Generic

Losartan Potassium + Hydrochlorothiazide

Indications

This medication is used to treat hypertension. It’s also used to lower the risk of stroke in those who have high blood pressure and left ventricular hypertrophy.

Pharmacology

Angiotensin II is formed in a reaction catalyzed by angiotensin converting enzyme (ACE). It is an effective vasoconstrictor, the main vasoactive hormone of the renin-angiotensin system, and an important part of the pathophysiology of hypertension. It also stimulates the adrenal cortex to secrete aldosterone. Losartan and its main active metabolite block the vasoconstriction and aldosterone secretion of angiotensin II by selectively blocking the binding of angiotensin II to AT1 receptors found in many tissues (such as vascular smooth muscle, adrenal glands). In vitro binding studies have shown that Losartan is a competitive and reversible AT1 receptor inhibitor. Neither losartan nor its active metabolite inhibit ACE (kinase II, an enzyme that converts angiotensin I to angiotensin II and breaks down bradykinin); neither do they bind to or block other known anticardial hormone receptors or ion channels that are important for vascular regulation.

Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular electrolyte reabsorption mechanism and directly increase the excretion of approximately equal amounts of sodium and chloride. Indirectly, the diuretic effect of hydrochlorothiazide reduces plasma volume, which increases plasma renin activity, increases aldosterone secretion, increases urinary potassium loss, and decreases serum potassium. Renal aldosterone binding is mediated by angiotensin II, so co-administration of angiotensin II receptor antagonists tends to reverse the potassium loss associated with these diuretics.

Dosage & Administration

Hypertension–

• The usual starting dose of 50/12.5 is one tablet once daily.
• For patients who do not respond adequately to one tablet the dosage may be increased to 100/25 once daily.
• A patient whose blood pressure is not adequately controlled with Losartan 100 mg monotherapy may be switched to this combination 100/12.5 once daily.
• In hypertensive patients with left ventricular hypertrophy initial dose is 50/12.5, if additional blood pressure reduction is needed, 100/12.5 may be given, followed by 100/25 if required. The maximum dose is 100/25 once daily.
• In general, the antihypertensive effect is attained within three weeks after initiation of therapy.
• No initial dosage adjustment of 50/12.5 is necessary for elderly patients. But maximum dose of 100/25 once daily dose should not be used as initial therapy in elderly patients.

Severe Hypertension:

• The starting dose for initial treatment of severe hypertension is one tablet of 50/12.5 once daily.
• For patients who do not respond adequately to this dose after 2 to 4 weeks of therapy, the dosage may be increased to 100/25 once daily. The maximum dose is one tablet of 100/25 once daily.

This preparation may be administered with other antihypertensive agents. This may be administered with or without food.

Interaction

Losartan potassium: No significant pharmacokinetic drug interactions were found in the interaction studies with hydrochlorothiazide, digoxin, warfarin, cimetidine and phenobarbital. Like other drugs that block angiotensin II or its effects, simultaneous use of potassium-sparing diuretics (such as spironolactone, triamterene, amiloride), potassium supplements, or potassium-containing salt substitutes may cause serum Potassium is elevated. Like other antihypertensive drugs, the antihypertensive effect of losartan may be weakened by the non-steroidal anti-inflammatory drug indomethacin.

Hydrochlorothiazide: When administered at the same time, the following drugs may interact with thiazide diuretics: alcohol, barbiturates or anesthetics may cause orthostatic hypotension.

Hypoglycemic drugs (oral drugs and insulin)-The dose of hypoglycemic drugs may need to be adjusted.

Other antihypertensives: additive effect or synergistic effect.

Cholestyramine and colestipol resin: In the presence of anion exchange resin, the absorption of hydrochlorothiazide is impaired.

Contraindications

In individuals who are hypersensitive to either component of this medication, the combination of Losartan and Hydrochlorothiazide is contraindicated. This medication is contraindicated in individuals with anuria or hypersensitivity to other sulfonamide-derived medicines due to the Hydrochlorothiazide component.

Side Effects

Side effects are usually mild. Symptomatic hypotension including dizziness may occur, especially in patients with insufficient intravascular volume (for example, patients taking high-dose diuretics). Hyperkalemia occurs occasionally; some angiotensin II receptor antagonists have also reported angioedema. Dizziness; less common gastrointestinal disorders, angina pectoris, palpitations, edema, dyspnea, headache, sleep disturbance, malaise, urticaria, itching, skin rash; rarely hepatitis, atrial fibrillation, cerebrovascular accident, syncope, paresthesia ; Pancreatitis, allergic reactions, cough, depression, erectile dysfunction, anemia, thrombocytopenia, hyponatremia, arthralgia, myalgia, renal failure, rhabdomyolysis, tinnitus, photosensitivity and vasculitis (including allergic purpura ) There are also reports.

Pregnancy & Lactation

Unless absolutely necessary, angiotensin-II receptor antagonists should be avoided during pregnancy. They have been linked to prenatal and newborn blood pressure regulation and renal function, as well as skull abnormalities and oligohy dramnios. There is a scarcity of information on the use of angiotensin-II receptor antagonists during breastfeeding. They are not suggested while nursing, and there are alternative therapy alternatives with better-established safety information.

Precautions & Warnings

• Angioedema: hypersensitivity
• At suitable intervals, serum electrolyte measurement should be conducted to detect potential electrolyte imbalance.
• Hypokalemia is an uncommon complication that can occur with brisk diuresis, severe cirrhosis, or long-term treatment.
• Renal impairment and symptomatic hypotension

Therapeutic Class

Combined antihypertensive preparations

Storage Conditions

Do not store above 30°C. Keep out of the reach of children.

Pharmaceutical Name

Eskayef Pharmaceuticals Ltd.