmethyl metabolite increased by up to 126% and 73%, respectively, compared to age-matched volunteers with normal renal function. However, due to high individual variability, these differences were not statistically significant. In volunteers with severe renal impairment (creatinine clearance <30 mL/min), sildenafil clearance was reduced, resulting in mean increases in AUC and Cmax by 100% and 88%, respectively, compared to age-matched volunteers with normal renal function. Additionally, AUC and Cmax of the N-desmethyl metabolite increased significantly by 200% and 79%, respectively.

Hepatic impairment. In volunteers with mild to moderate hepatic cirrhosis (Child-Pugh classes A and B), sildenafil clearance was reduced, leading to increases in AUC (84%) and Cmax (47%) compared to age-matched volunteers with normal liver function. The pharmacokinetics of sildenafil in patients with severe hepatic impairment have not been studied.

Clinical characteristics.

Indications.

VIAGRA® ODT is recommended for use in men with erectile dysfunction, defined as the inability to achieve or maintain a penile erection sufficient for successful sexual performance.

For effective action of VIAGRA® ODT, sexual stimulation is required.

Contraindications.

• Hypersensitivity to the active substance or to any of the excipients of the medicinal product.
• Concomitant use with nitric oxide donors (such as amyl nitrite) or nitrates in any form is contraindicated, as sildenafil is known to affect the nitric oxide/cyclic guanosine monophosphate (cGMP) pathway and may potentiate the hypotensive effect of nitrates.
• Concomitant use of PDE5 inhibitors (including sildenafil) with guanylate cyclase stimulators, such as riociguat, is contraindicated due to the risk of symptomatic hypotension (see section "Interaction with other medicinal products and other forms of interaction").
• Conditions in which sexual activity is not recommended (e.g., severe cardiovascular disorders such as unstable angina or severe heart failure).
• Unilateral loss of vision due to non-arteritic anterior ischemic optic neuropathy (NAION), regardless of whether this condition is associated with prior use of PDE5 inhibitors.
• Presence of severe hepatic impairment, arterial hypotension (blood pressure below 90/50 mm Hg), recent stroke or myocardial infarction, or known hereditary degenerative retinal disorders such as retinitis pigmentosa (a small number of such patients have genetic disorders of retinal phosphodiesterases), as the safety of sildenafil has not been studied in these conditions.

Interaction with other medicinal products and other forms of interaction.

Effect of other medicinal products on sildenafil.

In vitro studies.

Sildenafil is metabolized primarily by cytochrome P450 (CYP) isoform 3A4 (major pathway) and isoform 2C9 (minor pathway). Therefore, inhibitors of these isoenzymes may reduce sildenafil clearance, while inducers may increase its clearance.

In vivo studies.

Population pharmacokinetic analysis of clinical trial data demonstrated reduced sildenafil clearance when co-administered with CYP3A4 inhibitors (such as ketoconazole, erythromycin, cimetidine). Although no increase in adverse events was observed when sildenafil was used concomitantly with CYP3A4 inhibitors, consideration should be given to initiating treatment with a 25 mg dose of sildenafil.

Concomitant administration of the HIV protease inhibitor ritonavir, a very potent CYP450 inhibitor, at steady-state concentrations (500 mg once daily) and sildenafil (single 100 mg dose) resulted in a 300% increase (4-fold) in sildenafil Cmax and a 1000% increase (11-fold) in plasma AUC. After 24 hours, plasma sildenafil levels were still approximately 200 ng/mL compared to approximately 5 ng/mL when sildenafil was administered alone, consistent with the significant effect of ritonavir on a broad range of CYP450 substrates. Sildenafil does not affect the pharmacokinetics of ritonavir. Due to these pharmacokinetic data, concomitant use of sildenafil and ritonavir is not recommended (see section "Special precautions for use"); in any case, the maximum sildenafil dose should not exceed 25 mg within 48 hours.

