Lozol (Indapamide) - Side Effects and Adverse Reactions

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 Lozol 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

Incidence ≥ 5%	Incidence < 5%OTHER
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

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	Vertigo
of energy, lethargy, tiredness, or malaise	Insomnia
Muscle cramps or	Depression
spasm, or numbness of the extremities	Blurred Vision
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 Electrolytes (mEq/L) Potassium Sodium Chloride			Serum Uric Acid (mg/dL)	BUN (mg/dL)
Indapamide   1.25 mg   (n=255–257)	– 0.28	– 0.63	– 2.60	0.69	1.46
Placebo   (n=263–266)	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 5.0 mg
	Serum Electrolytes (mEq/L) Potassium Sodium Chloride			Serum Uric Acid (mg/dL)	BUN (mg/dL)
Indapamide   2.5 mg (n=76)	– 0.4	– 0.6	– 3.6	0.7	– 0.1
Indapamide   5.0 mg (n=81)	– 0.6	– 0.7	– 5.1	1.1	1.4

The following reactions have been reported with clinical usage of Lozol: 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.

REPORTS OF SUSPECTED LOZOL SIDE EFFECTS / ADVERSE REACTIONS

Possible Lozol side effects / adverse reactions in 55 year old female

Reported by a consumer/non-health professional from United States on 2011-10-12

Patient: 55 year old female

Reactions: Memory Impairment, Cardiac Disorder

Suspect drug(s):
Valsartan
    Dosage: 160 mg , 1 d, oral
    Administration route: Oral
    Indication: Hypertension
    Start date: 2002-01-01

Bupropion HCL
    Dosage: 300 mg, 1 d, oral
    Administration route: Oral
    Indication: Depression

Ventolin
    Dosage: 90 mcg, 2 hr
    Indication: Asthma

Gabapentin
    Dosage: 6 dosage forms (2 dosage forms, 3 in 1 d), oral
    Administration route: Oral
    Indication: Fibromyalgia
    Start date: 2004-01-01

Gabapentin
    Dosage: 6 dosage forms (2 dosage forms, 3 in 1 d), oral
    Administration route: Oral
    Indication: Diabetic Neuropathy
    Start date: 2004-01-01

Vicodin
    Dosage: 4 hr, oral
    Administration route: Oral
    Indication: Arthralgia
    Start date: 2006-01-01

Metformin Hydrodchloride/sitagliptin (Metformin and Sitagliptin)
    Dosage: 1 d, oral
    Administration route: Oral
    Indication: Diabetes Mellitus

Klonopin
    Dosage: 1 mg (0.5 mg, 2 in 1 d),oral
    Administration route: Oral
    Indication: Anxiety

Klonopin
    Dosage: 1 mg (0.5 mg, 2 in 1 d),oral
    Administration route: Oral
    Indication: Panic Attack

Prilosec
    Dosage: 40 mg (20 mg, 2 in d, oral
    Administration route: Oral
    Indication: Gastrooesophageal Reflux Disease

Epipen
    Dosage: transdermal
    Indication: Hypersensitivity

Imiprex (Imipraminoxide Hydrochloride)
    Dosage: 100 mg, as required, oral
    Administration route: Oral
    Indication: Migraine

Nitroglycerin
    Dosage: 0.4 mg, as required, other
    Indication: Chest Pain

Flovent
    Dosage: 220 mcg (110 mcg, 2 in 1 d)
    Indication: Asthma

Simvastatin
    Dosage: oral
    Administration route: Oral
    Indication: Product Used FOR Unknown Indication

Zyrtec
    Dosage: 10 mg (10 mg, 1 in 1 d),oral
    Administration route: Oral
    Indication: Hypersensitivity
    Start date: 2009-01-01

Lozol
    Dosage: 1.25 mg, 1 d, oral
    Administration route: Oral
    Indication: Fluid Retention
    Start date: 2002-01-01

Carafate
    Dosage: 2 gm (1 gm, 2 in 1 d),oral
    Administration route: Oral
    Indication: Gastrooesophageal Reflux Disease

Flonase
    Dosage: 500 mcg, 1 d), nasal
    Indication: Hypersensitivity

Multivitamin
    Dosage: oral
    Administration route: Oral
    Indication: Product Used FOR Unknown Indication

Zanaflex
    Dosage: 4 mg (2 mg, 2 in 1 d), oral
    Administration route: Oral
    Indication: Muscle Spasms
    Start date: 2009-01-01

Lortab
    Dosage: oral
    Administration route: Oral
    Indication: Product Used FOR Unknown Indication

Metofrmin (Metformin)
    Dosage: 500 mg, 1 in d, oral
    Administration route: Oral
    Indication: Diabetes Mellitus

Aggrenox
    Dosage: 2 in 1 d, oral
    Administration route: Oral
    Indication: Product Used FOR Unknown Indication
    Start date: 2009-12-01