Mizart 40 mg, 80 mg Tablets

MIZART is indicated in the treatment of mild to moderate hypertension, either alone, or in combination with hydrochlorothiazide.

Posology
Adults: The recommended dose is 40 mg once daily. In cases where the target blood pressure is not achieved, the MIZART dose can be increased to a maximum of 80 mg once daily. Alternatively, MIZART 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 MIZART. When considering raising the dose, it must be borne in mind that the maximum anti-hypertensive effect is generally attained four to eight weeks after the start of treatment.
Special populations
Elderly population: No dosing adjustment is necessary.
Renal impairment: No dosage adjustment is required for patients with mild to moderate renal impairment.
Hepatic impairment: In patients with mild to moderate hepatic impairment the dosage should not exceed 40 mg once daily.
Paediatric population: There are no data on the safety and efficacy of MIZART in children and adolescents up to 18 years.

Method of administration
For oral use.

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

Pregnancy: Should a woman become pregnant while receiving MIZART, the treatment should be stopped promptly and switched to a different class of antihypertensive medicine (see section 4.3).
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 medicines that affect the renin-angiotensin-aldosterone system (see section 4.3).
Renal impairment and kidney transplant: When MIZART is used in patients with mild to moderate impaired renal function, a periodic monitoring of potassium and creatinine serum levels is recommended (see section 4.3. There is no experience regarding the administration of MIZART in patients with a recent kidney transplant.
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 should be corrected before the administration of MIZART. Volume and/or sodium depletion should be corrected prior to administration of MIZART.
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 medicines that affect this system has been associated with acute hypotension, uraemia, oliguria, or acute renal failure (see section 4.3).
Primary aldosteronism: Patients with primary aldosteronism will generally not respond to antihypertensive medicines acting through inhibition of the renin-angiotensin system; the use of MIZART is therefore not recommended.
Aortic and mitral valve stenosis, obstructive hypertrophic cardiomyopathy: MIZART is contraindicated in patients suffering from aortic or mitral stenosis, or obstructive hypertrophic cardiomyopathy.
Ethnic differences: Angiotensin converting enzyme inhibitors such as MIZART 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 in the black hypertensive population.
Other: Excessive reduction in blood pressure in patients with ischaemic cardiopathy or ischaemic cardiovascular disease could result in a myocardial infarction or stroke.
Hyperkalaemia: Hyperkalaemia may occur, especially in the presence of renal impairment and/or heart failure. Adequate 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 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 to be considered are:

• Diabetes mellitus, renal impairment, age (>70 years).
• 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). Close monitoring of serum potassium in at risk patients is recommended (see section 4.5).
• Based on experience with the use of other medicines that affect the renin-angiotensin system, concomitant use with potassium-sparing diuretics, potassium supplements, salt substitutes containing potassium or other medicines that may increase the potassium level e.g. heparin (see section 4.5) may lead to an increase in serum potassium and should therefore not be co-administered with MIZART.

• Other antihypertensive medicines: MIZART may increase the hypotensive effect of other antihypertensive agents.
• Orthostatic hypotension may be aggravated by alcohol, barbiturates, narcotics, or antidepressants.
• Digoxin: For digoxin a 20 % increase in median plasma digoxin trough concentration has been observed (in a single case a 39 %) when given concomitantly with telmisartan. Monitoring of plasma digoxin levels should be considered.
• Lithium: 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 (see section 4.3).
• Non-steroidal anti-inflammatory medicinal products: 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 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. Compounds acting on the Renin-Angiotensin-System, like MIZART, may have synergistic effects. Patients receiving NSAIDs and MIZART should be adequately hydrated and be monitored for renal function at the beginning of combined treatment. A reduced effect of antihypertensive medicines, like MIZART, by inhibition of vasodilating/prostaglandins has been reported during combined treatment with NSAIDs.
• Corticosteroids (systemic route): Reduction of the antihypertensive effect.
• Other medicinal products acting on the renin-angiotensin-aldosterone system: 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 medicinal products (NSAIDs, including selective COX-2 inhibitors), heparin, immunosuppressives (cyclosporin or tacrolimus), and trimethoprim). The occurrence of hyperkalaemia depends on associated risk factors. The risk is increased in case of the above-mentioned treatment combinations. The risk is particularly high in combination with potassium sparing-diuretics, and when combined with salt substitutes containing potassium.
• Potassium sparing diuretics or potassium supplements: Angiotensin II receptor antagonists such as telmisartan, 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 (see section 4.4). If concomitant use is indicated because of documented hypokalaemia, they should be used with caution and with frequent monitoring of serum potassium.
• 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 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).
• Concomitant use of fluoroquinolones and ACE inhibitors/renin-angiotensin receptor blockers: may precipitate acute kidney injury (see section 4.3).

