Araten Plus50 mg+12.5 mg

Araten Plus 50 mg+12.5 mg is a fixed-dose combination tablet used for the management of high blood pressure (hypertension). By combining an angiotensin-II receptor blocker (ARB) with a thiazide diuretic, it delivers a dual mechanism of action that lowers blood pressure more effectively than either agent used alone.

This combination is specifically indicated for:

• Treatment of hypertension in patients who require more than one medication to achieve adequate blood pressure control.
• Reduction of the risk of stroke in hypertensive patients with left ventricular hypertrophy (LVH), an enlargement and thickening of the heart's main pumping chamber.

It is generally prescribed when treatment with a single antihypertensive agent has not brought blood pressure within the target range, or as a step-up therapy for patients already stabilised on the individual components.

*Always take medication according to the advice of a registered physician.

Combined antihypertensive preparations (Angiotensin-II Receptor Blocker + Thiazide Diuretic).

This medicine combines two complementary antihypertensive agents—Losartan Potassium and Hydrochlorothiazide—that act through different but synergistic pathways to control blood pressure.

Losartan Potassium is an orally active angiotensin-II receptor antagonist. Angiotensin II, formed from angiotensin I by the angiotensin-converting enzyme (ACE), is a potent vasoconstrictor and the primary vasoactive hormone of the renin-angiotensin system, playing a key role in the development of hypertension. It also stimulates aldosterone secretion by the adrenal cortex. Losartan and its principal active metabolite (E-3174) selectively block the binding of angiotensin II to the AT1 receptor found in tissues such as vascular smooth muscle and the adrenal gland, thereby inhibiting its vasoconstrictor and aldosterone-secreting effects. Binding studies indicate that losartan is a reversible, competitive inhibitor of the AT1 receptor. Unlike ACE inhibitors, neither losartan nor its metabolite inhibits ACE (kinase II)—the enzyme that degrades bradykinin—which explains its lower propensity to cause dry cough. It does not bind to or block other hormone receptors or ion channels important in cardiovascular regulation.

Hydrochlorothiazide is a thiazide diuretic. It acts on the renal tubular mechanisms of electrolyte reabsorption, directly increasing the excretion of sodium and chloride in approximately equivalent amounts. Indirectly, this diuretic action reduces plasma volume, leading to increased plasma renin activity, increased aldosterone secretion, increased urinary potassium loss, and a decrease in serum potassium.

The two components work in a mutually beneficial way: the renin-aldosterone response triggered by hydrochlorothiazide is mediated by angiotensin II, so co-administering an angiotensin-II receptor antagonist such as losartan helps counteract the potassium loss usually associated with thiazide diuretics. This complementary action delivers additive blood-pressure lowering with a more balanced electrolyte profile.

Araten Plus 50 mg+12.5 mg may interact with several other medicines. Inform your physician about all prescription drugs, over-the-counter products, and supplements you are taking.

Interactions with Losartan Potassium

• No significant pharmacokinetic interactions have been observed with hydrochlorothiazide, digoxin, warfarin, cimetidine, or phenobarbital.
• Potassium-sparing diuretics (e.g. spironolactone, triamterene, amiloride), potassium supplements, or salt substitutes containing potassium may lead to an increase in serum potassium (hyperkalaemia).
• The antihypertensive effect may be reduced (blunted) by the non-steroidal anti-inflammatory drug (NSAID) indomethacin.

Interactions with Hydrochlorothiazide

Side effects associated with Araten Plus 50 mg+12.5 mg are usually mild and transient. As with all medicines, not everyone will experience them.

Common effects: Symptomatic low blood pressure (hypotension), including dizziness, may occur—particularly in patients with reduced intravascular volume, such as those taking high-dose diuretics. Vertigo may also occur.

Occasional effects: Hyperkalaemia (raised blood potassium) may occur occasionally. Angioedema has been reported with some angiotensin-II receptor antagonists.

Less common effects: Gastro-intestinal disturbances, angina, palpitations, oedema, shortness of breath (dyspnoea), headache, sleep disorders, malaise, urticaria (hives), itching (pruritus), and rash.

Rare effects: Hepatitis, atrial fibrillation, cerebrovascular accident (stroke), fainting (syncope), and paraesthesia (tingling or numbness).

Also reported: Pancreatitis, anaphylaxis, cough, depression, erectile dysfunction, anaemia, thrombocytopenia, hyponatraemia (low blood sodium), joint pain (arthralgia), muscle pain (myalgia), renal impairment, rhabdomyolysis, tinnitus, photosensitivity, and vasculitis (including Henoch-Schönlein purpura).

Contact a physician promptly if any severe, persistent, or unusual symptoms develop, especially signs of an allergic reaction such as swelling of the face, lips, tongue, or throat.

