NEOSIMVA 10 mg. 28 tablets

Patients at high risk for developing ischemic heart disease (IHD) or with proven coronary artery disease
In patients with a high risk of developing coronary heart disease (with or without hyperlipidemia), i.e. in patients with diabetes, history of stroke or other cerebrovascular disease, peripheral vascular disease or with known coronary artery disease, Neosimva is indicated for:
Reduction of total mortality by reducing CHD mortality;
Reducing the risk of major cardiovascular events (nonfatal myocardial infarction, coronary death, stroke or revascularization procedures);
Reducing the risk of major coronary events (nonfatal myocardial infarction or coronary death);
Reducing the risk of stroke;
Reducing the need for coronary revascularization procedures (coronary artery bypass graft and percutaneous coronary intervention);
Reducing the need for peripheral and other nekoronarni revascularization procedures;
Reduce the risk of hospitalization for angina.
In patients with diabetes, Neosimva is indicated to reduce the risk of complications of the large peripheral vessels (peripheral revascularization procedures, amputations of the lower limbs or ulceration of the legs).
In patients with coronary artery disease and hypercholesterolemia, Neosimva is indicated to slow the progression of coronary atherosclerosis, incl. reducing the development of new lesions and new total occlusions.

Patients with hyperlipidemia
Neosimva is shown in addition to the diet to reduce elevated levels of total cholesterol (total-C) and LDL-C, triglycerides (TG) and apolipoprotein B (apo-B), and for increasing high density cholesterol (HDL-C) in patients with primary hypercholesterolaemia, including heterozygous familial hypercholesterolemia (Fredrickson Type IIa) or combined (mixed) hyperlipidemia (Fredrickson Type IIb), when response to diet and other relevant nonpharmacological measures is inadequate. Neosimva ratios lowers LDL / FTOL and total cholesterol / HDL.
Neosimva is indicated for treatment of patients with hypertriglyceridemia (Fredrickson Type IV hyperlipidemia);
Neosimva is indicated for treatment of patients with primary dysbetaliproteinemia (Fredrickson Type III hyperlipidemia);
Neosimva is also shown in addition to diet and other nedietichni measures for the treatment of patients with homozygous familial hypercholesterolemia to reduce elevated total-C, LDL-C, apo-B.
2. BEFORE YOU TAKE NEOSIMVA
Do not take Neosimva under the following conditions:
Hypersensitivity to any component of this preparation.
Active liver disease or unexplained persistent elevations of serum transaminases.
Pregnancy and lactation (see Pregnancy and lactation).
Special considerations for treatment Neosimva
Myopathy / rhabdomyolysis
The active ingredient Simvastatin, as well as other products with a similar mechanism of action sometimes causes myopathy manifested as muscle pain or weakness associated with elevated levels of creatine kinase (CK) more than 10 times the upper limit of normal. Myopathy sometimes takes the form of rhabdomyolysis with or without acute renal failure secondary to myoglobinuria, and in rare cases fatal outcome has occurred.
The risk of myopathy / rhabdomyolysis is increased by concomitant use of Neosimva with the following medications:
Medicaments containing: Itraconazole, Ketoconazole, Erythromycin, Clarithromycin, Telithromycin, HTV-protease inhibitors, or Nefazodone, especially at higher doses Neosimva.
Lipid lowering drugs that can cause myopathy. when given alone: Gemfibrozil, other fibrates, Niacin (nicotinic acid) lipid lowering doses (> 1 g / day), especially with the higher doses Neosimva.
Cyclosporine: especially with large doses Neosimva.
Diltiazem: The risk of myopathy is increased slightly in patients Diltiazem, which simultaneously take Neosimva 80 mg. In these patients, the risk of myopathy is approximately 1%.
The risk of myopathy / rhabdomyolysis is dose-dependent. In this connection should be the following:
Hepatic effects
In various clinical trials have seen constant increases (to more than 3 times ULN) in serum transaminases in a few adult patients who received Simvastatin, when treatment was interrupted or stopped in these patients, the transaminase levels They were decreasing gradually to predterapevtichnite. It is recommended that the conduct of liver function tests before initiation of treatment, and thereafter when clinically indicated. Patients whose dose was increased to 80 mg, should be tested further before the increase, three months after the increase to 80 mg, and thereafter periodically during treatment (eg 6 months) in the first year of treatment.
The preparation should be administered with caution in patients who consume substantial quantities of alcohol and / or have a history of liver disease. Active liver diseases or unexplained transaminase elevations are contraindications to the use of Neosimva.

