Amlodipine/ Losartan

Registered South African indications:

• Hypertension

Combination products may have additional pharmacological effects not accounted for by the action of the individual ingredients

Amlodipine
Contraindications

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Hypersensitivity to dihydropyridine derivatives
• Severe hypotension
• Shock
• Left ventricular outflow tract obstruction
• Haemodynamically unstable heart failure

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment 
• Hepatic impairment
• Elderly
• Hypertensive crisis
• Stable heart failure

Losartan
Contraindications

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Second and third trimester of pregnancy
• Coadministration of aliskiren-containing products in patients with diabetes mellitus or renal impairment

Cautions

• First trimester of pregnancy
• Breastfeeding 
• Renal impairment
• Hepatic impairment  
• Elderly 
• History of angioedema
• Hypotension in volume-depleted patients  
• Renal artery stenosis 
• Primary aldosteronism  
• Heart failure 
• Aortic or mitral stenosis 
• Obstructive hypertrophic cardiomyopathy 
• Ethnic differences 
• Dual blockade of the renin-angiotensin-aldosterone system 
• Galactose intolerance 
• Lapp lactase deficiency  
• Glucose-galactose malabsorption  
• Ischaemic cardiovascular disease 
• Cerebrovascular disease 

Additional contraindications for this combination product
Contraindications

• End-stage renal disease(CrCl ≤10ml/min/1.73m²)
• History of angioedema related to previous therapy with ACE inhibitors and angiotensin receptor blockers (ARBs)
• Hereditary or idiopathic angioedema
• Bilateral renal artery stenosis
• Renal artery stenosis in patients with a single kidney
• Porphyria
• Coadministration with lithium therapy
• Coadministration with potassium-sparing diuretics
• Coadministration with renin antagonists

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

Hypertension

Amlodipine/ Losartan
5/50 (mg)
5/100 (mg) 

• Oral (tab): 1 tab, dly; Max: 5/100mg/24hrs

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May be administered with or without food. It is recommended to take with water

Not established for use in children below 18 years

Recommendations for this combination product as per highest risk category when comparing individual active ingredients

Pregnancy

• First trimester: Caution (Amlodipine, Losartan)
• Second and third trimester: Contraindicated (Losartan)
• Refer to the single agent monograph for Amlodipine
• Refer to the single agent monograph for Losartan

Breastfeeding

• Caution; not recommended (Amlodipine, Losartan)
• Refer to the single agent monograph for Amlodipine
• Refer to the single agent monograph for Losartan

Renal Impairment

• eGFR ≥50-89ml/min/1.73 m²: No dose adjustment recommended
• eGFR ≥11-49ml/min/1.73m²: Caution; dose adjustment recommended
• eGFR ≤10ml/min/1.73m² or ESRD: Contraindicated
  It is recommended to use individual tablets instead of the combined tablet for better dose adjustment

eGFR (ml/min/1.73m2)	Dose
≥50-89	No adjustment necessary
≥30-49	Max: 5/50mg/24hrs, as a single dose
≥11-29	Amlodipine: Initial: 2.5mg, dly Losartan: Initial: 25mg, dly Closely monitor renal function and terminate therapy once deterioration in eGFR (CrCl) is observed
≤10 or ESRD	Contraindicated

Hepatic Impairment

• Mild (Child-Pugh class A): Caution; no dose adjustment recommended
  Max: 5/50mg/24hrs, as a single dose
• Moderate to severe (Child-Pugh class B and C): Caution; dose adjustment recommended
  Amlodipine: Initial: 2.5mg, dly
  Losartan: Initial: 25mg, dly
  Monitor liver function and terminate therapy once ALT increases by more than 2-folds from baseline
  It is recommended to use individual tablets instead of the combined tablet for better dose adjustment

Elderly

• Caution; no dose adjustment recommended (Amlodipine, Losartan)

Porphyria Information

• Not yet classified (NC)

Drugs in Sport

• Permitted - No warnings

Amlodipine
Central Nervous System Disorders

• Dizziness
• Headache
• Tremor
• Dysgeusia
• Syncope
• Hypoaesthesia
• Paraesthesia
• Hypertonia
• Peripheral neuropathy
• Extrapyramidal disorder
• Depression
• Mood changes
• Insomnia
• Confusion
• Fatigue

Cardiovascular Disorders

• Palpitations
• Arrhythmia
• Myocardial infarction
• Flushing
• Hypotension
• Vasculitis
• Chest pain

