Telmirin Plus

White, round biconvex, uncoated tablet, plain on both sides, packed in alu-alu blister.
Each uncoated tablet contains: Telmisartan 40 mg, Hydrochlorothiazide 12.5 mg.

Pharmacotherapeutic group: Angiotensin II Antagonists.
Pharmacology: Pharmacodynamics: Telmisartan/Hydrochlorothiazide 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. Telmisartan/Hydrochlorothiazide once daily produces effective and smooth reductions in blood pressure across the therapeutic dose range.
Mechanism of action: 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 to 48 hours. Hydrochlorothiazide is a thiazide diuretic. The mechanism of the antihypertensive effect of thiazide diuretics is not fully known. Thiazides have an effect on the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equivalent amounts. The diuretic action of hydrochlorothiazide reduces plasma volume, increases plasma renin activity, increases aldosterone secretion, with consequent increases in urinary potassium and bicarbonate loss, and decreases in serum potassium. Presumably through blockade of the renin-angiotensin aldosterone system, co-administration of telmisartan tends to reverse the potassium loss associated with these diuretics. With hydrochlorothiazide, onset of diuresis occurs in 2 hours, and peak effect occurs at about 4 hours, while the action persists for approximately 6-12 hours.
Pharmacodynamic effects: Treatment of essential hypertension: After the first dose of telmisartan, the antihypertensive activity gradually becomes evident within 3 hours. The maximum reduction in blood pressure is generally attained 4-8 weeks after the start of treatment and is sustained during long-term therapy. The antihypertensive effect persists constantly over 24 hours after dosing and includes the last 4 hours before the next dose as shown by ambulatory blood pressure measurements. This is confirmed by measurements made at the point of maximum effect and immediately prior to the next dose (through to peak ratios consistently above 80% after doses of 40 mg and 80 mg of telmisartan in placebo controlled clinical studies).
In patients with hypertension telmisartan reduces both systolic and diastolic blood pressure without affecting pulse rate. The antihypertensive efficacy of telmisartan is comparable to that of agents representative of other classes of antihypertensive medicinal products (demonstrated in clinical trials comparing telmisartan to amlodipine, atenolol, enalapril, hydrochlorothiazide, and lisinopril).
Upon abrupt cessation of treatment with telmisartan, blood pressure gradually returns to pre-treatment values over a period of several days without evidence of rebound hypertension. The incidence of dry cough was significantly lower in patients treated with telmisartan than in those given angiotensin converting enzyme inhibitors in clinical trials directly comparing the two antihypertensive treatments.
Pharmacokinetics: Concomitant administration of hydrochlorothiazide and telmisartan does not appear to affect the pharmacokinetics of either substance in healthy subjects.
Absorption: Telmisartan: Following oral administration peak concentrations of telmisartan are reached in 0.5-1.5 h after dosing. The absolute bioavailability of telmisartan at 40 mg and 160 mg was 42% and 58%, respectively. 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 19% after a 160 mg dose. By 3 hours after administration plasma concentrations are similar whether telmisartan is taken fasting or with food. The small reduction in AUC is not expected to cause a reduction in the therapeutic efficacy. Telmisartan does not accumulate significantly in plasma on repeated administration.
Hydrochlorothiazide: Following oral administration of telmisartan and hydrochlorothiazide peak concentrations of hydrochlorothiazide are reached in approximately 1.0-3.0 hours after dosing. Based on cumulative renal excretion of hydrochlorothiazide the absolute bioavailability was about 60%.
Distribution: Telmisartan is highly bound to plasma proteins (>99.5%) mainly albumin and alpha l-acid glycoprotein. The apparent volume of distribution for telmisartan is approximately 500 litres indicating additional tissue binding. Hydrochlorothiazide is 68% protein bound in the plasma and its apparent volume of distribution is 0.83-1.14 l/kg.
Biotransformation: Telmisartan is metabolised by conjugation to form a pharmacologically inactive acylglucuronide. The glucuronide of the parent compound is the only metabolite that has been identified in humans. After a single dose of ¹⁴C-labelled telmisartan the glucuronide represents approximately 11% of the measured radioactivity in plasma. The cytochrome P450 isoenzymes are not involved in the metabolism of telmisartan.
Hydrochlorothiazide is not metabolised in man.
Elimination: Telmisartan: Following either intravenous or oral administration of ¹⁴C-labelled telmisartan most of the administered dose (>97%) was eliminated in faeces via biliary excretion. Only minute amounts were found in urine. Total plasma clearance of telmisartan after oral administration is >1500 ml/min. Terminal elimination half-life was >20 hours.
Hydrochlorothiazide is excreted almost entirely as unchanged substance in urine. About 60% of the oral dose is eliminated within 48 hours. Renal clearance is about 250-300 ml/min. The terminal elimination half-life of hydrochlorothiazide is 10-15 hours.
Linearity/non-linearity: Telmisartan: The pharmacokinetics of orally administered telmisartan are non-linear over doses from 20-160 mg with greater than proportional increases of plasma concentrations C_max and AUC) with increasing doses.
Hydrochlorothiazide exhibits linear pharmacokinetics.
Elderly: Pharmacokinetics of telmisartan do not differ between the elderly and those younger than 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. There was a trend towards higher plasma concentrations of hydrochlorothiazide in female than in male subjects. This is not considered to be of clinical relevance.
Renal impairment: 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 30-60 ml/min, mean about 50 ml/min) no dosage adjustment is necessary in patients with decreased renal function. Telmisartan is not removed from blood by haemodialysis. In patients with impaired renal function the rate of hydrochlorothiazide elimination is reduced. In a typical study in patients with a mean creatinine clearance of 90 ml/min the elimination half-life of hydrochlorothiazide was increased. In functionally anephric patients the elimination half-life is about 34 hours.
Hepatic impairment: Pharmacokinetic studies in patients with hepatic impairment showed an increase in absolute bioavailability up to nearly 100%. The elimination half-life is not changed in patients with hepatic impairment.

