de is not recommended. non-steroidal anti-inflammatory agents including selective cyclooxygenase-2 inhibitors (cox-2 inhibitors) : in patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of nsaids, including selective cox-2 inhibitors, with angiotensin ii receptor antagonists, including telmisartan, may result in deterioration of renal function, including possible acute renal failure. these effects are usually reversible. monitor renal function periodically in patients receiving telmisartan and nsaid therapy. the antihypertensive effect of angiotensin ii receptor antagonists, including telmisartan may be attenuated by nsaids including selective cox-2 inhibitors. ramipril and ramiprilat: co-administration of telmisartan 80 mg once daily and ramipril 10 mg once daily to healthy subjects increases steady-state c max and auc of ramipril 2.3 and 2.1 fold, respectively, and c max and auc of ramiprilat 2.4 and 1.5 fold, respectively. in contrast, c max and auc of telmisartan decrease by 31% and 16%, respectively. when co-administering telmisartan and ramipril, the response may be greater because of the possibly additive pharmacodynamic effects of the combined drugs, and also because of the increased exposure to ramipril and ramiprilat in the presence of telmisartan. warfarin : telmisartan administered for 10 days slightly decreased the mean warfarin trough plasma concentration; this decrease did not result in a change in international normalized ratio (inr). other drugs : co-administration of telmisartan did not result in a clinically significant interaction with acetaminophen, amlodipine, glibenclamide, simvastatin, hydrochlorothiazide or ibuprofen. telmisartan is not metabolized by the cytochrome p450 system and had no effects in vitro on cytochrome p450 enzymes, except for some inhibition of cyp2c19. telmisartan is not expected to interact with drugs that inhibit cytochrome p450 enzymes; it is also not expected to interact with drugs metabolized by cytochrome p450 enzymes, except for possible inhibition of the metabolism of drugs metabolized by cyp2c19. hydrochlorothiazide when administered concurrently, the following drugs may interact with thiazide diuretics: alcohol, barbiturates, or narcotics : potentiation of orthostatic hypotension may occur. antidiabetic drugs (oral agents and insulin) : dosage adjustment of the antidiabetic drug may be required. other antihypertensive drugs : additive effect or potentiation. cholestyramine and colestipol resins : absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85% and 43%, respectively. corticosteroids, acth : intensified electrolyte depletion, particularly hypokalemia. pressor amines (e.g., norepinephrine) : possible decreased response to pressor amines but not sufficient to preclude their use. skeletal muscle relaxants, nondepolarizing (e.g., tubocurarine) : possible increased responsiveness to the muscle relaxant. lithium : should not generally be given with diuretics. diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity. refer to the package insert for lithium preparations before use of such preparations with telmisartan and hydrochlorothiazide tablets. non-steroidal anti-inflammatory drugs : in some patients, the administration of a non-steroidal anti-inflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing and thiazide diuretics. therefore, when telmisartan and hydrochlorothiazide tablets and non-steroidal anti-inflammatory agents are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.

