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 (426 patients given indapamide 2.5 mg or 5 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 Reactions from Studies of 1.25 mg | 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 | |
| Dizziness | Nervousness |
| Hypertonia |
| RESPIRATORY SYSTEM | |
| Rhinitis | Cough |
| 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 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 | Lightheadedness |
| Dizziness | Drowsiness |
| Fatigue, weakness, loss of energy, lethargy, tiredness or malaise | Vertigo |
| Muscle cramps or spasm, numbness of the extremities | Insomnia |
| Nervousness, tension, anxiety, irritability, or agitation | 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 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 Electrolytes (mEq/L) | Serum Uric Acid | BUN |
| Potassium | Sodium | Chloride | (mg/dL) | (mg/dL) |
| Indapamide 1.25 mg | -0.28 | -0.63 | -2.60 | 0.69 | 1.46 |
| (n=255-257) |
| Placebo | 0.00 | -0.11 | -0.21 | 0.06 | 0.06 |
| (n=263-266) |
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 | BUN |
| Potassium | Sodium | Chloride | (mg/dL) | (mg/dL) |
| Indapamide 2.5 mg | -0.4 | -0.6 | -3.6 | 0.7 | -0.1 |
| (n=76) |
| Indapamide 5 mg | -0.6 | -0.7 | -5.1 | 1.1 | 1.4 |
| (n=81) |
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, sialadentis, xanthopsia.
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