Novagra neo

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT NOVAgra NEO

Composition:

Active substance: sildenafil;

1 tablet contains sildenafil citrate equivalent to sildenafil 50 mg or 100 mg;

Excipients: microcrystalline cellulose, sodium croscarmellose, lactose monohydrate, polyvinylpyrrolidone, calcium hydrogen phosphate, talc, magnesium stearate, titanium dioxide (E 171), hydroxypropylmethylcellulose, macrogol 400, Ponceau 4R (E 124).

Pharmaceutical form. Film-coated tablets.

Main physico-chemical properties: round, biconvex, film-coated tablets of pink color.

Pharmacotherapeutic group.
Agents used in erectile dysfunction. Sildenafil.

ATC code G04BE03.

Pharmacological Properties

Pharmacodynamics

Mechanism of action. Sildenafil is an orally administered drug indicated 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 increases levels of cyclic guanosine monophosphate (cGMP). This, in turn, causes relaxation of smooth muscle in the corpus cavernosum, 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 degradation. The effects of sildenafil on erection are peripheral. Sildenafil does not directly relax isolated human corpus cavernosum tissue, but it 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. Therefore, sexual stimulation is required for sildenafil to produce its desired pharmacological effect.

Pharmacodynamic effects. In vitro studies have demonstrated that sildenafil is selective for PDE5, which actively participates in the erectile process. The effect of sildenafil on PDE5 is more potent than 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 is 80 times greater than for PDE1, 700 times greater than for PDE2, PDE3, PDE4, PDE7, PDE8, PDE9, PDE10, and PDE11. In particular, sildenafil’s selectivity for PDE5 is 4000 times greater than for PDE3—an isoform of cAMP-specific phosphodiesterase involved in regulating cardiac contractility.

Pharmacokinetics

Absorption. Sildenafil is rapidly absorbed. Maximum plasma concentrations are reached within 30–120 minutes (median: 60 minutes) after oral administration on an empty stomach. The mean absolute bioavailability after oral administration is 41% (range: 25%–63%). Within the recommended dose range (25–100 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 L, indicating extensive distribution of the drug into body tissues. 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 is about 96%, the mean peak plasma concentration of free sildenafil reaches approximately 18 ng/mL (38 nmol). The degree of plasma 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 after 90 minutes.

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. The total clearance of sildenafil is 41 L/h, resulting in an elimination half-life of 3–5 hours. After both oral and intravenous administration, excretion of sildenafil metabolites occurs primarily 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.

Novagra Neo is recommended for use in men with erectile dysfunction, defined as the inability to achieve and maintain an erection of the penis sufficient for successful sexual intercourse.

For Novagra Neo to be effective, 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, as it may lead to symptomatic hypotension (see section "Interaction with other medicinal products and other forms of interaction").
• Conditions in which sexual activity is inadvisable (e.g., severe cardiovascular disorders such as unstable angina or severe heart failure).
• Loss of vision in one eye due to non-arteritic anterior ischemic optic neuropathy (NAION), regardless of whether this condition is associated with prior use of PDE5 inhibitors or not.
• Presence of conditions such as severe hepatic impairment, arterial hypotension (blood pressure below 90/50 mm Hg), recent stroke or myocardial infarction, and known hereditary degenerative retinal disorders such as retinitis pigmentosa (a small number of such patients have genetic disorders of retinal phosphodiesterases), since the safety of sildenafil has not been studied in these patient subgroups.

Interaction with other medicinal products and other forms of interaction.

Effects of other medicinal products on sildenafil.

In vitro studies.

Sildenafil is metabolized primarily by cytochrome P450 isoenzyme 3A4 (main pathway) and to a lesser extent by isoenzyme 2C9 (secondary 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 clearance of sildenafil when co-administered with CYP3A4 inhibitors (such as ketoconazole, erythromycin, cimetidine). Although an increased incidence of adverse events was not observed when sildenafil was used concomitantly with CYP3A4 inhibitors, consideration should be given to initiating treatment with a sildenafil dose of 25 mg.