Women of childbearing potential/ Contraception in males and females: 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, MIZART should be discontinued. Medicines affecting the renin-angiotensin system, such as MIZART, can cause embryonal toxicity, foetal and neonatal morbidity and mortality when administered to pregnant women.
Breastfeeding: MIZART is not recommended in breastfeeding and alternative treatments with better established safety profiles during breastfeeding are preferable, especially while nursing a newborn or preterm infant.

No studies on the effect on the ability to drive and use machines have been performed. MIZART may cause dizziness or drowsiness and have no or negligible effect mental and/or physical abilities to perform or execute tasks or activities requiring mental alertness, judgment and/or sound coordination and vision.

Tabulated list of adverse reactions
Body System Undesirable effect Less frequent
Infections and Infestations: Urinary tract infection including cystitis, upper respiratory tract infection including pharyngitis and sinusitis, sepsis including fatal outcome
Blood and the lymphatic system disorders: Anaemia, eosinophilia, thrombocytopenia, neutropenia
Immune system disorders: Anaphylactic reaction, hypersensitivity, angioedema (also with fatal outcome)
Metabolism and nutrition disorders: Hyperkalaemia, hypoglycaemia (in diabetic patients)
Psychiatric disorders: Insomnia, depression, anxiety
Nervous system disorders: Syncope, somnolence, headache, dizziness, fatigue
Eye disorders: Visual disturbance
Ear and labyrinth disorders: Vertigo
Cardiac disorders: Bradycardia, tachycardia
Vascular disorders: Hypotension, orthostatic hypotension
Respiratory, thoracic and mediastinal disorders: Dyspnoea, cough, interstitial lung disease
Gastrointestinal disorders: Abdominal pain, diarrhoea, dyspepsia, flatulence, vomiting, dry mouth, stomach discomfort, dysgeusia
Hepato-biliary disorders: Abnormal hepatic function/liver disorder
Skin and subcutaneous tissue disorders: Pruritus, hyperhidrosis, rash, eczema, erythema, urticaria, drug eruption, toxic skin eruption, angioedema (also with fatal outcome)
Musculoskeletal, connective tissue and bone disorders: Back pain (e.g. sciatica), muscle spasms, myalgia, arthralgia, pain in extremity, tendon pain (tendinitis-like symptoms)
Renal and urinary disorders: Renal impairment including acute renal failure
General disorders and administrative site conditions: Chest pain, asthenia (weakness), influenza-like illness
Investigations: Increased blood creatine, decreased haemoglobin, increased blood uric acid, increased hepatic enzyme, increased blood creatinine phosphokinase
Description of selected adverse reactions
Sepsis: An increased incidence of sepsis has been reported with telmisartan as contained in MIZART compared with placebo.
Hypotension
Abnormal hepatic function/liver disorder: Most cases of abnormal hepatic function/liver disorder occurred in Japanese patients. Japanese patients are more likely to experience these adverse reactions.
Interstitial lung disease: Cases of interstitial lung disease have been reported in temporal association with the intake of MIZART.
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 on the SAHPRA website at: https://medsafety.sahpra.org.za/#download1, via email at: [email protected] or via telephone at: 0125010311

Symptoms: In overdose, side effects can be precipitated and/or be of increased severity (see section 4.8). No data are available with regard to overdose in humans. The most prominent manifestations of MIZART overdose were hypotension and tachycardia; bradycardia dizziness, increase in serum creatinine, and acute renal failure have also been reported.
Treatment: If symptomatic hypotension should occur, supportive treatment should be instituted. Telmisartan is not removed by haemodialysis.