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Logo REDICOR 10 (film-coated tablets)
REDICOR 20 (film-coated tablets)
REDICOR 40 (film-coated tablets)

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

REDICOR 10 (film-coated tablets)
REDICOR 20 (film-coated tablets)
REDICOR 40 (film-coated tablets)

COMPOSITION:
REDICOR 10:
Each film-coated tablet contains
simvastatin 10 mg
REDICOR 20: Each film-coated tablet contains simvastatin 20 mg
REDICOR 40: Each film-coated tablet contains simvastatin 40 mg

PHARMACOLOGICAL CLASSIFICATION
A 7.5 Serum-cholesterol reducers

PHARMACOLOGICAL ACTION
Simvastatin is a cholesterol-lowering agent derived synthetically from a fermentation product of Aspergillus terreus. After oral ingestion simvastatin, an inactive lactone, is hydrolysed to the corresponding beta-hydroxyacid, the active form. This is a principal metabolite and an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, the enzyme that catalyses the conversion of HMG-CoA to mevalonate, an early and rate-limiting step in the biosynthesis of cholesterol. As a result simvastatin reduces total plasma cholesterol, low-density lipoprotein (LDL)- and very low-density lipoprotein (VLDL)-cholesterol concentrations. Apolipoprotein B is also decreased. In addition, simvastatin moderately increases high-density lipoprotein (HDL)-cholesterol and variably reduces plasma triglycerides.
Pharmacokinetics
There is extensive first-pass extraction by the liver, with oral bioavailability of the active medicine or metabolites being less than 5 %. More than 95 % of simvastatin and its beta-hydroxy metabolite are bound to plasma proteins. Following an oral dose peak plasma concentrations of simvastatin are seen in 1 to 2 hours. Simvastatin is excreted primarily via the liver and less than 13 % of its metabolites are excreted in the urine.

INDICATIONS
Hypercholesterolaemia
REDICOR
is indicated in combination with diet, to decrease elevated serum total cholesterol and LDL-cholesterol in patients with:
1. Primary hypercholesterolaemia
2. Heterozygous familial hypercholesterolaemia, or
3. Mixed hyperlipidaemia when response to diet or other non-pharmacological measures alone is not adequate.
Coronary heart disease
REDICOR
is indicated in patients with coronary heart disease and hypercholesterolaemia unresponsive to diet to:
1. Reduce the risk of total mortality by reducing coronary death
2. Reduce the risk of non-fatal myocardial infarction
3. Reduce the risk of undergoing myocardial revascularization procedures (coronary artery bypass grafting and percutaneous transluminal coronary angioplasty) and
4. Slow the progression of coronary atherosclerosis.

CONTRAINDICATIONS
Hypersensitivity to simvastatin, other HMG-CoA reductase inhibitors or any of the ingredients.
Acute or chronic liver disease.
Unexplained persistent elevations of serum transaminases.
Pregnancy and lactation (see WARNINGS).
Porphyria: Safety has not been established.

WARNINGS
The active metabolite of REDICOR is fetotoxic and teratogenic in rats and it should therefore not be used in female patients of child-bearing potential.
Use in paediatric patients is not recommended as safety and efficacy have not been established.

INTERACTIONS
Myopathy caused by medicine interactions
Concomitant administration of medicines that inhibit cytochrome P450 isoenzyme CYP3A4 may result in high plasma levels of REDICOR thus increasing the risk of myopathy and is not recommended. Medicines that inhibit cytochrome P450 isoenzyme CYP3A4 include: cyclosporine, itraconazole, ketoconazole, erythromycin, clarithromycin, HIV-protease inhibitors and nefazodone.
The risk of myopathy is increased when other medicines that cause myopathy, such as fribrates and niacin, are given with REDICOR. A maximum dose of 10 mg REDICOR daily is recommended in patients taking cyclosporine, fibrates or lipid lowering doses of niacin (nicotinic acid).
Digoxin
REDICOR
may cause increases in digoxin levels.
Coumarin-derivatives (e.g. warfarin):
A possible increase in the anticoagulant effect of the coumarin anticoagulants may occur. Patients taking a coumarin anticoagulant should have their INR determined before starting REDICOR therapy. The INR should be monitored frequently enough in the early stages of therapy until stabilized. Once a stable INR has been documented, INR can be monitored at the intervals usually recommended for patients on coumarin anticoagulants. When there is a dose adjustment of REDICOR this procedure should be repeated.
Bile acid sequestrants:
REDICOR
should be taken 1 hour before or 4 hours after cholestyramine. Concurrent use may decrease the bioavailability of REDICOR.

PREGNANCY AND LACTATION
Safety in pregnancy and lactation has not been established.
The active metabolite of simvastatin is fetotoxic and teratogenic in rats, and it should therefore not be used in female patients of child-bearing potential.

DOSAGE AND DIRECTIONS FOR USE
The patient must follow a cholesterol-lowering diet before initiation of and while on REDICOR therapy.
Hypercholesterolaemia
Adults: An initial dose of 10 mg daily as a single dose in the evening.
The dose of REDICOR should be reduced if LDL-cholesterol levels fall below 1,94 mmol/L, or total plasma cholesterol levels fall below 3,6 mmol/L.

Coronary heart disease
Adults: An initial dose of 20 mg/day as a single dose in the evening.
Dosage Adjustments:
If required the dose should be adjusted at intervals of not less than 4 weeks, up to a maximum of 80 mg daily as a single dose in the evening.
REDICOR can be taken with meals or on an empty stomach.

