Telmisartan

Registered South African indications: 

• Hypertension - mild to moderate
• Reduction of cardiovascular morbidity and mortality

Contraindications

South African recommendations

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy 
• Breastfeeding
• Severe renal impairment (CrCl<30ml/min)
• Severe hepatic impairment 
• Porphyria 
• Bilateral renal artery stenosis
• Renal artery stenosis in patients with a single kidney
• History of angioedema related to previous therapy with angiotensin-converting enzyme inhibitors (ACE-inhibitors) or angiotensin receptor blockers (ARBs) 
• Hereditary or idiopathic angioedema
• Hypertrophic obstructive cardiomyopathy (HOCM)
• Aortic stenosis
• Biliary obstructive disorders and cholestasis
• Coadministration with potassium-sparing diuretics such as spironolactone, triamterene, amiloride
• Coadministration with lithium therapy
• Coadministration with aliskiren-containing products
• Coadministration with fluoroquinolones in patients with moderate to severe renal impairment and in elderly patients

Recommendations in other jurisdictions

• Hypersensitivity to the active ingredient or any of its excipients
• Second and third trimester of pregnancy
• Severe hepatic impairment 
• Biliary obstructive disorders and cholestasis
• Coadministration with aliskiren-containing products  in patients with diabetes mellitus or renal impairment (GFR<60ml/min/1.73m²)

Cautions

South African recommendations

• Women of childbearing age not using effective contraception
• Mild to moderate renal impairment, including those on haemodialysis
• Mild to moderate hepatic impairment 
• Black patients 
• Japanese patients 
• Recent kidney transplant
• Volume and/or sodium depletion
  - Vigorous diuretic therapy
  - Dietary salt restriction
  - Diarrhoea or vomiting
• Severe congestive heart failure
• Primary aldosteronism 
• Ischaemic cardiomyopathy or ischaemic cardiovascular disease
• Risk factors for hyperkalaemia
  - Renal impairment and/or heart failure
  - Older age (>70 years)
  - Diabetes mellitus
  - Intercurrent events, in particular, dehydration, acute cardiac decompensation, metabolic acidosis, worsening renal function, sudden worsening of the renal condition (e.g. infectious diseases), cellular lysis (e.g. acute limb ischaemia, rhabdomyolysis, extend trauma)
  -  Coadministration with other medicinal products that may increase potassium levels 
• Gastrointestinal disease
  - Active gastric or duodenal ulcer
• Diabetic patients treated with insulin or antidiabetics
• Coadministration of ACE-inhibitors and ARBs in those with diabetic neuropathy
• Galactose intolerance e.g. galactosaemia  (some formulations)
• Lapp lactase deficiency (some formulations)
• Glucose-galactose malabsorption (some formulations)
• Fructose intolerance (some formulations)
• May impair ability to drive and operate machinery 

Recommendations in other jurisdictions

• First trimester of pregnancy
• Breastfeeding
• Renal impairment 
• Mild to moderate hepatic impairment  
• Black patients
• Japanese patients
• Renal artery stenosis
  - Bilateral renal artery stenosis
  - In patients with a single kidney
• Obstructive hypertrophic cardiomyopathy
• Aortic or mitral stenosis
• Recent kidney transplant
• Volume and/or sodium depletion
  - Vigorous diuretic therapy
  - Dietary salt restriction
  - Diarrhoea or vomiting
• Severe congestive heart failure
• Primary aldosteronism 
• Ischaemic cardiomyopathy or ischaemic cardiovascular disease
• Risk factors for hyperkalaemia
  - Renal impairment
  - Older age (>70 years)
  - Diabetes mellitus
  - Intercurrent events, in particular, dehydration, acute cardiac decompensation, metabolic acidosis, worsening renal function, sudden worsening of the renal condition (e.g. infectious diseases), cellular lysis (e.g. acute limb ischaemia, rhabdomyolysis, extend trauma)
  -  Coadministration with other medicinal products that may increase potassium levels 
• Diabetic patients treated with insulin or antidiabetics
• Coadministration of ACE-inhibitors and ARBs in those with diabetic neuropathy
• Hereditary fructose intolerance
• May impair ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: tab

Dosages below include:

• South African registered indications and dosages
• Indications and dosages registered in other jurisdictions

South African registered indications and dosages

Hypertension - mild to moderate (Additional agent may be required)

• Oral (tab): 40mg, dly with or without food; Max dose: 80mg/24hrs

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Maximum antihypertensive effect is generally attained after 4-8 weeks of treatment

