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Logo NOVALES 20

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

NOVALES 20

COMPOSITION:
Each NOVALES 20 tablet contains
Pravastatin sodium 20 mg

PHARMACOLOGICAL CLASSIFICATION:
A 7.5 Serum cholesterol reducers

PHARMACOLOGICAL ACTION:
Pravastatin
is a cholesterol-lowering agent derived synthetically from a fermentation product of Aspergillus terreus. It is administered in an active beta-hydroxyacid 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 Pravastatin reduces total plasma cholesterol, low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) cholesterol concentrations. Apolipoprotein B is also decreased. In addition, Pravastatin moderately decreases high density lipoprotein (HDL) cholesterol and variably reduces plasma triglycerides.
Pharmacokinetics:
There is an extensive first pass extraction by the liver, with oral bioavailability of the active medicine or metabolites being less than 5%. More than 95% of Pravastatin and its beta-hydroxy metabolite are bound to plasma proteins. Following an oral dose, peak plasma concentrations of Pravastatin are seen in 1-2 hours. Pravastatin is excreted primarily via the liver, and less than 13% of its metabolites are excreted in the urine.

INDICATIONS:
HYPERCHOLESTEROLAEMIA
NOVALES 20 is indicated, in combination with diet, to decrease elevated serum total cholesterol and LDL cholesterol in patients with:
Primary hypercholesterolaemia
Heterozygous familial hypercholesterolaemia or;
Mixed hyperlipidaemia, when response to diet or other non-pharmacological measures alone are not adequate.
CORONARY HEART DISEASE (PREVENTION)
NOVALES 20 is indicated in patients with coronary heart disease and hypercholesterolaemia unresponsive to diet, to:
Reduce the risk of total mortality, by reducing coronary death
Reduce the risk of non-fatal myocardial infarction
Reduce the risk of undergoing myocardial revascularisation procedures (coronary artery bypass grafting and percutaneous transluminal coronary angioplasty) and
Slow the progression of coronary atherosclerosis

CONTRA-INDICATIONS:
Hypersensitivity to NOVALES 20, 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 NOVALES 20 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 NOVALES 20, 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 fibrates and niacin, are given with NOVALES 20. A maximum dose of 10 mg NOVALES daily is recommended in patients taking cyclosporine, fibrates or lipid lowering doses of niacin (nicotinic).
Digoxin:
NOVALES 20 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 coumarin anticoagulants should have their INR determined before starting NOVALES 20 therapy. The INR should be monitored frequently enough in the early stages of therapy until stabilised. 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 dosage adjustment of NOVALES 20, this procedure should be repeated.
Bile acid sequestrants
NOVALES 20 should be taken I hour before or 4 hours after cholestyramine. Concurrent use may decrease the bioavailability of NOVALES 20.

PREGNANCY AND LACTATION:
Safety in pregnancy and lactation have not been established.
The active metabolite of NOVALES 20 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 NOVALES 20 therapy.
HYPERCHOLESTEROLAEMIA
Adults: initial dose 10 mg daily as a single dose in the evening. The dose of NOVALES 20 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: Initial dose: 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.
NOVALES 20 can be taken on an empty stomach or with meals.
DOSAGE IN RENAL INSUFFICIENCY
NOVALES 20 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, NOVALES 20 therapy should be closely monitored and doses above 10 mg/day should be implemented with caution.
Concomitant therapy
NOVALES 20 is effective alone or in combination with bile acid sequestrants. When both medicines are prescribed, NOVALES 20 should be given 1 hour before or 4 hours after cholestyramine administration (see ‘Interactions’).
A maximum daily dose of 10 mg NOVALES 20 is recommended in patients taking cyclosporin, fibrates or niacin concomitantly (see ‘Interactions’).

SIDE EFFECTS AND SPECIAL PRECAUTIONS:
Very common (>1/10); common (>1/100, <1/10); uncommon (>1/1,000, <1/100); rare (>1/10,000, <1/1,000); very rare (<1/10,000)
Side effects
Gastrointestinal reactions:
Most Common: constipation, diarrhoea, nausea, vomiting, flatulence, dyspepsia, abdominal pain, cramps and pancreatitis.
Hypersensitivity reactions:
The following side effects have been reported and frequencies are unknown:
Angioedema, lupus-like syndrome, polymyalgia, rheumatica, thrombocytopenia, increased erythrocytes sedimentation rate, eosinophilia, arthritis, arthralgia, vasculitis, urticaria, photosensitivity, fever, flushing, malaise and dypsnoea
Haematological reactions:
The following side effects have been reported and frequencies are unknown:
Anaemia and neutropenia
Central Nervous System reactions:
The following side effects have been reported and frequencies are unknown:
Headache, fatigue, dizziness, parasthesia and peripheral neuropathy
Musculoskeletal reactions:
The following side effects have been reported and frequencies are unknown:
Myalgia, muscle cramps, myopathy, myositis
Rare: rhabdomyolysis presenting as muscle pain with elevated creatinine phosphokinase and myoglobinuria leading to renal failure
Skin and appendages reactions:
The following side effects have been reported and frequencies are unknown:
Skin rash and alopecia
Other:
Mass gain has been reported
Laboratory test findings:
Marked and persistent increases of serum transaminases and elevated alkaline phosphatase and gamma-glutamyl transpeptidase have been reported. Liver function test abnormalities have generally been mild and transient. Increases in serum creatinine kinase (CK) levels, derived from skeletal muscle, have been reported (see ‘Special Precautions’).
Special Precautions:
NOVALES 20
should be used with caution in patients who:
Consume large amounts of alcohol and/or who have a history of liver disease
May be predisposed to developing renal failure secondary to rhabdomyolysis, such as 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 rhabdomyolysis occurs
Have severe renal impairment
Hepatic effects:
Liver function tests, including serum transaminase determinations are recommended prior to initiation of NOVALES 20 therapy and periodically until one year after the last elevation in dose. NOVALES 20 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 NOVALES 20 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. NOVALES 20 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 NOVALES 20 concomitantly with immunosuppressants, fibrates or lipid-lowering doses of niacin should be carefully considered, and the dose of NOVALES 20 generally not exceeds 10 mg/day. Concomitant administration with cyclosporine, itraconazole, ketoconazole, erythromycin, clarithromycin, HIV-protease inhibitors and nefazodone is not recommended.
  In patients receiving cyclosporine, NOVALES 20 should be temporarily discontinued if systemic azole derivatives - antifungal therapy is required.

KNOWN SYMPTOMS OF OVER-DOSAGE 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:
NOVALES 20
- Pink, deep convex-void, film-coated tablet

PRESENTATION:
NOVALES 20
- Unit carton containing 30 tablets in silver foil blister strips of 10 tablets each.

STORAGE INSTRUCTIONS:
Store at room temperature not exceeding 25ºC
Protect from light and moisture. Do not remove tablets from unit carton until required for use.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER:
A40/7.5/0749

NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION:
Gulf Drug Company (Pty) Ltd.
22 Burnside Drive
Old Mill Industrial Park
Mount Edgecombe, 4300

DATE OF PUBLICATION OF THE PACKAGE INSERT:
05/03/2009

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

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