Instructions for Indapen SR film-coated tablets with modified release 1.5 mg blister No. 30
Composition
active ingredient: indapamide;
1 tablet contains indapamide 1.5 mg;
excipients: lactose monohydrate, carbomers, hydroxypropylcellulose, magnesium stearate, colloidal anhydrous silicon dioxide, talc;
Opadry II Pink shell (33 G24509): hypromellose, titanium dioxide (E 171), lactose monohydrate, macrogol 3000, glycerol triacetate, iron oxide yellow (E 172), iron oxide red (E 172), iron oxide black (E 172).
Dosage form
Modified-release film-coated tablets.
Main physicochemical properties: film-coated tablets, pale pink, round, biconvex.
Pharmacotherapeutic group
Non-thiazide diuretics with moderately pronounced activity. Antihypertensive agent. ATC code C0ZV A11.
Pharmacological properties
Pharmacodynamics
Indapamide is a diuretic drug. It belongs to the group of non-thiazide sulfonamide derivatives and contains an indole ring. In terms of pharmacological properties, it is close to thiazide diuretics. Like thiazide diuretics, it acts in the proximal part of the distal convoluted tubules of the nephron, where it causes increased excretion of sodium and chlorides and, to a lesser extent, potassium and magnesium, thus increasing the volume of urine excreted.
The hypotensive efficacy of indapamide persists for 24 hours. This effect is characteristic of doses with a moderate diuretic effect.
The antihypertensive properties of indapamide consist in improving arterial elasticity and reducing small artery resistance and total peripheral vascular resistance.
Indapamide reduces left ventricular hypertrophy.
For thiazides and thiazide-like diuretics, a dose has been established above which the therapeutic effect is not enhanced, but at the same time the likelihood of side effects increases. Therefore, if the treatment was ineffective, the dose of the drug should not be increased.
Indapamide also does not affect the concentration of lipids (total cholesterol, low-density lipoprotein cholesterol and triglycerides), does not disrupt glucose metabolism in patients with diabetes mellitus and arterial hypertension.
Pharmacokinetics
Absorption
Indapamide is slowly released from the tablet and is completely absorbed in the gastrointestinal tract. Food slightly accelerates absorption, but does not affect the amount of drug absorbed.
The maximum concentration of the drug in the blood serum is reached approximately 12 hours after administration.
Multiple doses help reduce the difference in serum drug concentration between doses, but there are individual differences.
Distribution
Indapamide is 79% bound to plasma proteins.
The elimination half-life is 14 to 24 hours (average 18 hours).
Saturation is reached after 7 days. Repeated dosing does not lead to accumulation of the drug.
Breeding
Indapamide is excreted from the body mainly in the urine (70%) and feces (22%) in the form of inactive metabolites. Only 5-7% of the dose is excreted in the urine unchanged.
In patients with renal insufficiency, pharmacokinetic parameters do not differ.
Indication
Essential hypertension.
Contraindication
Hypersensitivity to indapamide and/or to other components of the drug or to other sulfonamides.
Severe renal failure.
Hepatic encephalopathy or other severe liver dysfunction.
Hypokalemia.
Interaction with other medicinal products and other types of interactions
Not recommended combinations
Lithium
Increased plasma lithium levels and symptoms of overdose may occur due to decreased lithium excretion (as with a salt-free diet). If diuretic therapy is necessary, careful monitoring of plasma lithium levels and dose adjustment are necessary.
Drugs that should be used with caution with indapamide
Medications that affect heart rhythm and cause torsades de pointes:
group Ia antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide);
group III antiarrhythmic drugs (amiodarone, sotalol, dofetilide, ibutilide);
some antipsychotic medications:
phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoroperazine), benzamides (amisulpiride, sulpiride, sultopride, tiapride),
butyrophenones (droperidol, haloperidol);
others: bepridil, cisapride, diphemanil, erythromycin – intravenously, halofantrine, pentamidine, mizolastine, sparfloxacin, moxifloxacin, vincamine – intravenously.
When using indapamide with the above-mentioned drugs, the risk of ventricular arrhythmias increases, in particular torsades de pointes - paroxysmal ventricular tachycardia of the "pirouette" type (hypokalemia is a risk factor).
Nonsteroidal anti-inflammatory drugs (oral), including selective COX-2 inhibitors and high-dose salicylates (≥ 3 g/day)
Possible reduction in the hypotensive effect of indapamide.
