LOVASTATIN TABLETS, USP

/LOVASTATIN TABLETS, USP
LOVASTATIN TABLETS, USP2018-09-06T09:12:40+00:00

Prescription Drug Name:

LOVASTATIN TABLETS, USP

ID:

9069b3a6-2840-44b0-994d-797c038a1f38

Code:

34391-3

DESCRIPTION


id: 79d16c78-7023-4d53-a1e1-43b464f75c6e
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

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 β-hydroxyacid form. This is a principal metabolite and an 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 is [1S-[1α(R*),3α,7β,8β(2S*,4S*), 8aβ]]-1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2-(tetrahydro-4-hydroxy-6-oxo-2H-pyran-2-yl)ethyl]-1-naphthalenyl 2-methylbutanoate. The molecular formula of lovastatin is C24H36O5 and its molecular weight is 404.54. Its structural formula is: Lovastatin is a white, nonhygroscopic crystalline powder that is insoluble in water and sparingly soluble in ethanol, methanol, and acetonitrile. Each tablet for oral administration, contains 10 mg, 20 mg, or 40 mg of lovastatin. In addition, each tablet contains the following inactive ingredients: lactose monohydrate, magnesium stearate, microcrystalline cellulose, and pregelatinized starch. Butylated hydroxyanisole is added as a preservative. The 20 mg tablet also contains D&C Red #30 aluminum lake. The 40 mg tablet also contains D&C Yellow #10 HT aluminum lake.

CLINICAL PHARMACOLOGY


id: 20ad8d09-82f7-41ab-ba4c-671c2127baa2
displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1

The involvement of low-density lipoprotein cholesterol (LDL-C) in atherogenesis has been well-documented in clinical and pathological studies, as well as in many animal experiments. Epidemiological and clinical studies have established that high LDL-C and low high-density lipoprotein cholesterol (HDL-C) are both associated with coronary heart disease.  However, the risk of developing coronary heart disease is continuous and graded over the range of cholesterol levels and many coronary events do occur in patients with total cholesterol (total-C) and LDL-C in the lower end of this range. Lovastatin has been shown to reduce both normal and elevated LDL-C concentrations.  LDL is formed from very low-density lipoprotein (VLDL) and is catabolized predominantly by the high affinity LDL receptor. The mechanism of the LDL-lowering effect of lovastatin may involve both reduction of VLDL-C concentration, and induction of the LDL receptor, leading to reduced production and/or increased catabolism of LDL-C. Apolipoprotein B also falls substantially during treatment with lovastatin. Since each LDL particle contains one molecule of apolipoprotein B, and since little apolipoprotein B is found in other lipoproteins, this strongly suggests that lovastatin does not merely cause cholesterol to be lost from LDL, but also reduces the concentration of circulating LDL particles. In addition, lovastatin can produce increases of variable magnitude in HDL-C, and modestly reduces VLDL-C and plasma triglycerides (TG) (see Tables I-III under CLINICAL Studies). The effects of lovastatin on Lp(a), fibrinogen, and certain other independent biochemical risk markers for coronary heart disease are unknown. Lovastatin is a specific inhibitor of HMG-CoA reductase, the enzyme which catalyzes the conversion of HMG-CoA to mevalonate. The conversion of HMG-CoA to mevalonate is an early step in the biosynthetic pathway for cholesterol.

INDICATIONS AND USAGE


id: f95cdafa-518e-4fdd-835b-c6fdcf497ef8
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

Therapy with lovastatin should be a component of multiple risk factor intervention in those individuals with dyslipidemia at risk for atherosclerotic vascular disease.  Lovastatin should be used in addition to a diet restricted in saturated fat and cholesterol as part of a treatment strategy to lower total-C and LDL-C to target levels when the response to diet and other nonpharmacological measures alone has been inadequate to reduce risk. Primary Prevention Of Coronary Heart Disease: In individuals without symptomatic cardiovascular disease, average to moderately elevated total-C and LDL-C, and below average HDL-C, lovastatin tablets are indicated to reduce the risk of: –  Myocardial infarction –  Unstable angina –  Coronary revascularization procedures (See CLINICAL PHARMACOLOGY, Clinical Studies.)

CONTRAINDICATIONS


id: 81f4f999-769d-443e-81dd-ff467f264ef8
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

Hypersensitivity to any component of this medication. Active liver disease or unexplained persistent elevations of serum transaminases (see WARNINGS). Pregnancy And Lactation (see PRECAUTIONS, Pregnancy and Nursing mothers ). Atherosclerosis is a chronic process and the discontinuation of lipid-lowering drugs during pregnancy should have little impact on the outcome of long-term therapy of primary hypercholesterolemia. Moreover, cholesterol and other products of the cholesterol biosynthesis pathway are essential components for fetal development, including synthesis of steroids and cell membranes. Because of the ability of inhibitors of HMG-CoA reductase such as lovastatin to decrease the synthesis of cholesterol and possibly other products of the cholesterol biosynthesis pathway, lovastatin is contraindicated during pregnancy and in nursing mothers. Lovastatin should be administered to women of childbearing age only when such patients are highly unlikely to conceive. If the patient becomes pregnant while taking this drug, lovastatin should be discontinued immediately and the patient should be apprised of the potential hazard to the fetus (see PRECAUTIONS, Pregnancy).

