TELGEN Tablet Ref.[115277] Active ingredients: Telmisartan

Pregnancy

TELGEN should not be initiated during pregnancy.

Should a woman become pregnant while receiving TELGEN, the treatment should be stopped promptly and an alternate antihypertensive medicine used (see Section 4.3 and Section 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 medicinal products that affect the renin-angiotensin-aldosterone system (see Section 4.3).

Renal impairment and kidney transplant

When TELGEN is used in patients with moderate impaired renal function, a periodic monitoring of potassium and creatinine serum levels is recommended. There is no experience regarding the administration of TELGEN 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 diuretic therapy, dietary salt restriction, diarrhoea or vomiting. Such conditions should be corrected before the administration of TELGEN. Volume and/or sodium depletion should be corrected prior to administration of TELGEN.

Dual blockade of the renin-angiotensin-aldosterone system (RAAS)

There is evidence that the concomitant use of ace-inhibitors, angiotensin II receptor blockers (ARBS) or aliskiren may increase the risk of hypotension and hyperkalaemia, and decrease renal function (including acute renal failure). Dual blockade of RAAS through the combined use of TELGEN and aliskiren is therefore contra-indicated (see Section 4.3).

TELGEN 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 other medicinal products that affect this system, such as TELGEN , has been associated with acute hypotension, hyperureamia, hyperazotaemia, oliguria, or rarely acute renal failure (see Section 4.3).

Concomitant use of fluoroquinolones

Concomitant use of fluoroquinolones and ACE inhibitors/Angiotensin receptor blockers 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 ACE inhibitors/Angiotensin receptor blockers whether used separately and/or concomitantly.

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 TELGEN is not recommended.

Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy

See section 4.3.

Diabetic patients treated with insulin or antidiabetics

In these patients hypoglycaemia may occur under telmisartan treatment. Therefore, in these patients an appropriate blood glucose monitoring should be considered; a dose adjustment of insulin or antidiabetics may be required, when indicated.

In diabetic patients with an additional cardiovascular risk, i.e. patients with diabetes mellitus and co-existent coronary artery disease (CAD), the risk of fatal myocardial infarction and unexpected cardiovascular death may be increased when treated with blood pressure lowering agents such as ARBs or ACE-inhibitors. In patients with diabetes mellitus, CAD may be asymptomatic and therefore undiagnosed. Patients with diabetes mellitus should undergo appropriate diagnostic evaluation, e.g. exercise stress testing, to detect and to treat CAD accordingly before initiating treatment with TELGEN.

Hyperkalaemia

During treatment with products that affect the renin-angiotensin-aldosterone system such as TELGEN, 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 diabetic patients, in patients concomitantly treated with other medicinal products that may increase potassium levels, and/or in patients with intercurrent events, hyperkalaemia may be fatal.

Before considering the concomitant use of medicinal products that affect the renin-angiotensin- aldosterone system, the benefit risk ratio should be evaluated. The main risk factors for hyperkalaemia

• Diabetes mellitus, age (>70 years).

Based on experience with the use of medicinal products that affect the renin-angiotensin system, concomitant use with potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium or other medicinal products that may increase the potassium level (heparin, etc.) ACE inhibitors, angiotensin II receptor antagonists, non-steroidal anti-inflammatory medicinal products (NSAIDs, including selective COX-2 inhibitors), immunosuppressives (cyclosporin or tacrolimus), and trimethoprim may lead to an increase in serum potassium and should therefore not be co-administered with TELGEN.

to be considered are:

• Intercurrent events, in particular dehydratation, 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).

Close monitoring of serum potassium in at risk patients is recommended.

Hepatic impairment

TELGEN is mostly eliminated in the bile. Patients with biliary obstructive disorders or hepatic insufficiency can be expected to have reduced clearance. TELGEN should be used with caution in these patients (see Section 4.3). TELGEN should be used only with caution in patients with mild to moderate hepatic impairment.

Active gastric or duodenal ulcer or gastro-intestinal pathologies

In clinical trials with telmisartan as in TELGEN, gastro-intestinal adverse events apparently occurred more frequently than with placebo and gastro-intestinal bleedings have been reported infrequently and this has occurred mainly in patients with baseline gastro-intestinal disease. Therefore, caution should be exercised when administering TELGEN to this group of patients.