The risk of acute renal failure increases in dehydrated patients (reduced glomerular filtration).
The patient's hydration status should be monitored and renal function should be monitored.
Angiotensin-converting enzyme (ACE) inhibitors
If ACE inhibitors are started when the patient is sodium depleted (especially in patients with renal artery stenosis), there is a risk of a sharp decrease in blood pressure and the development of acute renal failure.
Given that previous treatment with diuretics can cause sodium deficiency, in primary arterial hypertension it is necessary to:
stop taking the diuretic three days before starting ACE inhibitors, and then, if necessary, resume taking the diuretic or
Start treatment with ACE inhibitors at low doses, gradually increasing them.
In congestive heart failure, treatment should be initiated with low doses of ACE inhibitors, preferably after reducing the dose of the diuretic (if possible).
Renal function (creatinine concentration) should be monitored during the first week of treatment with ACE inhibitors.
Other drugs causing hypokalemia
Amphotericin B when administered intravenously, glucocorticosteroids and mineralocorticosteroids (when administered orally), tetracosactide, laxative drugs that stimulate peristalsis.
Increased risk of hypokalemia. Serum potassium concentration should be monitored, especially during concomitant treatment with cardiac glycosides. Laxatives that stimulate intestinal peristalsis should not be taken.
Baclofen
Enhances the antihypertensive effect of indapamide. The patient should be adequately hydrated and renal function monitored.
Digitalis preparations
Hypokalemia and hypomagnesemia contribute to the toxicity of digitalis. It is recommended to monitor the level of potassium, magnesium in the blood plasma and ECG control and, if necessary, adjust the treatment.
Combination treatment that requires attention
Potassium-sparing diuretics (amiloride, spironolactone, triamterene)
If it is advisable to prescribe such a combination to some patients, the possibility of hypokalemia (especially in patients with diabetes mellitus or renal insufficiency) or hyperkalemia cannot be excluded. Monitoring of potassium in the blood plasma, ECG monitoring and, if necessary, adjustment of therapy should be carried out.
Metformin
Metformin may cause lactic acidosis. Acidosis may also develop in patients with functional renal failure due to the use of diuretics, especially loop diuretics. Metformin should not be prescribed if the serum creatinine concentration exceeds 15 mg/L (135 μmol/L) in men and 12 mg/L (110 μmol/L) in women.
Iodine-containing radiopaque agents
In case of dehydration caused by diuretics, the risk of acute renal failure increases, especially after the use of high doses of iodinated radiopaque contrast media. The patient should be adequately hydrated before the use of such media.
Tricyclic antidepressants, neuroleptics
Increased antihypertensive effect and risk of orthostatic hypotension (additive effect).
Calcium salts
Risk of hypercalcemia due to impaired renal calcium excretion.
Cyclosporine, tacrolimus
Risk of increased serum creatinine concentration without change in cyclosporine concentration, even without water or sodium depletion.
Corticosteroids, tetracosatide (taken orally)
Decreased antihypertensive effect (sodium and water retention due to the action of corticosteroids).
Application features
In patients with hepatic insufficiency, thiazide-like diuretics may accelerate the development of hepatic encephalopathy. Indapamide should be discontinued immediately if symptoms of hepatic encephalopathy appear.
Photosensitization
Allergic reactions to light caused by the use of thiazide diuretics and thiazide-like drugs are possible. If a photosensitivity reaction occurs during treatment, the drug should be discontinued. If it is necessary to re-use the diuretic, it is recommended to protect exposed skin areas that may be exposed to sunlight or artificial UV radiation.
Water and electrolyte balance
Serum sodium concentration
Serum sodium levels should be monitored before treatment is initiated and periodically thereafter. Any diuretic therapy may lead to hyponatremia, sometimes with serious consequences. The initial decrease in sodium levels may be asymptomatic, and serum sodium levels should be monitored regularly. These should be more frequently performed in the elderly or in patients with cirrhosis.
Serum potassium concentration
Such drugs should be prescribed with particular caution to patients at highest risk of developing hypokalemia, such as the elderly; debilitated patients; those taking many other medications; patients with malnutrition; patients with cirrhosis of the liver, edema and ascites; ischemic heart disease and heart failure. In hypokalemia, the cardiotoxicity of digitalis drugs and the risk of cardiac arrhythmias increase. Patients with prolonged QT interval, regardless of whether this disorder is congenital or iatrogenic, are at risk. Hypokalemia, like bradycardia, contributes to the development of serious cardiac arrhythmias, especially ventricular fibrillation (torsades de pointes).
