Timolol/ Amiloride/ Hydrochlorothiazide

Registered South African indications:

• Hypertension

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

Timolol
Contraindications

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Uncontrolled heart failure
• Sinus bradycardia
• Heart block
• Cardiogenic shock
• History of bronchospasm or bronchial asthma
• Chronic obstructive pulmonary disease
• Sick sinus syndrome
• Severe peripheral vascular disease
• Raynaud's disease
• Prinzmetal's angina
• Untreated phaeochromocytoma
• Metabolic acidosis
• Hypotension
• Coadministration with monoamine oxidase inhibitors

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Elderly
• Heart failure
• Ischaemic heart disease
• Diabetes mellitus
• History of psoriasis
• Myasthenia gravis
• Abrupt withdrawal
• Thyroid disease

Amiloride
Contraindications

• Hypersensitivity to the active ingredient or any its excipients
• Severe renal impairment
• Hyperkalaemia
• Children below 18 years 
• Coadministration with other potassium-sparing drugs and potassium supplements 

Cautions

• Breastfeeding
• Mild to moderate renal impairment 
• Hepatic impairment
• Elderly 
• Patients at risk of acidosis
• Diabetes mellitus 
• Resistant oedema
• May impair ability to drive and operate machinery 

Hydrochlorothiazide
Contraindications

• Hypersensitivity to the active ingredient or any of the excipients in this combination product
• Severe renal impairment
• Refractory hypokalaemia, hyponatremia, hypercalcaemia, hyperuricaemia
• Addison’s disease
• Pre-existing hypercalcaemia

Cautions 

• Breastfeeding
• Mild to moderate renal impairment
• Hepatic impairment
• Elderly
• Renal artery stenosis
• Gout
• Hyperglycaemia
• Systemic lupus erythematosus

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

Hypertension

Timolol/ Amiloride/ Hydrochlorothiazide
10/2.5/25mg (mg)

• Oral (tab): 1-2 tab, dly

Not established for use in children

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

Pregnancy

• FDA Pregnancy Category C (Timolol)

Breastfeeding

• Caution; not recommended (Timolol, Amiloride, Hydrochlorothiazide)

Renal Impairment

• Mild to moderate: Caution; dose adjustment recommended 
• Severe: Contraindicated (Amiloride)

Hepatic Impairment

• Caution; dose adjustment recommended (Timolol)

Elderly

• Caution; no dose adjustment recommended (Amiloride, Hydrochlorothiazide)

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

Timolol
Central Nervous System Disorders

• Psychotic disorder
• Hallucination
• Depression
• Disorientation
• Confusional state
• Nightmare
• Insomnia
• Sleep disorder
• Paraesthesia
• Dizziness
• Headache
• Somnolence
• Vertigo
• Fatigue

Cardiovascular Disorders

• Atrioventricular block
• Bradycardia
• Cardiac failure
• Cyanosis
• Hypotension
• Raynaud's phenomenon
• Increase of an existing intermittent claudication
• Peripheral coldness

Respiratory Disorders

• Dyspnoea
• Bronchospasm

Gastrointestinal Disorders

• Retroperitoneal fibrosis
• Dyspepsia
• Nausea and vomiting
• Diarrhoea

Genitourinary Disorders

• Erectile dysfunction

Musculoskeletal Disorders

• Arthralgia

Skin and Subcutaneous Tissue Disorders

• Dermatitis 
• Psoriasiform dermatitis
• Erythematous rash

Sensory Disorders

• Dry eye
• Visual impairment

Amiloride
Central Nervous System Disorders

• Decreased libido
• Somnolence
• Mental confusion
• Minor psychiatric changes 
• Encephalopathy
• Paraesthesia

Cardiovascular Disorders

• Angina pectoris
• Arrhythmias
• Palpitations
• Postural hypotension
• Dizziness