us. in the unusual case that there is no appropriate alternative to therapy with drugs affecting the renin-angiotensin system for a particular patient, apprise the mother of the potential risk to the fetus. perform serial ultrasound examinations to assess the intra-amniotic environment. if oligohydramnios is observed, discontinue telmisartan and hydrochlorothiazide, unless it is considered lifesaving for the mother. fetal testing may be appropriate, based on the week of pregnancy. patients and physicians should be aware, however, that oligohydramnios may not appear until after the fetus has sustained irreversible injury. closely observe infants with histories of in utero exposure to telmisartan and hydrochlorothiazide for hypotension, oliguria, and hyperkalemia (see precautions , pediatric use ). no teratogenic effects were observed when telmisartan was administered to pregnant rats at oral doses of up to 50 mg/kg/day and to pregnant rabbits at oral doses up to 45 mg/kg/day. in rabbits, embryolethality associated with maternal toxicity (reduced body weight gain and food consumption) was observed at 45 mg/kg/day [about 12 times the maximum recommended human dose (mrhd) of 80 mg on a mg/m 2 basis]. in rats, maternally toxic (reduction in body weight gain and food consumption) telmisartan doses of 15 mg/kg/day (about 1.9 times the mrhd on a mg/m 2 basis), administered during late gestation and lactation, were observed to produce adverse effects in neonates, including reduced viability, low birth weight, delayed maturation, decreased weight gain. telmisartan has been shown to be present in rat fetuses during late gestation and in rat milk. the no observed effect doses for developmental toxicity in rats and rabbits, 5 and 15 mg/kg/day, respectively, are about 0.64 and 3.7 times, on a mg/m 2 basis, the maximum recommended human dose of telmisartan (80 mg/day). studies in which hydrochlorothiazide was administered to pregnant mice and rats during their periods of major organogenesis at doses up to 3000 and 1000 mg/kg/day, respectively, provided no evidence of harm to the fetus. thiazides cross the placental barrier and appear in cord blood. there is a risk of fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults. hypotension in volume-depleted patients initiation of antihypertensive therapy in patients whose renin-angiotensin system are activated such as patients 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 tablets. treatment should be started under close medical supervision (see dosage and administration ). 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. hydrochlorothiazide hepatic impairment : thiazide diuretics should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma. hypersensitivity reaction : hypersensitivity reactions to hydrochlorothiazide may occur in patients with or without a history of allergy or bronchial asthma, but are more likely in patients with such a history. systemic lupus erythematosus : thiazide diuretics have been reported to cause exacerbation or activation of systemic lupus erythematosus. lithium interaction : lithium generally should not be given with thiazides (see precautions, drug interactions, hydrochlorothiazide , lithium ). 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 hydrochlorothiazide as rapidly as possible. prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.

omena (e.g., pancreatitis), the former much more common than the latter. therapy with any combination of telmisartan and hydrochlorothiazide will be associated with both sets of dose-independent side effects. telmisartan and hydrochlorothiazide tablets may be administered with other antihypertensive agents. telmisartan and hydrochlorothiazide tablets may be administered with or without food. replacement therapy the combination may be substituted for the titrated components. dose titration by clinical effect telmisartan and hydrochlorothiazide tablets are available as tablets containing either telmisartan 40 mg and hydrochlorothiazide 12.5 mg, or telmisartan 80 mg and hydrochlorothiazide 12.5 mg or 25 mg. a patient whose blood pressure is not adequately controlled with telmisartan monotherapy 80 mg (see above) may be switched to telmisartan and hydrochlorothiazide tablets, telmisartan 80 mg/hydrochlorothiazide 12.5 mg once daily, and finally titrated up to 160/25 mg, if necessary. a patient whose blood pressure is inadequately controlled by 25 mg once daily of hydrochlorothiazide may be switched to telmisartan 80 mg/hydrochlorothiazide 12.5 mg or telmisartan 80 mg/hydrochlorothiazide 25 mg tablets once daily. the clinical response to telmisartan and hydrochlorothiazide tablets should be subsequently evaluated and if blood pressure remains uncontrolled after 2 to 4 weeks of therapy, the dose may be titrated up to 160/25 mg, if necessary. those patients controlled by 25 mg hydrochlorothiazide but who experience hypokalemia with this regimen, may be switched to telmisartan 80 mg/hydrochlorothiazide 12.5 mg tablets once daily, reducing the dose of hydrochlorothiazide without reducing the overall expected antihypertensive response. 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 >30 ml/min. in patients with more severe renal impairment, loop diuretics are preferred to thiazides, so telmisartan and hydrochlorothiazide tablets are not recommended. patients with hepatic impairment 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 (see precautions ).

