Cilzec/Cilzec Plus

Cilzec/Cilzec Plus

telmisartan

telmisartan + hydrochlorothiazide

Manufacturer:

Mega Lifesciences

Distributor:

Maxxcare
Full Prescribing Info
Contents
Cilzec: Telmisartan.
Cilzec Plus: Telmisartan, hydrochlorothiazide.
Description
Telmisartan is a white to slightly yellowish solid. It is chemically described as 4'-[(1,4'-dimethyl-2'-propyl[2,6'-bi-1H-benzimidazol]-1'-yl)methyl]-[1,1'-biphenyl]-2-carboxylic acid. Its empirical formula is C33H30N4O2, its molecular weight is 514.63.
Hydrochlorothiazide is a white or almost white, crystalline powder. It is chemically described as [6-chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide]. Its empirical formula is C7H8CIN3O4S2. Its molecular weight is 297.74.
Cilzec/Cilzec Plus also contains the following inactive ingredients: Microcrystalline cellulose PH 101, croscarmellose sodium, meglumine, poloxamer 188, povidone K-30, microcrystalline cellulose PH 102, magnesium stearate, isopropyl alcohol.
Cilzec Plus also contains the following inactive ingredients: Anhydrous lactose (DC grade), sodium starch glycollate, lake sunset yellow.
Action
Pharmacology: Pharmacodynamics: Mechanism of Action: Telmisartan is a non-peptide angiotensin II receptor (type AT1) antagonist.
Angiotensin II is formed from angiotensin I in a reaction catalyzed by angiotensin-converting enzyme (ACE, kininase II). Angiotensin 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 AT1 receptor in many tissues eg, vascular smooth muscle and the adrenal gland. Its action is therefore independent of the pathways for angiotensin II synthesis. There is also an AT2 receptor found in many tissues, but AT2 is not known to be associated with cardiovascular homeostasis. Telmisartan has much greater affinity (>3000 fold) for the AT1 receptor than for the AT2 receptor.
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 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 co-administration 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 (Cmax) of telmisartan are reached in 0.5-1 hr 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 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 20-160 mg, with greater than proportional increases of plasma concentrations (Cmax and AUC) with increasing doses. Telmisartan shows bi-exponential  decay kinetics with a terminal elimination half-life of approximately 24 hrs. Trough plasma concentrations of telmisartan with once daily dosing are about 10-25% of peak plasma concentrations. Telmisartan has an accumulation index in plasma of 1.5-2  upon repeated once daily dosing.
Hydrochlorothiazide: When plasma levels have been followed for at least 24 hrs, the plasma half-life has been observed to vary between 5.6 and 14.8 hrs.
Metabolism and Elimination: Telmisartan: 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 hrs.
Distribution: Telmisartan is highly bound to plasma proteins (>99.5%), mainly albumin and α1-acid glycoprotein.
Plasma protein binding is constant over the concentration range achieved with recommended doses. The volume of distribution for telmisartan is approximately 500 L, 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.
Geriatric: The pharmacokinetics of telmisartan do not differ between the elderly and those <65 years.
Gender: Plasma concentrations of telmisartan are generally 2-3 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 30-80 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.
Hepatic Insufficiency: In patients with hepatic insufficiency, plasma concentrations of telmisartan are increased and absolute bioavailability of telmisartan approaches 100%.
Indications/Uses
Treatment of hypertension.
Cilzec: It may be used alone or in combination with other antihypertensive agents.
Cilzec Plus: This fixed dose combination is not indicated for initial therapy.
Dosage/Direction for Use
Cilzec: Dosage must be individualized. The usual starting dose is 40 mg once daily. Blood pressure response is dose-related over the range of 20-80 mg.
Special Populations: 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.
Most of the antihypertensive effect is apparent within 2 weeks and maximal reduction is generally attained after 4 weeks. When additional blood pressure reduction beyond that achieved within 80 mg of telmisartan tablets is required, a diuretic may be added.
No initial dosing adjustment is necessary for elderly patients or patients with renal impairment, including those on hemodialysis. Patients on dialysis may develop orthostatic hypotension; their blood pressure should be closely monitored.
Cilzec Plus: Cilzec Plus should be taken once daily with liquid, with or without food in patients whose blood pressure is not adequately controlled by telmisartan alone. Individual dose titration with each of the 2 components is recommended before changing to the fixed dose combination. When clinically appropriate, direct change from monotherapy to the fixed combination may be considered.
To minimize dose-independent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy. The side effects (see Warnings) of telmisartan are generally rare and apparently independent of dose; those of hydrochlorothiazide are a mixture of dose-dependent phenomena (primarily hypokalemia) and dose-independent phenomena (eg, 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. Cilzec Plus (telmisartan and hydrochlorothiazide) tablets may be administered with other antihypertensive agents.
