Telmisartan 40 mg/80 mg Tablets

Treatment of mild to moderate hypertension, either alone or in combination with hydrochlorothiazide. Reduction of cardiovascular morbidity and mortality in patients 55 years or older at high risk of cardiovascular disease; the benefit of treatment is evident after at least 6 months of continued treatment.

Posology:

Adults: Treatment of essential hypertension: The recommended dose is 40 mg once daily. In cases where the target blood pressure is not achieved, the TELMISARTAN TEVA dose can be increased to a maximum of 80 mg once daily. Alternatively, TELMISARTAN TEVA may be used in combination with a low dose thiazide diuretic such as hydrochlorothiazide 12,5 mg, which has been shown to have an additive blood pressure lowering effect with TELMISARTAN TEVA. When considering raising the dose, it must be borne in mind that the maximum antihypertensive effect is generally attained four to eight weeks after the start of treatment.

Reduction of cardiovascular morbidity and mortality: The recommended dose is 80 mg once daily. It is not known whether doses lower than 80 mg of TELMISARTAN TEVA are effective in preventing cardiovascular morbidity and mortality. When initiating TELMISARTAN TEVA therapy for the prevention of cardiovascular morbidity and mortality, monitoring of blood pressure is recommended and, if appropriate, adjustment of medications that lower blood pressure may be necessary. The benefit of treatment is evident only after 6 months of continued treatment.

Renal impairment: No dosage adjustment is required for patients with renal impairment, including those on haemodialysis. TELMISARTAN TEVA is not removed from blood by haemofiltration.

Hepatic impairment: In patients with mild to moderate hepatic impairment the dosage should not exceed 40 mg once daily.

Elderly: No dosing adjustment is necessary.

Children and adolescents up to 18 years: The safety and efficacy of TELMISARTAN TEVA for use in children below 18 years have not been established.

Method of administration: TELMISARTAN TEVA tablets are for once daily oral administration and should be taken with liquid, with or without food.

• Hypersensitivity to telmisartan or to any of the ingredients of TELMISARTAN TEVA (see section 2 and 6.1).
• A history of angioedema related to previous therapy with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs): These patients must never again be given these medicines.
• Hereditary or idiopathic angioedema.
• Hypertrophic obstructive cardiomyopathy (HOCM).
• Bilateral renal artery stenosis.
• Renal artery stenosis in patients with a single kidney.
• Severe renal function impairment (creatinine clearance less than 30 mL/min).
• Aortic stenosis.
• Concomitant therapy with potassium sparing diuretics such as spironolactone, triamterene, amiloride (see section 4.4).
• Porphyria.
• Lithium therapy: concomitant administration with TELMISARTAN TEVA may lead to toxic blood concentrations of lithium (see section 4.5).
• Pregnancy and lactation (see section 4.4 and 4.6).
• Severe hepatic impairment.
• Obstructive biliary disorders.
• The concomitant use of TELMISARTAN TEVA with aliskiren-containing products is contraindicated (section 4.4 and 4.5).
• Concomitant use of fluoroquinolones with Angiotensin-converting enzyme (ACE) inhibitors/Angiotensin receptor blockers (ARBs) is contraindicated in patients with moderate to severe renal impairment (Creatinine Clearance u2264 30 mL/min) and in elderly patients.

Should a woman become pregnant while receiving TELMISARTAN TEVA, the treatment should be stopped promptly and switched to a different class of antihypertensive medicine (see section 4.3 and 4.6).

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 TELMISARTAN TEVA (see section 4.3).

Renal impairment and kidney transplant: When TELMISARTAN TEVA is used in patients with impaired renal function, a periodic monitoring of potassium and creatinine serum levels is recommended. There is no experience regarding the administration of TELMISARTAN TEVA in patients with a recent kidney transplant (see section 4.3).

Intravascular volume depletion: 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, especially volume and/or sodium depletion, should be corrected before the administration of TELMISARTAN TEVA.

Dual blockade of the renin-angiotensin-aldosterone system (RAAS): There is evidence that the concomitant use of angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor blockers or aliskiren may increase the risk of hypotension, hyperkalaemia and decreases renal function (including acute renal failure). Dual blockade of RAAS through the combined use of TELMISARTAN TEVA and aliskiren is therefore contraindicated (see section 4.3). TELMISARTAN TEVA should not be used concomitantly with aliskiren (see section 4.3). 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 medicines that affect this system, such as TELMISARTAN TEVA, has been associated with acute hypotension, uraemia, oliguria, or acute renal failure.

Concomitant use of fluoroquinolones: Concomitant use of fluoroquinolones and Angiotensin-converting enzyme (ACE) inhibitors/Angiotensin receptor blockers (ARBs) may precipitate acute kidney injury in patients, especially those with moderate to severe renal impairment and elderly patients (see section 4.3). Renal function should be assessed before initiating treatment and monitored during treatment with fluoroquinolones or Angiotensin-converting enzyme (ACE) inhibitors/Angiotensin receptor blockers (ARBs) whether used separately and/or concomitantly.