Respiratory Disorders

• Dyspnoea
• Cough
• Rhinitis

Gastrointestinal Disorders

• Abdominal pain
• Nausea and vomiting
• Dyspepsia
• Altered bowel habits 
• Dry mouth
• Pancreatitis
• Gastritis
• Gingival hyperplasia

Hepatobiliary Disorders

• Hepatitis
• Jaundice
• Increased hepatic enzymes

Genitourinary Disorders

• Impotence
• Micturition disorder
• Nocturia
• Increased urinary frequency

Endocrine and Metabolic Disorders

• Weight gain
• Hyperglycaemia
• Gynaecomastia

Musculoskeletal Disorders

• Ankle swelling
• Muscle cramps
• Arthralgia
• Myalgia
• Back pain

Skin and Subcutaneous Tissue Disorders

• Alopecia
• Purpura
• Skin discolouration
• Hyperhidrosis
• Pruritus
• Rash
• Exanthema
• Urticaria
• Angioedema
• Erythema multiforme
• Exfoliative dermatitis
• Stevens-Johnson syndrome
• Quincke oedema
• Photosensitivity

Immune, Blood and Lymphatic System Disorders

• Leukocytopenia
• Thrombocytopenia
• Immune system disorders
• Allergic reactions

Sensory Disorders

• Tinnitus
• Visual disturbance

Losartan 
Central Nervous System Disorders 

• Depression
• Dizziness
• Somnolence
• Headache
• Sleep disorders
• Paraesthesia
• Migraine
• Insomnia
• Dysgeusia
• Fatigue

Cardiovascular Disorders 

• Palpitations
• Angina pectoris
• Syncope
• Atrial fibrillation
• Cerebrovascular accident
• Orthostatic hypotension

Respiratory Disorders

• Dyspnoea
• Cough

Gastrointestinal Disorders 

• Abdominal pain
• Obstipation
• Diarrhoea
• Nausea and vomiting
• Dyspepsia

Hepatobiliary Disorders 

• Pancreatitis
• Hepatitis
• Liver function abnormalities

Genitourinary Disorders 

• Renal impairment
• Renal failure
• Erectile dysfunction 
• Impotence

Endocrine and Metabolic Disorders

• Hyperkalaemia
• Hypoglycaemia

Musculoskeletal Disorders 

• Myalgia
• Arthralgia
• Rhabdomyolysis

Skin and Subcutaneous Tissue Disorders 

• Urticaria
• Pruritus
• Rash
• Photosensitivity

Immune, Blood and Lymphatic System Disorders 

• Anaemia
• Thrombocytopenia
• Hypersensitivity reactions
• Anaphylactic reactions
• Angioedema
• Vasculitis

Sensory Disorders  

• Visual disturbance
• Tinnitus

Others 

• Asthenia
• Oedema

Combination products may have additional pharmacological effects not accounted for by the action of the individual ingredients

Amlodipine

• CYP3A4 inhibitors
• CYP314 inducers
• Dantrolene
• Tacrolimus
• Cyclosporine
• Simvastatin

Losartan

• Angiotensin-converting enzyme inhibitors
• Antihypertensive agents
• CYP2C9 inhibitors
• CYP2C9 inducers
• Potassium supplements
• Potassium-sparing diuretics
• Lithium
• Non-steroidal anti-inflammatory agents
• Tricyclic antidepressants
• Antipsychotics
• Baclofen
• Amifostine
• Heparin
• Angiotensin II receptor blockers
• Aliskiren
• Potassium-containing salt substitutes

Combination products may have additional pharmacological effects not accounted for by the action of the individual ingredients

None routine. Specific cases may require

• Hepatic function
• Serum potassium
• Renal function

Amlodipine

Amlodipine is a calcium ion influx inhibitor and inhibits the transmembrane influx of calcium ions into cardiac and vascular smooth muscle. Amlodipine dilates peripheral arterioles and thus reduces afterload, it also dilates coronary arteries and arterioles which increases myocardial oxygen delivery.

Losartan

Losartan selectively binds to the angiotensin II AT1 receptors found in the vascular smooth muscle, adrenal gland, kidneys and the heart; this inhibits vasoconstriction and aldosterone secretion which results in a decrease in vascular resistance and blood pressure.

COMBINATION PREPARATIONS

Amlodipine/ Losartan

Tablet 5mg/50mg

• Amzaar (Organon) originator

Tablet 5mg/100mg

• Amzaar (Organon) originator