APPROVED BY

Order of the Ministry of Health of Ukraine

__31.10.14____№___798____

Registration certificate

№  __UA/14019/01/01___

      __UA/14019/01/02___

           __UA/14019/01/03___

 

INSTRUCTION

for medical use of the preparation

 

SIMVASTATIN 10 ANANTA

SIMVASTATIN 20 ANANTA

SIMVASTATIN 40 ANANTA

 

Composition:

Active substance: simvastatin EP;

1 tablet contains simvastatin EP 10 mg or 20 mg, or 40 mg;

Excipients: lactose monohydrate; microcrystalline cellulose; pregelatinized starch; butyl hydroxy anisole (Е 320); ascorbic acid (Е 300); anhydrous citric acid (Е 330); ethanol 96%; sterile water; colloidal anhydrous silica; talc; magnesium stearate

Film-Coating: hypromellose, iron oxide red (E 172), iron oxide yellow (E 172), triethyl citrate, titanium dioxide (E 171), talc, povidone, purified water.

Pharmaceutical form. Film-coated tablets.

Pharmaceutical group.

Lipid-lowering agents, monocomponent. HMG-CoA reductase inhibitor

ATC code: C10A A01

Clinical particulars.

Indications.

Hypercholesterolaemia

Treatment of primary hypercholesterolaemia or mixed dyslipidaemia, as an adjunct to diet, when response to diet and other non-pharmacological treatments (e.g. exercise, weight reduction) is inadequate.

Treatment of homozygous familial hypercholesterolaemia as an adjunct to diet and other lipid-lowering treatments (e.g. LDL apheresis) or if such treatments are not appropriate.

Cardiovascular prevention

Reduction of cardiovascular mortality and morbidity in patients with atherosclerotic cardiovascular disease or diabetes mellitus, normal or increased cholesterol levels, as an adjunct to correction of other risk factors and other cardioprotective therapy. 

Contraindications.

•  Hypersensitivity to simvastatin or to any of the excipients.
•  Active liver disease or unexplained persistent elevations of serum transaminases.
•  Concomitant administration of potent CYP3A4 inhibitors (medications that increase AUC approximately in 5 times or more) (e.g. itraconazole, ketoconazole, posaconazole, voriconazole, HIV protease inhibitors (e.g nelfinavir) boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin and nefazodone).
•  Concomitant administration of gemfibrozil, ciclosporin, or danazol.

Way of administration and dosage.

The dosage range is 5-80 mg/day given orally as a single dose in the evening. Adjustments of dosage, if required, should be made at intervals of not less than 4 weeks, to a maximum of 80 mg/day given as a single dose in the evening. The 80-mg dose is only recommended in patients with severe hypercholesterolaemia and high risk for cardiovascular complications, who have not achieved their treatment goals on lower doses and when the benefits are expected to outweigh the potential risks.

Hypercholesterolaemia

The patient should be placed on a standard cholesterol-lowering diet, and should continue on this diet during treatment with Simvastatin. The usual starting dose is 10-20 mg/day given as a single dose in the evening. Patients who require a large reduction in LDL-C (more than 45 %) may be started at 20-40 mg/day given as a single dose in the evening. Adjustments of dosage, if required, should be made as specified above.

Homozygous familial hypercholesterolaemia

Based on the results of a controlled clinical study, the recommended dosage is Simvastatin 40 mg/day in the evening. Simvastatin should be used as an adjunct to other lipid-lowering treatments (e.g., LDL apheresis) in these patients or if such treatments are unavailable.

Cardiovascular prevention

The initial dose of Simvastatin is 20 to 40 mg/day given as a single dose in the evening in patients at high risk of coronary heart disease (CHD, with or without hyperlipidaemia). Drug therapy can be initiated simultaneously with diet and exercise. Adjustments of dosage, if required, should be made as specified above.

Concomitant therapy

Simvastatin is effective alone or in combination with bile acid sequestrants. Dosing should occur either > 2 hours before or> 4 hours after administration of a bile acid sequestrant.

In patients taking Simvastatin concomitantly with fibrates, other than gemfibrozil (see section 4.3) or fenofibrate , the dose of Simvastatin should not exceed 10 mg/day. In patients taking amiodarone, amlodipine, verapamil or diltiazem concomitantly with Simvastatin, the dose of Simvastatin should not exceed 20 mg/day.

