MYTOR (TORASEMIDE TABLETS 10 MG)

Indications

• Oedema associated with heart failure
• Oedema associated with renal disease
• Hypertension

Dosage

Children: Refer to the BNF for Children for specific dosing information in paediatric patients.

Adults: The usual dose for adults is 5 mg once daily, which may be increased if necessary to 20 mg once daily.

Mechanism of action

Torasemide acts by inhibiting the Na+/K+/Cl- pump located on the luminal cell membrane of the medullary thick ascending loop of Henle. This inhibition occurs through the binding of torasemide to a chloride ion-binding site of the transport molecule. Additionally, it influences the renin-angiotensin-aldosterone system by inhibiting the downstream effects of angiotensin II activation, leading to reduced expression of aldosterone synthase and decreased aldosterone receptor binding.

Pharmacodynamics

Administration of torasemide increases urine output, aiding in fluid, acid-base, and potassium management, while also attenuating renal injury and reducing acute renal failure severity. It achieves a long-lasting diuretic effect with less potassium excretion, similar to combination therapy with furosemide and spironolactone, and is effective in lowering extracellular fluid volume and blood pressure in hypertensive patients with chronic kidney disease.

Pharmacokinetics

Torasemide is well absorbed from the gastrointestinal tract, with peak plasma concentrations occurring 1 to 2 hours after oral administration. It has a half-life of approximately 3 to 5 hours and is primarily excreted in urine, with a portion metabolized in the liver. Renal impairment may affect its clearance, and caution is advised in such patients.

Contra-indications

• Anuria
• Dehydration
• Severe hypokalaemia
• Hypersensitivity to torasemide or any excipients
• Severe renal failure with creatinine clearance less than 25 mL/minute

Adverse effects

• Asthenia
• Gastrointestinal disturbances
• Anemia
• Confusion
• Dry mouth
• Visual impairment
• Hypotension
• Myocardial infarction
• Cerebral ischemia
• Pancreatitis
• Syncope

Interactions

• Potassium-sparing diuretics (risk of hyperkalaemia)
• Selpercatinib (severe increase in exposure)
• Other diuretics
• ACE inhibitors and angiotensin receptor blockers

Precautions

• Caution in patients with diabetes mellitus
• Gout
• Elderly patients
• Impaired micturition
• Prostatic enlargement
• Hepatorenal syndrome
• Patients with raised intra-ocular pressure

Pregnancy

Manufacturer advises avoiding use due to potential toxicity in animal studies.

Breast-feeding

Manufacturer advises avoiding use; no information available on excretion in breast milk.

Storage

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

Formulations

• Torasemide 2.5 mg tablets
• Torasemide 5 mg tablets
• Torasemide 10 mg tablets
• Torasemide 10 mg per 1 ml solution for injection

Mechanism of action

As mentioned above, torasemide is part of the loop diuretics and thus, it acts by reducing the oxygen demand in the medullary thick ascending loop of Henle by inhibiting the Na+/K+/Cl- pump on the luminal cell membrane surface. This action is obtained by the binding of torasemide to a chloride ion-binding site of the transport molecule. Torasemide is known to have an effect in the renin-angiotensin-aldosterone system by inhibiting the downstream cascade after the activation of angiotensin II. This inhibition will produce a secondary effect marked by the reduction of the expression of aldosterone synthase, TGF-B1 and thromboxane A2 and a reduction on the aldosterone receptor binding.

Pharmacodynamics

It is widely known that administration of torasemide can attenuate renal injury and reduce the severity of acute renal failure. This effect is obtained by increasing urine output and hence, facilitating fluid, acid-base and potassium control. This effect is obtained by the increase in the excretion of urinary sodium and chloride. Several reports have indicated that torasemide presents a long-lasting diuresis and less potassium excretion which can be explained by the effect that torasemide has on the renin-angiotensin-aldosterone system. This effect is very similar to the effect observed with the administration of combination therapy with [furosemide] and [spironolactone] and it is characterized by a decrease in plasma brain natriuretic peptide and improved measurements of left ventricular function. Above the aforementioned effect, torasemide presents a dual effect .in which the inhibition of aldosterone which donates torasemide with a potassium-sparing action. Torasemide has been shown to reduce extracellular fluid volume and blood pressure in hypertensive patients suffering from chronic kidney disease. As well, some reports have indicated that torasemide can reduce myocardial fibrosis by reducing the collagen accumulation. This effect is suggested to be related to the decrease in aldosterone which in order has been shown to reduce the production of the enzyme procollagen type I carboxy-terminal proteinase which is known to be overexpressed in heart failure patients.