Patients with Renal Impairment: The usual regimens of Cilzec Plus, once daily 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 Cilzec Plus tablets are not recommended.
Patients with Hepatic Impairment: Cilzec Plus tablets are not recommended for patients with severe hepatic impairment. Patients with biliary obstructive disorders or hepatic insufficiency should have their treatment started under close medical supervision using the 40/12.5 mg combination.
Administration: Cilzec: Telmisartan tablets may be administered with other antihypertensive agents. Telmisartan may be taken with or without food.
Overdosage
Telmisartan: Limited data are available with regard to overdosage in humans. The most likely manifestations of overdosage with telmisartan would be hypotension, dizziness and tachycardia; bradycardia could occur from parasympathetic (vagal) stimulation. If symptomatic hypotension should occur, supportive treatment should be instituted. Telmisartan is not removed by hemodialysis.
Hydrochlorothiazide: The most common signs and symptoms observed in patients 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 hemodialysis has not been established. The oral LD50 of hydrochlorothiazide is >10 g/kg in both mice and rats.
Contraindications
Hypersensitivity to telmisartan and/or hydrochlorothiazide, or any other excipients of Cilzec/Cilzec Plus.
Telmisartan: Second and 3rd trimesters of pregnancy and lactation; biliary obstructive disorders; severe hepatic impairment.
Hydrochlorothiazide: Hypersensitivity to thiazides and derivatives of sulfonamides, manifest gout, anuria, Addison's disease, hypercalcemia, hyperuricemia, severe renal and hepatic insufficiency.
Warnings
Fetal/Neonatal Morbidity and Mortality: Drugs that act directly on the renin-angiotensin system can cause fetal and 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, Cilzec/Cilzec Plus should be discontinued as soon as possible.
The use of drugs that act directly on the renin-angiotensin system during the 2nd and 3rd trimesters of pregnancy has been associated with fetal and neonatal injury, including hypotension, neonatal skull hypoplasia, anuria, reversible or irreversible renal failure and death. Oligohydramnios has also been reported, presumably resulting from decreased fetal renal function; oligohydramnios in this setting has been associated with fetal limb contractures, craniofacial deformation and hypoplastic lung development. Prematurity, intrauterine growth retardation and patent ductus arteriosus have also been reported, although it is not clear whether these occurrences were due to exposure to the drug.
There is no clinical experience with the use of telmisartan in pregnant women.
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/m2 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/m2 basis), administered during late gestation and lactation, were observed to produce adverse effects. In neonates, including reduced viability, low birth weight, delayed maturation and 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/m2 basis, the maximum recommended human dose of Telmisartan (80 mg/day).
These adverse effects do not appear to have resulted from intrauterine drug exposure that has been limited to the 1st trimester. Mothers whose embryos and fetuses are exposed to an angiotensin II receptor antagonist only during the 1st trimester should be informed. Nonetheless, when patients become pregnant, the physician should inform the patient to discontinue the use of Cilzec Plus as soon as possible.
If oligohydramnios is observed, Cilzec Plus should be discontinued unless they are considered life-saving for the mother. Contraction stress testing (CST), a non-stress test (NST), or biophysical profiling (BPP) may be appropriate, depending  upon the week of pregnancy. Patients and physicians should be aware, however, that  oligohydramnios may not appear until after the fetus has sustained irreversible injury.
Infants with histories of in utero exposure to an angiotensin II receptor antagonist should be closely observed for hypotension, oliguria and hyperkalemia. If oliguria occurs, attention should be directed toward support of blood pressure and renal perfusion. Exchange transfusion or dialysis may be required as a means of reversing hypotension and/or substituting for disordered renal function.
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 eg, patients who are intravascular volume- or sodium-depleted eg, in patients treated vigorously with diuretics, should only be approached cautiously. These conditions should be corrected prior to administration of Cilzec/Cilzec Plus. Treatment 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.
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 Reactions: 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.
Special Precautions
Serum Electrolytes: Telmisartan and Hydrochlorothiazide: No discontinuations due to hypokalemia were reported during treatment with the telmisartan/hydrochlorothiazide combination. The absence of significant changes in serum potassium levels may be due to the opposing mechanisms of action of telmisartan and hydrochlorothiazide on potassium excretion on the kidney.