Dosage in renal insufficiency

No modification of dosage should be necessary in patients with moderate renal insufficiency. In patients with severe renal insufficiency (creatinine clearance < 30 ml/min), dosages above 10 mg/day should be carefully considered and, if deemed necessary, implemented cautiously.

Use in the elderly

No dosage adjustment is necessary.

Use in children and adolescents (10-17 years of age)

For children and adolescents (boys Tanner Stage II and above and girls who are at least one year post-menarche, 10-17 years of age) with heterozygous familial hypercholesterolaemia, the recommended usual starting dose is 10 mg once a day in the evening. Children and adolescents should be placed on a standard cholesterol-lowering diet before simvastatin treatment initiation; this diet should be continued during simvastatin treatment.

The recommended dosing range is 10-40 mg/day; the maximum recommended dose is 40 mg/day. Doses should be individualized according to the recommended goal of therapy as recommended by the paediatric treatment recommendations. Adjustments should be made at intervals of 4 weeks or more.

The experience of simvastatin in pre-pubertal children is limited.

Adverse reactions.

In general Simvastatin Ananta is well-tolerated.

Blood and lymphatic system disorders: anaemia.

Nervous system disorders: headache, paresthesia, dizziness, peripheral neuropathy, memory impairment.

Gastrointestinal disorders: constipation, abdominal pain, flatulence, dyspepsia, diarrhoea, nausea, vomiting, pancreatitis.

Skin and subcutaneous tissue disorders: rash, pruritus, alopecia.

Musculoskeletal, connective tissue and bone disorders: myopathy (including myositis), rhabdomyolysis, myalgia, muscle cramps.

General disorders: asthenia.

An apparent hypersensitivity syndrome has been reported rarely which has included some of the following features: angioedema, lupus-like syndrome, polymyalgia rheumatica, dermatomyositis, vasculitis, thrombocytopenia, eosinophilia, ESR increased, arthritis and arthralgia, urticaria, photosensitivity, fever, flushing, dyspnoea and malaise.

Hepato-biliary disorders: hepatitis/jaundice, hepatic failure.

Psychiatric disorders: insomnia, sleep disturbance, depression.

Respiratory, thoracic and mediastinal disorders: interstitial lung disease.

Reproductive system disorders: erectile dysfunction.

Investigations: increases in serum transaminases (alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase), elevated alkaline phosphatase; increase in serum CK levels.

Increases in HbA1c and fasting serum glucose levels have been reported with statins, including 'Simvastatin'.

There have been rare post-marketing reports of cognitive impairment (e.g. memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use, including simvastatin. The reports are generally non serious, and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks).

There were very rare observed immunomediated necrotizing myopathy, autoimmune myopathy associated with the use of statins. Immunomediated necrotizing myopathy is characterized by proximal muscle weakness and increased levels of creatine serum that persist despite the discontinuation of statins, signs of necrotizing myopathy on muscle biopsy without significant inflammation and improvement with the use of immunosuppressive drugs.

 

Overdose.

A few cases of overdose have been reported. The maximum dose was 3.6 g.

All patients recovered without sequelae. There is no specific treatment in the event of overdose. In this case, symptomatic and supportive measures should be adopted.

Pregnancy and lactation.

Pregnancy

Simvastatin is contraindicated during pregnancy.

Atherosclerosis is a chronic process, and ordinarily discontinuation of lipid-lowering medicinal products during pregnancy should have little impact on the long-term risk associated with primary hypercholesterolaemia. For these reasons, Simvastatin Ananta must not be used in women who are pregnant, trying to become pregnant or suspect they are pregnant. Treatment with Simvastatin Ananta must be discontinued for the duration of pregnancy or until it has been determined that the woman is not pregnant.

Lactation

It is not known whether simvastatin or its metabolites are excreted in human milk. Because many medicinal products are excreted in human milk and because of the potential for serious adverse reactions, women taking Simvastatin Ananta must not breast-feed their infants.

Children.

Safety and effectiveness of simvastatin in patients 10-17 years of age with heterozygous familial hypercholesterolaemia have been evaluated in a controlled clinical trial in adolescent boys Tanner Stage II and above and in girls who were at least one year post-menarche. Patients treated with simvastatin had an adverse experience profile generally similar to that of patients treated with placebo. Doses greater than 40 mg have not been studied in this group of patients. In this study, there was no detectable effect on growth or sexual maturation in the adolescent boys or girls, or any effect on menstrual cycle length in girls.