Concomitant administration of the HIV protease inhibitor ritonavir, a very potent inhibitor of CYP450, at steady-state concentration (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 levels of sildenafil were still approximately 200 ng/mL compared to approximately 5 ng/mL when sildenafil was administered alone, indicating a significant effect of ritonavir on a broad range of P450 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 dose (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). No effect of sildenafil on saquinavir pharmacokinetics was observed (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 to sildenafil (AUC). In healthy male volunteers, azithromycin (500 mg daily for 3 days) did not affect 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, when administered concomitantly with sildenafil 50 mg in healthy volunteers, increased plasma concentrations of sildenafil by 56%.

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

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

Although specific interaction studies with all medicinal products have not been conducted, population pharmacokinetic analysis showed 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 concentrations of sildenafil.

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

Effects of sildenafil on other medicinal products.

In vitro studies.

Sildenafil is a weak inhibitor of cytochrome P450 isoenzymes 1A2, 2C9, 2C19, 2D6, 2E1, and 3A4 (IC50 > 150 µmol). Since peak plasma concentrations of sildenafil are approximately 1 µmol, the effect of sildenafil 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 is known to affect the nitric oxide/cyclic guanosine monophosphate (cGMP) pathway, it has been established that sildenafil potentiates 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 demonstrated an additive systemic effect on lowering blood pressure when PDE5 inhibitors are used concomitantly with riociguat. Clinical studies have shown that riociguat enhances the hypotensive effect of PDE5 inhibitors. In patients participating in the study, no positive clinical effect was observed from the concomitant use of PDE5 inhibitors 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 specific drug interaction studies, the α-adrenoreceptor blocker doxazosin (4 mg and 8 mg) and sildenafil (25 mg, 50 mg, and 100 mg) were administered concomitantly to patients with benign prostatic hyperplasia (BPH) 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. Cases of symptomatic orthostatic hypotension have been reported when sildenafil was used concomitantly with doxazosin in patients whose condition was stabilized on doxazosin. These reports described episodes of dizziness and pre-syncope, but not 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 moderate maximum blood ethanol levels of 80 mg/dL.

In patients taking sildenafil, no differences in adverse effect profile were observed compared to placebo when co-administered with classes of antihypertensive drugs such as diuretics, β-adrenoreceptor blockers, ACE inhibitors, angiotensin II antagonists, antihypertensive agents (vasodilators and centrally acting), 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 reductions in blood pressure were comparable in magnitude to those observed with sildenafil alone in healthy volunteers (see section "Pharmacological properties").

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

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.

Adding a single dose of sildenafil to sacubitril/valsartan at steady state in patients with arterial hypertension was associated with a significantly greater reduction in blood pressure 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 assess the cardiovascular status of patients prior to initiating 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 such an effect could have an adverse impact on patients with underlying cardiovascular conditions, particularly in combination 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) or patients with the rare multisystem atrophy syndrome, one of the manifestations of which is severe autonomic nervous system dysfunction in blood pressure regulation.

Sildenafil 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, which temporally coincided with sildenafil use. In most patients, but not all, risk factors for cardiovascular disease were present. Many of these adverse reactions occurred during or immediately after sexual intercourse, and only a few occurred shortly after sildenafil use 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. Medicinal products for the treatment of erectile dysfunction, including sildenafil, should be administered with caution in patients with anatomical deformation of the penis (such as angulation, cavernous fibrosis, or Peyronie's disease) or in patients with conditions that may predispose to priapism (such as sickle cell anaemia, multiple myeloma, or leukaemia).

