1. Name Of The Medicinal Product
MicardisPlus 80 mg/25 mg tablets
2. Qualitative And Quantitative Composition
Each tablet contains 80 mg telmisartan and 25 mg hydrochlorothiazide.
Excipients: Each tablet contains 99 mg of lactose monohydrate and 338 mg sorbitol (E420).
For a full list of excipients, see section 6.1.
3. Pharmaceutical Form
Tablet.
Yellow and white oval shaped tablet engraved with the company logo and the code 'H9'.
4. Clinical Particulars
4.1 Therapeutic Indications
Treatment of essential hypertension.
MicardisPlus fixed dose combination (80 mg telmisartan/25 mg hydrochlorothiazide) is indicated in patients whose blood pressure is not adequately controlled on MicardisPlus 80 mg/12.5 mg (80 mg telmisartan/12.5 mg hydrochlorothiazide) or patients who have been previously stabilised on telmisartan and hydrochlorothiazide given separately.
4.2 Posology And Method Of Administration
Adults
MicardisPlus 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 two components is recommended before changing to the fixed dose combination. When clinically appropriate, direct change from monotherapy to the fixed combination may be considered
• MicardisPlus 80 mg/25 mg may be administered in patients whose blood pressure is not adequately controlled by MicardisPlus 80 mg/12.5 mg or in patients who have been previously stabilised on telmisartan and hydrochlorothiazide given separately.
MicardisPlus is also available at the dose strengths 40 mg/12.5 mg and 80 mg/ 12.5 mg
Renal impairment: Periodic monitoring of renal function is advised (see section 4.4).
Hepatic impairment: In patients with mild to moderate hepatic impairment the posology should not exceed MicardisPlus 40 mg/12.5 mg once daily. MicardisPlus is not indicated in patients with severe hepatic impairment. Thiazides should be used with caution in patients with impaired hepatic function (see section 4.4).
Elderly: No dosage adjustment is necessary.
Children and adolescents: MicardisPlus is not recommended for use in children below 18 years due to a lack of data on safety and efficacy.
4.3 Contraindications
• Hypersensitivity to any of the active substances or to any of the excipients (see section 6.1).
• Hypersensitivity to other sulphonamide-derived substances (since hydrochlorothiazide is a sulphonamide-derived medicinal product).
• Second and third trimesters of pregnancy (see section s 4.4 and 4.6).
• Cholestasis and biliary obstructive disorders.
• Severe hepatic impairment.
• Severe renal impairment (creatinine clearance <30 ml/min).
• Refractory hypokalaemia, hypercalcaemia.
4.4 Special Warnings And Precautions For Use
Pregnancy
Angiotensin II receptor antagonists should not be initiated during pregnancy. Unless continued angiotensin II receptor antagonist therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with angiotensin II receptor antagonists should be stopped immediately, and, if appropriate, alternative therapy should be started (see sections 4.3 and 4.6).
Hepatic impairment: MicardisPlus should not be given to patients with cholestasis, biliary obstructive disorders or severe hepatic insufficiency (see section 4.3) since telmisartan is mostly eliminated with the bile. These patients can be expected to have reduced hepatic clearance for telmisartan.
In addition, MicardisPlus 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. There is no clinical experience with MicardisPlus in patients with hepatic impairment.
Renovascular hypertension: There is an increased risk of severe hypotension and renal insufficiency when patients with bilateral renal artery stenosis or stenosis of the artery to a single functioning kidney are treated with medicinal products that affect the renin-angiotensin-aldosterone system.
Renal impairment and kidney transplantation: MicardisPlus should not be used in patients with severe renal impairment (creatinine clearance <30 ml/min) (see section 4.3). There is no experience regarding the administration of MicardisPlus in patients with recent kidney transplantation. Experience with MicardisPlus is modest in the patients with mild to moderate renal impairment, therefore periodic monitoring of potassium, creatinine and uric acid serum levels is recommended. Thiazide diuretic-associated azotaemia may occur in patients with impaired renal function.
Intravascular hypovolaemia: Symptomatic hypotension, especially after the first dose, may occur in patients who are volume and/or sodium depleted by vigorous diuretic therapy, dietary salt restriction, diarrhoea or vomiting. Such conditions should be corrected before the administration of MicardisPlus.