During treatment, serum potassium should be monitored regularly. The first measurement should be made in the first week of treatment. If hypokalemia develops, potassium deficiency should be replenished. Hypokalemia associated with low serum magnesium may be difficult to treat if serum magnesium levels are not corrected.
Magnesium in blood plasma
Thiazides and related diuretics, including indapamide, have been shown to increase urinary magnesium excretion, which may lead to hypomagnesemia (see sections 4.5 and 4.8).
Serum calcium concentration
Thiazide and thiazide-like diuretics may reduce urinary calcium excretion, causing mild transient hypercalcemia. Marked hypercalcemia may be due to unrecognized hyperparathyroidism. In such cases, treatment should be discontinued and the patient should be evaluated for parathyroid function.
Blood glucose concentration
In patients with diabetes mellitus, especially with concomitant hypokalemia, serum glucose concentrations should be monitored.
Patients with gout
Patients with hyperuricemia may have a tendency to have an increased frequency of gout attacks.
Kidney function and diuretics
Thiazides and thiazide-like diuretics are effective only in cases of normal or mildly impaired renal function (creatinine concentration < 25 mg/L, i.e. 220 μmol/L in adults). When assessing renal function based on creatinine concentration, the patient's age, sex and body weight should be taken into account.
Hypovolemia, caused by fluid and sodium loss, which may occur at the beginning of diuretic treatment, leads to a decrease in glomerular filtration, which in turn causes an increase in serum urea and creatinine concentrations. This temporary functional renal insufficiency resolves without sequelae in patients with normal renal function, but at the same time may worsen existing renal insufficiency.
Athletes
The drug may cause false positive results in anti-doping tests in athletes.
Choroidal effusion, acute myopia, and secondary angle-closure glaucoma
Drugs containing sulfonamide or sulfonamide derivatives may cause an idiosyncratic reaction resulting in choroidal effusion with visual field defect, transient myopia, and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or eye pain and usually occur within hours to weeks of starting the drug.
Untreated acute angle-closure glaucoma can lead to permanent vision loss. The main treatment is to stop the medication as soon as possible. If the intraocular pressure remains uncontrolled, urgent medical or surgical treatments may be necessary. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.
Excipients
The medicinal product contains lactose, therefore it should not be used in patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption.
Use during pregnancy or breastfeeding
Pregnancy
Diuretics should be avoided in pregnant women and should never be used to treat physiological edema in pregnant women. Diuretics can lead to fetoplacental ischemia with a risk of fetal growth retardation.
Breastfeeding period
The use of indapamide is not recommended during breastfeeding due to data on its penetration into breast milk.
Ability to influence reaction speed when driving vehicles or other mechanisms
Indapen SR does not affect alertness. However, in the event of adverse reactions (see section "Adverse reactions"), including symptoms associated with a decrease in blood pressure, especially at the beginning of treatment or in combination with another antihypertensive agent, the ability to drive a car or operate other mechanisms may be impaired.
Method of administration and doses
For oral use. Indaped SR should be taken 1 tablet per day, preferably in the morning.
The tablets should be swallowed whole with water.
Renal failure (see sections "Special instructions" and "Contraindications")
In patients with severe renal insufficiency (creatinine clearance < 30 ml/min), the use of the drug is contraindicated. Thiazide and thiazide-like diuretics are most effective if renal function is not impaired or if the impairment is minor.
Elderly (see section "Special instructions")
In elderly patients, plasma creatinine should be at a level appropriate for age, body weight and sex. Elderly patients may be given Indapen SR if renal function is not impaired or if the impairment is minor.
Patients with impaired liver function (see sections "Special instructions" and "Contraindications")
In case of severe liver dysfunction, treatment with the drug is contraindicated.
Children
Due to the lack of data on safety and efficacy, the use of the drug in pediatric practice is not recommended.
Overdose
Symptoms of overdose are primarily manifestations of water and electrolyte disturbances (hyponatremia, hypokalemia). Clinically, nausea, vomiting, hypotension, convulsions, drowsiness, dizziness (vertigo), confusion, polyuria or oliguria up to anuria (caused by hypovolemia) are possible.