In patients aged < 18 years, efficacy and safety have not been studied for treatment periods > 48 weeks' duration and long-term effects on physical, intellectual, and sexual maturation are unknown. Simvastatin has not been studied in patients younger than 10 years of age, nor in pre-pubertal children and pre-menarchal girls.

Precautions for use.

Myopathy/Rhabdomyolysis

Simvastatin, like other inhibitors of HMG-CoA reductase, occasionally causes myopathy manifested as muscle pain, tenderness or weakness with creatine kinase (CK) above ten times the upper limit of normal (ULN). Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and very rare fatalities have occurred. The risk of myopathy is increased by high levels of HMG-CoA reductase inhibitory activity in plasma.

As with other HMG-CoA reductase inhibitors, the risk of myopathy/rhabdomyolysis is dose related. According to the present data, the frequency of myopathy is approximately 0.03%, 0.08% and 0.61% at 20, 40 and 80 mg/day, respectively.

All patients starting therapy with simvastatin, or whose dose of simvastatin is being increased, should be advised of the risk of myopathy and told to report promptly any unexplained muscle pain, tenderness or weakness..

Caution should be exercised in patients with pre-disposing factors for rhabdomyolysis. In order to establish a reference baseline value, a CK level should be measured before starting a treatment in the following situations:

• Elderly (age ≥ 65 years)
• Female patients;
• Renal failure;
• Uncontrolled hypothyroidism;
• Personal or familial history of hereditary muscular disorders;
• Previous history of muscular toxicity with a statin or fibrate;
• Alcohol abuse.

In such situations, the risk of treatment should be considered in relation to possible benefit, and clinical monitoring is recommended. If a patient has previously experienced a muscle disorder on a fibrate or a statin, treatment with a different member of the class should only be initiated with caution. If CK levels are significantly elevated at baseline (> 5 x ULN), treatment should not be started.

During the treatment.

If muscle pain, weakness or cramps occur whilst a patient is receiving treatment with a statin, their CK levels should be measured. If these levels are found, in the absence of strenuous exercise, to be significantly elevated (> 5 x ULN), treatment should be stopped. If muscular symptoms are severe and cause daily discomfort, even if CK levels are < 5 x ULN, treatment discontinuation may be considered. If myopathy is suspected for any other reason, treatment should be discontinued. If symptoms resolve and CK levels return to normal, then re-introduction of the statin or introduction of an alternative statin may be considered at the lowest dose and with close monitoring.

A higher rate of myopathy has been observed in patients titrated to the 80mg dose. Periodic CK measurements are recommended as they may be useful to identify subclinical cases of myopathy. However, there is no assurance that such monitoring will prevent myopathy.

Therapy with simvastatin should be temporarily stopped a few days prior to elective major surgery and when any major medical or surgical condition supervenes.

Measures to reduce the risk of myopathy caused by medicinal product interactions.

The risk of myopathy and rhabdomyolysis is significantly increased by concomitant use of simvastatin with potent inhibitors of CYP3A4 (such as itraconazole, ketoconazole, posaconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors (e.g. nelfinavir), boceprevir, telaprevir, nefazodone), as well as gemfibrozil, ciclosporin and danazol.

The risk of myopathy and rhabdomyolysis is also increased by concomitant use of amiodarone, amlodipine, verapamil or diltiazem with certain doses of simvastatin. The risk is increased with concomitant use of diltiazem or amlodipine with simvastatin 80 mg. The risk of myopathy including rhabdomyolysis may be increased by concomitant administration of fusidic acid with statins.

Consequently, regarding CYP3A4 inhibitors, the use of simvastatin concomitantly with itraconazole, ketoconazole, posaconazole, HIV protease inhibitors (e.g nelfinavir), boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin and nefazodone is contraindicated. If treatment with itraconazole, ketoconazole, posaconazole, erythromycin, clarithromycin or telithromycin is unavoidable, therapy with simvastatin must be suspended during the course of treatment. Moreover, caution should be exercised when combining simvastatin with certain other less potent CYP3A4 inhibitors: fluconazole, verapamil, diltiazem.

Concomitant intake of grapefruit juice and simvastatin should be avoided.

the dose of simvastatin should not exceed 10 mg daily in patients treated with cyclosporine, danazol or gemfibrozil, simultaneously. Concomitant use of simvastatin with gemfibrozil, except when the expected benefits exceed the increased risk of the combination of these drugs (development of myopathy / rhabdomyolysis). The benefits of the concomitant use of simvastatin in the dose of 10 mg daily with other fibrates (except fenofibrate), cyclosporine or danazol should be perused in comparison with the potential risk of use of these combinations.

