INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo LOVACHOL 20 mg (tablets)
LOVACHOL 40 mg (tablets)

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

LOVACHOL 20 mg (tablets)
LOVACHOL 40 mg (tablets)

COMPOSITION
Each tablet contains
Lovastatin 20 mg or 40 mg.

PHARMACOLOGICAL CLASSIFICATION
A.7.5 Serum-cholesterol reducers

PHARMACOLOGICAL ACTION
Lovastatin is a cholesterol-lowering agent isolated from a strain of Aspergillus terreus. After oral ingestion, lovastatin, which is an inactive lactone, is hydrolyzed to the corresponding beta-hydroxyacid form. This principal metabolite is a specific inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase
This enzyme catalyzes the conversion of HMG-CoA to mevalonate, which is an early and rate-limiting step in the biosynthesis of cholesterol
Lovastatin reduces cholesterol production by the liver and induces some changes in cholesterol transport and disposition in the blood and tissues. The mechanism(s) of this effect is believed to involve both reduction of the synthesis of Low Density Lipoprotein (LDL), and an increase in LDL catabolism as a result of induction of the hepatic LDL receptors .

INDICATIONS
Lovastatin is indicated as an adjunct to diet for the reduction of elevated total and Low Density Lipoprotein Cholesterol (LDL-C) levels in patients with primary hypercholesterolemia (Types 11a and 11b), when the response to diet and other measures alone has been inadequate.

CONTRA-INDICATIONS
Hypersensitivity to any component of this medication.
Active liver disease or unexplained persistent elevations of serum-aminotransaminases and creatine-phosphokinase. If such a condition develops during therapy, the medicine should be discontinued.
Pregnancy due to possible interference with foetal sterol synthesis and lactation
The safe use of LOVACHOL in children have not been established and is thus not recommended.

WARNINGS
Based on present clinical experience in patients with liver dysfunction, it is recommended that liver function tests be performed at baseline and every 4 - 6 weeks during the first 15 months of therapy with Lovachol and periodically thereafter in all patients. Particular 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 three times the upper limit of normal and are persistent, the drug should be discontinued.
If elevations are persistent beyond discontinuation of the drug, further investigations should be carried out and liver biopsy may be considered if necessary. The medicine should be used with caution in patients who consume substantial quantities of alcohol and/or have a past history of liver disease.
Most of the patients who have developed myopathy were receiving concomitant therapy with immunosuppressive drugs which included cyclosporine, gemfibrozil or lipid-lowering doses of niacin. In clinical trials, about 30% of patients on immunosuppressive therapy, including cyclosporine, developed myopathy within a year after starting therapy with Lovachol. The corresponding incidence figures for concomitant therapy with gemfibrozil and niacin were approximately 5% and 2% respectively. It is not known whether the same phenomenon occurs with concomitant use of Lovachol and fibrates other than gemfibrozil.
Therefore, the benefits and risks of using lovastatin concomitantly with immunosuppressive medicines, fibrates or lipid-lowering doses of niacin should be carefully considered.
Interruption of therapy with lovastatin should be considered in any patient with a risk factor predisposing to the development of renal failure or rhabdomyolysis, such as severe acute infection, hypotension, major surgery, trauma, severe metabolic, endocrine or electrolyte disorders and uncontrolled seizures.

DOSAGE AND DIRECTIONS FOR USE
The patient should be placed on a standard cholesterol-lowering diet before receiving LOVACHOL and should continue on this diet during treatment with LOVACHOL. If appropriate, a program of weight control and physical exercise should be implemented.
The usual starting dose is 20 mg/day given as a single dose with the evening meal. Single daily doses given with the evening meal have been shown to be more effective than the same dose given with the morning meal, perhaps because cholesterol is synthesized mainly at night. Adjustments of dosage, if require, should be made at intervals of not less than 4 weeks, to a maximum of 80 mg daily given in single doses or divided doses with the morning and evening meals. Divided doses (i.e. twice daily) tend to be slightly more effective than single daily doses.
The safe use of LOVACHOL in children has not been established and is thus not recommended.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS
The most common side-effects are gastro-intestinal disturbances.
Other adverse effects reported include headache, skin rashes, dizziness, blurred vision and dysgeusia.
Reversible increases in serum-aminotransferase concentrations may occur and liver function should be monitored.
Myopathy characterised by myalgia and muscle weakness and associated with increased creatine phosphokinase concentrations has been reported, especially in patients taking LOVACHOL concurrently with immunosuppresive medicines, fibric acid derivatives or nicotinic acid.
Rarely rhabdomyolysis with acute renal failure may develop.
Before instituting therapy with LOVACHOL (lovastatin), an attempt should be made to control hypercholesterolemia with appropriate diet, exercise, weight reduction in overweight and obese patients, and to treat other underlying medical problems (see INDICATIONS AND DOSAGE AND DIRECTIONS FOR USE). The patient should be advised to inform subsequent physicians of the prior use of LOVACHOL.
There is no unequivocal evidence that LOVACHOL causes human lens opacities, but lack of an effect on the lens has not been established.
No clinically significant change in visual acuity was reported nor was any patient discontinued from therapy because of a decrease in visual acuity.
Nevertheless, until further experience is obtained, it is recommended that patients placed on LOVACHOL therapy be subjected to an examination of the lens before or shortly after initiation of treatment, and annually thereafter.
Use in Homozygous Familial Hypercholesterolemia
Lovastatin is less effective in patients with the rare homozygous familial hypercholesterolemia, possibly because these patients have no or very low levels of LDL receptor activity. LOVACHOL appears to be more likely to raise serum transaminases in these homozygous patients.
Use in patients with impaired renal function
Lovastatin does not undergo significant renal excretion. However, caution should be exercised in patients with significantly impaired renal function.

