Olmesartan Medoxomil

Registered South African indications:

• Essential hypertension in adults
• Hypertension in children and adolescents (6 to <18 years)

The use of olmesartan medoxomil is not recommended during the first trimester of pregnancy. The use of olmesartan medoxomil is contraindicated during the 2nd and 3rd trimester of pregnancy.

Registered South African contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Second and third trimesters of pregnancy
• Biliary obstruction
• Coadministration with aliskiren-containing products is contraindicated in patients with diabetes mellitus or renal impairment (GFR<60ml/min/1.73m²)

South African recommendations

Caution in the following patient groups

• Pregnancy (first trimester)
• Breastfeeding
• Renal impairment
• Moderate to severe hepatic impairment
• Elderly

Intravascular volume depletion

• Symptomatic hypotension may occur in patients with activated renin-angiotensin systems, such as those with volume or salt depletion from high-dose diuretics, dietary salt restriction, diarrhoea, or vomiting. Such conditions should be corrected before the administration of olmesartan medoxomil 

Other conditions with stimulation of the renin-angiotensin-aldosterone system

• Patients whose vascular tone and renal function depend predominantly on the renin-angiotensin-aldosterone system (e.g., severe congestive heart failure or underlying renal disease) may experience acute renal failure or oliguria when treated with olmesartan medoxomil

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 olmesartan medoxomil 

Renal impairment and kidney transplantation

• When olmesartan medoxomil is used in patients with impaired renal function, periodic monitoring of serum potassium and creatinine levels is recommended, use is not recommended in patients with severe renal impairment

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

• Evidence suggests that the combined use of ACE-inhibitors, angiotensin II receptor blockers, or aliskiren increases the risk of hypotension, hyperkalaemia, and decreased renal function

Hyperkalaemia

• The use of medicines that affect the renin–angiotensin–aldosterone system may cause hyperkalaemia. The risk, which may be fatal, is increased in elderly people (>70 years), in patients with renal insufficiency, in diabetic patients, in those receiving concomitant treatment with other medicines (including salt substitutes containing potassium) that may increase potassium levels, and in patients with intercurrent events
• Close monitoring of serum potassium in at risk patients is recommended

Lithium

• The combination of lithium and olmesartan medoxomil is not recommended due to the potential for increased lithium toxicity

Aortic or mitral valve stenosis; obstructive hypertrophic cardiomyopathy

• As with other vasodilators, special caution is indicated in patients suffering from aortic or mitral valve stenosis, or obstructive hypertrophic cardiomyopathy

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 olmesartan medoxomil is not recommended

Sprue-like enteropathy

• In very rare cases, severe, chronic diarrhoea with substantial weight loss has been reported in patients taking olmesartan medoxomil months to years after drug initiation, the drug should be discontinued if no other etiology is identified

Ethnic differences

• As with all other angiotensin II antagonists, the blood pressure lowering effect of olmesartan medoxomil is somewhat less in black patients than in non-black patients

Blood pressure reduction 

• Excessive reduction of blood pressure in patients with ischaemic heart disease or ischaemic cerebrovascular disease could result in a myocardial infarction or stroke

Excipient cautions

• Olmesartan medoxomil tablets contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp-lactase deficiency or glucose-galactose malabsorption should not take these tablets

Effects on ability to drive and use machines

• Olmesartan medoxomil may impair the ability to drive and use machines. Olmesartan medoxomil can cause dizziness or fatigue, which may impair the ability to react. Patients experiencing dizziness or fatigue should avoid driving or use of machines

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

South African registered indications and dosages

Essential hypertension

• Oral (fct): Initial: 10mg, once daily; In patients whose blood pressure is not adequately controlled at this dose; Increase to: 20mg, once daily as the optimal dose; If additional blood pressure reduction is required: Increase up to: 40mg, once daily; Max: 40mg/24hrs OR hydrochlorothiazide therapy may be added

---

The antihypertensive effect of olmesartan medoxomil is substantially present within 2 weeks of initiating therapy and is maximal by about 8 weeks after initiating therapy. This should be borne in mind when considering changing the dose regimen for any patient

---

Method of administration: In order to assist compliance, it is recommended that olmesartan medoxomil tablets be taken at about the same time each day, with or without food, for example at breakfast time. The tablet should be swallowed with a sufficient amount of fluid (e.g. one glass of water). The tablet should not be chewed

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

South African registered indications and dosages

Hypertension

Younger than 6 years

• Not established for use

6 years to less than 18 years

• Oral (fct): Initial: 10mg, once daily; In children whose blood pressure is not adequately controlled at this dose; Increase to: 20mg, once daily; For children who weigh <35kg: Max: 20mg/24hrs; For children who weigh ≥35kg: If additional blood pressure reduction is required: Increase up to: 40mg, once daily;  Max: 40mg/24hrs

---

The safety and efficacy of olmesartan medoxomil in children aged 1 to 5 years old have not yet been established. No recommendation on a posology can be made. Olmesartan medoxomil should not be used in children aged below 1 year, because of safety concerns and lack of data in this age group

---

Method of administration: In order to assist compliance, it is recommended that olmesartan medoxomil tablets be taken at about the same time each day, with or without food, for example at breakfast time. The tablet should be swallowed with a sufficient amount of fluid (e.g. one glass of water). The tablet should not be chewed