Dual blockade of the renin-angiotensin-aldosterone system: As a consequence of inhibiting the renin-angiotensin-aldosterone system, hypotension, syncope, hyperkalaemia, and changes in renal function (including acute renal failure) have been reported in susceptible individuals, especially if combining medicinal products that affect this system. Dual blockade of the renin-angiotensin-aldosterone system (e.g. by adding an ACE-inhibitor to an angiotensin II receptor antagonist) is therefore not recommended in patients with already controlled blood pressure and should be limited to individually defined cases with close monitoring of renal function.
Other conditions with stimulation of the renin-angiotensin-aldosterone system: In patients whose vascular tone and renal function depend predominantly on the activity of the renin-angiotensin-aldosterone system (e.g. patients with severe congestive heart failure or underlying renal disease, including renal artery stenosis), treatment with medicinal products that affect this system has been associated with acute hypotension, hyperazotaemia, oliguria, or rarely acute renal failure (see section 4.8).
Primary aldosteronism: Patients with primary aldosteronism generally will not respond to antihypertensive medicinal products acting through inhibition of the renin-angiotensin system. Therefore, the use of MicardisPlus is not recommended.
Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy: As with other vasodilators, special caution is indicated in patients suffering from aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy.
Metabolic and endocrine effects: Thiazide therapy may impair glucose tolerance. In diabetic patients dosage adjustments of insulin or oral hypoglycaemic agents may be required. Latent diabetes mellitus may become manifest during thiazide therapy.
An increase in cholesterol and triglyceride levels has been associated with thiazide diuretic therapy; however, at the 12.5 mg dose contained in MicardisPlus, minimal or no effects were reported.
Hyperuricaemia may occur or frank gout may be precipitated in some patients receiving thiazide therapy.
Electrolyte imbalance: As for any patient receiving diuretic therapy, periodic determination of serum electrolytes should be performed at appropriate intervals.
Thiazides, including hydrochlorothiazide, can cause fluid or electrolyte imbalance (including hypokalaemia, hyponatraemia, and hypochloraemic alkalosis). Warning signs of fluid or electrolyte imbalance are dryness of mouth, thirst, asthenia, lethargy, drowsiness, restlessness, muscle pain or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea or vomiting (see section 4.8).
- Hypokalaemia
Although hypokalaemia may develop with the use of thiazide diuretics, concurrent therapy with telmisartan may reduce diuretic-induced hypokalaemia. The risk of hypokalaemia is greater in patients with cirrhosis of liver, in patients experiencing brisk diuresis, in patients who are receiving inadequate oral intake of electrolytes and in patients receiving concomitant therapy with corticosteroids or Adrenocorticotropic hormone (ACTH) (see section 4.5).
- Hyperkalaemia
Conversely, due to the antagonism of the angiotensin II (AT1) receptors by the telmisartan component of MicardisPlus, hyperkalaemia might occur. Although clinically significant hyperkalaemia has not been documented with MicardisPlus, risk factors for the development of hyperkalaemia include renal insufficiency and/or heart failure, and diabetes mellitus. Potassium-sparing diuretics, potassium supplements or potassium-containing salt substitutes should be co-administered cautiously with MicardisPlus (see section 4.5).
- Hyponatraemia and hypochloraemic alkalosis
There is no evidence that MicardisPlus would reduce or prevent diuretic-induced hyponatraemia. Chloride deficit is generally mild and usually does not require treatment.
- Hypercalcaemia
Thiazides may decrease urinary calcium excretion and cause an intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism. Marked hypercalcaemia may be evidence of hidden hyperparathyroidism. Thiazides should be discontinued before carrying out tests for parathyroid function.
- Hypomagnesaemia
Thiazides have been shown to increase the urinary excretion of magnesium, which may result in hypomagnesaemia (see section 4.5).
Sorbitol and Lactose Monohydrate: This medicinal product contains lactose monohydrate and sorbitol. Patients with rare hereditary problems of fructose intolerance and/or with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
Ethnic differences: As with all other angiotensin II receptor antagonists, telmisartan is apparently less effective in lowering blood pressure in black patients than in non blacks, possibly because of higher prevalence of low renin states in the black hypertensive population.