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May be used in combination with a low dose thiazide diuretic such as hydrochlorothiazide 12.5mg which has been shown to have an additive blood pressure lowering effect with telmisartan

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Reduction of cardiovascular morbidity and mortality
- In patients ≥55 years at high risk of cardiovascular disease

• Oral (tab): 80mg, dly with or without food 

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It is not known whether doses <80mg are effective in reducing cardiovascular morbidity

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The benefit of treatment is evident after at least 6 months of continued treatment

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Indications and dosages registered in other jurisdictions

Essential hypertension

• Oral (tab): 20-40mg, dly with or without food; Max dose: 80mg/24hrs

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May be used in combination with thiazide-type diuretics such as hydrochlorothiazide which has been shown to have an additive blood pressure lowering effect with telmisartan

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Maximum antihypertensive effect is generally attained after 4-8 weeks of treatment

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Reduction of cardiovascular morbidity
- Manifest atherothrombotic cardiovascular disease (history of coronary heart disease, stroke, or peripheral arterial disease)
- Type 2 diabetes mellitus with documented target organ damage

• Oral (tab): 80mg, dly with or without food 

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It is not known whether doses <80mg are effective in reducing cardiovascular morbidity

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When initiating telmisartan therapy for the reduction of cardiovascular morbidity, close monitoring of blood pressure is recommended, and if appropriate adjustment of medications that lower blood pressure may be necessary

Not established for use in children below 18 years

Pregnancy

South African recommendations

• Contraindicated
• Safety in pregnancy has not been established. When pregnancy is planned or confirmed, telmisartan should be discontinued
• Medicines affecting the renin-angiotensin system, such as telmisartan, can cause embryonal toxicity, foetal and neonatal morbidity and mortality when administered to pregnant women. Should a woman become pregnant while receiving telmisartan, the treatment should be stopped promptly and switched to a different class of antihypertensive medicine
• Women of childbearing age should ensure effective contraception

Recommendations in other jurisdictions

• First trimester: Caution; not recommended 
• Second and third trimester: Contraindicated
• 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 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 agents. 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

Breastfeeding

South African recommendations

• Contraindicated
• Safety in breastfeeding has not been established
• Telmisartan is not recommended in breastfeeding and alternative treatments with better established safety profiles during breastfeeding are preferable, especially while breastfeeding a newborn or preterm infant

Recommendations in other jurisdictions

• Caution; not recommended 
• Because no information is available regarding the use of telmisartan during breastfeeding, telmisartan is not recommended and alternative treatments with better established safety profiles during breastfeeding are preferable, especially while breastfeeding a newborn or preterm infant

Fertility

South African recommendations

• In preclinical studies, effects of telmisartan on male and female fertility were observed

Recommendations in other jurisdictions

• In preclinical studies, no effects of telmisartan on male and female fertility were observed

Renal Impairment

South African recommendations

• Mild to moderate, including those on haemodialysis: Caution; no dose adjustment recommended 
• Severe: Contraindicated

Recommendations in other jurisdictions

• Mild to moderate: Caution; no dose adjustment recommended
• Severe or haemodialysis: Caution; dose adjustment recommended
  Lower starting dose of 20mg is recommended

Hepatic Impairment

• Mild to moderate: Caution; dose adjustment recommended
  Dosage should not exceed 40mg daily
• Severe: Contraindicated

Elderly

• No dose adjustment recommended

Race

• ACE-inhibitors such as telmisartan, and 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
• Most cases of abnormal hepatic function/liver disorder from post-marketing experience occurred in Japanese patients. Japanese patients are more likely to experience these adverse reactions

Porphyria Information

South African recommendations

• Contraindicated

Recommendations in other jurisdictions

• Probably not porphyrinogenic (PNP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders 

• Depression
• Insomnia
• Anxiety
• Syncope
• Somnolence
• Headache
• Dizziness
• Fatigue

Cardiovascular Disorders 

• Bradycardia
• Tachycardia
• Hypotension
• Chest pain
• Orthostatic hypotension

Respiratory Disorders

• Dyspnoea
• Cough
• Interstitial lung disease
• Upper respiratory tract infection
  - Pharyngitis
  - Sinusitis

Gastrointestinal Disorders 

• Abdominal pain
• Diarrhoea
• Dyspepsia
• Flatulence
• Vomiting
• Stomach discomfort
• Dry mouth