Respiratory Disorders

• Dyspnoea
• Cough

Gastrointestinal Disorders

• Nausea and vomiting
• Constipation 
• Diarrhoea
• Abdominal pain

Hepatobiliary Disorders

• Abnormal hepatic function
• Deepening of jaundice 

Genitourinary Disorders

• Increase in blood urea nitrogen concentrations 
• Impotence

Endocrine and Metabolic Disorders

• Hyperkalaemia 
• Hyponatraemia 

Skin and Subcutaneous Tissue Disorders

• Alopecia
• Rash
• Pruritus

Immune, Blood and Lymphatic System Disorders

• Aplastic anaemia
• Neutropenia

Sensory Disorders

•  Visual changes

Hydrochlorothiazide
Central Nervous System Disorders

• Weakness
• Lethargy
• Drowsiness
• Restlessness
• Seizures
• Headache
• Paraesthesia
• Dizziness

Cardiovascular Disorders

• Postural hypotension

Gastrointestinal Disorders

• Nausea and vomiting
• Constipation
• Diarrhoea
• Intestinal ulceration

Hepatobiliary Disorders

• Cholestatic jaundice
• Pancreatitis

Genitourinary Disorders

• Oliguria
• Impotence

Endocrine and Metabolic Disorders

• Hypochloraemic alkalosis
• Hyponatremia
• Hypokalaemia
• Hyperglycaemia
• Hyperuricaemia
• Gout
• Hypomagnesaemia
• Anorexia

Musculoskeletal Disorders

• Muscle pain
• Cramps

Skin and Subcutaneous Tissue Disorders

• Hypersensitivity reactions

Immune, Blood and Lymphatic System Disorders

• Thrombocytopaenia
• Granulocytopaenia
• Leucopenia
• Aplastic anaemia
• Haemolytic anaemia

Sensory Disorders

• Dry mouth
• Thirst
• Yellow vision

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

Timolol

• Beta blockers
• Antidiabetic agents
• Digoxin
• Clonidine
• Tricyclic antidepressants
• Barbiturates
• Phenothiazines
• Nifedipine
• Antihypertensive agents
• Anaesthetics
• Cimetidine
• Hydralazine
• Rifampicin
• Alcohol
• Prostaglandin-synthetase inhibiting agents
• Sympathomimmetic agents
• Ergot preparations
• Risperine
• Guanethidine

Amiloride

• Alcohol
• Aldesleukin
• Anaesthetics
• Antidiabetic agents
• Antiepileptics
• Non-steroidal anti-inflammatory drugs
• Antiarrhythmics
• Tricyclic antidepressants
• Monoamine oxidase inhibitors 
• Antihypertensives
• Lithium 
• Phenothiazines 
• Corticosteroids
• Dopaminergics
• Combined oral contraceptives and oestrogens 
• Trilostane
• Ciclosporin
• Tacrolimus
• Baclofen
• Nitrates
• Agents that increase serum potassium 
• Alprostadil 

Hydrochlorothiazide

• Digoxin
• Neuromuscular blocking agents
• Central nervous system depressants
• Corticosteroids
• Corticotrophin
• Beta-2 agonists
• Adrenaline
• Lithium

• Serum electrolytes

Specific cases may require 

• Renal function

Timolol
Timolol is a competitive antagonist at beta-1 and beta-2 receptors. It blocks beta sympathomimetic activity particularly in the heart, the bronchi and blood vessels. Timolol reduces heart rate and force of myocardial contraction and, therefore, myocardial oxygen consumption.

Amiloride
Amiloride is a pyrazinoylguanidine derivative which acts as a potassium-sparing diuretic. It binds to sodium channels in the distal convoluted tubules and collecting ducts in the kidney, thereby inhibiting sodium reabsorption. The net negative potential of the tubular lumen is decreased, leading to potassium retention.

Hydrochlorothiazide
Hydrochlorothiazide acts primarily in the distal convoluted tubule where it inhibits sodium chloride transport. It competes for the chloride site and affects the electrolyte reabsorption by increasing sodium and chloride excretion. This reduces plasma volume indirectly and increases plasma renin activity, aldosterone secretion and urinary potassium loss.

COMBINATION PREPARATIONS

Timolol/ Amiloride/ Hydrochlorothiazide

Tablet 10mg/2,5mg/25mg

• Servatrin (Pharmacare)