Other: As with any antihypertensive agent, excessive reduction of blood pressure in patients with ischaemic cardiopathy or ischaemic cardiovascular disease could result in a myocardial infarction or stroke.
General: 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.
Exacerbation or activation of systemic lupus erythematosus has been reported with the use of thiazide diuretics.
Cases of photosensitivity reactions have been reported with thiazide diuretics (see section 4.8). If a photosensitivity reaction occurs during treatment, it is recommended to stop the treatment. If a re-administration of the diuretic is deemed necessary, it is recommended to protect exposed areas to the sun or to artificial UVA.
4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction
Interaction studies have only been performed in adults.
Lithium: Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin converting enzyme inhibitors. Rare cases have also been reported with angiotensin II receptor antagonists (including MicardisPlus). Co-administration of lithium and MicardisPlus is not recommended (see section 4.4). If this combination proves essential, careful monitoring of serum lithium level is recommended during concomitant use.
Medicinal products associated with potassium loss and hypokalaemia (e.g. other kaliuretic diuretics, laxatives, corticosteroids, ACTH, amphotericin, carbenoxolone, penicillin G sodium, salicylic acid and derivatives): If these substances are to be prescribed with the hydrochlorothiazide-telmisartan combination, monitoring of potassium plasma levels is advised. These medicinal products may potentiate the effect of hydrochlorothiazide on serum potassium (see section 4.4).
Medicinal products that may increase potassium levels or induce hyperkalaemia (e.g. ACE inhibitors, potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium, cyclosporin or other medicinal products such as heparin sodium): If these medicinal products are to be prescribed with the hydrochlorothiazide-telmisartan combination, monitoring of potassium plasma levels is advised. Based on the experience with the use of other medicinal products that blunt the renin- angiotensin system, concomitant use of the above medicinal products may lead to increases in serum potassium and is, therefore, not recommended (see section 4.4).
Medicinal products affected by serum potassium disturbances: Periodic monitoring of serum potassium and ECG is recommended when MicardisPlus is administered with medicinal products affected by serum potassium disturbances (e.g. digitalis glycosides, antiarrhythmics) and the following torsades de pointes inducing medicinal products (which include some antiarrhythmics), hypokalaemia being a predisposing factor to torsades de pointes.
- class Ia antiarrythmics (e.g. quinidine, hydroquinidine, disopyramide)
- class III antiarrythmics (e.g. amiodarone, sotalol, dofetilide, ibutilide)
- some antipsychotics (e.g. thioridazine, chlorpromazine, levomepromazine, trifluoperazine, cyamemazine, sulpiride, sultopride, amisulpride, tiapride, pimozide, haloperidol, droperidol)
- others (e.g. bepridil, cisapride, diphemanil, erythromycin IV, halofantrin, mizolastin, pentamidine, sparfloxacine, terfenadine, vincamine IV.)
Digitalis glycosides: Thiazide-induced hypokalaemia or hypomagnesaemia favours the onset of digitalis-induced arrhythmia (see section 4.4).
Other antihypertensive agents: Telmisartan may increase the hypotensive effect of other antihypertensive agents.
Antidiabetic medicinal products (oral agents and insulin): Dosage adjustment of the antidiabetic medicinal products may be required (see section 4.4).
Metformin: Metformin should be used with precaution: risk of lactic acidosis induced by a possible functional renal failure linked to hydrochlorothiazide.
Cholestyramine and colestipol resins: Absorption of hydrochlorothiazide is impaired in the presence of anionic exchange resins.
Non-steroidal anti-inflammatory medicinal products: NSAIDs (i.e. acetylsalicylic acid at anti-inflammatory dosage regimens, COX-2 inhibitors and non-selective NSAIDs) may reduce the diuretic, natriuretic and antihypertensive effects of thiazide diuretics and the antihypertensive effects of angiotensin II receptor antagonists.
In some patients with compromised renal function (e.g. dehydrated patients or elderly patients with compromised renal function) the co-administration of angiotensin II receptor antagonists and agents that inhibit cyclo-oxygenase may result in further deterioration of renal function, including possible acute renal failure, which is usually reversible. Therefore the combination should be administered with caution, especially in the elderly. Patients should be adequately hydrated and consideration should be given to monitoring of renal function after initiation of concomitant therapy and periodically thereafter.
