Indapamide

INDICATIONS Indapamide tablets are indicated for the treatment of hypertension, alone or in combination with other antihypertensive drugs. Indapamide tablets are also indicated for the treatment of salt and fluid retention associated with congestive heart failure. Usage in Pregnancy : The routine use of diuretics in an otherwise healthy woman is inappropriate and exposes mother and fetus to unnecessary hazard (see PRECAUTIONS below). Diuretics do not prevent development of toxemia of pregnancy, and there is no satisfactory evidence that they are useful in the treatment of developed toxemia. Edema during pregnancy may arise from pathological causes or from the physiologic and mechanical consequences of pregnancy. Indapamide is indicated in pregnancy when edema is due to pathologic causes, just as it is in the absence of pregnancy (however, see PRECAUTIONS below). Dependent edema in pregnancy, resulting from restriction of venous return by the expanded uterus, is properly treated through elevation of the lower extremities and use of support hose; use of diuretics to lower intravascular volume in this case is illogical and unnecessary. There is hypervolemia during normal pregnancy which is not harmful to either the fetus or the mother (in the absence of cardiovascular disease), but which is associated with edema, including generalized edema in the majority of pregnant women. If this edema produces discomfort, increased recumbency will often provide relief. In rare instances, this edema may cause extreme discomfort which is not relieved by rest. In these cases, a short course of diuretics may provide relief and may be appropriate.

DOSAGE & ADMINISTRATION Hypertension : The adult starting indapamide dose for hypertension is 1.25 mg as a single daily dose taken in the morning. If the response to 1.25 mg is not satisfactory after 4 weeks, the daily dose may be increased to 2.5 mg taken once daily. If the response to 2.5 mg is not satisfactory after 4 weeks, the daily dose may be increased to 5.0 mg taken once daily, but adding another antihypertensive should be considered. Edema of Congestive Heart Failure : The adult starting indapamide dose for edema of congestive heart failure is 2.5 mg as a single daily dose taken in the morning. If the response to 2.5 mg is not satisfactory after one week, the daily dose may be increased to 5.0 mg taken once daily. If the antihypertensive response to indapamide is insufficient, indapamide may be combined with other antihypertensive drugs, with careful monitoring of blood pressure. It is recommended that the usual dose of other agents be reduced by 50% during initial combination therapy. As the blood pressure response becomes evident, further dosage adjustments may be necessary. In general, doses of 5.0 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 5.0 mg once a day.

CONTRAINDICATIONS Anuria. Known hypersensitivity to indapamide or to other sulfonamide-derived drugs.

ADVERSE REACTIONS Most adverse effects have been mild and transient. The clinical adverse reactions listed in Table 1 represent data from Phase II/III placebo-controlled studies (306 patients given indapamide 1.25 mg). The clinical adverse reactions listed in Table 2 represent data from Phase II placebo-controlled studies and long-term controlled clinical trials (426patients given indapamide 2.5 mg or 5.0 mg). The reactions are arranged into two groups: 1) a cumulative incidence equal to or greater than 5%; 2)a cumulative incidence less than 5%. Reactions are counted regardless of relation to drug. TABLE 1: Adverse Reaction from Studies of 1.25mg Incidence ≥ 5% Incidence < 5%* BODY AS A WHOLE Headache Asthenia Infection Flu Syndrome Pain Abdominal Pain Back Pain Chest Pain GASTROINTESTINAL SYSTEM Constipation Diarrhea Dyspepsia Nausea METABOLIC SYSTEM Peripheral Edema CENTRAL NERVOUS SYSTEM Nervousness Dizziness Hypertonia RESPIRATORY SYSTEM Cough RHINITIS Pharyngitis Sinusitis SPECIAL SENSES Conjunctivitis *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 eight weeks because of adverse reactions. In controlled clinical trials of six to eight weeks in duration, 20% of patients receiving indapamide 1.25 mg, 61% of patients receiving indapamide 5.0 mg, and 80% of patients receiving indapamide 10.0 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 5.0 mg Incidence ≥ 5% Incidence < 5% CENTRAL NERVOUS SYSTEM/ NEUROMUSCULAR Headache Lightheadedness Dizziness Drowsiness Fatigue, weakness, loss of energy, lethargy, tiredness, or malaise Vertigo Insomnia Depression Muscle cramps or spasm, or numbness of the extremities Blurred Visoin Nervousness, tension, anxiety, irritability, or agitation 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 six to eight 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 Electrolyt …

Drug Interactions Other Antihypertensives : Indapamide may add to or potentiate the action of other antihypertensive drugs. In limited controlled trials that compared the effect of indapamide combined with other antihypertensive drugs with the effect of the other drugs administered alone, there was no notable change in the nature or frequency of adverse reactions associated with the combined therapy. Lithium : See WARNINGS . Post-Sympathectomy Patient : The antihypertensive effect of the drug may be enhanced in the post-sympathectomized patient. Norepinephrine : Indapamide, like the thiazides, may decrease arterial responsiveness to norepinephrine, but this diminution is not sufficient to preclude effectiveness of the pressor agent for therapeutic use.

DESCRIPTION Indapamide is an oral antihypertensive/diuretic. Its molecule contains both a polar sulfamoyl chlorobenzamide moiety and a lipid-soluble methylindoline moiety. It differs chemically from the thiazides in that it does not possess the thiazide ring system and contains only one sulfonamide group. The chemical name of indapamide is 4-chloro-N-(2-methyl-1-indolinyl)-3-sulfamoyl benzamide, and its molecular weight is 365.8. The compound is a weak acid, pKa=9.35±0.60, and is soluble in methanol, in acetonitrile, in glacial acetic acid, and in ethyl acetate; very slightly soluble in ether and in chloroform; practically insoluble in water. It is a white to off- white, crystalline powder. Each tablet, for oral administration, contains 1.25 mg or 2.5 mg of indapamide, USP and the following inactive ingredients: anhydrous lactose, colloidal silicon dioxide, hypromellose, magnesium stearate, microcrystalline cellulose, polydextrose, polyethylene glycol, pregelatinized starch, sodium lauryl sulfate, titanium dioxide and triacetin. Additionally, the 1.25 mg product contains D&C Red# 30/ Helendon pink aluminum lake. indapamide-struct

OVERDOSAGE Symptoms of overdosage include nausea, vomiting, weakness, gastrointestinal disorders and disturbances of electrolyte balance. In severe instances, hypotension and depressed respiration may be observed. If this occurs, support of respiration and cardiac circulation should be instituted. There is no specific antidote. An evacuation of the stomach is recommended by emesis and gastric lavage after which the electrolyte and fluid balance should be evaluated carefully.

HOW SUPPLIED Indapamide Tablets, USP are available containing 1.25 mg or 2.5 mg of indapamide, USP. The 1.25 mg tablets are pink, film coated, round, biconvex, beveled edge tablet debossed with “875” on one side of the tablet and plain on the other side. They are available as follows: NDC 16571-875-01 bottles of 100 tablets The 2.5 mg tablets are white, film coated, round, biconvex, beveled edge tablet debossed with “876” on one side of the tablet and plain on the other side. They are available as follows: NDC 16571-876-01 bottles of 100 tablets Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Avoid excessive heat. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure. Manufactured for: Rising Pharma Holdings, Inc. East Brunswick, NJ 08816 Revised: 04/2023 200653 PIR87610-01