Losartan potassium, hydrochlorothiazide.
Each film-coated tablet contains: Losartan Potassium 100 mg, Hydrochlorothiazide 25 mg.
Pharmacology: It has an additive effect on blood pressure reduction, reducing blood pressure to a greater degree than either component alone. This effect is thought to be a result of the complimentary actions of both components. Further, as a result of its diuretic effect, hydrochlorothiazide increases plasma renin activity, increases aldosterone secretion, decreases serum potassium, and increases the levels of angiotensin II. Administration of losartan blocks all the physiologically relevant actions of angiotensin II and through inhibition of aldosterone could tend to attenuate the potassium loss associated with the diuretic. Losartan has been shown to have a mild and transient uricosuric effect. Hydrochlorothiazide has been shown to cause modest increases in uric acid; the combination of losartan and hydrochlorothiazide tends to attenuate the diuretic-induced hyperuricemia.
The antihypertensive effect of Losartan Potassium + Hydrochlorothiazide is sustained for a 24-hour period.
Pharmacokinetics: Losartan is readily absorbed from the gastrointestinal tract after oral doses, but undergoes substantial first-pass metabolism resulting in a systemic bioavailability of about 33%. It is metabolised to an active carboxylic acid metabolite E-3174 (EXP-3174), which has greater pharmacological activity than Losartan; some inactive metabolites are also formed. Metabolism is primarily by cytochrome P450 isoenzymes CYP2C9 and CYP3A4. Peak plasma concentrations of Losartan and E-3174 occur about 1 hour and 3 to 4 hours, respectively, after an oral dose. Both Losartan and E-3174 are more than 98% bound to plasma proteins. Losartan is excreted in the urine, and in the faeces via bile, as unchanged drug and metabolites. About 4% of an oral dose is excreted unchanged in urine and about 6% is excreted in urine as the active metabolite. The terminal elimination half-lives of Losartan and E-3174 are about 1.5 to 2.5 hours and 3 to 9 hours, respectively.
Hydrochlorothiazide: Hydrochlorothiazide is not metabolized but is eliminated rapidly by the kidney. When plasma levels have been followed for at least 24 hours, the plasma half-life has been observed to vary between 5.6 and 14.8 hours. At least 61 percent of the oral dose is eliminated unchanged within 24 hours.
It is indicated for the treatment of essential hypertension in patients whose blood pressure is not adequately controlled on losartan or hydrochlorothiazide alone.
Hypertension: The usual maintenance dose is once daily.
Or as prescribed by the physician.
Hypersensitivity to the active substance or to any of the excipients.
Losartan is contraindicated in pregnancy. It should be used with caution in patients with renal artery stenosis. Losartan is excreted in urine and in bile and reduced doses may therefore be required in patients with renal impairment and should be considered in patients with hepatic impairment. Patients with volume depletion (for example those who have received high-dose diuretic therapy) may experience hypotension; volume depletion should be corrected before starting therapy, or a low initial dose should be used. Since hyperkalaemia may occur, serum-potassium concentrations should be monitored, especially in the elderly and patients with renal impairment, and potassium-sparing diuretics should generally be avoided.
Thiazide therapy may precipitate hyperuricemia and/or gout in certain patients. Because losartan decreases uric acid, losartan in combination with hydrochlorothiazide attenuates the diuretic-induced hyperuricemia.
Use in Pregnancy: The use of Losartan Potassium + Hydrochlorothiazide is not recommended during the first trimester of pregnancy. The use of Losartan Potassium + Hydrochlorothiazide is contraindicated during the 2nd and 3rd trimester of pregnancy.
Use in Lactation: It is not known whether losartan is excreted in human milk. However, losartan is excreted in the milk of lactating rats. Thiazides pass into human milk and may inhibit lactation. Because of the potential for adverse effects on the nursing infant, Losartan Potassium + Hydrochlorothiazide is contraindicated during breastfeeding.
Adverse effects of losartan have been reported to be usually mild and transient, and include dizziness, headache, and dose-related orthostatic hypotension. Hypotension may occur particularly in patients with volume depletion (for example those who have received high-dose diuretics). Impaired renal function and, rarely, rash, urticaria, pruritus, angioedema, and raised liver enzyme values may occur. Hyperkalaemia, myalgia, and arthralgia have been reported. Losartan appears less likely than ACE inhibitors to cause cough. Other adverse effects that have been reported with angiotensin II receptor antagonists include respiratory-tract disorders, back pain, gastrointestinal disturbances, fatigue, and neutropenia. Rhabdomyolysis has been reported rarely.
The antihypertensive effects of losartan may be potentiated by drugs or other agents that lower blood pressure. An additive hyperkalaemic effect is possible with potassium supplements, potassium-sparing diuretics, or other drugs that can cause hyperkalaemia; losartan and potassium-sparing diuretics should not generally be given together. NSAIDs should be used with caution in patients taking losartan as the risk of renal impairment may be increased, particularly in those who are inadequately hydrated; use of NSAIDs may also attenuate the hypotensive effect of losartan. Losartan and some other angiotensin II receptor antagonists are metabolised by cytochrome P450 isoenzymes and interactions may occur with drugs that affect these enzymes.
Hydrochlorothiazide: When given concurrently, the following drugs may interact with thiazide diuretics: Alcohol, barbiturates, narcotics or antidepressants: Potentiation of orthostatic hypotension may occur.
Antidiabetic drugs (oral agents and insulin): The treatment with a thiazide may influence the glucose tolerance. Dosage adjustment of the antidiabetic drug may be required. Metformin should be used with caution because of the risk of lactic acidosis induced by possible functional renal failure linked to hydrochlorothiazide.
Store at temperatures not exceeding 30°C.
C09DA01 - losartan and diuretics ; Belongs to the class of angiotensin II receptor blockers (ARBs) in combination with diuretics. Used in the treatment of cardiovascular disease.