In one study the co-administration of telmisartan and ramipril led to an increase of up to 2.5 fold in the AUC0-24 and Cmax of ramipril and ramiprilat. The clinical relevance of this observation is not known.
Pressor amines (e.g. noradrenaline): The effect of pressor amines may be decreased.
Nondepolarizing skeletal muscle relaxants (e.g. tubocurarine): The effect of nondepolarizing skeletal muscle relaxants may be potentiated by hydrochlorothiazide.
Medicinal products used in the treatment for gout (e.g. probenecid, sulfinpyrazone and allopurinol): Dosage adjustment of uricosuric medications may be necessary as hydrochlorothiazide may raise the level of serum uric acid. Increase in dosage of probenecid or sulfinpyrazone may be necessary. Co-administration of thiazide may increase the incidence of hypersensitivity reactions of allopurinol.
Calcium salts: Thiazide diuretics may increase serum calcium levels due to the decreased excretion. If calcium supplements must be prescribed, serum calcium levels should be monitored and calcium dosage adjusted accordingly.
Beta-blockers and diazoxide: The hyperglycaemic effect of beta-blockers and diazoxide may be enhanced by thiazides.
Anticholinergic agents (e.g. atropine, biperiden) may increase the bioavailability of thiazide-type diuretics by decreasing gastrointestinal motility and stomach emptying rate.
Amantadine: Thiazides may increase the risk of adverse effects caused by amantadine.
Cytotoxic agents (e.g. cyclophosphamide, methotrexate): Thiazides may reduce the renal excretion of cytotoxic medicinal products and potentiate their myelosuppressive effects.
Based on their pharmacological properties it can be expected that the following medicinal product may potentiate the hypotensive effects of all antihypertensives including telmisartan: Baclofen, amifostine.
Furthermore, orthostatic hypotension may be aggravated by alcohol, barbiturates, narcotics or antidepressants.
4.6 Pregnancy And Lactation
Pregnancy:
The use of angiotensin II receptor antagonists is not recommended during the first trimester of pregnancy (see section 4.4). The use of angiotensin II receptor antagonists is contraindicated during the second and third trimesters of pregnancy (see sections 4.3 and 4.4).
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There are no adequate data from the use of MicardisPlus in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3).
Epidemiological evidence regarding the risk of teratogenicity following exposure to ACE inhibitors during the first trimester of pregnancy has not been conclusive; however a small increase in risk cannot be excluded. Whilst there is no controlled epidemiological data on the risk with angiotensin II receptor antagonists, similar risks may exist for this class of drugs. Unless continued angiotensin II receptor antagonist therapy is considered essential, patients planning pregnancy should be changed to alternative antihypertensive treatments which have an established safety profile for use in pregnancy. When pregnancy is diagnosed, treatment with angiotensin II receptor antagonists should be stopped immediately, and, if appropriate, alternative therapy should be started.
Exposure to angiotensin II receptor antagonist therapy during the second and third trimesters is known to induce human fetotoxicity (decreased renal function, oligohydramnios, skull ossification retardation) and neonatal toxicity (renal failure, hypotension, hyperkalaemia). (See section 5.3).
Should exposure to angiotensin II receptor antagonists have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended.
Infants whose mothers have taken angiotensin II receptor antagonists should be closely observed for hypotension (see sections 4.3 and 4.4).
Thiazides cross the placental barrier and appear in cord blood. They may cause foetal electrolyte disturbances and possibly other reactions that have occurred in the adults. Cases of neonatal thrombocytopenia, of foetal or neonatal jaundice have been reported with maternal thiazide therapy.
Lactation:
Because no information is available regarding the use of MicardisPlus during breast-feeding, MicardisPlus is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant. Thiazides appear in human milk and may inhibit lactation.
4.7 Effects On Ability To Drive And Use Machines
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.
4.8 Undesirable Effects
Fixed Dose Combination
The overall incidence and pattern of adverse events reported with MicardisPlus 80 mg/25 mg was comparable with MicardisPlus 80 mg/12.5 mg. A dose-relationship of undesirable effects was not established and they showed no correlation with gender, age or race of the patients.