Concomitant administration of the HIV protease inhibitor saquinavir, a CYP3A4 inhibitor, at steady-state concentrations (1200 mg three times daily) and sildenafil (single 100 mg dose) resulted in a 140% increase in sildenafil Cmax and a 210% increase in systemic exposure (AUC). Sildenafil had no effect on the pharmacokinetics of saquinavir (see section "Dosage and administration"). More potent CYP3A4 inhibitors, such as ketoconazole and itraconazole, are expected to have a more pronounced effect.

Administration of sildenafil (single 100 mg dose) with erythromycin, a moderate CYP3A4 inhibitor, at steady state (500 mg twice daily for 5 days) resulted in an 182% increase in systemic exposure (AUC) of sildenafil. In healthy male volunteers, azithromycin (500 mg daily for 3 days) had no effect on AUC, Cmax, Tmax, elimination rate constant, or subsequent half-life of sildenafil or its major circulating metabolite. Cimetidine (a cytochrome P450 inhibitor and non-specific CYP3A4 inhibitor), at a dose of 800 mg, increased plasma sildenafil concentration by 56% when co-administered with 50 mg sildenafil in healthy volunteers.

Grapefruit juice is a weak inhibitor of intestinal CYP3A4 and may cause a moderate increase in plasma sildenafil levels.

Single-dose administration of antacids (magnesium hydroxide/aluminum hydroxide) did not affect sildenafil bioavailability.

Although specific interaction studies with all medicinal products have not been conducted, population pharmacokinetic analysis data indicate that the pharmacokinetics of sildenafil were not altered when co-administered with medicinal products belonging to the CYP2C9 inhibitor group (tolbutamide, warfarin, phenytoin), CYP2D6 inhibitors (such as selective serotonin reuptake inhibitors, tricyclic antidepressants), thiazide and thiazide-like diuretics, loop and potassium-sparing diuretics, angiotensin-converting enzyme inhibitors, calcium channel blockers, β-adrenoreceptor antagonists, or CYP450 metabolism inducers (such as rifampicin, barbiturates).

In a study involving healthy male volunteers, concomitant administration of the endothelin antagonist bosentan (a moderate inducer of CYP3A4, CYP2C9, and possibly CYP2C19) at steady state (125 mg twice daily) and sildenafil at steady state (80 mg three times daily) resulted in a 62.6% and 55.4% reduction in AUC and Cmax of sildenafil, respectively. Therefore, concomitant use of potent CYP3A4 inducers such as rifampicin may lead to a more pronounced decrease in plasma sildenafil concentrations.

Nicorandil is a hybrid of a potassium channel activator and a nitrate. The nitrate component may lead to a serious interaction with sildenafil.

Effect of sildenafil on other medicinal products.

In vitro studies.

Sildenafil is a weak inhibitor of cytochrome P450 isoforms 1A2, 2C9, 2C19, 2D6, 2E1, and 3A4 (IC50 > 150 µmol). Since the peak plasma concentration of sildenafil is approximately 1 µmol, the effect of VIAGRA® ODT on the clearance of substrates of these isoenzymes is unlikely.

There are no data on the interaction between sildenafil and non-specific phosphodiesterase inhibitors such as theophylline and dipyridamole.

In vivo studies.

Since sildenafil affects the nitric oxide/cyclic guanosine monophosphate (cGMP) pathway, it is known to potentiate the hypotensive effect of nitrates. Therefore, concomitant use of sildenafil with nitric oxide donors or nitrates in any form is contraindicated (see section "Contraindications").

Riociguat. Preclinical studies have demonstrated an additive systemic blood pressure-lowering effect when PDE5 inhibitors are used concomitantly with riociguat. Clinical studies have shown that riociguat enhances the hypotensive effect of PDE5 inhibitors. No positive clinical effect was observed in patients participating in the study when PDE5 inhibitors were used concomitantly with riociguat. Concomitant use of riociguat with PDE5 inhibitors (including sildenafil) is contraindicated (see section "Contraindications").

