Lovastatin (Page 9 of 11)


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Manson, J.M., Freyssinges, C., Ducrocq, M.B., Stephenson, W.P., Postmarketing Surveillance of Lovastatin and Simvastin Exposure During Pregnancy. Reproductive Toxicology. 10(6):439–446, 1996.

Nursing Mothers

It is not known whether lovastatin is excreted in human milk. Because a small amount of another drug in this class is excreted in human breast milk and because of the potential for serious adverse reactions in nursing infants, women taking lovastatin should not nurse their infants (see CONTRAINDICATIONS).

Pediatric Use

Safety and effectiveness in patients 10 to 17 years of age with heFH have been evaluated in controlled clinical trials of 48 weeks duration in adolescent boys and controlled clinical trials of 24 weeks duration in girls who were at least one year post-menarche. Patients treated with lovastatin had an adverse experience profile generally similar to that of patients treated with placebo. Doses greater than 40 mg have not been studied in this population. In these limited controlled studies, there was no detectable effect on growth or sexual maturation in the adolescent boys or on menstrual cycle length in girls. See CLINICAL PHARMACOLOGY: Clinical Studies in Adolescent Patients; ADVERSE REACTIONS: Adolescent Patients; and DOSAGE AND ADMINISTRATION, Adolescent Patients (10 to 17 years of age) with Heterozygous Familial Hypercholesterolemia. Adolescent females should be counseled on appropriate contraceptive methods while on lovastatin therapy (see CONTRAINDICATIONS and PRECAUTIONS: Pregnancy). Lovastatin has not been studied in prepubertal patients or patients younger than 10 years of age.

Geriatric Use

A pharmacokinetic study with lovastatin showed the mean plasma level of HMG-CoA reductase inhibitory activity to be approximately 45% higher in elderly patients between 70 to 78 years of age compared with patients between 18 to 30 years of age; however, clinical study experience in the elderly indicates that dosage adjustment based on this age related pharmacokinetic difference is not needed. In the two large clinical studies conducted with lovastatin (EXCEL and AFCAPS/TexCAPS), 21% (3,094/14,850) of patients were ≥ 65 years of age. Lipid-lowering efficacy with lovastatin was at least as great in elderly patients compared with younger patients, and there were no overall differences in safety over the 20 to 80 mg/day dosage range (see CLINICAL PHARMACOLOGY). Because advanced age (≥ 65 years) is a predisposing factor for myopathy, including rhabdomyolysis, lovastatin should be prescribed with caution in the elderly.

ADVERSE REACTIONS

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%. 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 to 300 mg/dL [6.2 to 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=1,663) % Lovastatin 20 mg q.p.m. (N=1,642) % Lovastatin 40 mg q.p.m. (N=1,645) % Lovastatin 20 mg b.i.d. (N=1,646) % Lovastatin 40 mg b.i.d. (N=1,649) %

Body As a Whole

Asthenia

1.4

1.7

1.4

1.5

1.2

Gastrointestinal

Abdominal pain

1.6

2

2

2.2

2.5

Constipation

1.9

2

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

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

Myalgia

1.7

2.6

1.8

2.2

3

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

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% 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%.

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