Description
Generic
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 a strong vasoconstrictor, the major vasoactive hormone of the renin-angiotensin system, and a key component in the pathophysiology of hypertension. It is produced from angiotensin I in a process catalyzed by angiotensin converting enzyme (ACE). It also causes the adrenal cortex to secrete more aldosterone. Losartan and its main active metabolite inhibit angiotensin II’s vasoconstrictor and aldosterone-secreting actions by specifically blocking angiotensin II’s binding to the AT1 receptor, which is present in numerous tissues (e.g. vascular smooth muscle, adrenal gland).Losartan is a reversible, competitive AT1 receptor inhibitor, according to in vitro binding tests. Losartan and its active metabolite do not inhibit ACE (angiotensin-converting enzyme II, which converts angiotensin I to angiotensin II and degrades bradykinin), nor do they bind to or block other hormone receptors or ion channels that are known to be essential in cardiovascular control.
A thiazide diuretic is hydrochlorothiazide. Thiazides alter the electrolyte reabsorption processes in the kidney tubules, increasing sodium and chloride excretion in about equal quantities. Indirectly, Hydrochlorothiazide’s diuretic effect reduces plasma volume, resulting in increased plasma renin activity, increased Aldosterone production, increased urinary Potassium loss, and decreased serum Potassium. Because angiotensin II mediates the renin-aldosterone connection, using an angiotensin II receptor antagonist with these diuretics helps to restore the potassium loss.
Dosage
- 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.
Administration
Interaction
Losartan Potassium: Interaction tests with Hydrochlorothiazide, Digoxin, Warfarin, Cimetidine, and Phenobarbital revealed no significant drug-drug pharmacokinetic interactions. Concomitant use of potassium-sparing diuretics (e.g. Spironolactone, Triamterene, Amiloride), potassium supplements, or salt replacements containing potassium might cause a rise in serum potassium, just as other medicines that inhibit angiotensin II or its effects. Losartan’s antihypertensive impact, like that of other antihypertensive drugs, can be reduced by the nonsteroidal anti-inflammatory medication Indomethacin.
Alcohol, barbiturates, and narcotics may potentiate orthostatic hypotension when used simultaneously with Thiazide diuretics.
Antidiabetic medications (oral agents and Insulin): antidiabetic drug dose may need to be adjusted.
Other antihypertensive drugs: potentiation or additive effect
Cholestyramine with colestipol resins: Hydrochlorothiazide absorption is hampered when anionic exchange resins are present.
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
The majority of side effects are minor. Patients with intravascular volume loss may have symptomatic hypotension, including dizziness (e.g. those taking high-dose diuretics). Angioedema has been documented with certain angiotensin-II receptor antagonists, as well as hyperkalemia. Angina, palpitation, oedema, dyspnea, headache, sleep disorders, malaise, urticaria, pruritus, rash; rarely hepatitis, atrial fibrillation, cerebrovascular accident, syncope, paraesthesia; also reported pancreatitis, anaphylaxis, cough, depression, erectile dysfunction, anemia, thrombocytopenia, hyponatraemia, hyponatraemia, hypoarthralgia, myalgia, renal impairment, rhabdomyolysis, tinnitus, photosensitivity, and vasculitis are some of the conditions that might occur (including Henoch-Schonlein purpura)
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 may infrequently arise, especially with rapid diuresis, when severe cirrhosis is present, or after protracted treatment
- Impaired renal function and
- Hypotension with symptoms
Therapeutic Class
Storage Conditions