Renal insufficiency
REDICOR
does not undergo significant renal excretion, therefore modification of dose should not be necessary in patients with mild to moderate renal insufficiency. In patients with severe renal insufficiency REDICOR therapy should be closely monitored and doses above 10 mg/day should be implemented with caution.

Concomitant therapy
REDICOR
is effective alone or in combination with bile acid sequestrants.
When both medicines are prescribed REDICOR should be given 1 hour before or 4 hours after cholestyramine administration (see INTERACTIONS).
A maximum daily dose of 10 mg REDICOR is recommended in patients taking cyclosporine, fibrates or niacin concomitantly (see INTERACTIONS).

SIDE-EFFECTS AND SPECIAL PRECAUTIONS
Side-effects:
Very common (>1/10), Common (> 1/100 and <1/10), Uncommon (> 1/1000 and < 1/100), Rare (> 1/10 000 and <1/1000), Very rare (< 1/10 000)
Blood and lymphatic system disorders
Rare: Anaemia
Incidence unknown: Neutropenia
Metabolic and nutritional disorders
Incidence unknown: Weight gain
Nervous system disorders
Rare: Headache, dizziness, paraesthesia, peripheral neuropathy
Incidence unknown: Fatique
Gastrointestinal disorders
Rare: Constipation, abdominal pain, flatulence, dyspepsia, diarrhoea, nausea, vomiting, pancreatitis
Hepato-biliary disorders
Rare: Hepatitis, jaundice
Skin and subcutaneous tissue disorders
Rare: Rash, pruritis, alopecia
Musculoskeletal, connective tissue and bone disorders
Rare: Myalgia, muscle cramps, asthenia, myopathy, rhabdomyolysis (with or without acute renal failure)
General disorders and administration site conditions
Rare: An apparent hypersensitivity syndrome has been reported. Reactions may include angioedema, lupus-like syndrome, polymyalgia rheumatica, vasculitis, thrombocytopenia, increased erythrocyte sedimentation rate (ESR), eosinophilia, arthritis, arthralgia, urticaria, photosensitivity, fever, flushing, malaise and dyspnoea
Investigations
Rare: Increases in serum transaminases (alanine aminotransferase, gamma glutamyl transpeptidase), elevated alkaline phosphatase, increases in serum creatine kinase (CK) levels (derived from skeletal muscle) (see Special Precautions).

Special precautions
REDICOR
should be used with caution in patients who:
1. consume substantial amounts of alcohol and/or who have a history of liver disease
2. may be predisposed to developing renal failure secondary to rhabdomyolsis such as in those with severe acute infection, hypotension, severe metabolic, endocrine or electrolyte disorders, uncontrolled seizures, major surgery or trauma. There is an increased risk of developing renal failure if rhabdomyolsis occurs.
3. have severe renal impairment
Hepatic effects
Liver function tests, including serum transaminase determinations, are recommended prior to initiation of REDICOR therapy and periodically until one year after the last elevation in dose. REDICOR should be discontinued if the rise in transaminase levels is persistent and/or increases to three times or more the upper limit of normal (ULN).
Myopathy
Reducing the risk of myopathy
1. General measures
  Patients starting therapy with REDICOR should be advised of the risk of myopathy and should report promptly unexplained muscle pain, tenderness or weakness. A creatinine kinase (CK) level above 10 times the Upper Limit of Normal (ULN) in a patient, with unexplained symptoms, indicates myopathy. REDICOR should be discontinued if myopathy is diagnosed or suspected.
2. Measures to reduce the risk of myopathy caused by medicine interactions
The benefits and risks of using REDICOR concomitantly with immunosuppresants, fibrates or lipid lowering doses of niacin should be carefully considered and the dose of REDICOR should generally not exceed 10 mg/day. Concomitant administration with cyclosporine, itraconazole, ketoconazole, erythromycin, clarithromycin, HIV-protease inhibitors and nefazodone, is not recommended.
In patients receiving cyclosporine, REDICOR should be temporarily discontinued if systemic azole derivative-antifungal therapy is required.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
(See SIDE-EFFECTS AND SPECIAL PRECAUTIONS).
General measures should be adopted and liver function should be monitored.
Treatment is symptomatic and supportive.

IDENTIFICATION
REDICOR 10
: Brown coloured, round biconvex film-coated tablets debossed with “RDY”on one side and “198”on other side.
REDICOR 20: Brown coloured, round biconvex film-coated tablets debossed with “RDY”on one side and “199”on other side.
REDICOR 40: Brown coloured, round biconvex film-coated tablets debossed with “RDY”on one side and “200”on other side.

PRESENTATION
REDICOR 10
: 30 film-coated tablets packed in white HDPE bottles
REDICOR 20: 30 film-coated tablets packed in white HDPE bottles
REDICOR 40: 30 film-coated tablets packed in white HDPE bottles

STORAGE INSTRUCTIONS
Store below 25ºC
Protect from light. Ensure the bottle is well closed.
KEEP OUT OF REACH OF CHILDREN

REGISTRATION NUMBERS
REDICOR 10
: 41/7.5/0549
REDICOR 20: 41/7.5/0550
REDICOR 40: 41/7.5/0551

NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION
Dr Reddy’s Laboratories (Pty) Limited
381 Rossouw Street
Murrayfield
Pretoria
0184

DATE OF PUBLICATION OF PACKAGE INSERT
April 2008

New addition to this site: March 2010
Source
: Pharmaceutical Industry

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