Hepatobiliary Disorders

• Abnormal hepatic function/liver disorder
• Increased hepatic enzyme

Genitourinary Disorders

• Renal impairment
  - Acute renal failure
• Urinary tract infection
  - Cystitis
• Increased blood creatinine
• Increased blood uric acid

Endocrine and Metabolic Disorders

• Hyperkalaemia
• Hypoglycaemia (in diabetic patients)

Musculoskeletal Disorders 

• Myalgia
• Back pain (e.g. sciatica)
• Muscle spasms
• Arthralgia
• Pain in extremity
• Tendon pain (tendinitis-like symptoms)
• Increased blood creatine phosphokinase 

Skin and Subcutaneous Tissue Disorders 

• Hyperhidrosis
• Pruritus
• Rash
• Angioedema (also with fatal outcome)
• Eczema
• Erythema
• Urticaria
• Drug eruption
• Toxic skin eruption

Immune, Blood and Lymphatic System Disorders 

• Anaemia
• Eosinophilia
• Thrombocytopenia
• Neutropenia
• Anaphylactic reaction
• Hypersensitivity
• Influenza-like illness
• Sepsis (including fatal outcome)
• Decreased haemoglobin

Sensory Disorders

• Visual disturbance
• Vertigo
• Dysgeusia

• Digoxin
• Agents that provoke hyperkalaemia
• Potassium supplements
• Potassium-sparing diuretics
• Spirinolactone
• Eplerenone
• Triamterene
• Amiloride
• Angiotensin-converting enzyme inhibitors (ACE-inhibitors)
• Angiotensin-II receptors antagonists (ARBs)
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• COX-2 inhibitors
• Acetylsalicylic acid 
• Heparin
• Immunosuppressive agents
• Ciclosporin
• Tacrolimus
• Trimethoprim
• Agents that affect renin-angiotensin-aldosterone system
• Aliskiren
• Lithium
• Thiazide diuretics 
• Hydrochlorothiazide
• Loop diuretics
• Furosemide 
• Baclofen
• Amifostine
• Corticosteroids (systemic route)
• Antihypertensive agents
• Barbiturates
• Narcotics
• Antidepressants
• Fluoroquinolones

Other interactions

• Alcohol
• Salt substitutes containing potassium 

• Blood pressure
• Electrolytes
• Serum creatinine
• Blood urea nitrogen

Specific cases may require

• Glucose

Telmisartan is a specific angiotensin II receptor (type AT₁) antagonist. It displaces angiotensin II 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 at the AT₁ receptor. The binding is long-lasting. Telmisartan does not inhibit human plasma renin or block ion channels.  

Tablet 40mg 

• Adco Telmisartan 40 (Adcock Ingram)
• Cardiz (Innovata Pharmaceuticals)
• Micardis (Ingelheim) originator
• Mizart (Mylan)
• Pritor (Ingelheim) originator
• Telease 40 (Trinity Pharma)
• Telgen (Ranbaxy)
• Telmisartan 40 Teva (Teva Pharmaceuticals)
• Telpres 40 (Sandoz)
• Telza 40 (Forrester Pharma)
• Tesar (Pharma Dynamics)

Tablet 80mg 

• Adco Telmisartan 80 (Adcock Ingram)
• Cardiz (Innovata Pharmaceuticals)
• Micardis (Ingelheim) originator
• Mizart (Mylan)
• Pritor (Ingelheim) originator
• Telease 80 (Trinity Pharma)
• Telgen (Ranbaxy)
• Telmisartan 80 Teva (Teva Pharmaceuticals)
• Telpres 80 (Sandoz)
• Telza 80 (Forrester Pharma)
• Tesar (Pharma Dynamics)

COMBINATION PREPARATIONS

Telmisartan/Hydrochlorothiazide

Tablet 40mg/12.5mg

• Co-Micardis (Ingelheim) originator
• Co-Pritor (Ingelheim) originator
• Telpres Plus (Sandoz)

Tablet 80mg/12.5mg

• Co-Micardis (Ingelheim) originator
• Co-Pritor (Ingelheim) originator
• Telpres Plus (Sandoz)

Tablet 80mg/25mg

• Co-Micardis (Ingelheim) originator

Telmisartan/Amlodipine

Tablet 40mg/5mg 

• Twynsta (Ingelheim) originator

Tablet 40mg/10mg 

• Twynsta (Ingelheim) originator

Tablet 80mg/5mg 

• Twynsta (Ingelheim) originator

Tablet 80mg/10mg 

• Twynsta (Ingelheim) originator