Caution should be used when prescribing fenofibrate with simvastatin, as either agent can cause myopathy when given alone.

The combined use of simvastatin at doses higher than 20 mg daily with amiodarone, amlodipine, verapamil or diltiazem should be avoided, except when the expected benefits exceed the risk of the development of myopathy.

The combined use of simvastatin at doses higher than 40 mg daily with amlodipine or diltiazem should be avoided, except when the expected benefits exceed the risk of the development of myopathy.

Rare cases of myopathy/rhabdomyolysis have been associated with concomitant administration of HMG-CoA reductase inhibitors and lipid-modifying doses (≥ 1 g/day) of niacin (nicotinic acid), either of which can cause myopathy when given alone.

Physicians contemplating combined therapy with simvastatin and lipid-modifying doses (≥ 1 g/day) of niacin (nicotinic acid) or products containing niacin should carefully weigh the potential benefits and risks and should carefully monitor patients for any signs and symptoms of muscle pain, tenderness, or weakness, particularly during the initial months of therapy and when the dose of either medicinal product is increased.

Therefore, caution should be used when treating Chinese patients with simvastatin (particularly doses of 40 mg or higher) co-administered with lipid-modifying doses (≥ 1 g/day) of niacin (nicotinic acid) or products containing niacin. Because the risk of myopathy with statins is dose-related, the use of simvastatin 80 mg with lipid-modifying doses (≥ 1 g/day) of niacin (nicotinic acid) or products containing niacin is not recommended in Chinese patients.

Hepatic effects

It is recommended that liver function tests be performed before treatment begins and thereafter when clinically indicated. Patients titrated to the 80-mg dose should receive an additional test prior to titration, 3 months after titration to the 80-mg dose, and periodically thereafter (e.g., semi-annually) for the first year of treatment. Special attention should be paid to patients who develop elevated serum transaminase levels, and in these patients, measurements should be repeated promptly and then performed more frequently. If the transaminase levels show evidence of progression, particularly if they rise to 3 x ULN and are persistent, simvastatin should be discontinued.

The product should be used with caution in patients who abuse an alcohol.

Interstitial lung disease

Cases of interstitial lung disease have been reported with some statins, including simvastatin, especially with long term therapy. Presenting features can include dyspnoea, non-productive cough and deterioration in general health (fatigue, weight loss and fever). If it is suspected a patient has developed interstitial lung disease, statin therapy should be discontinued.

This product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Effects on ability to drive and use machines.

Considering the possibility of adverse reactions such as dizziness and convulsions you should refrain from driving or operating machines.

Interaction with other medicinal products and other forms of interaction.

Prescribing recommendations for interacting agents are summarised in the table below

Drug Interactions Associated with Increased Risk of Myopathy/Rhabdomyolysis

Interacting agents	Prescribing recommendations
Potent CYP3A4 inhibitors: Itraconazole Ketoconazole Posaconazole Voriconazole Erythromycin Clarithromycin Telithromycin HIV protease inhibitors  (e.g.nelfinavir) Boceprivir Telaprevir Nefazodone Ciclosporin Danazol Gemfibrozil	Contraindicated with simvastatin
Other fibrates (except fenofibrate)	Do not exceed 10 mg simvastatin daily
Amiodarone Amlodipine Verapamil Diltiazem	Do not exceed 10 mg simvastatin daily
Fusidic acid	Is not recommended with simvastatin
Grapefruit juice	Avoid grapefruit juice when taking simvastatin

 

Lipid-lowering agents that can lead to the development of myopathy

The risk of myopathy and rhabdomyolysis is increased by concomitant administration with fibrates. Moreover, there is a pharmacokinetic interaction with gemfibrozil, which leads to increased levels of simvastatin in plasma. In the combined administration of fenofibrate with simvastatin the risk of myopathy does not exceed the risk in monotherapy with each drug separately. Rare cases of myopathy/rhabdomyolysis are associated with the use of simvastatin along with lipidmodificating doses (≥1h/day) of niacin.