Hydrochlorothiazide: Periodic determinations of serum electrolytes to detect possible electrolyte imbalance should be performed at appropriate intervals. All patients receiving thiazide therapy should be observed for clinical signs of fluid or electrolyte imbalance: Hyponatremia, hypochloremic alkalosis and hypokalemia. Serum and urine electrolyte determinations are particularly important when the patient experiences excessive vomiting or receives parenteral fluids. Warning signs or symptoms of fluid and electrolyte imbalance, irrespective of cause, include dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, confusion, seizures, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia and gastrointestinal disturbances eg, nausea and vomiting.
In actual salt depletion, appropriate replacement is the therapy of choice.
Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving thiazide therapy.
In diabetic patients, dosage adjustments of insulin or oral hypoglycemic agents may be required.
Hyperglycemia may occur with thiazide diuretics. Thus, latent diabetes mellitus may manifest during thiazide therapy.
The antihypertensive effects of the drug may be enhanced in the post sympathectomy patient.
If progressive renal impairment becomes evident, consider withholding or discontinuing diuretic therapy.
Thiazides have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia.
Thiazides may decrease urinary calcium excretion. Thiazides may cause intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism. 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.
Impaired Hepatic Function: Telmisartan: As the majority of telmisartan is eliminated by biliary excretion, patients with biliary obstructive disorders or hepatic insufficiency can be expected to have reduced clearance. Cilzec/Cilzec Plus should therefore be used with caution in these patients.
Impaired Renal Function: Telmisartan: As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function may be anticipated in susceptible individuals. In patients whose renal function may depend on the activity of the renin-angiotensin-aldosterone system (eg, patients with severe congestive heart failure), treatment with angiotensin-converting enzyme inhibitors and angiotensin receptor antagonists has been associated with oliguria and/or progressive azotemia and (rarely) with acute renal failure and/or death. Similar results may be anticipated in patients treated with telmisartan.
There has been no long-term use of telmisartan in patients with unilateral or bilateral renal artery stenosis but an effect similar to that seen with ACE inhibitors should be anticipated.
Hydrochlorothiazide: Thiazides should be used with caution in severe renal disease. In patients with renal disease, thiazides may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function.
Dual Blockade of the Renin-Angiotensin-Aldosterone System: Telmisartan: As a consequence of inhibiting the renin-angiotensin-aldosterone system, changes in renal function (including acute renal failure) have been reported. Dual blockade of the renin-angiotensin-aldosterone system (eg, by adding an ACE inhibitor to an angiotensin II receptor antagonist) should include close monitoring of renal function.
Effects on the Ability to Drive or Operate Machinery: No studies on the effect on the ability to drive and use machines have been performed. However, when driving vehicles or operating machinery, it should be taken into account that dizziness or drowsiness may occasionally occur when taking antihypertensive therapy.
Carcinogenicity, Mutagenicity & Impairment of Fertility: Telmisartan and Hydrochlorothiazide: No carcinogenicity, mutagenicity or fertility studies have been conducted with the combination of telmisartan and hydrochlorothiazide.
Telmisartan: There was no evidence of carcinogenicity when telmisartan was administered in the diet of mice and rats for up to 2 years.
Genotoxicity assays did not reveal any telmisartan-related effects at either the gene or chromosomal level.
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/m2 basis, the MRHD of telmisartan.
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).
Hydrochlorothiazide was not genotoxic in vitro in the Ames mutagenicity assay of Salmonella typhimurium strains.
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.
Use in pregnancy: Female patients of childbearing age should be told about the consequences of 2nd and 3rd trimester exposure to drugs that act on the renin-angiotensin system, and they should also be told that these consequences do not appear to have resulted from intrauterine drug exposure that has been limited to the 1st trimester. These patients should be asked to report pregnancies to their physicians as soon as possible.
Use in lactation: 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.
Use in children: Safety and effectiveness in pediatric patients have not been established.
Use in the elderly: No overall differences in effectiveness and safety of telmisartan/hydrochlorothiazide were observed in geriatric patients compared to younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Use In Pregnancy & Lactation