Treatment of essential hypertension.
Telmisartan/Hydrochlorothiazide fixed dose combination (40 mg telmisartan/12.5 mg hydrochlorothiazide) is indicated in adults whose blood pressure is not adequately controlled on telmisartan alone.

Telmisartan + Hydrochlorothiazide 40 mg/12.5 mg may be administered once daily in patients whose blood pressure is not adequately controlled by Telmisartan 40 mg.
Hepatic impairment: In patients with mild to moderate hepatic impairment the posology should not exceed Telmisartan + Hydrochlorothiazide 40 mg/12.5 mg once daily. The fixed dose combination is contraindicated in patients with severe hepatic impairment. Thiazides should be used with caution in patients with impaired hepatic function.
Or as prescribed by the physician.

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.

Hypersensitivity to the active substance or to any of the excipients.
Hypersensitivity to other sulphonamide-derived substances (since hydrochlorothiazide is a sulphonamide-derived medicinal product).
Second and third trimester of pregnancy.
Cholestasis and biliary obstructive disorders.
Severe hepatic impairment.
Severe renal impairment (creatinine clearance <30 ml/min).
Refractory hypokalaemia, hypercalcaemia.
The concomitant use of telmisartan with aliskiren-containing products is contraindicated in patients with diabetes mellitus or renal impairment (GFR <60 ml/min/1.73 m²).