Effects of other medicinal products on simvastatin

Interactions with CYP3A4 inhibitors  

Simvastatin is a substrate of cytochrome P450 3A4. Potent inhibitors of cytochrome P450 3A4 increase the risk of myopathy and rhabdomyolysis by increasing the concentration of HMG-CoA reductase inhibitory activity in plasma during simvastatin therapy. Such inhibitors include itraconazole, ketoconazole, posaconazole, voriconazole, erythromycin, clarithromycin, telithromycin, HIV protease inhibitors (e.g.nelfinavir), boceprevir, telaprevir, and nefazodone. Concomitant administration of itraconazole resulted in a more than 10-fold increase in exposure to simvastatin acid (the active beta-hydroxyacid metabolite). Telithromycin caused an 11-fold increase in exposure to simvastatin acid.

Combination with itraconazole, ketoconazole, posaconazole, HIV protease inhibitors (e.g.nelfinavir), boceprevir, telaprevir, erythromycin, clarithromycin, telithromycin and nefazodone is contraindicated, as well as gemfibrozil, ciclosporin and danazol. If treatment with potent CYP3A4 inhibitors is unavoidable, therapy with simvastatin must be suspended (and use of an alternative statin considered) during the course of treatment. Caution should be exercised when combining simvastatin with certain other less potent CYP3A4 inhibitors: fluconazoleverapamil or diltiazem.

Ciclosporin

The risk of myopathy/rhabdomyolysis is increased by concomitant administration of ciclosporin with simvastatin at high doses. Therefore the dose of simvastatin should not exceed 10 mg daily in patients receiving concomitant use with ciclosporin.

Danazol

The risk of myopathy and rhabdomyolysis is increased by concomitant administration of danazol with high doses of simvastatin.

Gemfibrozil

Gemfibrozil increases the AUC of simvastatin acid by 1.9-fold, possibly due to inhibition of the glucuronidation pathway.

Amiodarone

The risk of myopathy and rhabdomyolysis is increased by concomitant administration of amiodarone with high doses of simvastatin. Therefore the dose of simvastatin should not exceed 20 mg daily in patients receiving concomitant use with amiodarone.

Verapamil

The risk of myopathy and rhabdomyolysis is increased by concomitant administration of verapamil with simvastatin 40 mg or 80 mg. Therefore, the dose of simvastatin should not exceed 20 mg daily in patients receiving concomitant use with verapamil.

Diltiazem

The risk of myopathy and rhabdomyolysis is increased by concomitant administration of diltiazem with simvastatin 80 mg. Therefore, the dose of simvastatin should not exceed 20 mg daily in patients receiving concomitant use with diltiazem.

Amlodipine

The risk of myopathy and rhabdomyolysis is increased by concomitant administration of amlodipine with simvastatin 80 mg. Therefore, the dose of simvastatin should not exceed 20 mg daily in patients receiving concomitant use with amlodipine.

Niacin 

Rare cases of myopathy/rhabdomyolysis have been associated with simvastatin co-administered with lipid-modifying doses (≥ 1 g/day) of niacin (nicotinic acid). In a pharmacokinetic study, the co-administration of a single dose of nicotinic acid prolonged-release 2 g with simvastatin 20 mg resulted in a modest increase in the AUC of simvastatin and simvastatin acid and in the C_max of simvastatin acid plasma concentrations.

Fusidic acid

The risk of myopathy may be increased by the concomitant administration of systemic fusidic acid with statins including simvastatin. If proven necessary, patients taking fusidic acid and simvastatin should be subjected to careful monitoring.

Grapefruit juice

Grapefruit juice inhibits cytochrome P450 3A4. Concomitant intake of large quantities (over 1 litre daily) of grapefruit juice and simvastatin resulted in a 7-fold increase in exposure to simvastatin acid. Intake of grapefruit juice during treatment with simvastatin should therefore be avoided.

Colchicine

There have been reports of myopathy and rhabdomyolysis with the concomitant administration of colchicine and simvastatin in patients with renal insufficiency. Close clinical monitoring of such patients taking this combination is recommended.

Rifampicin

Since rifampicin is a potent CYP3A4 inducer, patients undertaking long-term rifampicin therapy (e.g. treatment of tuberculosis) may experience loss of efficacy of simvastatin.

Effects of simvastatin on the pharmacokinetics of other medicinal products.

Simvastatin does not have an inhibitory effect on cytochrome P450 3A4. Therefore, simvastatin is not expected to affect plasma concentrations of substances metabolised via cytochrome P450 3A4.