14) (%) placebo (n=74) (%) telm (n=209) (%) hctz (n=121) (%) body as a whole fatigue 3 1 3 3 influenza-like symptoms 2 1 2 3 central/peripheral nervous system dizziness 5 1 4 6 gastrointestinal system diarrhea 3 0 5 2 nausea 2 0 1 2 respiratory system disorder sinusitis 4 3 3 6 upper respiratory tract infection 8 7 7 10 * includes all doses of telmisartan (20 to 160 mg), hydrochlorothiazide (6.25 to 25 mg), and combinations thereof the following adverse events were reported at a rate less than 2% in patients treated with telmisartan/hydrochlorothiazide and at a greater rate than in patients treated with placebo: back pain, dyspepsia, vomiting, tachycardia, hypokalemia, bronchitis, pharyngitis, rash, hypotension postural, abdominal pain. finally, the following adverse events were reported at a rate of 2% or greater in patients treated with telmisartan/hydrochlorothiazide, but were as, or more common in the placebo group: pain, headache, cough, urinary tract infection. adverse events occurred at approximately the same rates in men and women, older and younger patients, and black and non-black patients. in controlled trials (n=1017), 0.3% of patients treated with telmisartan and hydrochlorothiazide tablets 40/12.5 mg, 80/12.5 mg or 80/25 mg discontinued due to orthostatic hypotension, and the incidence of dizziness was 4%, 7%, and 1% respectively. telmisartan other adverse experiences that have been reported with telmisartan, without regard to causality, are listed below: autonomic nervous system : impotence, increased sweating, flushing body as a whole : allergy, fever, leg pain, malaise, chest pain cardiovascular : palpitation, dependent edema, angina pectoris, leg edema, abnormal ecg, hypertension, peripheral edema cns : insomnia, somnolence, migraine, vertigo, paresthesia, involuntary muscle contractions, hypoaesthesia gastrointestinal : flatulence, constipation, gastritis, dry mouth, hemorrhoids, gastroenteritis, enteritis, gastroesophageal reflux, toothache, non-specific gastrointestinal disorders metabolic : gout, hypercholesterolemia, diabetes mellitus musculoskeletal : arthritis, arthralgia, leg cramps, myalgia psychiatric : anxiety, depression, nervousness resistance mechanism : infection, fungal infection, abscess, otitis media respiratory : asthma, rhinitis, dyspnea, epistaxis skin : dermatitis, eczema, pruritus urinary : micturition frequency, cystitis vascular : cerebrovascular disorder special senses : abnormal vision, conjunctivitis, tinnitus, earache a single case of angioedema was reported (among a total of 3781 patients treated with telmisartan). hydrochlorothiazide other adverse experiences that have been reported with hydrochlorothiazide, without regard to causality, are listed below: body as a whole : weakness digestive : pancreatitis, jaundice (intrahepatic cholestatic jaundice), sialadenitis, cramping, gastric irritation hematologic : aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombocytopenia hypersensitivity : purpura, photosensitivity, urticaria, necrotizing angiitis (vasculitis and cutaneous vasculitis), fever, respiratory distress including pneumonitis and pulmonary edema, anaphylactic reactions metabolic : hyperglycemia, glycosuria, hyperuricemia musculoskeletal : muscle spasm nervous system/psychiatric : restlessness renal : renal failure, renal dysfunction, interstitial nephritis skin : erythema multiforme including stevens-johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis special senses : transient blurred vision, xanthopsia post-marketing experience the following adverse reactions have been identified during post-approval use of telmisartan tablets. because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure. decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting, or (3) strength of causal connection to telmisartan tablets. the most frequently spontaneously reported events include: headache, dizziness, asthenia, coughing, nausea, fatigue, weakness, edema, face edema, lower limb edema, angioneurotic edema, urticaria, hypersensitivity, sweating increased, erythema, chest pain, atrial fibrillation, congestive heart failure, myocardial infarction, blood pressure increased, hypertension aggravated, hypotension (including postural hypotension), hyperkalemia, syncope, dyspepsia, diarrhea, pain, urinary tract infection, erectile dysfunction, back pain, abdominal pain, muscle cramps (including leg cramps), myalgia, bradycardia, eosinophilia, thrombocytopenia, uric acid increased, abnormal hepatic function/liver disorder, renal impairment including acute renal failure, anemia, increased cpk, anaphylactic reaction, and tendon pain (including tendonitis, tenosynovitis), drug eruption (toxic skin eruption mostly reported as toxicoderma, rash, and urticaria), hypoglycemia (in diabetic patients), and angioedema (with fatal outcome). rare cases of rhabdomyolysis have been reported in patients receiving angiotensin ii receptor blockers, including