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.
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 Telmisartan/Hydrochlorothiazide.
Dual blockade of the renin-angiotensin-aldosterone system (RAAS): There is evidence that the concomitant use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren increases the risk of hypotension, hyperkalaemia and decreased renal function (including acute renal failure). Dual blockade of RAAS through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is therefore not recommended. If dual blockade therapy is considered absolutely necessary, this should only occur under specialist supervision and subject to frequent close monitoring of renal function, electrolytes and blood pressure.
ACE-inhibitors and angiotensin II receptor blockers should not be used concomitantly in patients with diabetic nephropathy.
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.
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 Telmisartan/Hydrochlorothiazide 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, whereas hypoglycaemia may occur in diabetic patients under insulin or antidiabetic therapy and telmisartan treatment. Therefore, in these patients blood glucose monitoring should be considered; a dose adjustment of insulin or antidiabetics may be required, when indicated. 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 Telmisartan/Hydrochlorothiazide, 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.
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).
Hyperkalaemia: Conversely, due to the antagonism of the angiotensin II (AT1) receptors by the telmisartan component of Telmisartan/Hydrochlorothiazide, hyperkalaemia might occur. Although clinically significant hyperkalaemia has not been documented with Telmisartan/Hydrochlorothiazide, 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 Telmisartan/Hydrochlorothiazide.
Hyponatraemia and hypochloraemic alkalosis: There is no evidence that Telmisartan/Hydrochlorothiazide 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.
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, including hydrochlorothiazide.
Cases of photosensitivity reactions have been reported with thiazide diuretics. 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.
Choroidal effusion, Acute Myopia and Angle-Closure Glaucoma: Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in choroidal effusion with visual field defect, 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 acute 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.
Non-melanoma skin cancer: An increased risk of non-melanoma skin cancer (NMSC) [basal cell carcinoma (BCC) and squamous cell carcinoma (SCC)] with increasing cumulative dose of hydrochlorothiazide (HCTZ) exposure has been observed in two epidemiological studies based on the Danish National Cancer Registry. Photosensitizing actions of HCTZ could act as a possible mechanism for NMSC.
Patients taking HCTZ should be informed of the risk of NMSC and advised to regularly check their skin for any new lesions and promptly report any suspicious skin lesions. Possible preventive measures such as limited exposure to sunlight and UV rays and, in case of exposure, adequate protection should be advised to the patients in order to minimize the risk of skin cancer. Suspicious skin lesions should be promptly examined potentially including histological examinations of biopsies. The use of HCTZ may also need to be reconsidered in patients who have experienced previous NMSC.
Acute Respiratory Toxicity: Very rare severe cases of acute respiratory toxicity, including acute respiratory distress syndrome (ARDS) have been reported after taking hydrochlorothiazide. Pulmonary oedema typically develops within minutes to hours after hydrochlorothiazide intake. At the onset, symptoms include dyspnoea, fever, pulmonary deterioration and hypotension. If diagnosis of ARDS is suspected, Telmisartan/Hydrochlorothiazide should be withdrawn and appropriate treatment given. Hydrochlorothiazide should not be administered to patients who previously experienced ARDS following hydrochlorothiazide intake.
Hepatic impairment: Telmisartan/Hydrochlorothiazide should not be given to patients with cholestasis, biliary obstructive disorders or severe hepatic insufficiency, since telmisartan is mostly eliminated with the bile. These patients can be expected to have reduced hepatic clearance for telmisartan.
In addition, Telmisartan/Hydrochlorothiazide 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 Telmisartan/Hydrochlorothiazide in patients with hepatic impairment.
Renal impairment and kidney transplantation: Telmisartan/Hydrochlorothiazide must not be used in patients with severe renal impairment (creatinine clearance <30 ml/min). There is no experience regarding the administration of Telmisartan/Hydrochlorothiazide in patients with recent kidney transplantation. Experience with Telmisartan/Hydrochlorothiazide 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.
Use in 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.

Pregnancy: The use of angiotensin II receptor antagonists is not recommended during the first trimester of pregnancy. The use of angiotensin II receptor antagonists is contraindicated during the second and third trimesters of pregnancy. There are no adequate data from the use of Telmisartan/Hydrochlorothiazide in pregnant women. Studies in animals have shown reproductive toxicity.
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).
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. There is limited experience with hydrochlorothiazide during pregnancy, especially during the first trimester. Animal studies are insufficient. Hydrochlorothiazide crosses the placenta. Based on the pharmacological mechanism of action of hydrochlorothiazide its use during the second and third trimester may compromise foeto-placental perfusion and may cause foetal and neonatal effects like icterus, disturbance of electrolyte balance and thrombocytopenia.
Hydrochlorothiazide should not be used for gestational oedema, gestational hypertension or preeclampsia due to the risk of decreased plasma volume and placental hypoperfusion, without a beneficial effect on the course of the disease.
Hydrochlorothiazide should not be used for essential hypertension in pregnant women except in rare situations where no other treatment could be used.
Lactation: Because no information is available regarding the use of Telmisartan/Hydrochlorothiazide during breast-feeding, Telmisartan/Hydrochlorothiazide is not recommended and alternative treatments with better established safety profiles during breast-feeding are preferable, especially while nursing a newborn or preterm infant.
Hydrochlorothiazide is excreted in human milk in small amounts. Thiazides in high doses causing intense diuresis can inhibit the milk production. The use of Telmisartan/Hydrochlorothiazide during breast feeding is not recommended. If Telmisartan/Hydrochlorothiazide is used during breast feeding, doses should be kept as low as possible.

