for medical use
active substance: sildenafil;
1 tablet contains sildenafil citrate equivalent to sildenafil 50 mg or 100 mg;
excipients: microcrystalline cellulose, dicalcium phosphate anhydrous, croscarmellose sodium, hypromellose, magnesium stearate, coating Opadry 03К80814 blue: hypromellose, titanium dioxide (Е 171), triacetin, indigo carmine (Е 132).
Pharmaceutical form. Film-coated tablets.
Pasic physico-chemical properties:round, biconvex tablets, smooth on both sides with blue film coating.
Drugs used in erectile dysfunction. Sildenafil. ATC code G04B Е03.
Mechanism of action.Sildenafil is an oral therapy for erectile dysfunction. With sexual stimulation, it restores impaired erectile function by increasing blood flow to the penis
The physiological mechanism responsible for erection of the penis involves the release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. The released nitric oxide activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood.
Sildenafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum, where PDE5 is responsible for degradation of cGMP. Sildenafil has a peripheral site of action on erections. Sildenafil has no direct relaxant effect on isolated human corpus cavernosum but potently enhances the relaxant effect of NO on this tissue. When the NO/cGMP pathway is activated, as occurs with sexual stimulation, inhibition of PDE5 by sildenafil results in increased corpus cavernosum levels of cGMP. Therefore sexual stimulation is required in order for sildenafil to produce its intended beneficial pharmacological effects
Pharmacodynamic effects.Sildenafil is known to be selective for PDE5, which is involved in the erection process. The effect of sildenafil is more potent on PDE5 than on other known phosphodiesterases. This effect is 10-fold more potent than on PDE6 which is involved in the phototransduction pathway in the retina. At maximum recommended doses, there is an 80-fold selectivity over PDE1, and over 700-fold over PDE2, PDE3, PDE4, PDE7, PDE8, 9, 10 and 11. In particular, sildenafil has greater than 4000-fold selectivity for PDE5 over PDE3, the cAMP-specific phosphodiesterase isoform involved in the control of cardiac contractility.
Absorption.Sildenafil is rapidly absorbed. Maximum observed plasma concentrations are reached within 30 to 120 minutes (median 60 minutes) of oral dosing in the fasted state. The mean absolute oral bioavailability is 41% (range 25-63%). After oral dosing of sildenafil AUC and Cmax increase in proportion with dose over the recommended dose range (25-100 mg).
When sildenafil is taken with food, the rate of absorption is reduced with a mean delay in Tmax of 60 minutes and a mean reduction in Cmax of 29%.
Distribution.The mean steady state volume of distribution (Vd) for sildenafil is 105 L, indicating distribution into the body tissues. After a single oral dose of 100 mg, the mean maximum total plasma concentration of sildenafil is approximately 440 ng/mL (coefficient of variation 40%). Since sildenafil and its major circulating N-desmethyl metabolite is 96% bound to plasma proteins, the mean maximum free plasma concentration for sildenafil is 18 ng/mL (38 nM). Protein binding is independent of total drug concentrations.
In healthy volunteers receiving sildenafil single dose of 100 mg, less than 0.0002% (average 188 ng) of the administered dose was present in ejaculate 90 minutes after dosing.
Biotransformation. Sildenafil is metabolized predominantly by the CYP3A4 (major route) and CYP2C9 (minor route) hepatic microsomal isoenzymes. The major circulating metabolite results from N-demethylation of sildenafil. This metabolite has a phosphodiesterase selectivity profile similar to sildenafil and potency for PDE5 approximately 50% that of the parent drug. Plasma concentrations of this metabolite are approximately 40% of those seen for sildenafil. The N-desmethyl metabolite is further metabolised, with a terminal half-life of approximately 4 hours.
Elimination. The total body clearance of sildenafil is 41 L/hour with a resultant terminal phase half-life of 3-5 hours. After either oral or intravenous administration, sildenafil is excreted as metabolites predominantly in the faeces (approximately 80% of administered oral dose) and to a lesser extent in the urine (approximately 13% of administered oral dose).
Pharmacokinetics in special populations of patients.
Healthy elderly volunteers (65 years or over) had a reduced clearance of sildenafil, resulting in approximately 90% higher plasma concentrations of sildenafil and the active N-desmethyl metabolite compared to those seen in healthy younger volunteers (18-45 years). Due to age-differences in plasma protein binding, the corresponding increase in free sildenafil plasma concentration was approximately 40%.