telmisartan tablets. clinical laboratory findings in controlled trials, clinically relevant changes in standard laboratory test parameters were rarely associated with administration of telmisartan and hydrochlorothiazide tablets. hemoglobin and hematocrit : decreases in hemoglobin (≥2 g/dl) and hematocrit (≥9%) were observed in 1.2% and 0.6% of telmisartan/hydrochlorothiazide patients, respectively, in controlled trials. changes in hemoglobin and hematocrit were not considered clinically significant and there were no discontinuations due to anemia. creatinine, blood urea nitrogen (bun) : increases in bun (≥11.2 mg/dl) and serum creatinine (≥0.5 mg/dl) were observed in 2.8% and 1.4%, respectively, of patients with essential hypertension treated with telmisartan and hydrochlorothiazide tablets in controlled trials. no patient discontinued treatment with telmisartan and hydrochlorothiazide tablets due to an increase in bun or creatinine. liver function tests : occasional elevations of liver enzymes and/or serum bilirubin have occurred. no telmisartan/ hydrochlorothiazide treated patients discontinued therapy due to abnormal hepatic function. serum electrolytes : see precautions .

de is not recommended. non-steroidal anti-inflammatory agents including selective cyclooxygenase-2 inhibitors (cox-2 inhibitors) : in patients who are elderly, volume-depleted (including those on diuretic therapy), or with compromised renal function, co-administration of nsaids, including selective cox-2 inhibitors, with angiotensin ii receptor antagonists, including telmisartan, may result in deterioration of renal function, including possible acute renal failure. these effects are usually reversible. monitor renal function periodically in patients receiving telmisartan and nsaid therapy. the antihypertensive effect of angiotensin ii receptor antagonists, including telmisartan may be attenuated by nsaids including selective cox-2 inhibitors. ramipril and ramiprilat: co-administration of telmisartan 80 mg once daily and ramipril 10 mg once daily to healthy subjects increases steady-state c max and auc of ramipril 2.3 and 2.1 fold, respectively, and c max and auc of ramiprilat 2.4 and 1.5 fold, respectively. in contrast, c max and auc of telmisartan decrease by 31% and 16%, respectively. when co-administering telmisartan and ramipril, the response may be greater because of the possibly additive pharmacodynamic effects of the combined drugs, and also because of the increased exposure to ramipril and ramiprilat in the presence of telmisartan. warfarin : telmisartan administered for 10 days slightly decreased the mean warfarin trough plasma concentration; this decrease did not result in a change in international normalized ratio (inr). other drugs : co-administration of telmisartan did not result in a clinically significant interaction with acetaminophen, amlodipine, glibenclamide, simvastatin, hydrochlorothiazide or ibuprofen. telmisartan is not metabolized by the cytochrome p450 system and had no effects in vitro on cytochrome p450 enzymes, except for some inhibition of cyp2c19. telmisartan is not expected to interact with drugs that inhibit cytochrome p450 enzymes; it is also not expected to interact with drugs metabolized by cytochrome p450 enzymes, except for possible inhibition of the metabolism of drugs metabolized by cyp2c19. hydrochlorothiazide when administered concurrently, the following drugs may interact with thiazide diuretics: alcohol, barbiturates, or narcotics : potentiation of orthostatic hypotension may occur. antidiabetic drugs (oral agents and insulin) : dosage adjustment of the antidiabetic drug may be required. other antihypertensive drugs : additive effect or potentiation. cholestyramine and colestipol resins : absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins. single doses of either cholestyramine or colestipol resins bind the hydrochlorothiazide and reduce its absorption from the gastrointestinal tract by up to 85% and 43%, respectively. corticosteroids, acth : intensified electrolyte depletion, particularly hypokalemia. pressor amines (e.g., norepinephrine) : possible decreased response to pressor amines but not sufficient to preclude their use. skeletal muscle relaxants, nondepolarizing (e.g., tubocurarine) : possible increased responsiveness to the muscle relaxant. lithium : should not generally be given with diuretics. diuretic agents reduce the renal clearance of lithium and add a high risk of lithium toxicity. refer to the package insert for lithium preparations before use of such preparations with telmisartan and hydrochlorothiazide tablets. non-steroidal anti-inflammatory drugs : in some patients, the administration of a non-steroidal anti-inflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-sparing and thiazide diuretics. therefore, when telmisartan and hydrochlorothiazide tablets and non-steroidal anti-inflammatory agents are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.