Concomitant use of sildenafil and α-adrenoreceptor blockers may lead to symptomatic hypotension in some susceptible patients. This reaction most commonly occurred within 4 hours after sildenafil administration (see sections "Dosage and administration" and "Special precautions for use"). In three drug interaction studies, the α-adrenoreceptor blocker doxazosin (4 mg and 8 mg) and sildenafil (25 mg, 50 mg, and 100 mg) were co-administered to patients with benign prostatic hyperplasia whose condition was stabilized on doxazosin. In these populations, mean additional reductions in supine blood pressure were 7/7 mm Hg, 9/5 mm Hg, and 8/4 mm Hg, and mean reductions in standing blood pressure were 6/6 mm Hg, 11/4 mm Hg, and 4/5 mm Hg, respectively. Symptomatic orthostatic hypotension was occasionally reported when sildenafil was used concomitantly with doxazosin in patients whose condition was stabilized on doxazosin. These reports included dizziness and pre-syncope, but no syncope.

No significant interactions were observed when sildenafil (50 mg) was co-administered with tolbutamide (250 mg) or warfarin (40 mg), both metabolized by CYP2C9.

Sildenafil (50 mg) did not prolong bleeding time induced by acetylsalicylic acid (150 mg).

Sildenafil (50 mg) did not potentiate the hypotensive effect of alcohol in healthy volunteers at a mean maximum blood ethanol concentration of 80 mg/dL.

In patients taking sildenafil, no differences in adverse event profile were observed compared to placebo when co-administered with antihypertensive drug classes such as diuretics, β-adrenoreceptor blockers, ACE inhibitors, angiotensin II antagonists, vasodilators and centrally acting antihypertensives, adrenergic neuron blockers, calcium channel blockers, and α-adrenoreceptor blockers. In a specific interaction study, co-administration of sildenafil (100 mg) and amlodipine in patients with arterial hypertension resulted in an additional 8 mm Hg reduction in supine systolic blood pressure and a 7 mm Hg reduction in diastolic blood pressure. These additional blood pressure reductions were comparable to those observed with sildenafil alone in healthy volunteers (see section "Pharmacological properties").

Sildenafil 100 mg did not affect the pharmacokinetic parameters of the HIV protease inhibitors saquinavir and ritonavir, which are CYP3A4 substrates.

In healthy male volunteers, administration of sildenafil at steady state (80 mg three times daily) increased AUC and Cmax of bosentan (125 mg twice daily) by 49.8% and 42%, respectively.

Single-dose administration of sildenafil with sacubitril/valsartan at steady state in patients with arterial hypertension was associated with significantly greater blood pressure reduction compared to sacubitril/valsartan alone. Therefore, sildenafil should be initiated with caution in patients receiving sacubitril/valsartan.

Special precautions for use.

Before initiating therapy, a medical history should be obtained and a physical examination performed to diagnose erectile dysfunction and determine its possible causes.

Cardiovascular risk factors. Since sexual activity carries a certain cardiovascular risk, physicians should evaluate the cardiovascular status of patients before starting any treatment for erectile dysfunction. Sildenafil has vasodilatory effects, resulting in mild and transient reduction in blood pressure (see section "Pharmacodynamics"). Before prescribing sildenafil, physicians should carefully consider whether this effect might adversely affect patients with underlying cardiovascular conditions, particularly when combined with sexual activity. Patients who may be more sensitive to vasodilators include those with left ventricular outflow tract obstruction (e.g., aortic stenosis, hypertrophic obstructive cardiomyopathy) and patients with the rare multisystem atrophy syndrome, one manifestation of which is severe autonomic nervous system dysfunction in blood pressure regulation.

VIA GRA® ODT potentiates the hypotensive effect of nitrates (see section "Contraindications").

In the post-marketing period, serious cardiovascular adverse reactions have been reported, including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, cerebrovascular haemorrhage, transient ischaemic attack, arterial hypertension, and arterial hypotension, occurring in temporal association with the use of VIA GRA® ODT. In most, but not all, patients, cardiovascular risk factors were present. Many of these adverse reactions occurred during or immediately after sexual intercourse, and only a few occurred shortly after taking VIA GRA® ODT without sexual activity. Therefore, it is not possible to determine whether the development of such adverse reactions is directly related to risk factors or whether other factors contributed to their occurrence.