Primary aldosteronism: Patients with primary aldosteronism generally will not respond to TELMISARTAN TEVA. Therefore, the use of TELMISARTAN TEVA is not recommended.

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy: TELMISARTAN TEVA is contraindicated in patients suffering from aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy (see section 4.3).

Excessive reduction in blood pressure in patients with ischaemic cardiopathy or ischaemic cardiovascular disease could result in a myocardial infarction or stroke.

Diabetic patients treated with insulin or antidiabetics: In these patients hypoglycaemia may occur with TELMISARTAN TEVA treatment. Therefore, in these patients, appropriate blood glucose monitoring should be considered; a dose adjustment of insulin or antidiabetics may be required, when indicated.

Hyperkalaemia: During treatment with TELMISARTAN TEVA, hyperkalaemia may occur, especially in the presence of renal impairment and/or heart failure. Monitoring of serum potassium in patients at risk is recommended. In the elderly, in patients with renal insufficiency, in diabetic patients, in patients concomitantly treated with other medicines that may increase potassium levels, and/or in patients with intercurrent events, hyperkalaemia may be fatal. The main risk factors for hyperkalaemia are:

• Diabetes mellitus, renal impairment, age (> 70 years).
• Combination with one or more other medicines that affect the renin-angiotensin-aldosterone system and/or potassium supplements. Medicines or therapeutic classes of medicines that may provoke hyperkalaemia are salt substitutes containing potassium, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, non-steroidal anti-inflammatory medicines (NSAIDs, including selective COX-2 inhibitors), heparin, immunosuppressives (ciclosporin or tacrolimus), and trimethoprim.
• Intercurrent events, in particular dehydration, acute cardiac decompensation, metabolic acidosis, worsening of renal function, sudden worsening of the renal condition (e.g. infectious diseases), cellular lysis (e.g. acute limb ischemia, rhabdomyolysis, extend trauma).

Hepatic impairment: TELMISARTAN TEVA is mostly eliminated in the bile. Patients with biliary obstructive disorders, cholestasis, or hepatic insufficiency can be expected to have reduced clearance (see section 4.3) and should not take TELMISARTAN TEVA. TELMISARTAN TEVA should be used only with caution in patients with mild to moderate hepatic impairment.

Other: Angiotensin receptor blockers, including TELMISARTAN TEVA, are apparently less effective in lowering blood pressure in black people than in non-blacks, possibly because of higher prevalence of low-renin states in the black hypertensive population. Patients with the rare hereditary condition of sorbitol intolerance should not take TELMISARTAN TEVA.

One dose (tablet) of TELMISARTAN 40 TEVA contains 4,66 mg sodium (found in table salt). This is equivalent to 0,24 % of the recommended maximum daily intake of sodium for an adult. One dose (tablet) of TELMISARTAN 80 TEVA contains 9,31 mg sodium (found in table salt). This is equivalent to 0,48 % of the recommended maximum daily intake of sodium for an adult.

TELMISARTAN TEVA may increase the hypotensive effect of other antihypertensive medicines. Co-administration of telmisartan did not result in a clinically significant interaction with warfarin, hydrochlorothiazide, glibenclamide, paracetamol, ibuprofen, simvastatin and amlodipine.

Digoxin: Co-administration of telmisartan did not result in a clinically significant interaction with digoxin, warfarin, hydrochlorothiazide, glibenclamide, paracetamol, ibuprofen, simvastatin and amlodipine. When telmisartan was co-administered with digoxin, median increases in digoxin peak plasma concentration (49 %) and in trough concentration (20 %) were observed (in a single case 39 %). When initiating, adjusting, and discontinuing telmisartan, monitor digoxin levels in order to maintain levels within the therapeutic range.

Potassium sparing diuretics or potassium supplements: As with other medicines acting on the renin-angiotensin-aldosterone system, telmisartan may provoke hyperkalaemia (see section 4.4). The risk may increase in case of treatment combination with other medicines that may also provoke hyperkalaemia (salt substitutes containing potassium, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, non-steroidal anti-inflammatory medicines [NSAIDs, including selective COX-2 inhibitors], heparin, immunosuppressives [ciclosporin or tacrolimus], and trimethoprim). Angiotensin II receptor antagonists such as telmisartan, attenuate diuretic induced potassium loss. Potassium sparing diuretics e.g. spironolactone, eplerenone, triamterene, or amiloride, potassium supplements, or potassium-containing salt substitutes may lead to a significant increase in serum potassium.

Lithium: Reversible increases in serum lithium concentrations and toxicity have been reported during concomitant administration of lithium with angiotensin converting enzyme inhibitors. Increased serum levels have also been reported with telmisartan. Careful monitoring of serum lithium levels is recommended during concomitant use.

Non-steroidal anti-inflammatory Drugs: Concomitant treatment with NSAIDs (including acetylsalicylic acid at anti-inflammatory dosage regimens, COX-2 inhibitors and non-selective NSAIDs) may reduce the antihypertensive effect 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 medicines 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. Compounds acting on the Renin-Angiotensin-System like TELMISARTAN TEVA may have synergistic effects. Patients receiving NSAIDs and TELMISARTAN TEVA should be adequately hydrated and be monitored for renal function at the beginning of combined treatment. A reduced effect of antihypertensive medicines like TELMISARTAN TEVA by inhibition of vasodilating prostaglandins has been reported during combined treatment with NSAIDs.