s, 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 has clinical relevance is not yet known. telmisartan does not bind to or block other hormone receptors or ion channels known to be important in cardiovascular regulation. 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 mechanisms of electrolyte reabsorption, directly increasing excretion 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 coadministration of an angiotensin ii receptor antagonist tends to reverse the potassium loss associated with these diuretics. the mechanism of the antihypertensive effect of thiazides is not fully understood. pharmacokinetics general telmisartan following oral administration, peak concentrations (c max ) of telmisartan are reached in 0.5 to 1 hour after dosing. food slightly reduces the bioavailability of telmisartan, with a reduction in the area under the plasma concentration-time curve (auc) of about 6% with the 40 mg tablet and about 20% after a 160 mg dose. the absolute bioavailability of telmisartan is dose dependent. at 40 and 160 mg the bioavailability was 42% and 58%, respectively. the pharmacokinetics of orally administered telmisartan are nonlinear over the dose range 20 to 160 mg, with greater than proportional increases of plasma concentrations (c max and auc) with increasing doses. telmisartan shows bi-exponential decay kinetics with a terminal elimination half-life of approximately 24 hours. trough plasma concentrations of telmisartan with once daily dosing are about 10 to 25% of peak plasma concentrations. telmisartan has an accumulation index in plasma of 1.5 to 2.0 upon repeated once daily dosing. hydrochlorothiazide 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. metabolism and elimination telmisartan following either intravenous or oral administration of 14 c-labeled telmisartan, most of the administered dose (>97%) was eliminated unchanged in feces via biliary excretion; only minute amounts were found in the urine (0.91% and 0.49% of total radioactivity, respectively). telmisartan is metabolized by conjugation to form a pharmacologically inactive acylglucuronide; the glucuronide of the parent compound is the only metabolite that has been identified in human plasma and urine. after a single dose, the glucuronide represents approximately 11% of the measured radioactivity in plasma. the cytochrome p450 isoenzymes are not involved in the metabolism of telmisartan. total plasma clearance of telmisartan is >800 ml/min. terminal half-life and total clearance appear to be independent of dose. hydrochlorothiazide hydrochlorothiazide is not metabolized but is eliminated rapidly by the kidney. at least 61% of the oral dose is eliminated as unchanged drug within 24 hours. distribution telmisartan telmisartan is highly bound to plasma proteins (>99.5%), mainly albumin and α 1 -acid glycoprotein. plasma protein binding is constant over the concentration range achieved with recommended doses. the volume of distribution for telmisartan is approximately 500 liters, indicating additional tissue binding. hydrochlorothiazide hydrochlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk. special populations pediatric : telmisartan pharmacokinetics have not been investigated in patients <18 years of age. geriatric : the pharmacokinetics of telmisartan do not differ between the elderly and those younger than 65 years (see dosage and administration ). gender : plasma concentrations of telmisartan are generally 2 to 3 times higher in females than in males. in clinical trials, however, no significant increases in blood pressure response or in the incidence of orthostatic hypotension were found in women. no dosage adjustment is necessary. renal insufficiency : renal excretion does not contribute to the clearance of telmisartan. based on modest experience in patients with mild-to-moderate renal impairment (creatinine clearance of 30 to 80 ml/min, mean clearance approximately 50 ml/min), no dosage adjustment is necessary in patients with decreased renal function. telmisartan is not