Cozaar - generic

Angiology. 2004 Nov;55(6):669-678.
Losartan Reduces Left Ventricular Hypertrophy Proportionally to Blood Pressure Reduction in Hypertensives, but Does Not Affect Diastolic Cardiac Function.
Zakynthinos E, Pierutsakos C, Konstantinidis K, Zakynthinos S, Papadogiannis D.
Department of Critical Care and Pulmonary Services, University of Athens Medical School, ``Evangelismos'' Hospital, Athens, Greece.

In contrast to the well-recognized salutary effects of angiotensin-converting enzyme inhibition, the value of angiotensin II type I (ATl)-receptor blockade on left ventricular hypertrophy (LVH) is controversial. In addition, the data on the influence of this therapy on cardiac diastolic function are scarce. Thirty-nine patients with moderate primary hypertension, LVH, and normal systolic function received losartan, 50 to 100 mg daily. Transthoracic echocardiography was performed at baseline and after 6 months of treatment. Thirty-one patients completed and were included in the study (16 males, 61.1 +/- .0 years). The patients were divided into responders if mean blood pressure (BP) decreased > 5 mm Hg at the end of the study (20 patients) and non-responders (mean BP decrease </= 5 mm Hg, 11 patients). The BP and the LVH were significantly reduced (systolic BP by 10.0%, diastolic BP 6.5%, mean BP 8.2%, left ventricular mass index [LVMI] 6.2%, interventricular septum 5.8%, posterior wall 3.0%) (p</=0.02), attributed to the reduction of BP and LVH in responders; the LVH in non-responders did not alter with treatment. A significant correlation was noted between changes in BP and LVMI (r=0.60, p<0.001). The systolic cardiac function remained normal. The Doppler parameters usually used to assess the diastolic function of the LV (early diastolic filling velocity [E wave], late diastolic filling velocity [A wave], ratio of E/A waves, isovolumic relaxation time), which were abnormal at baseline, did not change with treatment. The size of the left atrium increased (p<0.05) at the end of the study. In conclusion, a 6-month course with losartan decreased BP and LVH. However, the LVH regression was rather associated with the reduction of the hemodynamic stimulus per se, than any trophic effect of the drug in the myocardium. The diastolic cardiac function remained abnormal with treatment.

GENERIC NAME: losartan
BRAND NAME: Cozaar

DRUG CLASS AND MECHANISM: Losartan and its primary metabolite block the angiotensin receptor found in many tissues, primarily in vascular smooth muscle. Angiotensin, formed by the action of angiotensin converting enzyme (ACE), is a powerful chemical that causes blood vessel narrowing (vasoconstriction) which can lead to elevated blood pressure (hypertension).

PREPARATIONS: Cozaar 25 and 50 mg film coated tablets.

STORAGE: Tablets should be stored at room temperature in a tightly closed, light resistant container.

PRESCRIBED FOR: Losartan is indicated for the treatment of hypertension. It may be used alone or in combination with other agents. It has less of an effect in black patients, similar to ACE inhibitors, such as captopril (Capoten), enalapril (Vasotec), and lisinopril (Zestril).

DOSING: Losartan may be given with or without food. Losartan is metabolized in the liver by cytochrome P450 enzymes to an active metabolite that is responsible for most of the drug activity. Reduction in dose by 50% is suggested in patients with impaired liver function.

DRUG INTERACTIONS: Losartan must be used with caution in patients who are volume depleted due to excessive decreases in blood pressure after use. Losartan may compromise kidney function in patients dependent on angiotensin activity to maintain kidney blood flow, similar to ACE inhibitors. This is sometimes seen in diabetic patients with some degree of kidney impairment, as well as in patients with narrowings in one of the main arteries supplying one kidney.

No significant drug interactions have been found in any studies, but inhibitors of cytochrome P450 such as ketoconazole (Nizoral) have been shown in lab studies to inhibit the formation of the active drug metabolite. Therefore, caution should be used when adding losartan to a patient taking Nizoral, as reduced activity of losartan would be expected.

Losartan's safety and efficacy in children has not been established.

PREGNANCY: When used in the second or third trimester of pregnancy, drugs that act by the same mechanism as losartan can cause injury and even death to the fetus. Losartan should not be used during pregnancy. When pregnancy is detected, losartan should be stopped as soon as possible.

NURSING MOTHERS: Losartan is present in rat milk, and is toxic to rat neonates. Therefore, it should be avoided in nursing mothers.

SIDE EFFECTS: In studies of over 4000 patients, including 1200 treated for over 6 months and 800 for over 1 year, the overall incidence of side effects was similar to placebo. Losartan is generally well tolerated. Side effects reported included diarrhea, muscle cramps, dizziness, insomnia, and nasal congestion.

Caution! Before starting to take this medicine, it is vital that you should consult your doctor! Do not use it on your own initiative, without medical advice.