Adverse reactions reported in all clinical trials and occurring more frequently (p
Adverse reactions have been ranked under headings of frequency using the following convention:
very common (
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Infections and infestations
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Rare:
Not known:
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Bronchitis
Pharyngitis, sinusitis
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Metabolism and nutrition disorders
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Uncommon:
Rare:
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Hypokalaemia,
Hyperuricaemia, hyponatraemia
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Psychiatric disorders
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Uncommon:
Rare:
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Anxiety
Depression
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Nervous system disorders
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Common:
Uncommon:
Rare:
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Dizziness
Syncope, paraesthesia
Insomnia, sleep disorders
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Eye disorders
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Rare:
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Visual disturbance, vision blurred
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Ear and labyrinth disorders
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Uncommon:
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Vertigo
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Cardiac disorders
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Uncommon:
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Tachycardia, arrhythmias
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Vascular disorders
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Uncommon:
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Hypotension, orthostatic hypotension
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Respiratory, thoracic and mediastinal disorders
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Uncommon:
Rare:
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Dyspnoea
Respiratory distress (including pneumonitis and pulmonary oedema)
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Gastrointestinal disorders
|
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Uncommon:
Rare:
Not known:
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Diarrhoea, dry mouth, flatulence
Abdominal pain, constipation, dyspepsia, vomiting
Gastritis
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Hepatobiliary disorders
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Rare:
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Abnormal hepatic function/liver disorder
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Skin and subcutaneous tissue disorders
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Rare:
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Angioedema, erythema, pruritus, rash, hyperhidrosis, urticaria
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Muscoloskeletal, connective tissue and bone disorders
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Uncommon:
Rare:
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Back pain, muscle spasms, myalgia
Arthralgia, muscle cramps, pain in limb
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Reproductive system and breast disorders
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Uncommon:
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Erectile dysfunction
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General disorders and administration site conditions
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Uncommon:
Rare:
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Chest pain
Influenza-like illness, pain
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Investigations
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Uncommon:
Rare:
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Blood uric acid increased
Blood creatinine increased, blood creatine phosphokinase increased, hepatic enzyme increased
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Additional information on individual components
Undesirable effects previously reported with one of the individual components may be potential undesirable effects with MicardisPlus, even if not observed in clinical trials with this product.
Telmisartan:
Undesirable effects occurred with similar frequency in placebo and telmisartan treated patients.
The overall incidence of adverse events reported with telmisartan (41.4 %) was usually comparable to placebo (43.9 %) in placebo controlled trials. The following adverse drug reactions listed below have been accumulated from all clinical trials in patients treated with telmisartan for hypertension or in patients 50 years or older at high risk of cardiovascular events.
Adverse reactions of unknown frequency reported with the use of telmisartan alone include:
Infections and infestations
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Not known:
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Upper respiratory tract infection, urinary tract infection including cystitis, sepsis including fatal outcome*
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Blood and lymphatic system disorders
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Not known:
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Eosinophilia, anaemia, thrombocytopenia
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Immune system disorders
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Not known:
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Hypersensitivity, anaphylactic reactions
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Metabolism and nutrition disorders
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Not known:
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Hyperkalaemia
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Cardiac disorders
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Not known:
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Bradycardia
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Gastrointestinal disorders
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Not known:
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Stomach discomfort
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Skin and subcutaneous tissue disorders
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Not known:
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Eczema, drug eruption, toxic skin eruption
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Musculoskeletal, connective tissue and bone disorders
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Not known:
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Arthrosis, tendon pain
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Renal and urinary disorders
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Not known:
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Renal dysfunction, renal impairment (including acute renal failure)
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General disorders and administration site conditions
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Not known:
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Asthenia
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Investigations
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Not known:
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Haemoglobin decreased
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*In the PRoFESS trial, an increased incidence of sepsis was observed with telmisartan compared with placebo. The event may be a chance finding or related to a mechanism currently not known (see section 5.1).
Hydrochlorothiazide:
Hydrochlorothiazide may cause or exacerbate hypovolaemia which could lead to electrolyte imbalance (see section 4.4).