Priapism. Medications for the treatment of erectile dysfunction, including sildenafil, should be administered with caution in patients with anatomical deformation of the penis (such as angulation, cavernosal fibrosis, or Peyronie’s disease) and in patients with conditions predisposing to priapism (such as sickle cell anaemia, multiple myeloma, or leukaemia). Since the drug was introduced to the market, cases of prolonged erection and priapism have been reported. If an erection lasts longer than 4 hours, patients should seek immediate medical assistance. Without prompt treatment, priapism may lead to penile tissue damage and permanent loss of potency.

Concomitant use with other PDE5 inhibitors or other erectile dysfunction medications. The safety and efficacy of concomitant use of sildenafil with other PDE5 inhibitors or other medications for the treatment of pulmonary arterial hypertension containing sildenafil (e.g., Revatio) or with other erectile dysfunction medications have not been studied. Therefore, such combinations are not recommended.

Effect on vision. Spontaneous reports of visual disturbances have been associated with the use of sildenafil and other PDE5 inhibitors (see section "Adverse reactions"). Spontaneous reports and data from observational studies have indicated cases of non-arteritic anterior ischemic optic neuropathy (NAION), a rare condition, associated with the use of sildenafil and other PDE5 inhibitors (see section "Adverse reactions"). Patients should be advised to discontinue use of VIA GRA® ODT and seek immediate medical attention in case of sudden visual loss (see section "Contraindications").

Concomitant use with ritonavir. Concomitant use of sildenafil and ritonavir is not recommended (see section "Interaction with other medicinal products and other forms of interaction").

Concomitant use with alpha-blockers. Sildenafil should be used with caution in patients taking alpha-blockers, as this combination may lead to symptomatic hypotension in some susceptible individuals. Symptomatic hypotension usually occurs within 4 hours after taking sildenafil. To minimize the potential for postural hypotension, the patient's haemodynamic parameters should be stable on alpha-blocker therapy before initiating sildenafil treatment. Consideration should be given to starting with a 25 mg dose of sildenafil (see section "Dosage and administration"). Additionally, patients should be informed about appropriate actions to take if symptoms of orthostatic hypotension occur.

Effect on bleeding. In vitro studies on human platelets have shown that sildenafil potentiates the anti-aggregatory effect of sodium nitroprusside. There is no information on the safety of sildenafil use in patients with bleeding disorders or acute peptic ulcer. Therefore, sildenafil use in these patient groups should only be considered after careful benefit-risk assessment.

Excipients. This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, i.e., essentially "sodium-free". This information may be provided to patients on a low-sodium diet.

Hearing loss. Physicians should advise patients to discontinue use of PDE5 inhibitors, including VIA GRA® ODT, and seek immediate medical help in case of sudden decrease or loss of hearing. These events, which may also be accompanied by tinnitus and dizziness, have been reported in temporal association with the use of PDE5 inhibitors, including VIA GRA® ODT. It is not possible to determine whether these events are directly related to the use of PDE5 inhibitors or to other factors.

Concomitant use with antihypertensive agents. VIA GRA® ODT exerts systemic vasodilatory effects and may further reduce blood pressure in patients taking antihypertensive medications. In a specific drug interaction study, concomitant oral administration of amlodipine (5 mg or 10 mg) and VIA GRA® ODT (100 mg) resulted in a mean additional reduction in systolic pressure of 8 mm Hg and diastolic pressure of 7 mm Hg.

Sexually transmitted diseases. The use of VIA GRA® ODT does not protect against sexually transmitted diseases. Consideration should be given to informing patients about necessary preventive measures to protect against sexually transmitted diseases, including human immunodeficiency virus.

Fertility. After administration of a 100 mg dose to healthy volunteers, no effect on sperm morphology or motility was observed (see section "Pharmacodynamics").

Use during pregnancy or breastfeeding.

VIA GRA® ODT is not intended for use in women.