Since the drug's launch, cases of prolonged erection and priapism have been reported. If an erection lasts more than 4 hours, patients should seek immediate medical help. 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 treatments. The safety and efficacy of concomitant use of sildenafil with other PDE5 inhibitors or other treatments for pulmonary arterial hypertension containing sildenafil (e.g., Revatio), or with other erectile dysfunction treatments, have not been studied. Therefore, the use of such combinations is 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 also reported cases of non-arteritic anterior ischaemic optic neuropathy, a rare condition, associated with sildenafil and other PDE5 inhibitors (see section "Adverse reactions"). Patients should be advised that in the event of sudden visual impairment, use of Novagra Neo should be discontinued and immediate medical advice sought (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 α-adrenoreceptor blockers. Sildenafil should be used with caution in patients taking α-adrenoreceptor blockers, as this combination may lead to symptomatic hypotension in some susceptible patients. Symptomatic hypotension usually occurs within 4 hours after sildenafil administration. To minimize the potential for postural hypotension in patients taking α-adrenoreceptor blockers, their condition should be stabilized on α-blocker therapy before initiating sildenafil. Consideration should also be given to starting with an initial dose of 25 mg (see section "Dosage and administration"). In addition, patients should be informed about appropriate actions to take if symptoms of orthostatic hypotension occur.

Effect on bleeding. Studies on human platelets have demonstrated that sildenafil potentiates the anti-aggregatory effects of sodium nitroprusside in vitro. There is no information on the safety of sildenafil use in patients with bleeding disorders or acute peptic ulcer. Therefore, sildenafil may be used in such patients only after careful assessment of the benefit-risk ratio.

Novagra Neo contains lactose and should not be administered to men with rare hereditary conditions such as galactose intolerance, Lapp lactase deficiency, or glucose-galactose malabsorption.

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

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

Hearing loss. Physicians should advise patients to discontinue use of PDE5 inhibitors, including Novagra Neo, 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 PDE5 inhibitor use. It is not possible to determine whether these events are directly related to PDE5 inhibitor use or to other factors.

Concomitant use with antihypertensive agents. Novagra Neo has systemic vasodilatory effects and may further reduce blood pressure in patients taking antihypertensive medicinal products. In a specific drug interaction study, concomitant oral administration of amlodipine (5 mg or 10 mg) and sildenafil (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. Use of Novagra Neo does not protect against sexually transmitted diseases. Consideration should be given to advising patients on appropriate preventive measures to protect against sexually transmitted diseases, including human immunodeficiency virus.

Use during pregnancy or breastfeeding.

Novagra Neo is not intended for use in women.

Ability to affect reaction speed when driving or operating machinery.

Novagra Neo 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 Novagra Neo before driving a vehicle or operating machinery.

Dosage and Administration

The medication is taken orally.

Adults. The recommended dose of Viagra Neo is 50 mg, taken approximately 1 hour before sexual activity, as needed. Depending on efficacy and tolerability, the dose may be increased to 100 mg or decreased to 25* mg. The maximum recommended dose is 100 mg. The maximum recommended dosing frequency is once daily. When Viagra Neo is taken with food, the onset of action may be delayed compared to administration on an empty stomach.

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 of 30–80 mL/min), the recommended dose is the same as stated above in the section "Adults."

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

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

Patients taking other medications. If patients are concurrently using CYP3A4 inhibitors (see section "Interaction with Other Medicinal Products and Other Forms of Interaction"), a starting dose of 25* mg should be considered (except for ritonavir, which is not recommended to be used concomitantly with sildenafil; see section "Special Warnings and Precautions for Use").

To minimize the potential risk of postural hypotension in patients taking α-adrenoreceptor blockers, their condition should be stabilized with α-blockers prior to initiating sildenafil therapy. Additionally, a starting dose of 25* mg should be considered (see sections "Special Warnings and Precautions for Use" and "Interaction with Other Medicinal Products and Other Forms of Interaction").

* - administer sildenafil-containing medications at the appropriate dosage.

Children.

This medication is not indicated for use in individuals under 18 years of age.

Overdose.

When single doses of sildenafil up to 800 mg were administered, adverse reactions were similar to those observed with lower doses but occurred more frequently and were more severe. Administration of sildenafil at a dose of 200 mg did not result in increased efficacy but led to a higher incidence of adverse reactions (headache, flushing, dizziness, dyspepsia, nasal congestion, visual disturbances).