Telmisartan: Contraindicated in 2nd and 3rd trimesters of pregnancy and lactation.
Use in pregnancy: Female patients of childbearing age should be told about the consequences of 2nd and 3rd trimester exposure to drugs that act on the renin-angiotensin system, and they should also be told that these consequences do not appear to have resulted from intrauterine drug exposure that has been limited to the 1st trimester. These patients should be asked to report pregnancies to their physicians as soon as possible.
Use in lactation: 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.
Adverse Reactions
Cilzec: Adverse events like back pain, sinusitis, diarrhea, pharyngitis occurred at an incidence of ≥1% in patients treated with telmisartan and at a greater rate than in patients treated with placebo, irrespective of their causal association.
In addition, the following events occurred at a rate of 1% but were at least as frequent in the placebo group: Influenza-like symptoms, dyspepsia, myalgia, urinary tract infection, abdominal pain, headache, dizziness, pain, fatigue, coughing, hypertension, chest pain, nausea and peripheral edema. The incidence of adverse events is not dose-related and do not correlate with gender, age or race of patients.
The incidence of cough occurring with telmisartan was identical to that noted for placebo-treated patients (1.6%).
Cilzec Plus: The following adverse events were reported at a rate of ≥2% in patients treated with telmisartan/hydrochlorothiazide, but were as, or more common in the placebo group: Pain, headache, cough, urinary tract infection.
The following adverse events were reported at a rate <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, postural hypotension and abdominal pain.
Adverse events occurred at approximately the same rates in men and women, older and younger patients, and black and non-black patients.
Telmisartan: Other adverse experiences that have been reported with telmisartan, without regard to causality, are listed as follows: Autonomic Nervous System: Impotence, increased sweating, flushing.
Body as a Whole: Allergy, fever, leg pain, malaise, chest pain.
Cardiovascular: Palpitation, dependent and leg edema, angina pectoris, abnormal ECG, hypertension, peripheral edema.
Central Nervous System: Insomnia, somnolence, migraine, vertigo, paresthesia, involuntary muscle contractions, hypoaesthesia.
Gastrointestinal: Flatulence, constipation, gastritis, dry mouth, hemorrhoids, gastroenteritis, enteritis, gastroesophageal reflux, toothache, nonspecific 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 as follows: 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 and dysfunction, interstitial nephritis.
Skin: Erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis.
Special Senses: Transient blurred vision, xanthopsia.
Drug Interactions
Telmisartan: Digoxin: When telmisartan was co-administered with digoxin, median increases in digoxin peak plasma concentration (49%) and in trough concentration (20%) were observed. It is, therefore, recommended that digoxin levels be monitored when initiating, adjusting and discontinuing telmisartan to avoid possible over- or under- digitalization.
Lithium: Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin converting enzyme inhibitors. Cases have also been reported with angiotensin II receptor antagonists including telmisartan. Because lithium should not be used with diuretics, the use of lithium with telmisartan and hydrochlorothiazide is not recommended.
Ramipril and Ramiprilat: 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. Combined use is not recommended.
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 Drug (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 (eg, norepinephrine): Possible decreased response to pressor amines but not sufficient to preclude their use.
Skeletal Muscle Relaxants, Non-depolarizing (eg, 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 Cilzec Plus (telmisartan and hydrochlorothiazide) tablets.
Nonsteroidal Anti-inflammatory Drugs: In some patients, the administration of a nonsteroidal anti-inflammatory agent can reduce the diuretic, natriuretic and antihypertensive effects of loop, potassium-sparing and thiazide diuretics. Therefore, when Cilzec Plus tablets and nonsteroidal anti-inflammatory agents are used concomitantly, the patient should be observed closely to determine if the desired effect of the diuretic is obtained.
Storage
Store below 25°C in a dry place. Protect from light and moisture.
Shelf-Life: 24 months.
ATC Classification
C09CA07 - telmisartan ; Belongs to the class of angiotensin II receptor blockers (ARBs). Used in the treatment of cardiovascular disease.
C09DA07 - telmisartan and diuretics ; Belongs to the class of angiotensin II receptor blockers (ARBs) in combination with diuretics. Used in the treatment of cardiovascular disease.
Presentation/Packing
Cilzec: Tab (uncoated, white or off-white) 20 mg x 3 x 10's. 40 mg x 3 x 10's.
Cilzec Plus: Tab (uncoated, circular, bilayered, smooth with 1 layer white to off-white in colour and the other layer light orange coloured) 40 /12.5 mg x 3 x 10's.
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