Pregnancy: Angiotensin-II receptor antagonists such as losartan should be avoided during pregnancy unless considered essential. They can adversely affect fetal and neonatal blood pressure control and renal function; skull defects and oligohydramnios (reduced amniotic fluid) have also been reported. If pregnancy is detected during treatment, the medication should be discontinued as soon as possible and switched to a suitable alternative under medical supervision.

Lactation: Information on the use of angiotensin-II receptor antagonists during breastfeeding is limited. This combination is not recommended for breastfeeding mothers, and alternative treatments with better-established safety profiles during lactation should be preferred.

The following precautions should be observed during treatment with Araten Plus 50 mg+12.5 mg:

• Hypersensitivity: Watch for signs of angioedema (swelling of the face, lips, tongue, or throat), which requires immediate medical attention.
• Electrolyte balance: Periodic determination of serum electrolytes should be performed at appropriate intervals to detect any imbalance.
• Hypokalaemia: Low blood potassium may rarely develop, especially with brisk diuresis, in the presence of severe cirrhosis, or after prolonged therapy.
• Impaired renal function: Use with caution and monitor kidney function in patients with pre-existing renal impairment.
• Symptomatic hypotension: May occur, particularly in volume- or salt-depleted patients; correct such depletion before starting therapy where possible.

Losartan Potassium: Limited data are available on overdosage in humans. The most likely manifestations would be low blood pressure (hypotension) and rapid heart rate (tachycardia); bradycardia (slow heart rate) could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension develops, supportive treatment should be given. Neither losartan nor its active metabolite can be removed by haemodialysis.

Hydrochlorothiazide: The most common signs and symptoms result from electrolyte depletion—hypokalaemia, hypochloremia, and dehydration caused by excessive diuresis. If digitalis has also been administered, hypokalaemia may aggravate cardiac arrhythmias. The extent to which hydrochlorothiazide is removed by haemodialysis has not been established.

In case of suspected overdose, seek emergency medical care immediately.

Store below 30°C in a cool, dry place, protected from light and moisture. Keep the medicine in its original packaging and out of the reach of children. Do not use after the expiry date printed on the pack.

Patients with Renal Impairment: The usual regimen of 50/12.5 mg may be followed as long as the patient's creatinine clearance is greater than 30 mL/min. In patients with more severe renal impairment, loop diuretics are preferred to thiazides; in such cases, hydrochlorothiazide is not recommended.

Patients with Hepatic Impairment: This combination is not recommended for dose titration in patients with hepatic impairment, because the appropriate 25 mg starting dose of losartan cannot be provided by the fixed-dose tablet.

Paediatric Patients: The safety and effectiveness of this combination in children have not been established, so its use is not recommended in this age group.

Combined antihypertensive preparations

Angiotensin II formed from angiotensin I in a reaction catalyzed by angiotensin converting enzyme (ACE), is a potent vasoconstrictor, the primary vasoactive hormone of the renin-angiotensin system and an important component in the pathophysiology of hypertension. It also stimulates aldosterone secretion by the adrenal cortex. Losartan and its principal active metabolite block the vasoconstrictor and aldosterone-secreting effects of angiotensin II by selectively blocking the binding of angiotensin II to the AT1 receptor found in many tissues, (e.g. vascular smooth muscle, adrenal gland). In vitro binding studies indicate that losartan is a reversible, competitive inhibitor of the AT1 receptor. Neither Losartan nor its active metabolite inhibits ACE (kinase II, the enzyme that converts angiotensin I to angiotensin II and degrades bradykinin); nor do they bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation.Hydrochlorothiazide is a thiazide diuretic. Thiazides affect the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of Sodium and Chloride in approximately equivalent amounts. Indirectly, the diuretic action of Hydrochlorothiazide reduces plasma volume, with consequent increases in plasma renin activity, increases in Aldosterone secretion, increases in urinary Potassium loss, and decreases in serum Potassium. The renin-aldosterone link is mediated by angiotensin II, so co-administration of an angiotensin II receptor antagonist tends to reverse the Potassium loss associated with these diuretics.

Angiotensin-II receptor antagonists should be avoided in pregnancy unless essential. They may adversely affect fetal and neonatal blood pressure control and renal function; skull defects and oligohy dramnios have also been reported. Information on the use of angiotensin-II receptor antagonists in breastfeeding is limited. They are not recommended in breastfeeding and alternative treatment options, with better-established safety information during breastfeeding, are available.

Use in Patients with Renal Impairment: The usual regimens of therapy with 50/12.5 may be followed as long as the patient's creatinine clearance is >30 ml/min. In patients with more severe renal impairment, loop diuretics are preferred to thiazides. In that case, hydrochlorothiazide is not recommended.Use in Patients with Hepatic Impairment: The combination of Losartan and Hydrochlorothiazide is not recommended for titration in patients with hepatic impairment because the appropriate 25 mg starting dose of Losartan cannot be given.Use in pediatric patients: The safety and effectiveness in pediatric patients have not been established.