Adverse reactions have been ranked under headings of frequency using the following convention: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).
Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness.
Infections and infestations: Rare: Bronchitis, pharyngitis, sinusitis.
Immune system disorders: Rare: Exacerbation or activation of systemic lupus erythematosus.
Metabolism and nutrition disorders: Uncommon: Hypokalaemia.
Rare: Hyperuricaemia, hyponatraemia.
Psychiatric disorders: Uncommon: Anxiety.
Rare: Depression.
Nervous system disorders: Common: Dizziness.
Uncommon: Syncope, paraesthesia.
Rare: Insomnia, sleep disorders.
Eye disorders: Rare: Visual disturbance, vision blurred.
Ear and labyrinth disorders: Uncommon: Vertigo.
Cardiac disorders: Uncommon: Tachycardia. arrhythmias.
Vascular disorders: Uncommon: Hypotension, orthostatic hypotension.
Respiratory, thoracic and mediastinal disorders: Uncommon: Dyspnoea.
Rare: Respiratory distress (including pneumonitis and pulmonary oedema).
Gastrointestinal disorders: Uncommon: Diarrhoea, dry mouth, flatulence.
Rare: Abdominal pain, constipation, dyspepsia, vomiting, gastritis.
Hepatobiliary disorders: Rare: Abdominal hepatic function/liver disorder.
Skin and subcutaneous tissue disorders: Rare: Angioedema (also with fatal outcome), erythema, pruritus, rash, hyperhidrosis, urticaria.
Musculoskeletal, connective tissue and bone disorders: Uncommon: Back pain, muscle spasms, myalgia.
Rare: Arthralgia, muscle cramps, pain in limb.
Reproductive system and breast disorders: Uncommon: Erectile dysfunction.
General disorders and administration site conditions: Uncommon: Chest pain.
Rare: Influenza-like illness, pain.
Investigations: Uncommon: Blood uric acid increased.
Rare: Blood creatinine increased, Blood creatinine phosphokinase increased, hepatic enzyme increased.
Telmisartan: Adverse reactions occurred with similar frequency in placebo and telmisartan treated patients. The overall incidence of adverse reactions reported with telmisartan (41.4%) was usually comparable to placebo (43.9%) in placebo controlled trials. The following adverse reactions listed as follows 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.
Infections and infestations: Uncommon: Upper respiratory tract infection, urinary tract infections including cystitis.
Rare: Sepsis including fatal outcome.
Blood and lymphatic system disorders: Uncommon: Anaemia.
Rare: Eosinophilia, thrombocytopenia.
Immune system disorders: Rare: Hypersensitivity, anaphylactic reactions.
Metabolism and nutrition disorders: Uncommon: Hyperkalaemia.
Rare: Hypoglycaemia (in diabetic patients).
Cardiac disorders: Uncommon: Bradycardia.
Nervous system disorders: Rare: Somnolence.
Respiratory, thoracic and mediastinal disorders: Uncommon: Cough.
Very rare: Interstitial lung disease.
Gastrointestinal disorders: Rare: Stomach discomfort.
Skin and subcutaneous tissue disorders: Rare: Eczema, drug eruption, toxic skin eruption.
Musculoskeletal, connective tissue and bone disorders: Rare: Arthrosis, tendon pain.
Renal and urinary disorders: Uncommon: Renal impairment (including acute renal failure).
General disorders and administration site conditions: Uncommon: Asthenia.
Investigations: Rare: Haemoglobin decreased.
Hydrochlorothiazide: Hydrochlorothiazide may cause or exacerbate hypovolaemia which could lead to electrolyte imbalance.
Adverse reactions of unknown frequency reported with the use of hydrochlorothiazide alone include: Infection and infestations: Not known: Sialadenitis.
Neoplasms benign, malignant and unspecified (incl cysts and polyps): Not known: Non-melanoma skin cancer (Basal cell carcinoma and Squamous cell carcinoma).
Blood and lymphatic system disorders: Rare: Thrombocytopenia (sometimes with purpura).
Not known: Aplastic anaemia, haemolytic anaemia, bone marrow failure, leukopenia, neutropenia, agranulocytosis.
Immune system disorders: Not known: Anaphylactic reactions, hypersensitivity.
Endocrine disorders: Not known: Diabetes mellitus inadequate control.
Metabolism and nutrition disorders: Common: Hypomagnesaemia.
Rare: Hypercalcaemia.
Very rare: Hypochloraemic alkalosis.
Not known: Anorexia, appetite decreased, electrolyte imbalance, hypercholesterolaemia, hyperglycaemia, hypovolaemia.
Psychiatric disorders: Not known: Restlessness.
Nervous system disorders: Rare: Headache.
Not known: Light-headedness.
Respiratory, thoracic and mediastinal disorders: Very rare: Acute respiratory distress syndrome (ARDS).
Eye disorders: Not known: Xanthopsia, acute myopia, acute angle-closure glaucoma, choroidal effusion.
Vascular disorders: Not known: Vasculitis necrotizing.
Gastrointestinal disorders: Common: Nausea.
Not known: Pancreatitis, stomach discomfort.
Hepatobiliary disorders: Not known: Jaundice hepatocellular, jaundice cholestatic.
Skin and subcutaneous tissue disorders: Not known: Lupus-like syndrome, photosensitivity reactions, skin vasculitis, toxic epidermal necrolysis, erythema multiforme.
Musculoskeletal, connective tissue and bone disorders: Not known: Weakness.
Renal and urinary disorders: Not known: Nephritis interstitial, renal dysfunction, glycosuria.
General disorders and administration site conditions: Not known: Pyrexia.
Investigations: Not known: Triglycerides increased.