ADVERSE REACTIONS


id: 9d007889-0a8c-478c-94eb-e87b67222cb2
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

Lovastatin is generally well tolerated; adverse reactions usually have been mild and transient. Phase III Clinical Studies:  In Phase III controlled clinical studies involving 613 patients treated with lovastatin, the adverse experience profile was similar to that shown below for the 8,245-patient EXCEL study (see Expanded Clinical Evaluation Of Lovastatin (EXCEL) Study:). Persistent increases of serum transaminases have been noted (see WARNINGS, Liver Dysfunction). About 11% of patients had elevations of CK levels of at least twice the normal value on one or more occasions. The corresponding values for the control agent cholestyramine was 9 percent. This was attributable to the noncardiac fraction of CK. Large increases in CK have sometimes been reported (see WARNINGS, Myopathy/Rhabdomyolysis ). Expanded Clinical Evaluation Of Lovastatin (EXCEL) Study:  Lovastatin was compared to placebo in 8,245 patients with hypercholesterolemia (total-C 240-300 mg/dL [6.2-7.8 mmol/L]) in the randomized, double-blind, parallel, 48-week EXCEL study. Clinical adverse experiences reported as possibly, probably or definitely drug-related in ≥ 1% in any treatment group are shown in the table below. For no event was the incidence on drug and placebo statistically different.

Placebo

(N = 1663)
%
________

Lovastatin
20 mg q.p.m.
(N = 1642)
%
________
Lovastatin
40 mg q.p.m.
(N = 1645)
%
________
Lovastatin
20 mg b.i.d.
(N = 1646)
%
________
Lovastatin
40 mg b.i.d.
(N = 1649)
%
________
Body As a Whole
  Asthenia 1.4 1.7 1.4 1.5 1.2
Gastrointestinal
  Abdominal pain 1.6 2.0 2.0 2.2 2.5
  Constipation 1.9 2.0 3.2 3.2 3.5
  Diarrhea 2.3 2.6 2.4 2.2 2.6
  Dyspepsia 1.9 1.3 1.3 1.0 1.6
  Flatulence 4.2 3.7 4.3 3.9 4.5
  Nausea 2.5 1.9 2.5 2.2 2.2
Musculoskeletal
  Muscle cramps 0.5 0.6 0.8 1.1 1.0
  Myalgia 1.7 2.6 1.8 2.2 3.0
Nervous System/Psychiatric
  Dizziness 0.7 0.7 1.2 0.5 0.5
  Headache 2.7 2.6 2.8 2.1 3.2
Skin
  Rash 0.7 0.8 1.0 1.2 1.3
Special Senses
  Blurred vision 0.8 1.1 0.9 0.9 1.2
Other clinical adverse experiences reported as possibly, probably or definitely drug-related in 0.5 to 1.0 percent of patients in any drug-treated group are listed below. In all these cases the incidence on drug and placebo was not statistically different. Body as a Whole: chest pain; Gastrointestinal: acid regurgitation, dry mouth, vomiting; Musculoskeletal: leg pain, shoulder pain, arthralgia; Nervous System/Psychiatric: insomnia, paresthesia; Skin: alopecia, pruritus; Special Senses: eye irritation. In the EXCEL study (see CLINICAL PHARMACOLOGY, Clinical Studies), 4.6% of the patients treated up to 48 weeks were discontinued due to clinical or laboratory adverse experiences which were rated by the investigator as possibly, probably or definitely related to therapy with lovastatin.  The value for the placebo group was 2.5%. Air Force/Texas Coronary Atherosclerosis Prevention Study (AFCAPS/TexCAPS): In AFCAPS/TexCAPS  (see CLINICAL PHARMACOLOGY, Clinical Studies) involving 6,605 participants treated with 20-40 mg/day of lovastatin  (n=3,304) or placebo (n=3,301), the safety and tolerability profile of the group treated with lovastatin was comparable to that of the group treated with placebo during a median of 5.1 years of follow-up. The adverse experiences reported in AFCAPS/TexCAPS were similar to those reported in EXCEL (see ADVERSE REACTIONS, Expanded Clinical Evaluation Of Lovastatin (EXCEL) Study:). Concomitant Therapy: In controlled clinical studies in which lovastatin was administered concomitantly with cholestyramine, no adverse reactions peculiar to this concomitant treatment were observed. The adverse reactions that occurred were limited to those reported previously with lovastatin or cholestyramine. Other lipid-lowering agents were not administered concomitantly with lovastatin during controlled clinical studies. Preliminary data suggests that the addition of gemfibrozil to therapy with lovastatin is not associated with greater reduction in LDL-C than that achieved with lovastatin alone. In uncontrolled clinical studies, most of the patients who have developed myopathy were receiving concomitant therapy with cyclosporine, gemfibrozil or niacin (nicotinic acid). The combined use of lovastatin at doses exceeding 20 mg/day with cyclosporine, gemfibrozil, other fibrates or lipid-lowering doses (≥ 1g/day) of niacin should be avoided (see WARNINGS, Myopathy/Rhabdomyolysis). The following effects have been reported with drugs in this class. Not all the effects listed below have necessarily been associated with lovastatin therapy. Skeletal: muscle cramps, myalgia, myopathy, rhabdomyolysis, arthralgias. Neurological: dysfunction of certain cranial nerves (including alteration of taste, impairment of extraocular movement, facial paresis), tremor, dizziness, vertigo, memory loss, paresthesia, peripheral neuropathy, peripheral nerve palsy, psychic disturbances, anxiety, insomnia, depression. Hypersensitivity Reactions: An apparent hypersensitivity syndrome has been reported rarely which has included one or more of the following features: anaphylaxis, angioedema, lupus erythematous-like syndrome, polymyalgia rheumatica, dermatomyositis, vasculitis, purpura, thrombocytopenia, leukopenia, hemolytic anemia, positive ANA, ESR increase, eosinophilia, arthritis, arthralgia, urticaria, asthenia, photosensitivity, fever, chills, flushing, malaise, dyspnea, toxic epidermal necrolysis, erythema multiforme, including Stevens-Johnson syndrome. Gastrointestinal: pancreatitis, hepatitis, including chronic active hepatitis, cholestatic jaundice, fatty change in liver; and rarely, cirrhosis, fulminant hepatic necrosis, and hepatoma; anorexia, vomiting. Skin: alopecia, pruritus. A variety of skin changes (e.g., nodules, discoloration, dryness of skin/mucous membranes, changes to hair/nails) have been reported. Reproductive: gynecomastia, loss of libido, erectile dysfunction. Eye: progression of cataracts (lens opacities), ophthalmoplegia. Laboratory Abnormalities: elevated transaminases, alkaline phosphatase, g-glutamyl transpeptidase, and bilirubin; thyroid function abnormalities.

