DARZOX

Darzox (Tablets)
(Indapamide)


CONTENT
Prolonged-release tablet. Each tablet contains indapamide 1.5 mg.

PHARMACOLOGIC PROPERTIES

PHARMACODYNAMICS
Darzox is antihypertensive preparation, non-thiazide-type sulphonamides diuretic with vasodilative properties. It decreases the reabsorption of sodium ions in the cortical segment of nephron that increases the excretion with urine of sodium and chloride ions. To a lesser extent the preparation increases the excretion of potassium and magnesium ions. Due to block selectively block of "slow" calcium channel it increases elasticity of artery walls and reduces the total peripheral vascular resistance. It produses the reduction of left ventricle hypertrophy. It doesn't lipid profile (triglycerides, lipoproteins of low density, and lipoproteins of high density) or carbohydrate metabolism (including the patients with diabetes). It reduces the sensitivity of vascular wall to the noradrenaline and angiotensin II, stimulates the synthesis of prostaglandin ?2, and reduces the production of free radicals. Duration of antihypertensive action is above 24 hours. A hypotensive effect developes by the end of the first week.

PHARMACOKINETICS
After intake it absorbs rapidly and completely from gastro-intestinal tract. The bioavailability is high (93%). The food intake slows down partly the rate of absorption, but it doesn't affect bioavailability. Maximal concentration in blood plasma is reached in about 12 h after the application of a single dose. The variations in blood concentration during inter-dose interval reduces at the repeated administration. A steady-state concentration is established in 7 days of the regular administration. The half-life is 18 hours. Bounding to plasma proteins - 79%. It has a large distribution volume and penetrates blood-tissue barriers (including placental), and it penetrates in breast milk. It is metabolized in the liver. It is excreted 60 - 80% by kidney in form of metabolites (about 5% of the drug in unchanged form) and 20% - by intestine. Pharmacokinetics doesn't change in patients with renal insufficiency.

THERAPEUTIC INDICATIONS
- arterial hypertension.

DOSEGE AND ADMINISTRATION
1 tablet of Darzox per day should be intake with water, not chewing, preferably in the morning. The increase of the drug dose doesn't further increase an antihypertensive effect.

CONTRAINDICATIONS
- hypersensitivity to the preparation and other derivatives of sulphonamide; - severe renal insufficiency (anuria); - hypokaliemia; - advanced hepatic insufficiency (with encephalopathy); - intolerance of lactose, galactosemia, glucose/galactose malabsorption syndrome.

SIDE EFFECTS
Digestive system: nausea, anorexia, dry mouth, gastralgia, vomiting, diarrhea, constipation, abdominal pain, the development of hepatic encephalopathy can occur, in rare cases - pancreatitis. Central nervous system: dizziness, asthenia, parestesia, headache. Cardiovascular system: orthostatic hypotension, changes on electrocardiogram (hypokaliemia), arrhythmia, heartbeats. Allergic reaction: rush, urticaria, itch, hemorrhagic vasculitis. Laboratory parameters: hyperurikemia, hyperglycemia, hypokaliemia, hypochloremia, hyponatriemia, the urea nitrogen heightening in blood, hipercreatininemia, glucosuria. Other: aggravation of systemic lupus erythematosus. In rare cases: thrombocytopenia, leucopenia, agranulocytosis, bone marrow aplasia and hemolytic anemia.

PACKAGING
10 prolonged-release tablets in a blister. 3 blisters with the enclosed leaflet in a carton box.