Oral anticoagulants

In patients taking coumarin anticoagulants, prothrombin time should be determined before starting simvastatin and frequently enough during early therapy to ensure that no significant alteration of prothrombin time occurs. Once a stable prothrombin time has been documented, prothrombin times can be monitored at the intervals usually recommended for patients on coumarin anticoagulants.  If the dose of simvastatin is changed or discontinued, the same procedure should be repeated. Simvastatin therapy has not been associated with bleeding or with changes in prothrombin time in patients not taking anticoagulants.

Pharmacological propeties.

Pharmacodynamics.

After oral ingestion, simvastatin, which is an inactive lactone, is hydrolyzed in the liver to the corresponding active beta-hydroxyacid form which has a potent activity in inhibiting HMG-CoA reductase (3 hydroxy – 3 methylglutaryl CoA reductase). This enzyme catalyses the conversion of HMG-CoA to mevalonate, an early and rate-limiting step in the biosynthesis of cholesterol.

Simvastatin has been shown to reduce both normal and elevated LDL-C concentrations. LDL is formed from very-low-density protein (VLDL) and is catabolised predominantly by the high affinity LDL receptor. The mechanism of the LDL-lowering effect of Simvastatin may involve both reduction of VLDL cholesterol (VLDL-C) concentration and induction of the LDL receptor, leading to reduced production and increased catabolism of LDL-C. Apolipoprotein B also falls substantially during treatment with Simvastatin. In addition, Simvastatin moderately increases HDL-C and reduces plasma TG. As a result of these changes the ratios of total- to HDL-C and LDL- to HDL-C are reduced.

Pharmacokinetics.

Simvastatin is an inactive lactone which is readily hydrolyzed in vivo to the corresponding beta-hydroxyacid, a potent inhibitor of HMG-CoA reductase. Hydrolysis takes place mainly in the liver; the rate of hydrolysis in human plasma is very slow.

Absorption

Simvastatin is well absorbed and undergoes extensive hepatic first-pass extraction. The extraction in the liver is dependent on the hepatic blood flow. The liver is the primary site of action of the active form. The availability of the betahydroxyacid to the systemic circulation following an oral dose of simvastatin was found to be less than 5 % of the dose. Maximum plasma concentration of active inhibitors is reached approximately 1-2 hours after administration of simvastatin. Concomitant food intake does not affect the absorption. The pharmacokinetics of single and multiple doses of simvastatin showed that no accumulation of medicinal product occurred after multiple dosing.

Distribution

The protein binding of simvastatin and its active metabolite is> 95 %.

Elimination

Simvastatin is a substrate of CYP3A4 (see sections 4.3 and 4.5). The major metabolites of simvastatin present in human plasma are the beta-hydroxyacid and four additional active metabolites. Following an oral dose of radioactive simvastatin to man, 13 % of the radioactivity was excreted in the urine and 60 % in the faeces within 96 hours. Following an intravenous injection of the beta-hydroxyacid metabolite, its half-life averaged 1.9 hours. An average of only 0.3 % of the IV dose was excreted in urine as inhibitors.

Pharmaceutical particulars.

Basic physical and chemical properties:.

SIMVASTATIN 10 ANANTA: light beige to dark beige coloured, oval-shaped, biconvex, film-coated tablets.

SIMVASTATIN 20 ANANTA: beige to yellow-brown coloured, oval-shaped, biconvex, film-coated tablets.

SIMVASTATIN 40 ANANTA: peach to red-brown coloured, oval-shaped, biconvex, film-coated tablets.

Shelf life. 3 years.

Storage conditions. Store in the original package at temperature not exceeding 25 °С. Keep out of the reach of children.

Package.

SIMVASTATIN 10 ANANTA. film-coated tablets, 10 mg in 14 tablets in a blister, 2 blisters in a carton box.

SIMVASTATIN 20 ANANTA. film-coated tablets, 20 mg in 14 tablets in a blister, 2 blisters in a carton box.

SIMVASTATIN 40 ANANTA. film-coated tablets, 40 mg in 14 tablets in a blister, 2 blisters in a carton box.

Terms of dispensing. On prescription.

Manufacturer. Marksans Pharma Ltd.

Manufacturer’s registered address.

Legal address:

Lotus Business Park, Off New Link Road, Andheri (West), Mumbai – 400053, India.

Manufacturing site address:

Plot No. L-82, L-83, Verna Industrial Estate, Verna Goa, ІN - 403 722, India.

Applicant. Ananta Medicare Ltd.

Applicant’s registered address.

Suite 1, 2 Station Court, Imperial Wharf, Townmead Road, Fulham, London, United Kingdom.

Date of last update. 31.10.2014.