Side Effects of Lozol (indapamide)

Lozol (indapamide) is a diuretic (water pill) used primarily to treat high blood pressure (hypertension) and accumulation of excess fluid (edema), which may result from congestive heart failure. 

Lozol works by preventing the kidney from reabsorbing (retaining in the body) salt and water that is destined to be eliminated in the urine. This results in increased urine output (diuresis). It is also thought to reduce the salt in the smooth muscle of the walls of blood vessels. (The salt ultimately is eliminated in the urine.) 

The loss of salt from the muscle causes the muscle to relax, and the relaxation of the vessels results in reduced blood pressure. The brand name Lozol is discontinued; generic indapamide is available. 

Common side effects of Lozol include

• dehydration and low blood potassium due to elimination of potassium in the urine (hypokalemia), which causes abnormal cardiac rhythms and weakness.
• Low blood magnesium (hypomagnesemia) may also occur.

Other important side effects of Lozol include

• low blood pressure,
• excessive loss of sodium (particularly of concern in elderly patients),
• increased cholesterol (this effect tends to diminish with continued use),
• increased blood glucose,
• increased uric acid concentrations in the blood,
• dizziness,
• lightheadedness,
• headache,
• blurred vision,
• tingling of the extremities,
• nervousness,
• impotence,
• rash,
• photosensitivity (skin rashes due to sunlight),
• fatigue,
• irritability, and
• agitation.

Drug interactions of Lozol include digoxin, because like other diuretics, Lozol can cause low potassium and low magnesium, which can increase the risk of digoxin toxicity, possibly resulting in fatal abnormal heart rhythms. 

Use of amiodarone and indapamide also can lead to cardiac arrhythmias. The ability of the kidney to eliminate lithium is decreased in patients receiving diuretics, including indapamide. The use of these two drugs together could result in lithium toxicity. 

The use of Lozol in pregnancy has not been well studied. Physicians may elect to use it if its benefits are judged to outweigh its potential risks. 

The use of Lozol in nursing mothers has not been studied. Consult your doctor before breastfeeding.

Common adverse side effects of indapamide are dehydration, and hypokalemia (low blood potassium due to elimination of potassium in the urine), which causes abnormal cardiac rhythms. The most common symptom associated with hypokalemia is muscle weakness. Patients receiving indapamide may need potassium supplements to prevent hypokalemia. Hypomagnesemia (low blood magnesium) also may occur.

Other important side effects include:

• low blood pressure,
• excessive loss of sodium (particularly of concern in elderly patients),
• increased cholesterol (this effect tends to diminish with continued use),
• increased blood glucose,
• increased uric acid concentrations in the blood,
• dizziness,
• lightheadedness,
• headache,
• blurred vision,
• tingling of the extremities,
• nervousness,
• impotence,
• rash,
• photosensitivity (skin rashes due to sunlight),
• fatigue,
• irritability, and
• agitation.

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 Lozol (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 Reactions from Studies of 1.25 mg

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

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.

No patients receiving indapamide 1.25 mg experienced hyponatremia considered possibly clinically significant ( < 125 mEq/L). Indapamide had no adverse effects on lipids.

The following reactions have been reported with clinical usage of Lozol (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, and
• xanthopsia.

Other Antihypertensives

• Lozol (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 prescribing information.

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.