given concomitantly with lithium because they reduce its renal clearance and add a high risk of lithium toxicity. read prescribing information for lithium preparations before use of such concomitant therapy.

ticosteroids or acth. interference with adequate oral intake of electrolytes will also contribute to hypokalemia. hypokalemia can sensitize or exaggerate the response of the heart to the toxic effects of digitalis, such as increased ventricular irritability. dilutional hyponatremia may occur in edematous patients; the appropriate treatment is restriction of water rather than administration of salt, except in rare instances when the hyponatremia is life threatening. however, in actual salt depletion, appropriate replacement is the treatment of choice. any chloride deficit that may occur during treatment is generally mild and usually does not require specific treatment except in extraordinary circumstances as in liver or renal disease. thiazide-like diuretics have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia. hyperuricemia and gout serum concentrations of uric acid increased by an average of 0.69 mg/100 ml in patients treated with indapamide 1.25 mg, and by an average of 1 mg/100 ml in patients treated with indapamide 2.5 mg and 5 mg, and frank gout may be precipitated in certain patients receiving indapamide (see adverse reactions ). serum concentrations of uric acid should, therefore, be monitored periodically during treatment. renal impairment indapamide, like the thiazides, should be used with caution in patients with severe renal disease, as reduced plasma volume may exacerbate or precipitate azotemia. if progressive renal impairment is observed in a patient receiving indapamide, withholding or discontinuing diuretic therapy should be considered. renal function tests should be performed periodically during treatment with indapamide. impaired hepatic function indapamide, like the thiazides, should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma. glucose tolerance latent diabetes may become manifest and insulin requirements in diabetic patients may be altered during thiazide administration. a mean increase in glucose of 6.47 mg/dl was observed in patients treated with indapamide 1.25 mg, which was not considered clinically significant in these trials. serum concentrations of glucose should be monitored routinely during treatment with indapamide. calcium excretion calcium excretion is decreased by diuretics pharmacologically related to indapamide. after 6 to 8 weeks of indapamide 1.25 mg treatment and in long-term studies of hypertensive patients with higher doses of indapamide, however, serum concentrations of calcium increased only slightly with indapamide. prolonged treatment with drugs pharmacologically related to indapamide may in rare instances be associated with hypercalcemia and hypophosphatemia secondary to physiologic changes in the parathyroid gland; however, the common complications of hyperparathyroidism, such as renal lithiasis, bone resorption, and peptic ulcer, have not been seen. treatment should be discontinued before tests for parathyroid function are performed. like the thiazides, indapamide may decrease serum pbi levels without signs of thyroid disturbance. interaction with systemic lupus erythematosus thiazides have exacerbated or activated systemic lupus erythematosus and this possibility should be considered with indapamide as well. acute angle-closure glaucoma, acute myopia, and choroidal effusion sulfonamide or sulfonamide-derivative drugs, like indapamide, can cause an idiosyncratic reaction resulting in acute angle-closure glaucoma and elevated intraocular pressure with or without a noticeable acute myopic shift and/or choroidal effusions. symptoms may include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. untreated, the angle-closure glaucoma may result in permanent visual field loss. the primary treatment is to discontinue indapamide as rapidly as possible. prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.

apy. as the blood pressure response becomes evident, further dosage adjustments may be necessary. in general, doses of 5 mg and larger have not appeared to provide additional effects on blood pressure or heart failure, but are associated with a greater degree of hypokalemia. there is minimal clinical trial experience in patients with doses greater than 5 mg once a day.