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 Telmisartan/Hydrochlorothiazide). Co-administration of lithium and Telmisartan/Hydrochlorothiazide is not recommended. 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.
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 previously mentioned medicinal products may lead to increases in serum potassium and is, therefore, not recommended.
Medicinal products affected by serum potassium disturbances: Periodic monitoring of serum potassium and ECG is recommended when Telmisartan/Hydrochlorothiazide is administered with these 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 antiarrhythmics (e.g. quinidine, hydroquinidine, disopyramide); class III antiarrhythmics (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.
Digoxin: When telmisartan was co-administered with digoxin, median increases in digoxin peak plasma concentration (49%) and in trough concentration (20%) were observed. When initiating, adjusting, and discontinuing telmisartan, monitor digoxin levels in order to maintain levels within the therapeutic range.
Other antihypertensive agents: Telmisartan may increase the hypotensive effect of other antihypertensive agents.
Clinical trial data has shown that dual blockade of the renin-angiotensin-aldosterone-system (RAAS) through the combined use of ACE-inhibitors, angiotensin II receptor blockers or aliskiren is associated with a higher frequency of adverse events such as hypotension, hyperkalaemia and decreased renal function (including acute renal failure) compared to the use of a single RAAS-acting agent.
Antidiabetic medicinal products (oral agents and insulin): Dosage adjustment of the antidiabetic medicinal products may be required.
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 C_max 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 or calcium sparing medicinal products (e.g. vitamin D therapy) 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 products may potentiate the hypotensive effects of all antihypertensives including telmisartan: Baclofen, amifostine.
Furthermore, orthostatic hypotension may be aggravated by alcohol, barbiturates, narcotics or antidepressants.

Store at temperatures not exceeding 30°C.

Angiotensin II Antagonists / Diuretics

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.

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