Not applicable.
No additional preclinical studies have been performed with the Fixed Dose Combination product 80 mg/25 mg. Previous preclinical safety studies performed with co-administration of telmisartan and hydrochlorothiazide in normotensive rats and dogs, in doses producing exposure comparable to that in the clinical therapeutic range, caused no additional findings not already observed with administration of either substance alone. The toxicological findings observed appear to have no relevance to human therapeutic use.
Toxicological findings also well known from preclinical studies with angiotensin converting enzyme inhibitors and angiotensin II receptor antagonists were: a reduction of red cell parameters (erythrocytes, haemoglobin, haematocrit), changes of renal haemodynamics (increased blood urea nitrogen and creatinine), increased plasma renin activity, hypertrophy/hyperplasia of the juxtaglomerular cells and gastric mucosal injury. Gastric lesions could be prevented/ameliorated by oral saline supplementation and group housing of animals. In dogs renal tubular dilation and atrophy were observed. These findings are considered to be due to the pharmacological activity of telmisartan.
No clear evidence of a teratogenic effect was observed, however at toxic dose levels of telmisartan an effect on the postnatal development of the offsprings such as lower body weight and delayed eye opening was observed.
Telmisartan showed no evidence of mutagenicity and relevant clastogenic activity in in vitro studies and no evidence of carcinogenicity in rats and mice. Studies with hydrochlorothiazide have shown equivocal evidence for a genotoxic or carcinogenic effect in some experimental models. However, the extensive human experience with hydrochlorothiazide has failed to show an association between its use and an increase in neoplasms.
Micardis Plus should be kept in the sealed blister due to the hygroscopic property of the tablets. Tablets should be taken out of the blister shortly before administration.
Occasionally, the outer layer of the blister pack has been observed to separate from the inner layer between the blister pockets. No action needs to be taken if this is observed.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