INTERACTIONS
Other lipid-lowering agents

Preliminary evidence suggests that the cholesterol lowering effects of LOVACHOL and the bile acid sequestrant, cholestyramine, are additive.
There is insufficient information to date on the co-administration of Lovachol with other lipid-lowering agents. Therefore caution must be exercised, particularly in the case of gemfibrozil and niacin.
Coumarin Anticoagulants
Clinically evident bleeding and/or increased prothrombin time have been reported occasionally in patients taking coumarin anticoagulants concomitantly with lovastatin.
Careful monitoring of prothrombin time is therefore recommended in such cases.
Digoxin
In patients with hypercholesterolemia, concomitant administration of LOVACHOL and digoxin resulted in no effect on digoxin plasma concentrations.
Beta-Adrenergic Blocking Medicines
In healthy volunteers, the co-administration of propranolol and LOVACHOL resulted in a slight decrease of the AUC of Lovachol and its metabolites as well as in a significant decrease of the Cmax for the lovastatin metabolites. The clinical interpretation of this phenomenon is difficult as it may indicate a greater uptake of lovastatin by the liver.
There was no clinically relevant interaction reported in patients who have been receiving lovastatin concomitantly with beta-adrenergic blocking agents.
Antipyrine
Antipyrine was used as a model for drugs metabolized by the microsomal hepatic enzyme system (cytochrome P450 system). LOVACHOL had no effect on the pharmacokinetics of antipyrine.
Other Medicines
Although specific interaction studies were not performed, in clinical studies, LOVACHOL was used concomitantly with calcium-channel blockers (such as verapamil HCI, nifedipine and diltiazem HCI) and a number of diuretics and non-steroidal anti-inflammatory drugs (NSAIDs), without evidence of clinically significant adverse interactions.
Drug/Laboratory Test Interactions
Lovastatin may elevate creatine phosphokinase and transaminase levels. In the differential diagnosis of chest pain in a patient on therapy with lovastatin, cardiac and noncardiac fractions of these enzymes should be determined.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
See Side-Effects and Special Precautions.
Treatment should be symptomatic and supportive, liver function should be monitored, and appropriate therapy instituted. No specific therapy of overdosage can be recommended. The dialyzability of LOVACHOL and its metabolites in man is not known.

IDENTIFICATION
LOVACHOL 20 mg:
Octagonal, light blue, flat-faced with bevelled edge tablets, engraved “APO”on one side, scored and engraved “LOVA”over “20”on one side.
LOVACHOL 40 mg:
Light green, octagonal, flat-faced with bevelled edge tablets, engraved “APO”on one side and “LOVA”over “40”on the other side.

PRESENTATION
LOVACHOL 20 mg:
White, High Density Polyethylene Bottles in 30’s, 100’s, 250’s, 500’s and 1 000’s.
LOVACHOL 40 mg:
White, High Density Polyethylene Bottles in 30’s, 100’s, 250’s, 500’s and 1 000’s.

STORAGE INSTRUCTIONS
Store below 25°C, in well-closed containers. Protect from light.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER
Lovachol 20 mg: 33/7.5/0257
Lovachol 40 mg: 33/7.5/0258

NAME AND BUSINESS ADDRESS OF APPLICANT
PHARMACARE LIMITED
Building 12
Healthcare Park
Woodlands Drive
Woodmead
Sandton, 2148

DATE OF PUBLICATION OF THIS PACKAGE INSERT
September 1997

575017/050818 UNIPRINT-POS

New addition to this site: November 2005
Source: Pharmaceutical Industry

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