Irbesartan

Registered South African indications:

• Essential hypertension
  - May be used either alone or in combination with other antihypertensive medicines
• Diabetic nephropathy
  - Associated with elevated serum creatinine and proteinuria (>300mg/day) in patients with type 2 diabetes and hypertension

Should a woman become pregnant while receiving irbesartan, treatment must be stopped promptly and switched to a different class of antihypertensive medicine

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Pregnancy
• Breastfeeding
• Severe renal function impairment (CrCl<30ml/min)
• Moderate to severe renal impairment in patients concomitantly using fluoroquinolones
• Severe hepatic impairment
• Porphyria
• 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)
• Bilateral renal artery stenosis
• Renal artery stenosis in patients with a single kidney, or a transplanted kidney
• Aortic stenosis
• Coadministration with potassium-sparing diuretics such as spironolactone, triamterene, amiloride
• Lithium therapy: Coadministration with irbesartan may lead to toxic blood concentrations of lithium
• Coadministration with renin inhibitors such as aliskiren-containing products
• Safety and efficacy in paediatric patients has not been established

• Mild to moderate renal impairment
• Patients on haemodialysis  
• Volume and/or sodium depleted patients (e.g. vigorous diuretic therapy, dietary salt restriction, diarrhoea or vomiting)
• Kidney transplant
• Hypertensive non insulin-dependent diabetics with advanced renal disease
• Heart failure
• Ischaemic cardiopathy
• Ischaemic cardiovascular disease
• Risk factors for hyperkalaemia
• Aortic stenosis
• Mitral stenosis
• Obstructive hypertrophic myopathy
• Primary aldosteronism
• Black patients
• Galactose intolerance
• Lapp lactase deficiency  
• Glucose-galactose malabsorption
• May impair ability to drive and operate machinery

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

South African registered indications and dosages

Essential hypertension
- May be used either alone or in combination with other antihypertensive medicines
Diabetic nephropathy
- Associated with elevated serum creatinine and proteinuria (>300mg/day) in patients with type 2 diabetes and hypertension

• Oral (fct, tab): Usual recommended initial and maintenance dose: 150mg, once daily; If insufficiently controlled: Increase to 300mg, daily OR other anti-hypertensive medicines may be added

---

For oral use. Irbesartan can be taken with or without food

---

In patients with hypertension and type 2 diabetic renal disease: The preferred maintenance dose is 300mg, once daily

---

Intravascular volume depletion: A lower initial dose of irbesartan is recommended

---

Missed dose
Doctors should advise patients who forget to take irbesartan to take a dose as soon as possible and then continue with the normal dose. Patients should not take a double dose to compensate for the missed dose

Contraindicated

Pregnancy

South African recommendations

• Contraindicated
• Safety in pregnancy has not been established
• When pregnancy is planned or confirmed, irbesartan should be discontinued. Medicines affecting the renin-angiotensin system, such as irbesartan can cause embryonal toxicity, foetal and neonatal morbidity and mortality when administered to pregnant women. Irbesartan passes through the placenta and can be presumed to cause disturbance in foetal blood pressure regulatory mechanisms
• The use of irbesartan during the first trimester of pregnancy has been associated with an increased risk of birth defects, in particular, to the cardiovascular and the central nervous systems
• Oligohydramnios as well as hypotension, oliguria and anuria in newborns, have been reported after administration of irbesartan in the second and third trimester. Cases of defective skull ossification have been observed. Prematurity and low birth mass can occur
• Patients planning pregnancy should be changed to alternative antihypertensive treatments, which have an established safety profile for use in pregnancy

Women of childbearing potential

• Women of childbearing age should ensure effective contraception

Breastfeeding

South African recommendations

• Contraindicated
• It is not known whether irbesartan is distributed into breast milk. However, because of potential for adverse effects in the breastfeeding infant, irbesartan should not be administered to breastfeeding mothers
• Available pharmacodynamic/toxicological data in rats have shown excretion of irbesartan or its metabolites in milk

Fertility

South African recommendations

• Irbesartan had no effect upon fertility of treated rats and their offspring up to the dose levels inducing the first signs of parental toxicity

South African recommendations

• Mild to moderate: Caution; no dose adjustment recommended
• Moderate to severe: In patients concomitantly using fluoroquinolones: Contraindicated
• Severe: Contraindicated

South African recommendations

• Mild to moderate: No dose adjustment recommended
• Severe: Contraindicated

South African recommendations

• No dose adjustment recommended

Central Nervous System Disorders

• Dizziness
• Headache
• Vertigo
• Fatigue

Cardiovascular Disorders

• Orthostatic hypotension
• Flushing
• Tachycardia

Respiratory Disorders

• Cough

Gastrointestinal Disorders

• Nausea and vomiting
• Diarrhoea
• Dyspepsia
• Heartburn
• Dysgeusia

Hepatobiliary Disorders

• Jaundice  
• Hepatitis
• Abnormal liver function

Genitourinary Disorders

• Impaired renal function
• Renal failure
• Sexual dysfunction

Endocrine and Metabolic Disorders

• Hyperkalaemia
• Increased plasma creatine kinase

Musculoskeletal Disorders

• Musculoskeletal pain
• Arthralgia
• Myalgia
• Muscle cramps

Skin and Subcutaneous Tissue Disorders

• Rash
• Urticaria
• Angioedema

Immune, Blood and Lymphatic System Disorders

• Thrombocytopenia
• Hypersensitivity reactions
• Anaphylactic reactions
• Anaphylactic shock
• Leukocytoclastic vasculitis
• Decreased haemoglobin production

Sensory Disorders

• Tinnitus

Other

• Chest pain

• Antihypertensive agents
• Diuretics
• Aliskiren-containing products
• ACE inhibitors
• Angiotensin II receptor
  blockers
• Agents that increase serum potassium
• Potassium supplements
• Potassium-sparing diuretics
• Heparin
• Lithium
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Selective COX-2 inhibitors
• Acetylsalicylic acid (> 3 g/day)

• Renal function
• Electrolytes

Specific cases may require

• Serum potassium
• Blood pressure

Irbesartan is a potent, orally active, selective angiotensin-II receptor (type AT1) antagonist. It blocks all actions of angiotensin-II mediated by the AT1 receptor, regardless of the source or route of synthesis of angiotensin-II. The selective antagonism of the angiotensin-II (AT1) receptors results in increases in plasma renin levels and angiotensin-II levels, and a decrease in plasma aldosterone concentration.

Tablet 150mg 

• Adco Irbesartan (Adcock Ingram)
• Antosart fct (Brimpharm)
• Approvel (Sanofi) originator
• Dynarb (Pharma Dynamics)
• Irbewin (Zentiva)
• Irtanel (Brimpharm)
• Jubitan fct (LeBasi)

Tablet 300mg 

• Adco Irbesartan (Adcock Ingram)
• Antosart fct (Brimpharm)
• Approvel (Sanofi) originator
• Dynarb (Pharma Dynamics)
• Irbewin (Zentiva)
• Irtanel (Brimpharm)
• Jubitan fct (LeBasi)

COMBINATION PREPARATION

Irbesartan/ Hydrochlorothiazide

Tablet 150mg/12.5mg

• Co Approvel (Sanofi) originator
• Co-Irbewin (Zentiva)

Tablet 300mg/12.5mg 

• Co Approvel (Sanofi) originator
• Co-Irbewin (Zentiva)

Tablet 300mg/25mg 

• Co-Irbewin (Sanofi)