First aid measures include rapid drug elimination by gastric lavage and/or administration of activated charcoal, followed by restoration of fluid and electrolyte balance in a hospital setting.
Side effects
The most frequently reported adverse reactions were hypokalemia, hypersensitivity reactions, mainly dermatological, in individuals with a predisposition to allergic and asthmatic reactions, and maculopapular rashes.
Most of the undesirable effects, detected both by clinical signs and laboratory parameters, are dose-dependent.
Thiazide-like diuretics, including indapamide, may cause side effects listed below by frequency: very common (≥ 1/10), common (≥ 1/100, <1/10), uncommon (≥ 1/1000, <1/100), rare (≥ 1/10000), very rare (<1/10000), frequency unknown (cannot be estimated from the available information).
Blood and lymphatic system disorders
Very rare: thrombocytopenia, leukopenia, agranulocytosis, aplastic anemia, hemolytic anemia.
Neurological disorders
Rarely – dizziness (vertigo), fatigue, headache, paresthesia;
frequency unknown – fainting.
Cardiac disorders
Very rare – arrhythmia, arterial hypotension;
frequency unknown - paroxysmal ventricular tachycardia of the "pirouette" type (torsades de pointes), which can be fatal (see sections "Special instructions", "Interaction with other medicinal products and other types of interactions").
Gastrointestinal tract
Uncommon: vomiting;
rarely - nausea, constipation, dry mouth;
very rarely - pancreatitis.
From the urinary system
Very rare - renal failure.
Hepatobiliary system
Very rare - liver dysfunction;
frequency unknown – in case of liver failure, hepatic encephalopathy may occur (see sections “Special instructions for use”, “Contraindications”), hepatitis.
Skin and subcutaneous tissue disorders
Hypersensitivity reactions, mainly of the skin, in patients with a predisposition to allergic and asthmatic reactions:
often – maculopapular rashes;
infrequently – purpura;
very rarely - angioedema and/or urticaria, toxic epidermal necrolysis, Stevens-Johnson syndrome;
frequency unknown - possible exacerbation of existing acute systemic lupus erythematosus. Cases of photosensitivity reactions have been reported (see section "Special warnings and precautions for use").
From the organs of vision
frequency unknown - myopia, blurred vision, visual impairment, choroidal effusion.
Research
Frequency unknown - prolongation of the QT interval on the electrocardiogram (see sections "Special instructions for use", "Interaction with other medicinal products and other types of interactions"); increased levels of uric acid and glucose in the blood plasma during treatment with diuretics, the rationality of their administration should be carefully weighed before prescribing to patients with gout or diabetes mellitus; increased levels of liver enzymes.
From the side of metabolism, metabolism
Common: hypokalemia (see section "Special warnings and precautions for use").
Uncommon: hyponatremia (see section "Special warnings and precautions for use").
Rarely – hypochloremia, hypomagnesemia.
Very rare: hypercalcemia.
Reproductive system and breast disorders
Uncommon: erectile dysfunction.
Description of selected adverse reactions
In phase II and III studies, a dose-dependent effect of indapamide on plasma potassium levels was observed when comparing doses of indapamide 1.5 mg and 2.5 mg:
Indapamide 1.5 mg: Plasma potassium levels <3.4 mmol/L were observed in 10% of patients and <3.2 mmol/L in 4% of patients after 4-6 weeks of treatment. After 12 weeks of treatment, the mean decrease in plasma potassium levels was 0.23 mmol/L.
Indapamide 2.5 mg: Plasma potassium levels <3.4 mmol/L were observed in 25% of patients and <3.2 mmol/L in 10% of patients after 4-6 weeks of treatment. After 12 weeks of treatment, the mean decrease in plasma potassium levels was 0.41 mmol/L.
Expiration date
Storage conditions
Store in a dry, dark place at a temperature below 25 ° C. Keep out of the reach of children.
Packaging
14 tablets in a blister, 2 blisters or 4 blisters in a cardboard box.
15 tablets in a blister, 2 blisters or 4 blisters in a cardboard box.
Vacation category
According to the recipe.
Producer
Pharmaceutical Works «POLPHARMA» SA/Pharmaceutical Works «POLPHARMA» SA
Location of the manufacturer and its business address
19, Pelplinska Str., 83-200 Starogard Gdanski, Poland.