Ability to affect reaction speed when driving or operating machinery.

VIA GRA® ODT may have a minor influence on the ability to drive or operate machinery.

Since dizziness and visual disturbances have been reported during clinical trials with sildenafil, patients should determine their individual response to VIA GRA® ODT before driving a vehicle or operating machinery.

Method of administration and dosage.

The drug is administered orally.

The tablet should be taken immediately after removal from the blister. The tablet should be placed on the tongue, allowed to disintegrate, and then swallowed. The drug may be taken with or without water.

If a 100 mg dose is required, the second tablet should be taken only after complete disintegration of the first tablet.

It is recommended to take the drug on an empty stomach, since administration with fatty food results in a significant delay in absorption compared to administration on an empty stomach.

Adults. If necessary, VIAGRA® ODT should be taken approximately 1 hour before sexual activity. The recommended dose is 50 mg. Since concomitant administration with food delays absorption and slows the drug's effect (see section "Pharmacokinetics"), it is recommended to take the drug on an empty stomach.

Depending on efficacy and tolerability, the dose may be increased to 100 mg. The maximum recommended dose is 100 mg. If a 100 mg dose is required, two 50 mg tablets should be taken sequentially.

The maximum recommended frequency of administration is once daily.

If a 25 mg dose is required, sildenafil 25 mg coated tablets are recommended.

Elderly patients. Dose adjustment is not required for elderly patients (≥ 65 years of age).

Patients with renal impairment. For patients with mild to moderate renal impairment (creatinine clearance 30–80 mL/min), the recommended dose is the same as described above in the section "Adults".

Since sildenafil clearance is reduced in patients with severe renal impairment (creatinine clearance < 30 mL/min), a starting dose of 25 mg should be considered. Depending on efficacy and tolerability, the dose may be gradually increased to 50 mg and then to 100 mg, if necessary.

Patients with hepatic impairment. Since sildenafil clearance is reduced in patients with hepatic impairment (e.g., cirrhosis), a starting dose of 25 mg should be considered. Depending on efficacy and tolerability, the dose may be gradually increased to 50 mg and then to 100 mg, if necessary.

Patients taking other medicinal products. If patients are concurrently taking CYP3A4 inhibitors (except ritonavir, which is not recommended to be used concomitantly with sildenafil; see sections "Special precautions for use" and "Interaction with other medicinal products and other forms of interaction"), a starting dose of 25 mg should be considered.

To minimize the potential for postural hypotension in patients taking α-adrenoreceptor blockers, the clinical status of such patients should be stabilized before initiating sildenafil therapy. A starting dose of 25 mg should also be considered (see sections "Special precautions for use" and "Interaction with other medicinal products and other forms of interaction").

Children.

The drug is not indicated for use in individuals under 18 years of age.

Overdose.

In clinical studies involving healthy volunteers, administration of single doses of sildenafil up to 800 mg resulted in adverse reactions similar to those observed with lower doses, but they occurred more frequently and were more severe. Administration of sildenafil at a dose of 200 mg did not increase efficacy but led to an increased incidence of adverse reactions (headache, flushing, dizziness, dyspepsia, nasal congestion, visual disturbances).

In case of overdose, standard supportive measures should be implemented as necessary. Hemodialysis is unlikely to accelerate sildenafil clearance due to the high degree of plasma protein binding and lack of urinary elimination of sildenafil.

Side effects.

The safety profile of the medicine VIAGRA® ODT is based on data obtained from 74 double-blind, placebo-controlled clinical studies (9570 patients). The most commonly reported adverse reactions were headache, flushing, dyspepsia, nasal congestion, back pain, dizziness, nausea, hot flushes, visual disturbances, cyanopsia, and blurred vision. Information on adverse reactions from post-marketing surveillance was collected over a period of more than 10 years. Since not all adverse reactions were reported to the marketing authorization holder and not all adverse reactions were included in the safety database, the frequency of such reactions cannot be reliably determined.

