Composition, form of production and packaging
Tablets coated with a white film coating , round, biconvex, with a risk on both sides of the tablet and with lateral risks, labeled "LH" on the one side of the risks and "1" on the other side of the risks.
1 tab.
Losartan potassium 50 mg
hydrochlorothiazide 12.5 mg
Auxiliary substances: mannitol - 82.5 mg, microcrystalline cellulose - 40 mg, croscarmellose sodium - 8 mg, povidone - 4 mg, magnesium stearate - 3 mg, opadrai white - 4 mg (hypromellose 3cP - 1.4 mg, hydroxypropyl cellulose - 1.2 mg, titanium dioxide - 0.8 mg, macrogol - 0.4 mg, hypromellose 50cP - 0.2 mg).
7 pcs. - blisters (4) - packs of cardboard.
Tablets coated with a white film coating , round, biconvex, with a risk on both sides of the tablet and with lateral risks, with the designation "LH" on the one side of the risks and "2" on the other side of the risks.
1 tab.
Losartan Potassium 100 mg
hydrochlorothiazide 25 mg
Auxiliary substances: mannitol - 165 mg, microcrystalline cellulose - 80 mg, croscarmellose sodium - 16 mg, povidone - 8 mg, magnesium stearate - 6 mg, opadrai white - 6 mg (hypromellose 3cP - 2.8 mg, hydroxypropyl cellulose - 2.4 mg, titanium dioxide - 1.6 mg, macrogol - 0.8 mg, hypromellose 50cP - 0.4 mg).
7 pcs. - blisters (4) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2008.
PHARMACHOLOGIC EFFECT
The combined drug has an antihypertensive effect. Contains potassium losartan - angiotensin II receptor antagonist (subtype AT1) and hydrochlorothiazide - diuretic.
Losartan is a specific antagonist of angiotensin II receptors (subtype AT1). Does not inhibit kinase II - an enzyme that destroys bradykinin. Reduces the overall peripheral resistance (OPSS), the concentration in the blood of adrenaline and aldosterone, blood pressure (BP), pressure in the small circle of the circulation; reduces afterload, has a diuretic effect. It prevents the development of myocardial hypertrophy, increases tolerance to physical activity in patients with chronic heart failure.
Hydrochlorothiazide is a thiazide diuretic. Reduces the reabsorption of sodium ions, increases the release of urine ions of potassium, bicarbonate and phosphate.Reduces blood pressure by reducing the volume of circulating blood (BCC), changes in the reactivity of the vascular wall, reducing the pressor effect of vasoconstrictors and increasing the depressor effect on the ganglion.
PHARMACOKINETICS
Losartan is rapidly absorbed from the digestive tract. Bioavailability is about 30%. It is exposed to the effect of the first passage through the liver, is metabolized by carboxylation with the formation of an active metabolite. Connection with blood plasma proteins - 99%. T max in blood plasma losartan is 1 hour, the active metabolite - 3-4 hours after ingestion.
T 1/2 - 1.5-2 h, and its main metabolite - 3-4 h, respectively. About 35% of the dose is excreted in the urine, about 60% - through the intestine.
Hydrochlorothiazide is rapidly absorbed from the digestive tract.
T 1/2 is 5.8-14.8 hours. It is not metabolized by the liver. About 61% is excreted by the kidneys unchanged.
INDICATIONS
- Arterial hypertension (in patients for whom combination therapy is optimal).
DOSING MODE
Inside, regardless of food intake.
The usual initial and maintenance dose of the drug is 50 mg losartan / 12.5 mg hydrochlorothiazide (1 tab.) Per day. For those patients who do not manage to achieve adequate blood pressure control at this dosage, the dose can be increased to 2 tab. (50 mg / 12.5 mg) or 1 tab. (100 mg / 25 mg) 1 time / day. The maximum dose is 2 tablets. (50 mg / 12.5 mg) or 1 tab. (100 mg / 25 mg) 1 time / day.
In general, the maximum hypotensive effect is achieved within 3 weeks after the start of treatment.
There is no need for a special selection of an initial dose for elderly patients .
SIDE EFFECT
Adverse reactions are limited to those previously observed with the use of losartan potassium and / or hydrochlorothiazide.
The most common side effects in the treatment of essential hypertension include dizziness.
Allergic reactions : anaphylactoid reactions, angioedema, including laryngeal and / or tongue edema, resulting in airway obstruction, and / or swelling of the face, lips, throat and / or tongue occasionally noted with losartan. Some of these patients had angioedema earlier with other drugs, including ACE inhibitors. Very rarely, when taking losartan, vasculitis, including Shenlain-Henoch disease, was noted.
From the cardiovascular system: a decrease in blood pressure.
From the side of the digestive tract: when receiving losartan, rare (1%) cases of hepatitis, diarrhea were registered.
On the part of the respiratory system: when taking losartan - cough.
From the skin: urticaria.
On the part of laboratory indicators: rarely (1%) - hyperkalemia (serum potassium more than 5.5 mmol / l), increased activity of hepatic enzymes.
