Arifam, 10 mg+1.5 mg 30 pcs

Mechanism of action

Amlodipine is a calcium ion influx inhibitor, dihydropyridine derivative (slow calcium channel blocker, or calcium ion antagonist), which inhibits transmembrane influx of calcium ions into cardiomyocytes and smooth muscle cells of the vascular wall. The mechanism of antihypertensive action of amlodipine is due to direct relaxing effect on vascular smooth muscle.

Indapamide is a sulfonamide derivative with an indole ring, belonging to the pharmacological group of thiazide-like diuretics. It acts by reducing sodium reabsorption in the cortical segment of the nephron loop. Indapamide increases urinary excretion of sodium and chloride and, to a lesser extent, excretion of potassium and magnesium, thereby increasing diuresis and having antihypertensive effect.

Pharmacodynamic effects

In patients with arterial hypertension, administration of amlodipine once daily provides clinically significant BP reduction in the supine and standing position for 24 hours. Due to the slow development of the effect, amlodipine usually does not cause acute hypotension.

Amlodipine has no adverse effect on lipid metabolism and does not cause changes in plasma lipid profile, therefore it is suitable for use in patients with bronchial asthma, diabetes mellitus and gout.

The antihypertensive activity of indapamide is associated with improvement of elastic properties of arteries and reduction of arteriolar and total peripheral vascular resistance.

In phase II and phase III clinical studies, a 24-hour hypotensive effect has been demonstrated when using indapamide in monotherapy at doses with no pronounced diuretic effect.

Indapamide reduces left ventricular hypertrophy.

Indapamide increases the dose of thiazide diuretics above the defined ones are accompanied by achievement of a plateau of therapeutic effect, but are accompanied by the occurrence of adverse reactions. If therapy does not produce the desired therapeutic effect, the drug dose should not be increased.

Indapamide has also been shown with short-, medium-, and long-term use in patients with arterial hypertension to:

• not affect parameters of lipid metabolism, including triglyceride levels.including triglyceride, cholesterol, LDL and HDL levels;
• does not affect parameters of carbohydrate metabolism, including in patients with diabetes.

Pharmacokinetics

Indications

arterial hypertension in patients who require therapy with amlodipine and indapamide.

Pharmacological effect

Mechanism of action

Amlodipine is a calcium influx inhibitor, a dihydropyridine derivative (slow calcium channel blocker, or calcium ion antagonist), which inhibits the transmembrane influx of calcium ions into cardiomyocytes and smooth muscle cells of the vascular wall. The mechanism of the antihypertensive effect of amlodipine is due to a direct relaxing effect on vascular smooth muscle.

Indapamide is a sulfonamide derivative with an indole ring, belonging to the pharmacological group of thiazide-like diuretics. Acts by reducing sodium reabsorption in the cortical segment of the nephron loop. Indapamide increases the urinary excretion of sodium and chloride and, to a lesser extent, the excretion of potassium and magnesium, thereby increasing diuresis and exerting an antihypertensive effect.

Pharmacodynamic effects

In patients with arterial hypertension, taking amlodipine 1 time per day provides a clinically significant decrease in blood pressure in the supine and standing position for 24 hours. Due to the slow development of the effect, amlodipine usually does not cause acute hypotension.

Amlodipine does not have undesirable effects on lipid metabolism and does not cause changes in the lipid profile of the blood plasma, so it is suitable for use in patients with bronchial asthma, diabetes mellitus and gout.

The antihypertensive activity of indapamide is associated with an improvement in the elastic properties of arteries and a decrease in arteriolar and total peripheral vascular resistance.

In phase II and III clinical studies, a 24-hour hypotensive effect was demonstrated when indapamide was used as monotherapy at doses that did not have a pronounced diuretic effect.

Indapamide reduces left ventricular hypertrophy of the heart.

Increasing the dose of thiazide diuretics above certain levels is accompanied by the achievement of a plateau of the therapeutic effect, but is accompanied by the occurrence of adverse reactions. If therapy does not lead to the desired therapeutic effect, the dose of the drug should not be increased.

Indapamide has also been shown to: with short-term, intermediate-term and long-term use in patients with hypertension:

does not affect lipid metabolism indicators, incl. on the level of triglycerides, cholesterol, LDL and HDL;
does not affect carbohydrate metabolism, incl. in patients with diabetes mellitus.