Ophthalmic manifestations
Even if the application of any drug therapy, gradual reduction transparency of the lens can be explained by the aging process. At present the results from a long period of clinical trials have not shown adverse side effects of Simvastatin on human ocular lens.

Pediatric Use
The safety and efficacy of its use in children has not yet been established. Currently Simvastatin is not recommended for pediatric use.

Use in Elderly
In patients older than 65 years who are receiving Simvastatin in different controlled clinical studies, the efficacy, as measured by the degree of reduction in the levels of total and LDL-cholesterol is similar to that in the general population, and also there was no increased incidence abnormal clinical and laboratory findings.

Information about intolerance to some sugars
If your doctor has told you that you have an intolerance to some sugars, contact him before taking this medicine. Neosimva contains lactose.

Taking other medicines
Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines, including medicines obtained without a prescription.

Interactions:
Cyclosporine: The risk of myopathy / rhabdomyolysis is increased by concomitant administration of cyclosporine, especially with high doses Neosimva.
Amiodarone or Verapamil: The risk of myopathy / rhabdomyolysis is increased by concomitant use of higher doses Neosimva c Amiodarone or Verapamil.
Diltiazem: Patients taking both Diltiazem and Neosimva 80 mg have a slightly increased risk of myopathy.
Interactions
Grapefruit juice contains one or more components which inhibit CYP3A4 and can increase plasma levels of drugs which are metabolized by CYP3A4. The effect of usual consumption (one 250 mL glass daily) is minimal and not clinically significant. Very large quantities (more than 1 liter per day), however, must be avoided.

Coumarin derivatives
It was found that Simvastatin 20-40 mg daily moderately potentiates the effect of coumarin 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, it should be monitored during normal for patients on coumarin anticoagulants intervals. If the dose of Simvastatin is changed or it is stopped it must proceed in the same way. Simvastatin therapy is not associated with bleeding or with changes in prothrombin time in patients not taking anticoagulants.

Propranolol
In healthy volunteers, there was no clinically significant pharmacokinetic or pharmacodynamic interactions when co-administration of single doses of Simvastatin and Propranolol.

Digoxin
Co-administration of Simvastatin and Digoxin in healthy volunteers resulted in a slight increase (less than 0,3 mg / ml) of drug concentration (as measured by radioimmunoassay experience with digoxin) in plasma, as compared to co-administration of placebo and Digoxin .

Other concomitant therapy
In clinical studies Simvastatin was administered concomitantly with angiotensin converting enzyme (ACE) inhibitors, beta blockers, diuretics, non-steroidal anti-inflammatory drugs (NSAIDs) without evidence of clinically significant adverse interactions.

Pregnancy and lactation
Ask your doctor or pharmacist before taking any medicine.

Pregnancy
Neosimva is contraindicated during pregnancy.
Safety in pregnant women has not been established. No controlled clinical trials with Simvastatin, conducted in pregnant women.
Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on long-term risk associated with primary hypercholesterolemia. For these reasons Neosimva should not be used in pregnant women, women intending to become pregnant or those suspected of being pregnant. Neosimva treatment should be discontinued during pregnancy or until it is established that the woman is not pregnant.

Use during lactation
It is not known if Simvastatin or its metabolites are excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious side effects, women receiving Neosimva, should not breastfeed.

Driving and using machines
There is no evidence to suggest that the adoption of Neosimva would affect the ability to drive and use machines.

3. HOW TO TAKE NEOSIMVA
Always take Neosimva, exactly as your doctor has told you. If you're not sure, ask your doctor or pharmacist.
Neosimva dosage varies from 5 to 80 mg per day taken once daily in the evening. When appropriate, dose adjustments were made at intervals of no less than 4 weeks, up to a maximum dose of 80 mg once daily in the evening.

Patients at high risk for developing ischemic heart disease (IHD) or with proven coronary artery disease
Patients at high risk of developing CHD (with or without hyperlipidaemia), ie patients with diabetes, history of stroke or other cerebrovascular disease, peripheral vascular disease or with known coronary artery disease, the usual starting dose of Neosimva is 40 mg once daily in the evening. Medical treatment can be started simultaneously with diet or exercise.

