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  • REPACE H ( Losartan Potassium ) medicine information: Description, side effects

    REPACE H

    Losartan Potassium and Hydrochlorothiazide Tablets

    Composition

    Each  film  coated  tablet  contains  Losartan  potassium  INN  50  mg  and

    Hydrochlorothiazide BP 12.5 mg.

    Clinical Pharmacology

    Repace H combines losartan, a specific angiotensin-ll receptor (type AT1)

    antagonist and hydrochlorothiazide, a thiazide diuretic

    Losartan is an oral, specific angiotensin-ll receptor (type AT1) antagonist. Angiotensin II binds to the AT1 receptor found in many tissues (e.g. vascular smooth muscle, adrenal gland, Kidneys, and the heart) and elicits several important biological actions, including vasoconstriction and the release of aldosterone. Hydrochlorothiazide is a diuretic and antihypertensive. It affects the distal renal tubular mechanism of electrolyte reabsorption.

    The components of Repace-H have been shown to have 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: Following oral administration, losartan is well absorbed and undergoes first-pass metabolism forming an active carboxylic acid metabolite and other inactive metabolites. The systeir^ bioavailability of losartan tablets is approximately 33%. Mean peak concentrations of losartan and its active metabolite are reached in 1 hour and in 3-4 hours, respectively. There was no clinically significant effect on the plasma concentration profile ;                                 the drug was administered with a

    standardised meal. Both losartan and its active metabolite are 99% bound to plasma proteins, primarily albumir, Trie volume of distribution of losHan is 34 litres. About 14% of an intravenously or orally administered dose of losartan is converted to its active metabolite, Followng oral and intravenous administration of 14C-labelled losartan pota-                                    na radioactivity primarily is attributed to losartan

    and its active metabotoe ‘.  addition *o the ac^ve metabolite inactive metabolites are -Giites formed Dy hydroxyiation of the butyl side

    chain and a minor meta*xtfte. an N-2 tetrazoie giucurc                     ‘- clearance of

    iosartan and its active metabolite is about 600 rrivmin and EO ml/min. respectively. Renal clearance of losartan and its active metabolite is about 74 ml/min and 26 mi/mm, respectively. Wr^                                  ^e^ed orally, about 4% of the dose is

    excreted unchanged in the urine, and about 6% of the dose is excreted in the urine as active metabolite. The pnarmacokinetics of losartan and its active metabolite are linear with oral losartan potassium doses up to 200 mg. Following oral administration, plasma concentrations of losartan and its active metabolite decline polyexponentially with a terminal half life of about 2 hours and 69 hours, respectively. Both biliary and urinary excretion contribute to the elimination of losartan and its metabolites. Following an oral dose of 14C-labelled losartan in man, about 35% of radioactivity is recovered in the urine and 58% in the faeces. Hydrochlorothiazide: Hydrochlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk. Hydrochlorothiazide is not metabolised 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% of the oral dose is eliminated unchanged within 24 hours.

    Repace H is indicated for the treatment of hypertension in patients whose blood pressure is not adequately controlled on hydrochlorothiazide or .osartan monotherapy. Centra-indications

    •    Pregnancy.

    •    Patients who are hypersensitive to any component of this product and to other sulphonamide derived drugs.

    •    Patients with anuria.

    Warnings and Precautions

    Losartan and hydrochlorothiazide tablet is not recommended for patients with hepatic impairment or moderate to severe renal impairment.

    consequence of inhibiting the renin angiotensin aldosterone system, changes in renal function, including renal failure, have been reported. Increases in blood urea and serum creatinine have also been reported in patients with bilateral renal artery stenosis or stenosis of the artery to a solitary kidney; these changes in renal function may be reversible upon discontinuation of therapy. Caution is required in patients with significant renal disease and renal transplant recipients as there have been reports of anemia developing in such patients treated with losartan. Hydrochlorothiazide

    Symptomatic hypotension may occur in some patients. Periodic determination of serum electrolytes should be performed at appropriate intervals. Thiazide therapy may impair glucose tolerance. Dosage adjustment of antidiabetic agents, including insulin, may be required. Thiazides may decrease urinary calcium excretion and may cause elevation of serum calcium. Marked hypercalcemia may be evidence of hidden hyperparathyroidism. Thiazides should be discontinued before carrying out tests for parathyroid function. Increases in cholesterol and triglyceride levels may be associated with thiazide diuretic therapy. 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 hyperuricaemia. In patients receiving thiazides, hypersensitivity reactions may occur with or without a history of allergy or bronchial asthma. Exacerbation or activation of systemic lupus erythematosus has been reported with the use of thiazides. Pregnancy & Lactation

    In humans, foetal renal perfusion, which is dependent upon the development of the renin angiotensin system, begins in the second trimester; thus, risk to the foetus increases if losartan and hydrochlorothiazide tablet is administered during the second or third trimesters of pregnancy. Thiazides cross the placental barrier and appear in cord blood. The routine use of diuretics in healthy pregnant women is not recommended and exposes mother and foetus to unnecessary hazard, including foetal or neonatal jaundice, thrombocytopenia and possibly other adverse reactions.