Adverse reactions of unknown frequency reported with the use of hydrochlorothiazide alone include:
Infections and infestations
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Not known:
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Sialoadenitis
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Blood and lymphatic system disorders
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Not known:
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Anaemia aplastic, haemolytic anaemia, bone marrow failure, leukopenia, neutropenia, agranulocytosis, thrombocytopenia
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Immune system disorders
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Not known:
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Anaphylactic reactions, hypersensitivity
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Endocrine disorders
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Not known:
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Diabetes mellitus inadequate control
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Metabolism and nutrition disorders
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Not known:
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Anorexia, appetite decreased, electrolyte imbalance, hypercholesterolaemia, hyperglycaemia, hypovolaemia
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Psychiatric disorders
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Not known:
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Restlessness
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Nervous system disorders
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Not known:
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Light-headedness
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Eye disorders
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Not known:
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Xanthopsia
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Vascular disorders
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Not known:
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Vasculitis necrotizing
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Gastrointestinal disorders
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Not known:
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Pancreatitis, stomach discomfort
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Hepatobiliary disorders
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Not known:
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Jaundice hepatocellular, jaundice cholestatic
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Skin and subcutaneous tissue disorders
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Not known:
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Lupus-like syndrome, photosensitivity reactions, skin vasculitis, toxic epidermal necrolysis
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Musculoskeletal, connective tissue and bone disorders
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Not known:
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Weakness
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Renal and urinary disorders
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|
Not known:
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Nephritis interstitial, renal dysfunction, glycosuria
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General disorders and administration site conditions
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Not known:
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Pyrexia
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Investigations
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Not known:
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Triglycerides increased
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4.9 Overdose
There is limited information available for telmisartan with regard to overdose in humans. The degree to which hydrochlorothiazide is removed by haemodialysis has not been established.
Symptoms: The most prominent manifestations of telmisartan overdose were hypotension and tachycardia; bradycardia, dizziness, vomiting, increase in serum creatinine, and acute renal failure have also been reported. Overdose with hydrochlorothiazide is associated with electrolyte depletion (hypokalaemia, hypochloraemia) and hypovolaemia resulting from excessive diuresis. The most common signs and symptoms of overdose are nausea and somnolence. Hypokalaemia may result in muscle spasms and/or accentuate arrhythmia associated with the concomitant use of digitalis glycosides or certain anti-arrhythmic medicinal products.
Treatment: Telmisartan is not removed by haemodialysis. The patient should be closely monitored, and the treatment should be symptomatic and supportive. Management depends on the time since ingestion and the severity of the symptoms. Suggested measures include induction of emesis and/or gastric lavage. Activated charcoal may be useful in the treatment of overdose. Serum electrolytes and creatinine should be monitored frequently. If hypotension occurs, the patient should be placed in a supine position, with salt and volume replacements given quickly.
5. Pharmacological Properties
5.1 Pharmacodynamic Properties
Pharmacotherapeutic group: Angiotensin II receptor antagonists and diuretics, ATC code: C09DA07
MicardisPlus is a combination of an angiotensin II receptor antagonist, telmisartan, and a thiazide diuretic, hydrochlorothiazide. The combination of these ingredients has an additive antihypertensive effect, reducing blood pressure to a greater degree than either component alone. MicardisPlus once daily produces effective and smooth reductions in blood pressure across the therapeutic dose range.
Telmisartan is an orally effective and specific angiotensin II receptor subtype 1 (AT1) antagonist. Telmisartan displaces angiotensin II with very high affinity from its binding site at the AT1 receptor subtype, which is responsible for the known actions of angiotensin II. Telmisartan does not exhibit any partial agonist activity at the AT1 receptor. Telmisartan selectively binds the AT1 receptor. The binding is long-lasting. Telmisartan does not show affinity for other receptors, including AT2 and other less characterised AT receptors. The functional role of these receptors is not known, nor is the effect of their possible overstimulation by angiotensin II, whose levels are increased by telmisartan. Plasma aldosterone levels are decreased by telmisartan. Telmisartan does not inhibit human plasma renin or block ion channels. Telmisartan does not inhibit angiotensin converting enzyme (kininase II), the enzyme which also degrades bradykinin. Therefore, it is not expected to potentiate bradykinin-mediated adverse effects.
An 80 mg dose of telmisartan administered to healthy volunteers almost completely inhibits the angiotensin II evoked blood pressure increase. The inhibitory effect is maintained over 24 hours and still measurable up