removed from blood by hemofiltration (see precautions and dosage and administration ). hepatic insufficiency : in patients with hepatic insufficiency, plasma concentrations of telmisartan are increased, and absolute bioavailability approaches 100% (see precautions and dosage and administration ). drug interactions : see precautions, drug interactions . pharmacodynamics telmisartan in normal volunteers, a dose of telmisartan 80 mg inhibited the pressor response to an intravenous infusion of angiotensin ii by about 90% at peak plasma concentrations with approximately 40% inhibition persisting for 24 hours. plasma concentration of angiotensin ii and plasma renin activity (pra) increased in a dose-dependent manner after single administration of telmisartan to healthy subjects and repeated administration to hypertensive patients. the once-daily administration of up to 80 mg telmisartan to healthy subjects did not influence plasma aldosterone concentrations. in multiple dose studies with hypertensive patients, there were no clinically significant changes in electrolytes (serum potassium or sodium), or in metabolic function (including serum levels of cholesterol, triglycerides, hdl, ldl, glucose, or uric acid). in 30 hypertensive patients with normal renal function treated for 8 weeks with telmisartan 80 mg or telmisartan 80 mg in combination with hydrochlorothiazide 12.5 mg, there were no clinically significant changes from baseline in renal blood flow, glomerular filtration rate, filtration fraction, renovascular resistance, or creatinine clearance. hydrochlorothiazide after oral administration of hydrochlorothiazide, diuresis begins within 2 hours, peaks in about 4 hours and lasts about 6 to 12 hours. clinical trials telmisartan the antihypertensive effects of telmisartan have been demonstrated in six principal placebo-controlled clinical trials, studying a range of 20 to 160 mg; one of these examined the antihypertensive effects of telmisartan and hydrochlorothiazide in combination. the studies involved a total of 1773 patients with mild to moderate hypertension (diastolic blood pressure of 95 to 114 mmhg), 1031 of whom were treated with telmisartan. following once daily administration of telmisartan, the magnitude of blood pressure reduction from baseline after placebo subtraction was approximately (sbp/dbp) 6-8/6 mmhg for 20 mg, 9-13/6-8 mmhg for 40 mg, and 12-13/7-8 mmhg for 80 mg. larger doses (up to 160 mg) did not appear to cause a further decrease in blood pressure. upon initiation of antihypertensive treatment with telmisartan, blood pressure was reduced after the first dose, with a maximal reduction by about 4 weeks. with cessation of treatment with telmisartan tablets, blood pressure gradually returned to baseline values over a period of several days to one week. during long-term studies (without placebo control) the effect of telmisartan appeared to be maintained for up to at least one year. the antihypertensive effect of telmisartan is not influenced by patient age, gender, weight or body mass index. blood pressure response in black patients (usually a low-renin population) is noticeably less than that in caucasian patients. this has been true for most, but not all, angiotensin ii antagonists and ace inhibitors. the onset of antihypertensive activity occurs within 3 hours after administration of a single oral dose. at doses of 20, 40, and 80 mg, the antihypertensive effect of once daily administration of telmisartan is maintained for the full 24-hour dose interval. with automated ambulatory blood pressure monitoring and conventional blood pressure measurements, the 24-hour trough-to-peak ratio for 40 to 80 mg doses of telmisartan was 70 to 100% for both systolic and diastolic blood pressure. the incidence of symptomatic orthostasis after the first dose in all controlled trials was low (0.04%). there were no changes in the heart rate of patients treated with telmisartan in controlled trials. telmisartan and hydrochlorothiazide in controlled clinical trials with over 2500 patients, 