Telmisartan and hydrochlorothiazide
Telmisartan and hydrochlorothiazide are indicated for the treatment of hypertension. This fixed dose combination is not indicated for initial therapy.
Dosage and administration
As indicated by the physician or pharmacist.
The usual starting dose of telmisartan is 40 mg once a day; blood pressure response is dose related over the range of 20-80 mg. Patients with depletion of intravascular volume should have the condition corrected or telmisartan tablets should be initiated under close medical supervision. Patients with biliary obstructive disorders or hepatic insufficiency should have treatment started under close medical supervision Hydrochlorothiazide is effective in doses of 12.5 mg to 50 mg once daily. Telmisartan and hydrochlorothiazide may be administered with other antihypertensive agents. Telmisartan and hydrochlorothiazide tablets may be administered with or without food.
Patients with renal impairment
The usual regimens of therapy with telmisartan and hydrochlorothiazide tablets may be followed as long as the patient’s creatinine clearance is greater than 30ml/min. In patients with more severe renal impairments loop diuretics are preferred to thiazides, so telmisartan and hydrochlorothiazide are not recommended.
Patients with hepatic impairments
Telmisartan and hydrochlorothiazide tablets are not recommended for patients with severe hepatic impairment. Patients with biliary obstructive disorders or hepatic insufficiency should have treatment started under close medical supervision using the 40/12.5 mg combination.
Fetal/ Neonatal morbidity and mortality:
Drugs that act directly on the renin-angiotensin system can cause fetal or neonatal morbidity and death when administered to pregnant women. Several dozen cases have been reported in the world literature in patients who were taking angiotensin converting enzyme inhibitors. When pregnancy is detected, telmisartan and hydrochlorothiazide tablets should be discontinued as soon as possible.
Hypotension in volume-depleted patients:
Initiation of hypertensive therapy in patients whose renin-angiotensin system are activated such as aptients who are intravascular volume or sodium-depleted, e.g., in patients treated vigorously with diuretics, should only be approached cautiously. These conditions should be corrected prior to administration of telmisartan and hydrochlorothiazide.
Telmisartan should be started under close medical supervision. If hypotension occurs, the patients should be placed in the supine position and if necessary given an intravenous infusion of normal saline. A transient hypotensive response is not a contraindication to further treatment which usually can be continued without difficulty once the blood pressure has stabilized.
Systemic lupus erythematous: Thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus.
Lithium interaction: Lithium generally should not be given with thiazides
Acute myopia and secondary angle-closure glaucoma: Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue.
Carcinogenesis, mutagenesis, impairment of fertility: No carcinogenicity, mutagenicity or fertility studies have been conducted with the combination of telmisartan and hydrochlorothiazide.
Pregnancy and nursing mothers
Contraindicated to pregnancy category C (first trimester) and D (second trimester). It is not known whether telmisartan is excreted in human milk, but telmisartan was shown to be present in the milk of lactating rats. Thiazides appear in human milk because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.
Mechanism of action
Angiotensin іі is formed from angiotensin I in a reaction catalyzed by angiotensin converting enzyme (ACE, kininase ii). Angiotensio ii is the principal pressor agent of the renin-angiotensin system, with effects that include vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation and renal reabsorption of sodium.
Telmisartan blocks the vasoconstrictor and aldosterone secreting effects of angiotensin ii by selectively blocking the binding of angiotensin ii to the AT, receptor in many tissues, such as vascular smooth muscle and the adrenal gland. Its action is therefore independent of the pathways for angiotensin ii synthesis. Blockade of the renin-angiotensin system with ACE inhibitors, which inhibit the biosynthesis of angiotensin ii from angiotensin I, is widely used in the treatment of hypertension. ACE inhibitors also inhibit the degradation of bradykinin, a reaction also catalyzed by ACE. Because telmisartan does not inhibit ACE (kininase ii), it does not affect the response to bradykinin. Whether this difference clinical relevance is not yet known.
Blockade of the angiotensin ii receptor inhibits the negative regulatory feedback of angiotensin ii on renin secretion, but the resulting increased plasma renin activity and angiotensin ii circulating levels do not overcome the effect of telmisartan on blood pressure.
Hydrochlorothiazide is a thiazide diuretic.
Thiazides affect the renal tubular mechanism of electrolyte re-absorption, directly increasing secretion of sodium salt 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.