All clinically significant adverse reactions observed during clinical trials more frequently than with placebo are listed below according to the "System Organ Class" and frequency: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), and rare (≥ 1/10,000 to < 1/1000). Within each frequency grouping, adverse reactions are listed in order of decreasing severity.

Infections and infestations.

Uncommon: rhinitis.

Immune system disorders.

Uncommon: hypersensitivity.

Nervous system disorders.

Very common: headache.

Common: dizziness.

Uncommon: somnolence, hypoesthesia.

Rare: stroke, transient ischaemic attack, seizures*, seizure recurrence*, syncope.

Eye disorders.

Common: colour vision disorders**, visual disturbances, blurred vision.

Uncommon: lacrimation disorders***, eye pain, photophobia, photopsia, eye hyperaemia, visual brightness, conjunctivitis, eye haemorrhage.

Rare: non-arteritic anterior ischaemic optic neuropathy*, retinal vessel occlusion*, retinal haemorrhage, arteriosclerotic retinopathy, retinal disorders, glaucoma, visual field defects, diplopia, decreased visual acuity, myopia, asthenopia, floaters, iris disorders, mydriasis, halos around lights in the visual field, eye oedema, eye swelling, eye disorders, conjunctival hyperaemia, eye irritation, abnormal sensations in the eye, eyelid oedema, scleral discolouration.

Ear and labyrinth disorders.

Uncommon: vertigo, tinnitus.

Rare: deafness.

Cardiac disorders.

Uncommon: tachycardia, palpitations.

Rare: sudden cardiac death*, myocardial infarction, ventricular arrhythmia*, atrial fibrillation, unstable angina.

Vascular disorders.

Common: facial flushing, hot flushes.

Uncommon: hypertension, hypotension.

Respiratory, thoracic and mediastinal disorders.

Common: nasal congestion.

Uncommon: epistaxis, nasal sinus congestion.

Rare: throat tightness, nasal mucosal oedema, nasal dryness.

Gastrointestinal disorders.

Common: nausea, dyspepsia.

Uncommon: gastroesophageal reflux disease, vomiting, upper abdominal pain, dry mouth.

Rare: oral cavity hypoesthesia.

Skin and subcutaneous tissue disorders.

Uncommon: rash.

Rare: Stevens-Johnson syndrome*, toxic epidermal necrolysis*.

Musculoskeletal and connective tissue disorders.

Uncommon: myalgia, limb pain.

Renal and urinary disorders.

Uncommon: haematuria.

Reproductive system and breast disorders.

Rare: penile haemorrhage, priapism*, haemospermia, prolonged erection.

General disorders and administration site conditions.

Uncommon: chest pain, increased fatigue, feeling of warmth.

Rare: irritation.

Investigations.

Uncommon: increased heart rate.

* Reported only in post-marketing studies.

** Colour vision disorders: chloropsia, chromatopsia, cyanopsia, erythropsia, xanthopsia.

*** Lacrimation disorders: dry eyes, lacrimation disorder, increased lacrimation.

The following adverse reactions were observed in < 2% of patients during controlled clinical trials; their causal relationship with VIAGRA® ODT is uncertain. Adverse reactions with a probable relationship to the use of the medicine were reported. Mild adverse reactions were not reported. Adverse reactions with very imprecise reports were also not included.

General: facial oedema, photosensitivity reactions, shock, asthenia, pain, sudden fall, abdominal pain, sudden injury.

Cardiovascular system: angina pectoris, AV block, migraine, postural hypotension, myocardial ischaemia, cerebral vessel thrombosis, sudden cardiac arrest, ECG abnormalities, cardiomyopathy.

Gastrointestinal disorders: glossitis, colitis, dysphagia, gastritis, gastroenteritis, oesophagitis, stomatitis, abnormal liver function tests, rectal bleeding, gingivitis.

Blood and lymphatic system disorders: anaemia, leukopenia.

Metabolism and nutrition disorders: thirst, oedema, gout, unstable diabetes, hyperglycaemia, peripheral oedema, hyperuricaemia, hypoglycaemia, hypernatraemia.