Pharmacokinetics

Special instructions

Hepatic encephalopathy

If liver function is impaired, thiazide-like diuretics can cause hepatic encephalopathy, especially in the case of electrolyte imbalance. Due to the presence of indapamide in the composition, if this phenomenon develops, the use of Arifam® should be stopped immediately.

Photosensitivity

Cases of photosensitivity reactions have been described when taking thiazide and thiazide-like diuretics (see section “Side effects”). If a photosensitivity reaction occurs during treatment, it is recommended to discontinue treatment. If re-administration of a diuretic is considered necessary, it is recommended to protect exposed parts of the body from exposure to the sun or artificial ultraviolet rays.

Hypertensive crisis

The safety and effectiveness of amlodipine in hypertensive crisis have not been established.

Water and electrolyte balance

Content of sodium ions in blood plasma. Before starting treatment, it is necessary to determine the content of sodium ions in the blood plasma. While taking the drug, this indicator should be regularly monitored. All diuretics can cause hyponatremia, which sometimes leads to serious complications. Hyponatremia at the initial stage may not be accompanied by clinical symptoms, so regular laboratory monitoring is necessary. More frequent monitoring of sodium ion levels is indicated in elderly patients and patients with liver cirrhosis (see sections “Side effects” and “Overdose”).

Content of potassium ions in blood plasma. Potassium depletion with the development of hypokalemia is the main risk associated with thiazide and thiazide-like diuretics. It is necessary to prevent the development of hypokalemia (<3.4 mmol/l) in high-risk patients, namely, elderly, debilitated and/or receiving concomitant drug therapy, patients with liver cirrhosis, peripheral edema and ascites, coronary artery disease, and heart failure. In such patients, hypokalemia increases the cardiotoxicity of cardiac glycosides and the risk of arrhythmia.

Persons with a long QT interval are also at risk, regardless of the origin of this disorder – congenital or iatrogenic. Hypokalemia, as well as bradycardia, are factors contributing to the occurrence of severe arrhythmias, in particular the potentially fatal tachycardia of the torsade de pointes type.

In all of the above situations, it is necessary to measure the concentration of potassium in the blood plasma more often. The first measurement of the level of potassium ions in the blood plasma should be carried out within the first week from the start of treatment.

If hypokalemia occurs, appropriate treatment should be prescribed.

Calcium content in blood plasma. Thiazide and thiazide-like diuretics may reduce urinary calcium excretion and cause a slight and temporary increase in plasma calcium levels. True hypercalcemia may be associated with previously undiagnosed hyperparathyroidism. Treatment should be discontinued until parathyroid function is examined.

Plasma glucose levels

Due to the presence of indapamide, it is necessary to monitor blood glucose levels in patients with diabetes mellitus, especially in the presence of hypokalemia.

Heart failure

In patients with heart failure, treatment should be carried out with caution. In a long-term placebo-controlled study in patients with severe heart failure (NYHA class III and IV), the incidence of pulmonary edema was higher in the amlodipine group than in the placebo group. Calcium channel blockers, incl. amlodipine should be used with caution in patients with congestive heart failure as it may increase the risk of cardiovascular events and death.

Kidney function

Thiazide and thiazide-like diuretics are fully effective only with normal or slightly impaired renal function (plasma creatinine level below 25 mg/l, i.e. 220 µmol/l in adult patients). In elderly patients, normal plasma creatinine levels should be calculated according to age, body weight and sex.

At the beginning of treatment, patients may experience a decrease in GFR due to hypovolemia, which, in turn, is caused by the loss of water and sodium ions while taking diuretics. This may lead to increased concentrations of urea and creatinine in the blood plasma. Such transient functional renal failure has no clinical significance if renal function is normal, but may worsen pre-existing renal failure.

In patients with renal failure, amlodipine can be used in normal doses. Changes in plasma concentrations of amlodipine do not correlate with the degree of renal dysfunction. Amlodipine is not excreted from the body by dialysis.

The effects of the combination drug Arifam® in renal impairment have not been studied. If renal function is impaired, the dose of the drug should be selected taking into account the content of individual components.

Uric acid

Due to the presence of indapamide, patients with hyperuricemia may have an increased risk of developing gout attacks.