Renal insufficiency. In volunteers with mild to moderate renal impairment (creatinine clearance = 30-80 mL/min), the pharmacokinetics of sildenafil were not altered after receiving a 50 mg single oral dose. The mean AUC and Cmax of the N-desmethyl metabolite increased up to 126% and up to 73% respectively, compared to age-matched volunteers with no renal impairment. However, due to high inter-subject variability, these differences were not statistically significant. In volunteers with severe renal impairment (creatinine clearance less than 30 mL/min), sildenafil clearance was reduced, resulting in mean increases in AUC and Cmax of 100% and 88% respectively compared to age-matched volunteers with no renal impairment. In addition, N-desmethyl metabolite AUC and Cmax values were significantly increased by 200% and 79% respectively.
Hepatic insufficiency.In volunteers with mild to moderate hepatic cirrhosis (Child-Pugh A and B) sildenafil clearance was reduced, resulting in increases in AUC (84%) and Cmax (47%) compared to age-matched volunteers with no hepatic impairment. The pharmacokinetics of sildenafil in patients with severely impaired hepatic function has not been studied.
The drug Moginin® is recommended for use in men with erectile dysfunction, which is the inability to achieve or maintain a penile erection sufficient for satisfactory sexual performance.
In order for the drug Moginin® sexual stimulation is required.
– Hypersensitivity to the active substance or to any of the excipients.
– Co-administration with nitric oxide donors (such as amyl nitrite) or nitrates in any form is therefore contraindicated since it is known that sildenafil has effect on the nitric oxide/cyclic guanosine monophosphate (cGMP) pathway and potentiates the hypotensive effects of nitrates.
– The co-administration of PDE5 inhibitors (including sildenafil) with guanylate cyclase stimulators, such as riociguat, is contraindicated as it may potentially 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 cardiac failure).
– Loss of vision in one eye because of non-arteritic anterior ischaemic optic neuropathy, regardless of whether this episode was in connection or not with previous PDE5 inhibitor exposure.
– The presence of such diseases as severe hepatic impairment, hypotension (blood pressure less than 90/50 mmHg), recent history of stroke or myocardial infarction and known hereditary degenerative retinal disorders such as retinitis pigmentosa (a minority of these patients have genetic disorders of retinal phosphodiesterases), since the safety of sildenafil has not been studied in such sub-groups of patients.
Interaction with other medicinal products and other forms of interaction.
Effects of other medicinal products on sildenafil.
In vitro studies.
Sildenafil metabolism is principally mediated by the cytochrome P450 (CYP) isoforms 3A4 (major route) and 2C9 (minor route). Therefore, inhibitors of these isoenzymes may reduce sildenafil clearance and inducers of these isoenzymes may increase sildenafil clearance.
In vivo studies.
A reduction in sildenafil clearance when co-administered with CYP3A4 inhibitors (such as ketoconazole, erythromycin, cimetidine) has been shown. Although no increased incidence of adverse events was observed in these patients, when sildenafil is administered concomitantly with CYP3A4 inhibitors, a starting dose of 25 mg should be considered.
Co-administration of the HIV protease inhibitor ritonavir, which is a highly potent P450 inhibitor, at steady state (500 mg 1 time a day) with sildenafil (100 mg single dose) resulted in a 300% (4-fold) increase in sildenafil Cmax and a 1000% (11-fold) increase in sildenafil plasma AUC. At 24 hours, the plasma levels of sildenafil were still approximately 200 ng/mL, compared to approximately 5 ng/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 “Administration details”) 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 (1200 mg three times a day) with sildenafil (100 mg 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 “Dosage and administration”). Stronger CYP3A4 inhibitors such as ketoconazole and itraconazole would be expected to have greater effects.
When using sildenafil (100 mg single dose) and erythromycin, a moderate CYP3A4 inhibitor, at steady state (500 mg 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 (500 mg daily for 3 days) on the AUC, Cmax, Tmax, elimination rate constant or subsequent half-life of sildenafil or its principal circulating metabolite. Cimetidine (a cytochrome P450 inhibitor and non-specific CYP3A4 inhibitor) at a dose of 800 mg caused a 56% increase in plasma sildenafil concentrations when co-administered with sildenafil at a dose of 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 (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).
Co-administration of the endothelin antagonist, bosentan, (a moderate inducer of CYP3A4, CYP2C9 and possibly of CYP2C19) at steady state dose of 125 mg twice a day with sildenafil at steady state dose of 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. The nitrate component gives the potential of a serious interaction with sildenafil.