Musculoskeletal system disorders: arthritis, arthrosis, tendon rupture, tenosynovitis, bone pain, myasthenia, synovitis.

Nervous system disorders: ataxia, neuralgia, neuropathy, paraesthesia, tremor, vertigo, depression, insomnia, abnormal dreams, decreased reflexes.

Respiratory system disorders: asthma, dyspnoea, laryngitis, pharyngitis, sinusitis, bronchitis, increased salivation, increased cough.

Skin disorders: urticaria, herpes, pruritus, sweating, skin ulcers, contact dermatitis, exfoliative dermatitis.

Specific sensations: sudden decrease or loss of hearing, ear pain, eye haemorrhage, cataract, dry eyes.

Urogenital system disorders: cystitis, nocturia, increased frequency of urination, gynaecomastia, urinary incontinence, ejaculation disorders, genital swelling, anorgasmia.

Post-marketing experience. The following adverse reactions have been identified after marketing authorization. Since these reactions are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These adverse reactions have been considered due to one or more of the following factors: seriousness, frequency of reporting, lack of clear alternative cause, or a combination of these factors.

Cardiovascular and cerebrovascular events. Serious cardiovascular, cerebrovascular, and vascular events have been reported, including cerebral haemorrhage, subarachnoid haemorrhage, intracerebral haemorrhage, and pulmonary haemorrhage, which occurred in temporal association with VIAGRA® ODT use. Most, but not all, patients had underlying cardiovascular risk factors. Many of these events occurred during or immediately after sexual activity, and several occurred shortly after taking VIAGRA® ODT without sexual activity. Other events occurred within hours or days after taking VIAGRA® ODT and sexual activity. It is not possible to determine whether these events are related to the use of the medicine, sexual activity, underlying risk factors, a combination of these factors, or other factors.

Blood and lymphatic system: vaso-occlusive crisis. In a prematurely terminated study of Revatio (sildenafil) in patients with pulmonary arterial hypertension secondary to sickle cell anaemia, vaso-occlusive crises requiring hospitalization were reported more frequently with sildenafil than with placebo. The clinical significance of this information for patients taking VIAGRA® ODT for the treatment of erectile dysfunction is unknown.

Nervous system: anxiety, transient global amnesia.

Specific sensations.

Hearing. After marketing authorization, cases of sudden decrease or loss of hearing temporally associated with VIAGRA® ODT use have been reported. In some cases, medical conditions and other factors that could have contributed to hearing-related adverse reactions were reported. In many cases, follow-up medical information is lacking. It is not possible to determine whether these events are directly related to VIAGRA® ODT use, underlying risk factors for hearing loss, a combination of these factors, or other factors.

Vision: transient vision loss, eye redness, eye burning, increased intraocular pressure, retinal oedema, retinal vascular disorders or haemorrhage, vitreous detachment.

Rare cases of non-arteritic anterior ischaemic optic neuropathy (NAION), leading to visual impairment including permanent vision loss, have been reported after marketing authorization, occurring in temporal association with PDE5 inhibitors, including VIAGRA® ODT. In many, but not all, patients, anatomical or vascular risk factors for NAION were present, including (but not limited to): small cup-to-disc ratio (crowded optic disc), age over 50 years, hypertension, coronary artery disease, hyperlipidaemia, and smoking. It is not possible to determine whether these events are directly related to PDE5 inhibitor use, underlying anatomical or vascular risk factors, a combination of these factors, or other factors.

Reporting suspected adverse reactions. Reporting suspected adverse reactions after medicine authorization is important. It allows continued monitoring of the benefit-risk balance of the medicine. Healthcare professionals should report any suspected adverse reactions in accordance with applicable legislation.

Shelf life. 3 years.

Storage conditions.

Keep out of the reach of children.

Store in the original packaging to protect from moisture.

No special storage conditions required.

Packaging.

2 or 4 tablets in a blister; 1 blister in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

Fareva Amboise/Fareva Amboise.

Manufacturer's address and place of business.

Zone Industrielle, 29 route des Industries, 37530 Poce-sur-Cisse, France.