Patients with hyperlipidemia (not included in the higher risk category)
The patient should be placed on a standard cholesterol-lowering diet before Neosimva implementation of and compliance with this diet should be continued during treatment with Neosimva. The usual starting dose is 20 mg per day to be administered in a single night. For patients who need large reductions in LDL-C (over 45%) may be initiated at a dose of 40 mg once daily in the evening. Patients with mild to moderate hypercholesterolemia can be treated with a starting dose of 10 mg Neosimva. Must be carried out adjusting the dose if necessary, as shown above.

Patients with homozygous familial hypercholesterolemia
The recommended dosage for patients with homozygous familial hypercholesterolemia is Neosimva 40 mg daily in the evening or 80 mg daily in 3 divided doses - 20 mg, 20 mg, and an evening dose of 40 mg. Neosimva must be used in addition to other cholesterol reducing treatment (eg. LDL apheresis) in these patients or if such treatment exists.

Accompanying therapy
Neosimva is effective alone or in combination with bile acid sequestrants. Patients taking Cyclosporine, Gemfibrozil, other fibrates (except Fenofibrate) or Niacin (nicotinic acid) lipid lowering doses (> 1g daily) in combination with Neosimva, the dose should not exceed 10 mg daily. In patients receiving Neosimva with Amiodarone or Verapamil, the dose should not exceed 20 mg daily.

Dosage in renal insufficiency
Because Simvastatin does not undergo significant renal excretion is not necessary dose adjustment in patients with moderate renal insufficiency.
In patients with severe renal insufficiency (creatinine clearance <30ml / min) doses exceeding 10 mg daily should be carefully discussed, and assuming that needed to be applied with great care.
If you have any further questions on the use of this product, ask your doctor or pharmacist.

4. POSSIBLE SIDE EFFECTS
Like all medicines, Neosimva can cause side effects, although not everybody gets them.
If any of the side effects gets serious, or you notice other effects not listed in this leaflet, please tell your doctor or pharmacist.
Neosimva generally well tolerated; the majority of reported adverse reactions were mild and transient.
Observed adverse reactions occurring at a frequency of 1% or more and considered as possibly, probably or definitely related to the drug were abdominal pain, constipation and flatulence.
Other side effects were asthenia and headache. Myopathy has been reported rarely. The following additional adverse reactions have been observed in daily use: nausea, diarrhea, rash, dyspepsia, pruritus, alopecia, dizziness, muscle cramps, myalgia, pancreatitis, paresthesia, peripheral neuropathy, vomiting and anemia. Rarely occur rhabdomyolysis and hepatitis / jaundice. Comparatively rarely observed pronounced hypersensitivity syndrome, which include some of the following symptoms: angioedema, lupus-like syndrome, polymyalgia rheumatica, dermatomyositis, vasculitis, thrombocytopenia, eosinophilia, increased ESR, arthritis, arthralgia, urticaria, photosensitivity, fever, flushing, dyspnea and fatigue.

Laboratory abnormalities
For significant and persistent increases of serum transaminases have been reported rarely. There have been reports of an increase in alkaline phosphatase and g-glutamyl transpeptidase. Deviations in liver function tests have been mild and transient. Reported elevated levels of serum creatine kinase (CK) released from skeletal muscle.
There is evidence for these side effects, but not established a causal relationship to therapy with Simvastatin: depression, erythema multiforme, including syndrome Stevens-Johnson, leukopenia and purpura.

5. HOW TO STORE NEOSIMVA
Keep at temperatures below 25 ° C. Keep out of reach of children.
Do not use Neosimva after the expiry date stated on the label and carton. The expiry date refers to the last day of that month.
Medicines should not be disposed of in wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

6. FURTHER INFORMATION
What Neosimva
The active ingredient is simvastatin (Simvastatiri).
The other ingredients are lactose, microcrystalline cellulose, pregelatinized starch (starch 1500), ascorbic acid, citric acid monohydrate, butylated hydroxyl anisole, magnesium stearate, Opadry 20A54692 pink.

Neosimva looks like and contents of the pack
Film-coated tablets for oral administration in blister PVC / aluminum foil, packaged in a carton containing patient information leaflet. The package is 14 or 28 tablets.