Olmetec Special Precautions

General: Impaired Renal Function: As a consequence of inhibiting the RAS, changes in renal function may be anticipated in susceptible individuals treated with olmesartan medoxomil. In patients whose renal function may depend predominantly on the activity of the RAS (e.g., patients with severe congestive heart failure), treatment with ACE inhibitors and angiotensin receptor antagonists has been associated with oliguria and/or progressive azotemia and (rarely) with acute renal failure and/or death. Similar results may be anticipated in patients treated with olmesartan medoxomil (see PHARMACOLOGY: Pharmacokinetics: Pharmacokinetics in Special Populations under Actions).
In studies of ACE inhibitors in patients with unilateral or bilateral renal artery stenosis, increases in serum creatinine or blood urea nitrogen (BUN) have been reported. There has been no long-term use of olmesartan medoxomil in patients with unilateral or bilateral renal artery stenosis, but similar results may be expected.
There is an increased risk of renal insufficiency when patients with bilateral renal artery stenosis (or stenosis of the artery to a single functioning kidney) are treated with medicinal products that affect the RAS.
Information for Patients: Pregnancy: Female patients of childbearing age should be told about the consequences of second and third trimester exposure to drugs that act on the RAS and they should be told also that these consequences do not appear to have resulted from intrauterine drug exposure that has been limited to the first trimester. These patients should be asked to report pregnancies to their physicians as soon as possible.
Carcinogenesis, Mutagenesis, Impairment of Fertility: Olmesartan medoxomil was not carcinogenic when administered by dietary administration to rats for up to 2 years. The highest dose tested (2,000 mg/kg/day) was, on a mg/m² basis, about 480 times the maximum recommended human dose (MRHD) of 40 mg/day. Two carcinogenicity studies conducted in mice, a 6-month gavage study in the p53 knockout mouse and a 6-month dietary administration study in the Hras2 transgenic mouse, at doses of up to 1,000 mg/kg/day (about 120 times the MRHD), revealed no evidence of a carcinogenic effect of olmesartan medoxomil.
Both olmesartan medoxomil and olmesartan tested negative in the in vitro Syrian hamster embryo cell transformation assay and showed no evidence of genetic toxicity in the Ames (bacterial mutagenicity) test. However, both were shown to induce chromosomal aberrations in cultured cells in vitro (Chinese hamster lung) and tested positive for thymidine kinase mutations in the in vitro mouse lymphoma assay. Olmesartan medoxomil tested negative in vivo for mutations in the Muta Mouse intestine and kidney and for clastogenicity in mouse bone marrow (micronucleus test) at oral doses of up to 2000 mg/kg (olmesartan not tested).
Fertility of rats was unaffected by administration of olmesartan medoxomil at dose levels as high as 1,000 mg/kg/day (240 times the MRHD) in a study in which dosing was begun 2 (female) or 9 (male) weeks prior to mating.
Use in Pregnancy: Use of drugs that act directly on the RAS during the second and third trimesters of pregnancy has been associated with fetal injury and even death. Patients who become pregnant whilst using olmesartan medoxomil should discontinue treatment as soon as possible.
If Olmetec is used during pregnancy, or if the patient becomes pregnant while taking Olmetec, the patient should be apprised of the potential hazard to a fetus. Should exposure to Olmetec have occurred from the second trimester forward, ultrasound examinations of the renal function and of the skull are recommended. Newborns exposed to angiotensin II antagonists in utero must be closely monitored for the occurrence of hypotension, oliguria, and hyperkalaemia. See Fetal/Neonatal Morbidity and Mortality under WARNINGS.
Use in Lactation: It is not known whether olmesartan is excreted in human milk, but olmesartan is secreted at low concentration in the milk of lactating rats. Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Use in Children: Safety and effectiveness in pediatric patients have not been established.
Use in the Elderly: Of the total number of hypertensive patients receiving olmesartan medoxomil in clinical studies, more than 20% were 65 years of age and above, while more than 5% were 75 years of age and older. No overall differences in effectiveness or safety were observed between elderly patients and younger patients. 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.