indication

For the treatment of hypertension, alone or in combination with other antihypertensive drugs, as well as for the treatment of salt and fluid retention associated with congestive heart failure or edema from pregnancy (appropriate only in the management of edema of pathologic origin during pregnancy when clearly needed). Also used for the management of edema as a result of various causes.

pharmacology

Indapamide is an antihypertensive and a diuretic. It contains both a polar sulfamoyl chlorobenzamide moiety and a lipid- soluble methylindoline moiety. Indapamide bears a structural similarity to the triazide diuretics which are known to decrease vascular smooth muscle reactivity. However, it differs chemically from the thiazides in that it does not possess the thiazide ring system and contains only one sulfonamide group. Indapamide appears to cause vasodilation, probably by inhibiting the passage of calcium and other ions (sodium, potassium) across membranes. This same effect may cause hypokalcemia in susceptible individuals. Indapamide has also been shown to cause uterine myometrial relaxation in experimental animals. Overall, indapamide has an extra-renal antihypertensive action resulting in a decrease in vascular hyperreactivity and a reduction in total peripheral and arteriolar resistance.

mechanism of action

Indapamide blocks the slow component of delayed rectifier potassium current (IKs) without altering the rapid component (IKr) or the inward rectifier current. Specifically it blocks or antagonizes the action the proteins KCNQ1 and KCNE1. Indapamide is also thought to stimulate the synthesis of the vasodilatory hypotensive prostaglandin PGE2.

toxicity

Side effects include electrolyte imbalance (potassium or salt depletion due to too much fluid loss), nausea, stomach disorders, vomiting, weakness

biotransformation

Primarily hepatic. Indapamide is an extensively metabolized drug with only about 7+ACU- of the total dose administered, recovered in the urine as unchanged drug during the first 48 hours after administration.

absorption

Rapidly absorbed from gastrointestinal tract.

half life

14 hours (biphasic)

route of elimination

Indapamide is an extensively metabolized drug, with only about 7% of the total dose administered, recovered in the urine as unchanged drug during the first 48 hours after administration.

drug interactions

Artemether: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Deslanoside: Possible electrolyte variations and arrhythmias

Diazoxide: Significant hyperglycemic effect

Digitoxin: Possible electrolyte variations and arrhythmias

Digoxin: Possible electrolyte variations and arrhythmias

Dofetilide: Increased risk of cardiotoxicity and arrhythmias

Lithium: The thiazide diuretic, indapamide, may increase serum levels of lithium.

Lumefantrine: Additive QTc-prolongation may occur. Concomitant therapy should be avoided.

Tacrolimus: Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Thiothixene: May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.

Toremifene: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.

Trandolapril: The thiazide diuretic, Indapamide, may increase the hypotensive effect of Trandolapril. Indapamide may also increase the nephrotoxicity of Trandolapril. Monitor for postural hypotension at initiation of concomitant therapy and renal dysfunction during chronic therapy.

Treprostinil: Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.

Trimipramine: Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.

Voriconazole: Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

Vorinostat: Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).

Ziprasidone: Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.

Zuclopenthixol: Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).