CONTRAINDICATIONS
- Hypersensitivity to the components of the drug, increased sensitivity to other derivatives of sulfonamides;
anuria;
- severe arterial hypotension;
- pronounced violations of the liver function;
- pronounced impairment of kidney function (QC-30 ml / min.);
- Hypovolemia (including against a background of high doses of diuretics);
- pregnancy and lactation;
- age under 18 years (efficiency and safety not established).
With caution: patients with bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney, with violations of water-electrolyte balance of blood (dehydration, hyponatremia, hypochloraemic alkalosis, hypomagnesemia, hypokalemia).
With caution, the drug is used in patients with diabetes mellitus, hypercalcemia, hyperuricemia and / or gout, as well as patients with a history of allergic anamnesis and bronchial asthma, as well as systemic connective tissue diseases (including systemic lupus erythematosus), with concomitant administration with NSAIDs, in t.ch. inhibitors of COX-2).
PREGNANCY AND LACTATION
Contraindicated in pregnancy and lactation.
The intake of drugs directly acting on the renin / angiotensin system during the second and third trimesters of pregnancy can lead to fetal death. When pregnancy occurs, the drug is canceled.
Pregnant women use of diuretics is usually not recommended due to the risk of jaundice in the fetus and newborn, thrombocytopenia of the mother. Diuretic therapy does not prevent the development of pregnancy toxicity.
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindication - marked impairment of kidney function (creatinine clearance ≥ 30 ml / min.)
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Contraindication - marked violations of the liver.
APPLICATION FOR CHILDREN
The effectiveness and safety of the use of the drug to 18 years are not established.
APPLICATION IN ELDERLY PATIENTS
There is no need for a special selection of an initial dose for elderly patients.
SPECIAL INSTRUCTIONS
Can be prescribed together with other antihypertensive drugs.
There is no need for a special selection of an initial dose for elderly patients.
The drug can increase the concentration of urea and creatinine in the blood plasma in patients with bilateral stenosis of the renal arteries or stenosis of the artery of a single kidney.
Hydrochlorothiazide can increase arterial hypotension and disturbances in water-electrolyte balance (decrease in the volume of circulating blood, hyponatremia, hypochloraemic alkalosis, hypomagnesemia, hypokalemia), impair glucose tolerance, reduce calcium excretion in the urine and cause a transient, insignificant increase in calcium concentration in the blood plasma, increase the concentration of cholesterol and triglycerides, provoke the occurrence of hyperuricemia and / or gout.
Impact on the ability to drive vehicles and manage mechanisms
There is no information on the effect on the ability to drive and other mechanisms.
OVERDOSE
Symptoms caused by an overdose of losartan: a marked decrease in blood pressure, tachycardia, bradycardia (as a result of vagal stimulation).
Symptoms caused by an overdose of hydrochlorothiazide: loss of electrolytes (hypokalemia, hyperchloremia, hyponatremia), as well as dehydration caused by excess diuresis.
Treatment: symptomatic and supportive therapy. If the drug is taken recently, the stomach should be washed; if necessary, correct the water-electrolyte disturbances.
Lozartan and its active metabolites are not removed by hemodialysis.
DRUG INTERACTION
Lozartan enhances the effect of other antihypertensive drugs. There was no clinically significant interaction with hydrochlorothiazide, digoxin, indirect anticoagulants, cimetidine, phenobarbital, ketoconazole, erythromycin. There are reports that rifampicin and fluconazole reduce the level of the active metabolite. The clinical significance of these interactions has not been studied.
Like other drugs that block angiotensin II or its effect, the simultaneous administration of potassium-sparing diuretics (eg, spironolactone, triamterene, amiloride), potassium or salt substitutes containing potassium, can lead to hyperkalemia.
NSAIDs, incl. selective inhibitors of cyclooxygenase-2 can reduce the effect of diuretics and other antihypertensive agents .
In some patients with impaired renal function receiving NSAID therapy (including COX-2 inhibitors), treatment with angiotensin II receptor antagonists can cause further impairment of kidney function, including acute kidney failure, which is usually reversible.
The hypotensive effect of losartan, as well as other antihypertensive agents, may be weakened by taking indomethacin.
Hydrochlorothiazide
The following drugs can interact with thiazide diuretics when taken with them:
Barbiturates, narcotic drugs, ethanol - potentiation of orthostatic hypotension may occur.
Hypoglycemic agents (oral and insulin) - a dose adjustment for hypoglycemic agents may be required.
Other antihypertensives - additive effect is possible.
Colestramine and colestipol reduce the absorption of hydrochlorothiazide.
SCS, ACTH - increased loss of electrolytes, especially potassium.
Pressor amines - there may be a slight decrease in the effect of pressor amines, not interfering with their use.
Non-depolarizing muscle relaxants (for example, tubocurarine chloride) - it is possible to increase the effect of muscle relaxants.
Lithium preparations - diuretics reduce renal clearance of lithium and increase the risk of lithium intoxication, so simultaneous use is not recommended.
NSAIDs, incl. selective inhibitors of COX-2: can reduce the diuretic, natriuretic and antihypertensive effect of diuretics.
Impact on laboratory results
Due to the effect on calcium excretion, thiazides can affect the results of parathyroid function analysis.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
At a temperature not exceeding 30 В° C in a place inaccessible to children.
Shelf life - 3 years. Do not use after expiry date.