special senses conjunctivitis 1 other all other clinical adverse reactions occurred at an incidence of < 1%. approximately 4% of patients given indapamide 1.25 mg compared to 5% of the patients given placebo discontinued treatment in the trials of up to 8 weeks because of adverse reactions. in controlled clinical trials of 6 to 8 weeks in duration, 20% of patients receiving indapamide 1.25 mg, 61% of patients receiving indapamide 5 mg, and 80% of patients receiving indapamide 10 mg had at least one potassium value below 3.4 meq/l. in the indapamide 1.25 mg group, about 40% of those patients who reported hypokalemia as a laboratory adverse event returned to normal serum potassium values without intervention. hypokalemia with concomitant clinical signs or symptoms occurred in 2% of patients receiving indapamide 1.25 mg. table 2: adverse reactions from studies of 2.5 mg and 5 mg incidence ≥ 5% incidence < 5% central nervous system/neuromuscular headache dizziness fatigue, weakness, loss of energy, lethargy, tiredness, or malaise muscle cramps or spasm, or numbness of the extremities nervousness, tension, anxiety, irritability, or agitation lightheadedness drowsiness vertigo insomnia depression blurred vision gastrointestinal system constipation nausea vomiting diarrhea gastric irritation abdominal pain or cramps anorexia cardiovascular system orthostatic hypotension premature ventricular contractions irregular heart beat palpitations genitourinary system frequency of urination nocturia polyuria dermatologic/hypersensitivity rash hives pruritus vasculitis other impotence or reduced libido rhinorrhea flushing hyperuricemia hyperglycemia hyponatremia hypochloremia increase in serum urea nitrogen (bun) or creatinine glycosuria weight loss dry mouth tingling of extremities because most of these data are from long-term studies (up to 40 weeks of treatment), it is probable that many of the adverse experiences reported are due to causes other than the drug. approximately 10% of patients given indapamide discontinued treatment in long-term trials because of reactions either related or unrelated to the drug. hypokalemia with concomitant clinical signs or symptoms occurred in 3% of patients receiving indapamide 2.5 mg q.d. and 7% of patients receiving indapamide 5 mg q.d. in long-term controlled clinical trials comparing the hypokalemic effects of daily doses of indapamide and hydrochlorothiazide, however, 47% of patients receiving indapamide 2.5 mg, 72% of patients receiving indapamide 5 mg, and 44% of patients receiving hydrochlorothiazide 50 mg had at least one potassium value (out of a total of 11 taken during the study) below 3.5 meq/l. in the indapamide 2.5 mg group, over 50% of those patients returned to normal serum potassium values without intervention. in clinical trials of 6 to 8 weeks, the mean changes in selected values were as shown in the tables below. mean changes from baseline after 8 weeks of treatment - 1.25 mg serum electrolytes (meq/l) serum uric acid (mg/dl) bun (mg/dl) potassium sodium chloride indapamide 1.25 mg (n=255 to 257) -0.28 -0.63 -2.60 0.69 1.46 placebo (n=263 to 266) 0.00 -0.11 -0.21 0.06 0.06 no patients receiving indapamide 1.25 mg experienced hyponatremia considered possibly clinically significant (< 125 meq/l). indapamide had no adverse effects on lipids. mean changes from baseline after 40 weeks of treatment - 2.5 mg and 5 mg serum electrolytes (meq/l) serum uric acid (mg/dl) bun (mg/dl) potassium sodium chloride indapamide 2.5 mg (n=76) -0.4 -0.6 -3.6 0.7 -0.1 indapamide 5 mg (n=81) -0.6 -0.7 -5.1 1.1 1.4 the following reactions have been reported with clinical usage of indapamide: jaundice (intrahepatic cholestatic jaundice), hepatitis, pancreatitis, and abnormal liver function tests. these reactions were reversible with discontinuance of the drug. also reported are erythema multiforme, stevens-johnson syndrome, bullous eruptions, purpura, photosensitivity, fever, pneumonitis, anaphylactic reactions, agranulocytosis, leukopenia, thrombocytopenia, and aplastic anemia. other adverse reactions reported with antihypertensive/diuretics are necrotizing angiitis, respiratory distress, sialadenitis, xanthopsia. postmarketing experience eye disorders choroidal effusion, acute myopia, and angle-closure glaucoma (frequency not known). 1 1 module 2.5 ser-indapamide-choroidal effusion-acute myopia and angle-closure glaucoma-jul2020.

proteins. 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. the urinary elimination of 14 c-labeled indapamide and metabolites is biphasic with a terminal half-life of excretion of total radioactivity of 26 hours. in a parallel design double-blind, placebo controlled trial in hypertension, daily doses of indapamide between 1.25 mg and 10 mg produced dose-related antihypertensive effects. doses of 5 mg and 10 mg were not distinguishable from each other although each was differentiated from placebo and 1.25 mg indapamide. at daily doses of 1.25 mg, 5 mg and 10 mg, a mean decrease of serum potassium of 0.28, 0.61 and 0.76 meq/l, respectively, was observed and uric acid increased by about 0.69 mg/100 ml. in other parallel design, dose-ranging clinical trials in hypertension and edema, daily doses of indapamide between 0.5 mg and 5 mg produced dose related effects. generally, doses of 2.5 mg and 5 mg were not distinguishable from each other although each was differentiated from placebo and from 0.5 mg or 1 mg indapamide. at daily doses of 2.5 mg and 5 mg a mean decrease of serum potassium of 0.5 and 0.6 meq/liter, respectively, was observed and uric acid increased by about 1 mg/100 ml. at these doses, the effects of indapamide on blood pressure and edema are approximately equal to those obtained with conventional doses of other antihypertensive/diuretics. in hypertensive patients, daily doses of 1.25 mg, 2.5 mg and 5 mg of indapamide have no appreciable cardiac inotropic or chronotropic effect. the drug decreases peripheral resistance with little or no effect on cardiac output, rate or rhythm. chronic administration of indapamide to hypertensive patients has little or no effect on glomerular filtration rate or renal plasma flow. indapamide had an antihypertensive effect in patients with varying degrees of renal impairment, although in general, diuretic effects declined as renal function decreased. in a small number of controlled studies, indapamide taken with other antihypertensive drugs such as hydralazine, propranolol, guanethidine, and methyldopa, appeared to have the additive effect typical of thiazide-type diuretics.