OVERDOSAGE


id: 55450b75-aea4-47d4-8230-e1289dc3d872
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5

After oral administration of lovastatin to mice, the median lethal dose observed was >15 g/m2. Five healthy human volunteers have received up to 200 mg of lovastatin as a single dose without clinically significant adverse experiences. A few cases of accidental overdosage have been reported; no patients had any specific symptoms, and all patients recovered without sequelae. The maximum dose taken was 5-6 g. Until further experience is obtained, no specific treatment of overdosage with lovastatin can be recommended. The dialyzability of lovastatin and its metabolites in man is not known at present.

DOSAGE AND ADMINISTRATION


id: 45cdd07c-459a-4a67-8231-c285bc7d0236
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

The patient should be placed on a standard cholesterol-lowering diet before receiving lovastatin and should continue on this diet during treatment with lovastatin (see NCEP Treatment Guidelines for details on dietary therapy). Lovastatin should be given with meals. Adult Patients: The usual recommended starting dose is 20 mg once a day given with the evening meal. The recommended dosing range is 10-80 mg/day in single or two divided doses; the maximum recommended dose is 80 mg/day. Doses should be individualized according to the recommended goal of therapy (see NCEP Guidelines and CLINICAL PHARMACOLOGY). Patients requiring reductions in LDL-C of 20% or more to achieve their goal (see INDICATIONS AND USAGE) should be started on 20 mg/day of lovastatin. A starting dose of 10 mg may be considered for patients requiring smaller reductions. Adjustments should be made at intervals of 4 weeks or more. Cholesterol levels should be monitored periodically and consideration should be given to reducing the dosage of lovastatin if cholesterol levels fall significantly below the targeted range.

HOW SUPPLIED


id: 1ab0e1c1-f05c-4dd1-88e0-13ad25392bb3
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Lovastatin Tablets, USP are available as follows: 10 mg — Each white, round, flat faced beveled edge tablet imprinted with on one side and 633 on the other side contains 10 mg of lovastatin. Bottle of 30 – 68788-9180-3 Bottle of 60 – 68788-9180-6 Bottle of 90 – 68788-9180-9 Bottle of 120 – 68788-9180-8

PRINCIPAL DISPLAY PANEL – 10 mg


id: 967b8b63-071e-410b-ae12-6e629499ba9e
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4