Altace

[Ramipril]

Carcinogenesis, Mutagenesis, Impairment of Fertility

No evidence of a tumorigenic effect was found when ramipril was given by gavage to rats for up to 24 months at doses of up to 500 mg/ kg/ day or to mice for up to 18 months at doses of up to 1000 mg/ kg/ day. (For either species, these doses are about 200 times the maximum recommended human dose when compared on the basis of body surface area.) No mutagenic activity was detected in the Ames test in bacteria, the micronucleus test in mice, unscheduled DNA synthesis in a human cell line, or a forward gene-mutation assay in a Chinese hamster ovary cell line. Several metabolites and degradation products of ramipril were also negative in the Ames test. A study in rats with dosages as great as 500 mg/ kg/ day did not produce adverse effects on fertility.

Pregnancy

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Pregnancy Categories C (first trimester) and D (second and third trimesters). See WARNINGS: Fetal/ Neonatal Morbidity and Mortality.

Nursing Mothers

Ingestion of single 10 mg oral dose of ALTACE resulted in undetectable amounts of ramipril and its metabo-lites in breast milk. However, because multiple doses may produce low milk concentrations that are not pre-dictable from single doses, women receiving ALTACE should not breast feed.

Geriatric Use

Of the total number of patients who received ramipril in US clinical studies of ALTACE 11.0% were 65 and over while 0.2% were 75 and over. No overall differences in effectiveness or safety were observed between these patients and younger patients, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

One pharmacokinetic study conducted in hospitalized elderly patients indicated that peak ramiprilat levels and area under the plasma concentration time curve (AUC) for ramiprilat are higher in older patients.

Pediatric Use

Safety and effectiveness in pediatric patients have not been established.

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