RIDAFLO 25

Indications

• Hypertension
• Edema associated with congestive heart failure
• Edema due to renal dysfunction

Dosage

Children: Refer to the BNF for Children for specific dosing information.

Adults: 2.5 mg daily, taken in the morning for hypertension; higher doses may be used for other indications.

Mechanism of action

Hydrochlorothiazide is transported into epithelial cells of the distal convoluted tubule via organic anion transporters OAT1, OAT3, and OAT4. It inhibits the sodium-chloride symporter (SLC12A3), preventing sodium reabsorption. This action reduces the concentration gradient that promotes water reabsorption, leading to increased urine production.

Pharmacodynamics

Hydrochlorothiazide increases the excretion of sodium and water, thereby promoting diuresis. It is effective in lowering blood pressure and has a wide therapeutic range, with doses typically ranging from 25 to 100 mg. The drug exhibits a greater antihypertensive effect at lower doses due to enhanced vasodilation, while higher doses primarily exert their effects through diuresis. Caution is advised in patients with renal or hepatic impairment.

Pharmacokinetics

Hydrochlorothiazide is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring within 1-2 hours post-administration. It has a half-life of about 6-15 hours, depending on individual patient factors. The drug is primarily excreted unchanged in the urine. Dosage adjustments may be necessary in patients with renal impairment due to the risk of accumulation.

Contra-indications

• History of hypersensitivity to sulfonamides
• Acute porphyrias
• Severe renal impairment

Adverse effects

• Angina pectoris
• Arrhythmias
• Arthralgia
• Asthenia
• Chest pain
• Confusion
• Dry mouth
• Haemolytic anaemia
• Hepatic disorders
• Hyperkalaemia
• Hypokalemia
• Nausea
• Rhabdomyolysis
• Syncope
• Vertigo

Interactions

• Potassium-sparing diuretics
• Other antihypertensives
• Lithium
• Non-steroidal anti-inflammatory drugs (NSAIDs)
• Corticosteroids

Precautions

• Diabetes mellitus
• Elderly patients
• Basal cell carcinoma
• Cutaneous lupus erythematosus
• Patients with hepatic impairment
• Monitoring of electrolytes

Pregnancy

Hydrochlorothiazide should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is advisable to avoid use, especially during the first trimester.

Breast-feeding

Hydrochlorothiazide is present in breast milk; however, the amount is probably too small to be harmful. Caution is advised as large doses may suppress lactation.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Tablets: 12.5 mg, 25 mg
• Oral solution
• Combination products with amiloride

Mechanism of action

Hydrochlorothiazide is transported from the circulation into epithelial cells of the distal convoluted tubule by the organic anion transporters OAT1, OAT3, and OAT4. From these cells, hydrochlorothiazide is transported to the lumen of the tubule by multidrug resistance associated protein 4 (MRP4). Normally, sodium is reabsorbed into epithelial cells of the distal convoluted tubule and pumped into the basolateral interstitium by a sodium-potassium ATPase, creating a concentration gradient between the epithelial cell and the distal convoluted tubule that promotes the reabsorption of water. Hydrochlorothiazide acts on the proximal region of the distal convoluted tubule, inhibiting reabsorption by the sodium-chloride symporter, also known as Solute Carrier Family 12 Member 3 (SLC12A3). Inhibition of SLC12A3 reduces the magnitude of the concentration gradient between the epithelial cell and distal convoluted tubule, reducing the reabsorption of water.

Pharmacodynamics

Hydrochlorothiazide prevents the reabsorption of sodium and water from the distal convoluted tubule, allowing for the increased elimination of water in the urine. Hydrochlorothiazide has a wide therapeutic window as dosing is individualized and can range from 25-100mg. Hydrochlorothiazide should be used with caution in patients with reduced kidney or liver function.