Other

As observed for angiotensin converting enzyme inhibitors, TELGEN and the other angiotensin antagonists are apparently less effective in lowering blood pressure in black people than in non-blacks, possibly because of higher prevalence of low-renin states the black hypertensive population.

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

Concomitant use of fluoroquinolones and ACE inhibitors/renin-angiotensin receptor blockers 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 ACE inhibitors/renin-angiotensin receptor blockers.

Sorbitol

TELGEN 40 and TELGEN 80 tablets contain 176,64 mg and 349,28 mg sorbitol, respectively. Patients with the rare hereditary condition of sorbitol intolerance should not take TELGEN.

TELGEN may increase the hypotensive effect of other antihypertensive agents.

Co-administration of telmisartan did not result in a clinically significant interaction with digoxin, warfarin, hydrochlorothiazide, glibenclamide, paracetamol, ibuprofen, simvastatin and amlodipine. For digoxin a 20% increase in median plasma digoxin trough concentration has been reported (in a single case a 39%). Monitoring of plasma digoxin levels should be considered.

As with other medicinal products 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 medicinal products that may also provoke hyperkalaemia [salt substitutes containing potassium, potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, non-steroidal anti-inflammatory medicinal products (NSAIDs, including selective COX-2 inhibitors), heparin immunosuppressives (cyclosporin or tacrolimus), and trimethoprim]. In one reported study the co-administration of telmisartan and ramipril led to an increase of up to 2,5 fold in the AUC_0-24 and C_max of ramipril and ramiprilat. The clinical relevance of this observation is not known.

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.

Concomitant treatment with NSAIDs (including aspirin at anti-inflammatory dosage regimens, COX-2 inhibitors and non-selective NSAIDs) is associated with the potential for acute renal insufficiency in patients who are dehydrated. Compounds acting on the Renin-Angiotensin-System like telmisartan may have synergistic effects. Patients receiving NSAIDs and telmisartan should be adequately hydrated and be monitored for renal function at the beginning of combined treatment.

A reduced effect of antihypertensive medicines like telmisartan by inhibition of vasodilating prostaglandins has been reported during combined treatment with NSAIDs.

Dual blockade of the RAAS with ARBs, ACE inhibitors or aliskiren

Reported 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 (see Section 4.3 and 4.4).

Diuretics (loop diuretics)

Prior treatment with high dose diuretics such as furosemide (loop diuretic) may result in volume depletion, and in a risk of hypotension when initiating therapy with telmisartan.

Other antihypertensive agents

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.

Corticosteroids (systemic route)

Reduction of the antihypertensive effect.

Concomitant use of fluoroquinolones and ACE inhibitors/renin-angiotensin receptor blockers 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).

TELGEN may increase the hypotensive effect of other antihypertensive agents.

Compounds which have been studied in pharmacokinetic trials include digoxin, warfarin, hydrochlorothiazide, glibenclamide, paracetamol, ibuprofen, simvastatin and amlodipine.

For digoxin a 20% increase in median plasma digoxin trough concentration has been observed (in a single case a 39%), monitoring of plasma digoxin levels should be considered.

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 as in TELGEN (see Section 4.4).

Potassium sparing diuretics or potassium supplements

Angiostenin II receptor antagonists such as TELGEN, attenuate diuretic induced potassium loss. Potassium sparing diuretics e.g. spirinolactone, eplerenone, triamterene, or amiloride, potassium supplements, or potassium-containing salt substitutes may lead to a significant increase in serum potassium. If concomitant use is indicated because of documented hypokalaemia, they should be used with caution and with frequent monitoring of serum potassium.

Safety in pregnancy and lactation has not been established (see Section 4.3). When pregnancy is planned or confirmed, TELGEN should be discontinued.

Medicines affecting the rennin-angiotensin system, such as TELGEN, can cause embryonal toxicity, foetal and neonatal morbidity and mortality when administered to pregnant women. Women of childbearing age should ensure effective contraception.

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).

No studies on the effect on the ability to drive and use machines have been performed. However, when driving vehicles or operating machinery it must be borne in mind that dizziness or drowsiness may occasionally occur when taking antihypertensive therapy, such as TELGEN.

Reporting of suspected adverse reactions

Reporting 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 SAHPRA’s publications: https://www.sahpra.org.za/Publications/Index/8.

Not applicable.