    When used in pregnancy during the second and third trimesters, drugs that act directly on the renin angiotensin system can cause injury and even death to the developing foetus. When pregnancy is detected, Repace H should be discontinued as soon as possible. It is not known whether losartan is excreted in human milk. Thiazides appear in human milk. Because of the potential for adverse effects on the breast feeding infant, a decision should be made whether to discontinue breast feeding or discontinue the drug, taking into account the importance of the drug to the mother. Drug Interactions

    No drug interactions of clinical significance have been identified with hydrochlorothiazide, digoxin, warfarin, cimetidine, phenobarbital, ketoconazole and erythromycin. Rifampicin and fluconazole have been reported to reduce levels of active metabolite. Concomitant use of other drugs which retain potassium or may increase potassium levels may lead to increases in serum potassium. Co medication is not advisable. The antihypertensive effect of losartan may be attenuated by non steroidal anti inflammatory drugs such as indomethacin.

    i given concurrently, the following drugs may interact with thiazide diuretics: Potentiation of orthostatic hypotension may occur with concurrent administration of alcohol, barbiturates, or narcotics. Dosage adjustment of the antidiabetic drug may be required in combination with antidiabetic drugs (oral agents and insulin). There may be an additive effect with concurrent administration of other antihypertensive drugs. Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins (cholestyramine and colestipol). There may be intensified electrolyte depletion, particularly hypokalemia in combination with corticosteroids, and ACTH. Possible increased responsiveness to the muscle relaxant have been observed with concurrent administration of skeletal muscle relaxants, and non depolarising agents (e.g. tubocurarine). Diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity. Therefore, concomitant use is not recommended. In some patients, the administration of a nonsteroidal antiinflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effe
    Adverse experiences have been limited to those that were reported previously with losartan potassium and/ or hydrochlorothiazide. Dizziness was the only commonly reported adverse event with the fixed dose combination of losartan and hydrochlorothiazide. Anaphylactic reactions, angioedema including swelling of the larynx and glottis causing airway obstruction and/or swelling of the face, lips, pharynx, tongue, vasculitis including Henoch-Schonlein purpura, hepatitis, urticaria, diarrhea and cough has been reported rarely in patients treated with losartan. Additional side effects that have been seen with one of the individual components and may be potential side effects with Repace H are dose related orthostatic effects, liver function abnormalities, myalgia, migraine, rash, anemia, pruritus, anorexia, gastric irritation, nausea, vomiting, cramping, constipation, jaundice (intrahepatic cholestatic jaundice), pancreatitis, sialoadenitis, vertigo, paraesthesiae, headache, xanthopsia, leucopenia, agranulocytosis, thrombocytopenia, aplastic anaemia, haemolytic anaemia, purpura, photosensitivity, fever, necrotising angiitis, respiratory distress (including pneumonitis and pulmonary edema), toxic epidermal necrolysis, hyperglycemia, glycosuria, hyperuricemia, electrolyte imbalance (including hyponatremia and hypokalemia), renal dysfunction, interstitial nephritis, renal failure, muscle spasm, weakness, restlessness, and transient blurred vision.

    No specific information is available on the treatment of overdosage with Repace H. Treatment is symptomatic and supportive. Therapy with Repace H should be discontinued and the patient observed closely. Suggested measures include induction of emesis if ingestion is recent, and correction of dehydration, electrolyte imbalance, hepatic coma, and hypotension by established procedures. Losartan

    Limited data are available in regard to overdosage in humans. The most likely manifestation of overdosage would be hypotension and tachycardia; bradycardia could occur from parasympathetic stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted. Neither losartan nor the active metabolite can be removed by hemodialysis. Hydrochlorothiazide

    The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias. The degree to which hydrochlorothiazide is removed by haemodialysis has not been established.

    Where   possible   titration   with   individual   component   (i.e.   losartan   and

    hydrochlorothiazide) is recommended. When clinically appropriate direct change

    from monotherapy to the fixed combinations may be considered in patients whose

    blood pressure is not adequately controlled.

    The usual starting and maintenance dose is 1 tablet once daily for most patients. For

    patients who do not respond adequately, the dosage may be increased to 2 tablets

    once daily. The maximum dose is 2 tablets once daily. In general, the

    antihypertensive effect is attained within three weeks after initiation of therapy. It may

    be administered with or without food.

    Pediatric Use: Safety and efficacy in children have not been established.

    Elderly: Patients over 75 years: Clinical experience in patients over 75 years of age is

    limited. Any therapy involving the angiotensin II antagonist, losartan, should be

    initiated with 25 mg losartan in these patients.

    Use in patients with intravascular volume depletion: Repace H should not be

    initiated in patients who are intravascularly volume depleted (e.g. those treated

    with high-dose diuretics).

    Renal Impairment: No initial dosage adjustment is necessary in patients with mild

    renal impairment. It is not recommended for patients with moderate to severe renal

    impairment or patients on dialysis.

    Hepatic Impairment: Repace H is not recommended for patients with hepatic impairment.

    Concomitant therapy: Repace H may be administered with other antihypertensive agents.

    Storage: Store in a cool and dry place, protected from the light.

    Presentation : Box containing 5 x 10′ s Repace H tablets in Alu PVC Blister pack.

    Published on September 30, 2013 · Filed under: Science and Medicine; Tagged as: , ,
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