1017 patients were exposed to telmisartan (20 to 160 mg) and concomitant hydrochlorothiazide (6.25 to 25 mg). these trials included one factorial trial with combinations of telmisartan (20, 40, 80, 160 mg, or placebo) and hydrochlorothiazide (6.25, 12.5, 25 mg and placebo). four other studies of at least six months duration allowed add- on of hydrochlorothiazide for patients who either were not adequately controlled on the randomized monotherapy dose or had not achieved adequate response after completing the up-titration of telmisartan. the combination of telmisartan and hydrochlorothiazide resulted in additive placebo-adjusted decreases in systolic and diastolic blood pressure at trough of 16-21/9-11 mmhg for doses between 40/12.5 mg and 80/25 mg, compared to 9-13/7-8 mmhg for telmisartan 40 mg to 80 mg and 4/4 mmhg for hydrochlorothiazide 12.5 mg alone. in active controlled studies, the addition of 12.5 mg hydrochlorothiazide to titrated doses of telmisartan in patients who did not achieve or maintain adequate response with telmisartan monotherapy further reduced systolic and diastolic blood pressure. the antihypertensive effect was independent of age or gender. there was essentially no change in heart rate in patients treated with the combination of telmisartan and hydrochlorothiazide in the placebo controlled trial.

ytogenetic test with human lymphocytes, and a mouse micronucleus test. no drug-related effects on the reproductive performance of male and female rats were noted at 100 mg/kg/day (the highest dose administered), about 13 times, on a mg/m 2 basis, the mrhd of telmisartan. this dose in the rat resulted in an average systemic exposure (telmisartan auc as determined on day 6 of pregnancy) at least 50 times the average systemic exposure in humans at the mrhd (80 mg/day). hydrochlorothiazide two-year feeding studies in mice and rats conducted under the auspices of the national toxicology program (ntp) uncovered no evidence of a carcinogenic potential of hydrochlorothiazide in female mice (at doses of up to approximately 600 mg/kg/day) or in male and female rats (at doses of up to approximately 100 mg/kg/day). the ntp, however, found equivocal evidence for hepatocarcinogenicity in male mice. hydrochlorothiazide was not genotoxic in vitro in the ames mutagenicity assay of salmonella typhimurium strains ta 98, ta 100, ta 1535, ta 1537, and ta 1538 and in the chinese hamster ovary (cho) test for chromosomal aberrations, or in vivo in assays using mouse germinal cell chromosomes, chinese hamster bone marrow chromosomes, and the drosophila sex-linked recessive lethal trait gene. positive test results were obtained in the in vitro cho sister chromatid exchange (clastogenicity) assay, in the mouse lymphoma cell (mutagenicity) assay, and in the aspergillus nidulans non-disjunction assay. hydrochlorothiazide had no adverse effects on the fertility of mice and rats of either sex in studies wherein these species were exposed, via their diet, to doses of up to 100 and 4 mg/kg, respectively, prior to mating and throughout gestation.

lor layer and one yellow color mottled layer debossed with ‘l201’. white to off white color layer may contains yellow color specks. ndc 46708-211-30 bottle of 30 units ndc 46708-211-91 bottle of 1000 units ndc 46708-211-10 100 tablets (i.e.; 10 blister cards of 10 tablets each) storage store at 20° to 25°c (68° to 77°f); excursions permitted to 15-30°c (59-86°f) [see usp controlled room temperature]. tablets should not be removed from blisters until immediately before administration. call your doctor for medical advice about side effects. you may report side effects to fda at 1-800-fda-1088. manufactured by: alembic pharmaceuticals limited (formulation division), village panelav, p. o. tajpura, near baska, taluka-halol, panchmahal, gujarat, india. revised: 03/2014

receiving telmisartan and hydrochlorothiazide tablets should be told not to use potassium supplements or salt substitutes that contain potassium without consulting the prescribing physician.