Ramipril: 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.

Dual blockade of the RAAS with ARBs, ACE inhibitors or aliskiren: Clinical trial data has shown that dual blockade of the renin-angiotensin-aldosterone-system (RAAS) through the combined use of angiotensin-converting enzyme (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 (see section 4.3 and 4.4). Based on their pharmacological properties it can be expected that the following medicines may potentiate the hypotensive effects of all antihypertensives including telmisartan: Baclofen, amifostine. Furthermore, orthostatic hypotension may be aggravated by alcohol, barbiturates, narcotics, or antidepressants.

Concomitant use of fluoroquinolones: Concomitant use of fluoroquinolones and Angiotensin-converting enzyme (ACE) inhibitors/Angiotensin receptor blockers (ARBs) may precipitate acute kidney injury. The mechanism of the possible interaction between the different classes of medicines, over and above different mechanisms of kidney damage, is unknown (see section 4.3).

Diuretics (thiazide or loop diuretics): Prior treatment with high dose diuretics such as furosemide (loop diuretic) and hydrochlorothiazide (thiazide diuretic) may result in volume depletion, and there is a risk of hypotension when initiating therapy with telmisartan. To be taken into account with concomitant use.

Corticosteroids (systemic route): Reduction of the antihypertensive effect.

Women of childbearing potential: Women of childbearing age should ensure effective contraception.

Pregnancy: Safety in pregnancy and lactation has not been established (see section 4.3). When pregnancy is planned or confirmed TELMISARTAN TEVA should be discontinued. Medicines affecting the renin-angiotensin system, such as TELMISARTAN TEVA, can cause embryonal toxicity, foetal and neonatal morbidity and mortality when administered to pregnant women.

Breastfeeding: TELMISARTAN TEVA is contraindicated during lactation (see section 4.3).

Fertility: In preclinical studies, no effects of TELMISARTAN TEVA on male and female fertility were observed.

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 including TELMISARTAN TEVA.

Infections and infestations: Less frequent: Urinary tract infections (including cystitis), upper respiratory tract infections including pharyngitis and sinusitis. Frequency unknown: Sepsis including fatal outcome.

Blood and the lymphatic system disorders: Less frequent: Anaemia, thrombocytopenia. Frequency unknown: Eosinophilia.

Immune system disorders: Less frequent: Hypersensitivity, angio-oedema (with fatal outcome). Frequency unknown: Anaphylactic reaction.

Metabolism and nutrition disorder: Less frequent: Hyperkalaemia. Frequency unknown: Hypoglycaemia (in diabetic patients).

Psychiatric disorders: Less frequent: Depression, insomnia, anxiety.

Nervous system disorders: Less frequent: Syncope/fainting, somnolence.

Eye disorders: Less frequent: Visual disturbance.

Ear and labyrinth disorders: Less frequent: Vertigo.

Cardiac disorders: Less frequent: Bradycardia, tachycardia.

Vascular disorders: Less frequent: Hypotension, orthostatic hypotension.

Respiratory, thoracic and mediastinal disorders: Frequent: Cough. Less frequent: Dyspnoea, interstitial lung disease.

Gastrointestinal disorders: Less frequent: Abdominal pain, diarrhoea, dyspepsia, flatulence, vomiting, dry mouth, stomach discomfort, dysgeusia.

Hepato-biliary disorders: Frequency unknown: Hepatic function abnormal/liver disorder.

Skin and subcutaneous tissue disorders: Less frequent: Increased sweating (hyperhidrosis), pruritus, rash, eczema, erythema, drug eruption, toxic skin eruption. Frequency unknown: Urticaria.

Musculoskeletal, and connective tissue disorders: Less frequent: Back pain (e.g. sciatica), muscle spasms (cramps in legs), myalgia, arthralgia, pain in extremity (leg pain). Frequency unknown: Tendon pain (tendinitis like symptoms).

Renal and urinary disorders: Less frequent: Renal impairment including acute renal failure.

General disorders and administration site conditions: Less frequent: Chest pain, asthenia (weakness), influenza-like symptoms.

Investigations: Less frequent: Blood creatinine increased, haemoglobin decreased, blood uric acid increased, hepatic enzymes increased, blood creatine phosphokinase increased.

Reporting of suspected adverse reactions: Reporting of suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the 6.04 Adverse Drug Reactions Reporting Form, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8.

Symptoms: Limited information is available with regard to overdose in humans. The most prominent manifestations of telmisartan overdose were hypotension and tachycardia; bradycardia, dizziness, increase in serum creatinine, and acute renal failure also occurred.

Management: If symptomatic hypotension should occur, supportive treatment should be instituted. Telmisartan, as in TELMISARTAN TEVA is not removed by haemodialysis. Management depends on the time since ingestion and the severity of the symptoms. Serum electrolytes and creatinine should be monitored frequently. If hypotension occurs, the patient should be placed in a supine position, with salt and volume replacement given quickly.