Effects of sildenafil on other medicinal products
In vitro studies.
Sildenafil is a weak inhibitor of the cytochrome P450 isoforms 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 (IC50 >150 μM). Given sildenafil peak plasma concentrations of approximately 1 μM, the effect of sildenafil on clearance of substrates of these isoenzymes is unlikely.
There are no data on the interaction of sildenafil and non-specific phosphodiesterase inhibitors such as theophylline or dipyridamole.
In vivo studies.
Since it is known that sildenafil has effect on metabolism of nitric oxide/cyclic guanosine monophosphate (cGMP) 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 (see section “Contraindications”).
Riociguat. There are preclinical data regarding additive systemic blood pressure lowering effect when co-administration of PDE5 inhibitors with riociguat. The data of clinical studies have shown riociguat to augment the hypotensive effects of PDE5 inhibitors. There was no evidence of favourable clinical effect of the combination in the population studied. Concomitant use of riociguat with PDE5 inhibitors (including sildenafil) is contraindicated (see section “Contraindications”).
Concomitant administration of sildenafil and alpha-blockers may lead to symptomatic hypotension in a few susceptible individuals. Such reaction most often occurred within 4 hours post sildenafil dosing (see sections “Dosage and administration” and “Administration details”). In 3 specific drug-drug interaction studies, the alpha-blocker doxazosin (4 mg and 8 mg) and sildenafil (25 mg, 50 mg, or 100 mg) were administered simultaneously to patients with benign prostatic hyperplasia stabilized on doxazosin therapy. In these study populations, mean additional reductions of supine blood pressure of 7/7 mmHg, 9/5 mmHg, and 8/4 mmHg, and mean additional reductions of standing blood pressure of 6/6 mmHg, 11/4 mmHg, and 4/5 mmHg, 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 (50 mg) was co-administered with tolbutamide (250 mg) or warfarin (40 mg), both of which are metabolised by CYP2C9
Sildenafil (50 mg) did not potentiate the increase in bleeding time caused by acetyl salicylic acid (150 mg).
Sildenafil (50 mg) did not potentiate the hypotensive effects of alcohol in healthy volunteers with mean maximum blood alcohol levels of 80 mg/dL.
Patients using sildenafil showed no difference in the side effect profile in patients taking sildenafil compared to placebo treatment in co-administration of such classes of hypotensive medicinal products as 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. In a specific interaction study, where sildenafil (100 mg) was co-administered with amlodipine in hypertensive patients, there was an additional reduction on supine systolic blood pressure of 8 mmHg. The corresponding additional reduction in supine diastolic blood pressure was 7 mmHg. These additional blood pressure reductions were of a similar magnitude to those seen when sildenafil was administered alone to healthy volunteers (see section “Pharmacological properties”).
Sildenafil at a dose of100 mg did not affect the pharmacokinetic parameters of the HIV protease inhibitors, saquinavir and ritonavir, which are CYP3A4 substrates.
In healthy male volunteers, sildenafil at steady state (80 mg three times a day) resulted in an increase in bosentan AUC and Cmax by 49.8% and 42%, respectively (125 mg two times a day).
A medical history and physical examination should be undertaken to diagnose erectile dysfunction and determine potential underlying causes, before starting the treatment.
Cardiovascular risk factors.
Prior to initiating any treatment for erectile dysfunction, physician should consider the cardiovascular status of their patients, since there is a degree of cardiac risk associated with sexual activity. Sildenafil has vasodilator effect resulting in mild and transient decreases in blood pressure (see section “Pharmacodynamics”). 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.
Sildenafil potentiates the hypotensive effect of nitrates (see section “Contraindications”).
Serious cardiovascular events, including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, cerebrovascular haemorrhage, transient ischaemic attack, hypertension and hypotension have been reported in temporal association with the use of sildenafil. Most patients had pre-existing cardiovascular risk factors. Mostly, adverse events were reported to occur during or shortly after sexual intercourse and a few were reported to occur shortly after the use of the drug without sexual activity. Therefore, it is not possible to determine whether these events are related directly to these factors or to other factors.
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)
There are data regarding prolonged erection and priapism when using sildenafil. In the event of an erection that persists for longer than 4 hours, the patient should seek immediate medical assistance. If priapism is not treated immediately, penile tissue damage and permanent loss of potency could result.
Concomitant use with other PDE5 inhibitors or other treatments for erectile dysfunction.
