Amiloride/ Hydrochlorothiazide

Registered South African indications:

• Hypertension
• Cardiac failure
• Oedema

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients
• Hypersensitivity to other sulfonamide-derived drugs
• Severe renal impairment
• Severe hepatic impairment
• Hyperkalaemia 
• Precoma associated with hepatic cirrhosis
• Addison's disease
• Hypercalcaemia
• Diabetic nephropathy
• Serum urea over 10mmol/l
• Diabetes mellitus
• Serum creatinine over 130 μmol/l in whom serum electrolyte and blood urea levels cannot be monitored carefully and frequently
• Children
• Coadministration with agents that increase serum potassium
• Coadministration with spironolactone or triamterene
• Coadministration with lithium

Cautions

• Pregnancy
• Breastfeeding
• Mild to moderate renal impairment
• Mild to moderate hepatic impairment
• Elderly
• Risk factors for hyperkalaemia
• Brisk diuresis
• Severe cirrhosis
• Gout
• Diabetes mellitus
• Systemic lupus erythematosus

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

Essential hypertension

Amiloride/ Hydrochlorothiazide
2.5mg/ 25mg

• Oral (tab): 1-2 tabs, dly, in 1-2 divided doses

5mg/ 50mg

• Oral (tab): 0.5-1 tab, dly, in 1-2 divided doses

Congestive cardiac failure
Oedema associated with hepatic cirrhosis or steroid therapy

Amiloride/ Hydrochlorothiazide
2.5mg/ 25mg

• Oral (tab): 1-4 tabs, dly; Max: 4 tabs/24hrs

5mg/ 50mg

• Oral (tab): 0.5-2 tabs, dly; Max: 2 tabs/24hrs

Maintenance dosages may be lower than those required to initiate diuresis

Not established for use in children

Pregnancy

• Caution; no evidence of risk in studies
• The routine use of diuretics in otherwise healthy pregnant women with or without mild oedema is not indicated, because they may be associated with hypovolaemia, increased blood viscosity, and decreased placental perfusion. Diuretics do not prevent the development of toxaemia of pregnancy and there is no satisfactory evidence that they are useful for its treatment
• There is limited experience with hydrochlorothiazide during pregnancy, especially during the first trimester. Animal studies are insufficient. Hydrochlorothiazide crosses the placenta. Based on the pharmacological mechanism of action of hydrochlorothiazide its use during the second and third trimester may compromise foeto-placental perfusion and may cause foetal and neonatal effects like icterus, disturbance of electrolyte balance, bone marrow depression and thrombocytopenia
• Hydrochlorothiazide should not be used for gestational oedema, gestational hypertension or preeclampsia due to the risk of decreased plasma volume and placental hypoperfusion, without a beneficial effect on the course of the disease
• Hydrochlorothiazide should not be used for essential hypertension in pregnant women except in rare situations where no other treatment could be used

Breastfeeding

• Caution; not recommended
• Although it is not known whether amiloride hydrochloride is excreted in human milk, it is known that hydrochlorothiazide is excreted in human milk in small amounts. Thiazides in high doses causing intense diuresis can inhibit the milk production. The use of amiloride/ hydrochlorothiazide during breastfeeding is not recommended. If amiloride/ hydrochlorothiazide is used during breastfeeding, doses should be kept as low as possible

Renal Impairment

• Mild to moderate: Caution; no dose adjustment recommended
• Severe: Contraindicated 

Hepatic Impairment

• Mild to moderate: Caution: no dose adjustment recommended
• Severe: Contraindicated 

Elderly

• Caution; no dose adjustment recommended
  Initiate at lower end of dosage range

Porphyria Information

• Not yet classified (NC)

Drugs in Sport

• Prohibited - At all times

Central Nervous System Disorders

• Dizzines
• Vertigo
• Paraesthesiae
• Stupor
• Insomnia
• Nervousness
• Mental confusion
• Depression
• Sleepiness
• Headache
• Weakness
• Fatigue

Cardiovascular Disorders

• Arrhythmias
• Tachycardia
• Digitalis toxicity
• Orthostatic hypotension
• Angina pectoris

Respiratory Disorders

• Dyspnoea
• Nasal congestion

Gastrointestinal Disorders

• Anorexia
• Nausea and vomiting
• Diarrhoea
• Constipation
• Abdominal pain
• Gastrointestinal bleeding
• Appetite changes
• Abdominal fullness
• Flatulence
• Thirst
• Hiccups

Genitourinary Disorders

• Impotence
• Dysuria
• Nocturia
• Incontinence
• Renal dysfunction

Endocrine and Metabolic Disorders

• Hyperkalaemia
• Hyponatraemia
• Gout
• Dehydration
• Electrolyte imbalances

Musculoskeletal Disorders

• Leg ache
• Muscle cramps
• Arthralgia
• Back pain

Immune, Blood and Lymphatic System Disorders

• Rash
• Pruritus
• Flushing
• Diaphoresis
• Anaphylactic reactions

Sensory Disorders

• Bad taste
• Visual disturbances

• Agents that increase serum potassium
• Spironolactone
• Triamterene
• Lithium
• Non-steroidal anti-inflammatory drugs
• Angiotensin-converting enzyme inhibitors
• Angiotensin II antagonists
• Trilostane
• Ciclosporin
• Tacrolimus
• Central nervous system depressants
• Antidiabetic agents
• Antihypertensives
• Corticosteroids
• Cholestyramine
• Colestipol resins
• Epinephrine
• Non-depolarising muscle relaxants
• Digoxin

• Renal function
• Electrolytes
• Fluid balance

Specific cases may require

• ECG

Hydrochlorothiazide
Hydrochlorothiazide is a diuretic with antihypertensive properties. It acts by inhibiting the renal tubular reabsorption of sodium and chloride ions, which are excreted with an accompanying volume of water. Potassium excretion is also promoted.

Amiloride
Amiloride hydrochloride is a potassium-sparing diuretic. It promotes the excretion of sodium and chloride by blocking epithelial channels in the late distal convoluted tubule and collecting duct. This reduces intracellular sodium which reduces the function of sodium/potassium exchange channels thus reducing the excretion of potassium.

COMBINATION PREPARATIONS

Amiloride/ Hydrochlorothiazide

Tablet 2.5mg/25mg

• Amiloretic hs (Pharmacare)

Tablet 5mg/50mg

• Adco-Retic (Adcock)
• Amiloretic (Pharmacare)
• Betaretic (Be-Tabs)
• Dezretic (Dezzo)
• Moduretic (MSD) originator
• Sandoz Co-Amilozide (Sandoz)
• Spec-co-Amiloride (Specpharm)