Pregnancy

South African recommendations

• Contraindicated (second and third trimester)
• Caution; not recommended (first trimester)
• Olmesartan medoxomil should not be initiated during pregnancy
• 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 antagonists, similar risks may exist for this class of medicines. Unless continued angiotensin receptor blocker 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 olmesartan medoxomil should be stopped immediately, and, if appropriate, alternative therapy should be started
• Olmesartan medoxomil therapy exposure 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 have occurred from the second trimester of pregnancy, ultrasound check of renal function and skull is recommended. Infants whose mothers have taken olmesartan medoxomil should be closely observed for hypotension

Breastfeeding

South African recommendations

• Caution; not recommended
• Olmesartan medoxomil is excreted in the milk of lactating rats but it is not known whether olmesartan medoxomil is excreted in human milk
• Because no information is available regarding the use during breastfeeding, olmesartan medoxomil is not recommended and alternative treatments with better established safety profiles during breastfeeding are preferable, especially while nursing a newborn or preterm infant

Fertility

South African recommendations

• No information available (human safety data)

South African recommendations

• Mild to moderate (CrCl≥20-60ml/min): Caution; dose adjustment recommended
  Max. dose: 20mg, once daily owing to limited experience of higher dosages in this patient group
• Severe (CrCl<20ml/min): Caution; not recommended
  There is limited expereince in this patient group
• Coadministration with aliskiren-containing products in patients with renal impairment (GFR<60ml/min/1.73m²): Contraindicated

South African recommendations

• Mild: No dose adjustment recommended
• Moderate: Caution; dose adjutment recommended
  Recommended initial dose: 10mg, once daily; Max: 20mg/24hrs (20mg, once daily)
  Close monitoring of blood pressure and renal function is advised in hepatically-impaired patients who are already receiving diuretics and/or other antihypertensive medicines
• Severe: Caution; not recommended
  There is no experience of olmesartan medoxomil in patients with severe hepatic impairment, therefore use is not recommended in this patient group
• Biliary obstruction: Contraindicated

South African recommendations

• Caution; no dose adjustment recommended
  No adjustment of dosage is generally required in elderly people (see dose recommendations in patients with renal impairment)
  If up-titration to the maximum dose of 40mg daily is required, blood pressure should be closely monitored

Blood and Lymphatic System Disorders

Uncommon

• Thrombocytopenia

Immune System Disorders

Uncommon

• Anaphylactic reaction

Metabolism and Nutrition Disorders

Common

• Hypertriglyceridaemia
• Hyperuricaemia

Rare

• Hyperkalaemia

Nervous System Disorders

Common

• Dizziness
• Headache

Ear and Labyrinth Disorders

Uncommon

• Vertigo

Cardiac Disorders

Uncommon

• Angina pectoris

Vascular Disorders

Rare

• Hypotension (slightly increased from rare to uncommon in elderly patients)

Respiratory, Thoracic and Mediastinal Disorders

Common

• Bronchitis
• Pharyngitis
• Cough
• Rhinitis
• Epistaxis (in children and adolescents)

Gastrointestinal Disorders

Common

• Gastroenteritis
• Diarrhoea
• Abdominal pain
• Nausea
• Dyspepsia

Uncommon

• Vomiting

Very Rare

• Sprue-like enteropathy

Skin and Subcutaneous Tissue Disorders

Uncommon

• Exanthema
• Allergic dermatitis
• Urticaria
• Rash
• Pruritus

Rare

• Angioedema

Musculoskeletal and Connective Tissue Disorders

Common

• Arthritis
• Back pain
• Skeletal pain

Uncommon

• Myalgia

Rare

• Muscle spasm

Renal and Urinary Disorders

Common

• Haematuria
• Urinary tract infection

Rare

• Acute renal failure
• Renal insufficiency

General Disorders and Administration Site Conditions

Common

• Pain
• Chest pain
• Peripheral oedema
• Influenza-like symptoms
• Fatigue

Uncommon

• Face oedema
• Asthenia
• Malaise

Rare

• Lethargy

Investigations

Common

• Increased hepatic enzymes
• Increased blood urea
• Increased blood creatine phosphokinase

Rare

• Increased blood creatinine

• Other antihypertensive medicines
• ACE-inhibitors
• Angiotensin II receptor blockers
• Aliskiren
• Potassium supplements
• Potassium sparing diuretics
• Salt substitutes containing potassium or other medicines that may increase serum potassium levels
• Heparin
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Acetylsalicylic acid (at doses >3g/day)
• COX-2 inhibitors
• Colesevelam hydrochloride (Bile acid sequestering agent)
• Lithium

Specific cases may require

• Renal function
• Electrolytes
  - Serum potassium
• Creatinine levels
• Blood pressure
• Lithium levels (when coadministered)
• Pregnancy status

Additional observations

• Signs of hypotension (especially after the first dose (see Warnings and Precautions) or in infants whose mothers were on olmesartan medoxomil during pregnancy, see Pregnancy section)
• Gastrointestinal symptoms (chronic diarrhoea)
• Hydration status (when coadministered with non-steroidal anti-inflammatory drugs (NSAIDs)

Olmesartan medoxomil is a potent, orally active, selective angiotensin II receptor (type AT1) antagonist. It is expected to block 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 I and II concentrations, and some decrease in plasma aldosterone concentrations. Angiotensin II is the primary vasoactive hormone of the renin-angiotensin-aldosterone system and plays a significant role in the pathophysiology of hypertension via the type 1 (AT1) receptor.