The safety and efficacy of combinations of sildenafil with other PDE5 inhibitors, or other pulmonary arterial hypertension treatments containing sildenafil, or 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 (see section “Adverse reactions”). Patients should be advised that in the event of any sudden visual defect, they should stop taking the drug Moginin®and consult a physician immediately (see section “Contraindications”).
Concomitant use with ritonavir.
Co-administration of sildenafil with ritonavir is not advised (see sectionInteraction with other medicinal products and other forms of interaction”).
Concomitant use with α-adrenergic receptors blockers.
Caution is advised when sildenafil is administered to patients taking α-adrenergic receptors blockers, as the co-administration may lead to symptomatic hypotension in a few susceptible individuals. Symptomatic hypotension usually occurs 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 25 mg should be considered (see section “Dosage and administration”). In addition, patients should be informed what to do in the event of postural hypotensive symptoms.
Effects on blood clotting.
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.
There was no effect on sperm motility or morphology after single 100 mg oral doses of sildenafil (see section “Pharmacodynamics”).
Loss of hearing.
The physicians should advice the patients that in the event of a sudden decrease or loss of hearing, they should stop using PDE5 inhibitors, including Moginin®, and seek immediate medical assistance. These phenomena, which can also be accompanied by tinnitus and dizziness, have been reported in temporal association with the use of PDE5 inhibitors, including sildenafil. It is not possible to determine whether these events are related directly to the use of PDE5 inhibitors or to other factors.
Concomitant use with hypotensive drugs.
Sildenafil has systemic vasodilatory effect and may further reduce blood pressure in patients who use antihypertensive drugs. There is evidence that the concomitant use of amlodipine (5 mg or 10 mg) and sildenafil (100 mg) orally, average additional reduction in systolic blood pressure by 8 mmHg and in diastolic – by 7 mmHg.
Sexually transmitted diseases.
The use of sildenafil does not protect against sexually transmitted diseases. The possibility to instruct patients about the necessary precautions to protect against sexually transmitted diseases, including human immunodeficiency virus, should be considered.
Use during pregnancy or lactation.
The drug Moginin® is not intended for use by women.
Effects on ability to drive a car or 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 sildenafil, before driving or operating machinery.
Dosage and administration.
The drug is used orally.
The recommended dose of sildenafil is 50 mg and is taken approximately one hour before sexual activity.
Based on efficacy and tolerability, the dose may be increased to 100 mg or decreased to 25 mg (the medicinal product with appropriate dosage is used). The maximum recommended dose is 100 mg/
The maximum recommended dosing frequency is 1 time a day. If Moginin® is taken with food, the onset of activity may be delayed compared to the fasted state.
Elderly patients (≥ 65 years old).
Dosage adjustments are not required in elderly patients.
Patients with renal impairment.
Patients with mild to moderate renal impairment (creatinine clearance 30 to 80 mL/min) are recommended the drug dose similar to the dose described above in the section “Adults”.
Since sildenafil clearance is reduced in patients with severe renal impairment (creatinine clearance < 30 mL/min) a 25 mg dose should be considered. Based on efficacy and tolerability, the dose may be increased step-wise to 50 mg up to 100 mg as necessary.
Patients with hepatic impairment.
Since sildenafil clearance is reduced in patients with hepatic impairment (e.g. cirrhosis) a 25 mg dose should be considered(the medicinal product with appropriate dosage is used). Based on efficacy and tolerability, the dose may be increased step-wise to 50 mg up to 100 mg as necessary.
Patients taking other medicinal products.
If the patients use concomitantly 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, co-administration of which with sildenafil is not recommended, see section “Administration details”).
In order to minimise the potential of developing postural hypotension in patients receiving α-adrenergic receptors blocker treatment patients should be stabilised on alpha-blocker therapy prior to initiating sildenafil treatment. In addition, initiation of sildenafil at a dose of 25 mg should be considered (see sections “Administration details” and “Interaction with other medicinal products and other forms of interaction”).
The drug is not indicated for use in persons less than 18 years old.
In single dose volunteer studies of doses up to 800 mg, adverse reactions were similar to those seen at lower doses, but the incidence rates and severities were increased. Doses of 200 mg did not result in increased efficacy but the incidence of adverse reactions (headache, flushing, dizziness, dyspepsia, nasal congestion, altered vision) was increased.
In cases of overdose, standard supportive measures should be adopted as required. Renal dialysis is not expected to accelerate clearance as sildenafil is highly bound to plasma proteins and not eliminated in the urine.
Infections and infestations: rhinitis.