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

Adverse Reactions

The safety profile of sildenafil is based on data from 9,570 patients in 74 double-blind, placebo-controlled clinical trials. 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 has been collected over a period of more than 10 years. Since not all adverse reactions were reported to the marketing authorization holder and not all 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 by System Organ Class and frequency: very common (≥ 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1,000 to < 1/100), and rare (≥ 1/10,000 to < 1/1,000). Within each frequency group, 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, hypaesthesia.

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

Eye disorders.

Common: Colour vision disturbance**, visual disturbance, blurred vision.

Uncommon: Lacrimation disorders***, eye pain, photophobia, photopsia, eye hyperaemia, brightness of vision, conjunctivitis.

Rare: Non-arteritic anterior ischaemic optic neuropathy*, retinal vessel occlusion*, retinal haemorrhage, arteriosclerotic retinopathy, retinal disorder, glaucoma, visual field defects, diplopia, decreased visual acuity, myopia, asthenopia, floaters, iris disorder, mydriasis, halos around light sources in visual field, eye swelling, eye oedema, eye irritation, abnormal sensation in eye, eyelid oedema, scleral discoloration.

Ear and labyrinth disorders.

Uncommon: Dizziness, 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 hypaesthesia.

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 disturbance: chloropsia, chromatopsia, cyanopsia, erythropsia, xanthopsia.

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

The following events were observed in < 2% of patients in controlled clinical trials; causal relationship has not been established. Reports included events with a probable relationship to drug use. Events not listed were mild and reports were too imprecise to be meaningful.

General: Facial oedema, photosensitivity reactions, shock, asthenia, pain, sudden collapse, 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 tract: Glossitis, colitis, dysphagia, gastritis, gastroenteritis, oesophagitis, stomatitis, abnormal liver function tests, rectal haemorrhage, gingivitis.

Blood and lymphatic system disorders: Anaemia, leucopenia.

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

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

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

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

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

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

Urogenital system disorders: Cystitis, nocturia, increased urinary frequency, gynaecomastia, urinary incontinence, ejaculation disorder, genital swelling, anorgasmia.

Post-marketing experience. The following adverse reactions have been identified after the drug was marketed. Because 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 events were reported due to their seriousness, frequency of reporting, lack of clear alternative explanation, 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 sildenafil use. Most, but not all, patients had pre-existing cardiovascular risk factors. Many of these events occurred during or immediately after sexual activity, and several occurred immediately after sildenafil use without sexual activity. Other events occurred within hours or days after sildenafil use and sexual activity. It is not possible to determine whether these events are directly related to drug use, sexual activity, pre-existing risk factors, a combination of these, or other factors.

Blood and lymphatic system: Vaso-occlusive crisis. In a small, 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 Neo for the treatment of erectile dysfunction is unknown.

Nervous system: Anxiety, transient global amnesia.

Specific senses.

Hearing. After marketing, cases of sudden decrease or loss of hearing, occurring in temporal association with sildenafil use, have been reported. In some cases, medical conditions and other factors that may 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 sildenafil use, pre-existing risk factors for hearing loss, a combination of these, or other factors.

Vision: Temporary 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), a cause of decreased vision including permanent vision loss, have been reported after marketing in temporal association with PDE5 inhibitors, including this product. Many, but not all, patients had pre-existing anatomical or vascular risk factors for NAION, 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, pre-existing anatomical or vascular risk factors, a combination of these, or other factors.

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

Shelf life. 2 years.

Storage conditions. Store at a temperature not exceeding 25 °C. Keep out of the reach of children.

Packaging.

50 mg tablets: 1 or 2 tablets per blister; 1 blister per cardboard box;

4 tablets per blister; 1 or 2 blisters per cardboard box.

100 mg tablets: 1 tablet per blister; 1 blister per cardboard box;

4 tablets per blister; 1 or 2 blisters per cardboard box.

Prescription status. Prescription only.

Manufacturer. FDS Limited.

Manufacturer's address and place of business.

L-56/57, Phase II-D, Verna Industrial Estate, Verna, Salcette, Goa – 403 722, India.