Immune system disorders: hypersensitivity.
Nervous system disorders: headache, migraine, dizziness, somnolence, hypoesthesia, stroke, cerebrovascular haemorrhage, subarachnoid and intracerebral bleeding, cerebral thrombosis, transient ischemic attack, seizures, recurrent seizures, syncope, anxiety, transient global amnesia, ataxia, neuralgia, neuropathy, paresthesia, tremor, vertigo, depression, insomnia, abnormal dreams, reduced reflexes.
Eye disorders:visual colour distortions (chloropsia, chromatopsia, cyanopsia, erythropsia, xanthopsia), visual disturbances, vision blurred,lacrimation disorders (dry eyes, violation of lacrimation and increased lacrimation), eye pain, photophobia, photopsia, ocular hyperaemia, eye redness, visual brightness, conjunctivitis, non-arteritic anterior ischaemic optic neuropathy , retinal vascular occlusion, retinal haemorrhage, arteriosclerotic retinopathy, retinal disorders, glaucoma, increased intraocular pressure, visual field defects, diplopia, decreased visual acuity, myopia, asthenopia, vitreous floaters, iris disorders, mydriasis, halo vision, eye oedema, eye swelling, eye disorders, conjunctival hyperaemia, eye irritation, abnormal sensations in eyes, eyelid oedema, scleral discoloration, temporary loss of vision, burning sensation in the eyes, swelling of the retina, retinal vascular disease or bleeding, vitreous detachment, eye haemorrhage, cataract, dry eyes.
Ear and labyrinth disorders: vertigo, tinnitus, deafness, sudden decrease or loss of hearing, ear pain.
Cardiovascular system disorders:tachycardia, increased heart rate, palpitation, sudden cardiac arrest, sudden cardiac death, myocardial infarction, ventricular arrhythmia, atrial fibrillation, unstable angina, hypertension, hypotension, angina, AV block, postural hypotension, myocardial ischemia, abnormal EKG, cardiomyopathy.
Respiratory, thoracic and mediastinal disorders:nasal congestion, epistaxis, sinus congestion, throat tightness, nasal oedema, nasal dryness, pulmonary haemorrhage, asthma, dyspnoea, laryngitis, pharyngitis, sinusitis, bronchitis, increased cough.
Gastrointestinal tract disorders:nausea, dyspepsia, gastro-oesophageal reflux disease, vomiting, pain in the upper abdomen, abdominal pain, dry mouth, hypoesthesia of the oral cavity, glossitis, colitis, dysphagia, gastritis, gastroenteritis, esophagitis, stomatitis, abnormal liver function tests, rectal haemorrhage, gingivitis, increased salivation.
Skin and subcutaneous tissue disorders: rash, Stevens-Johnson Syndrome , Toxic Epidermal Necrolysis , photosensitivity reactions, urticaria, herpes, itching, sweating, skin ulcer, contact dermatitis, exfoliative dermatitis.
Musculoskeletal and connective tissue disorders: myalgia, pain in the extremities, arthritis, arthrosis, tendon rupture, tenosynovitis, bone pain, myasthenia, synovitis, back pain.
Urinary system disorders:haematuria, cystitis, nocturia, increased frequency of urination, urinary incontinence.
Reproductive system and breast disorders:penile haemorrhage, priapism, haematospermia, prolonged erection, breast enlargement, abnormal ejaculation, genital oedema, anorgasmia.
Blood and lymplhatic systems disorders: anaemia, leukopenia, vaso-occlusive crisis.
Metabolic and nutrition disorders: thirst, oedema, gout, unstable diabetes, hyperglycaemia, peripheral oedema, hyperuricemia, hypoglycaemia, hypernatremia.
General disorders: chest pain, fatigue, feeling hot, hot flushes, irritation, swelling of the face, shock, asthenia, pain, sudden fall, sudden injury, flushing, including blushing of the face.
Reporting suspected adverse reactions. Reporting suspected adverse reactions after registration of medicinal product is important. It gives the possibility of a safe monitoring of the benefit/risk ratio, associated with the use of this drug. The physicians should report any suspected adverse reactions accordance with the legislative requirements.
Store at the temperature below 25 С.
Keep out of reach of children.
1 or 4 tablets in a blister; 1 blister in a carton package.
Prescription Only Medicine.
KUSUM HEALTHCARE PVT LTD.
SP-289 (A), RIICO Industrial area, Chopanki, Bhiwadi, Dist. Alwar (Rajasthan), India.
Date of last revision.