Liver function

In patients with impaired liver function, T1/2 and AUC of amlodipine increase. Dosing recommendations for these patients have not been established. Taking amlodipine should be started with the lowest doses and precautions should be taken both at the beginning of treatment and when increasing the dose.

The effects of combined administration of amlodipine + indapamide in liver dysfunction have not been studied. Taking into account the effects of separate use of indapamide and amlodipine, Arifam® is contraindicated for use in patients with severe hepatic impairment; caution should be used in the treatment of patients with mild to moderate hepatic impairment.

Elderly patients

Elderly patients can take Arifam® taking into account renal function (see sections “Dosage regimen” and “Pharmacological action”).

Excipients

Arifam® should not be used to treat patients with rare hereditary diseases associated with galactose intolerance, lactase deficiency and glucose-galactose malabsorption.

Impact on the ability to drive vehicles and operate machinery

Arifam® has a slight or moderate effect on the ability to drive vehicles and operate machinery.

Amlodipine has a slight or moderate effect on the ability to drive vehicles and operate machinery. If patients receiving amlodipine experience dizziness, headache, fatigue or nausea, the ability to respond may be impaired. Caution is recommended, especially at the beginning of treatment.

Indapamide does not affect alertness, but in isolated cases, various reactions associated with a decrease in blood pressure may occur, especially at the beginning of treatment or when another antihypertensive drug is added. As a result, the ability to drive vehicles and operate machinery may be impaired.

Active ingredient

Amlodipine, Indapamide

Composition

Modified-release, pink, round, biconvex film-coated tablets with company logo engraved on one side.

1 tab.
amlodipine besylate
13.87 mg,
which corresponds to the content of amlodipine
10 mg
indapamide
1.5 mg

Excipients:

hypromellose-4 thousand – 84 mg,

lactose monohydrate – 104.5 mg,

magnesium stearate – 2.05 mg,

povidone K-30 – 8.6 mg,

colloidal silicon dioxide – 0.82 mg,

calcium hydrogen phosphate dihydrate – 56.7 mg,

microcrystalline cellulose – 121.16 mg,

croscarmellose sodium – 10.5 mg,

pregelatinized corn starch – 6.3 mg.

Film shell composition:

glycerol – 0.61992 mg, hypromellose-6 thousand – 10.30445 mg, macrogol-6000 – 0.65797 mg, magnesium stearate – 0.61992 mg, titanium dioxide (E171) – 1.75162 mg, red iron oxide dye (E172) – 0.23213 mg.

Contraindications

severe renal failure (creatinine clearance <30 ml/min); severe liver failure or hepatic encephalopathy; hypokalemia; severe hypotension; shock (including cardiogenic shock); obstruction of the left ventricular outflow tract (for example, high-grade aortic stenosis); heart failure after acute myocardial infarction with unstable hemodynamics; galactose intolerance, lactase deficiency or glucose-galactose malabsorption (since the drug contains lactose); breastfeeding period; children under 18 years of age; hypersensitivity to the active substances, other sulfonamides, dihydropyridine derivatives or any of the excipients.

The drug should be prescribed with caution when there is a decrease in blood volume (taking diuretics, a salt-free diet, vomiting, diarrhea), patients with mild to moderate liver dysfunction, peripheral edema and ascites, with ischemic heart disease, chronic heart failure, patients with an extended QT interval, with bradycardia, chronic heart failure of functional class III-IV according to the NYHA classification, diabetes mellitus, renal artery stenosis (in including bilateral), patients with a single functioning kidney, with renal failure, gout, and elderly patients.

Side Effects

The most commonly observed adverse reactions during treatment with amlodipine and indapamide include drowsiness, dizziness, headache, palpitations, facial flushing, abdominal pain, nausea, leg swelling, edema and fatigue.

During treatment with amlodipine and indapamide, the following adverse reactions were observed. The frequency is classified as follows: very common (≥1/10); often (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10,000, <1/1000); very rare (< 1/10,000), frequency unknown (frequency cannot be estimated from available data).

Adverse reactions
Frequency
Indapamide
Amlodipine
From the blood and lymphatic system
Leukocytopenia
Very rarely
Very rarely
Thrombocytopenia
Very rarely
Very rarely
Agranulocytosis
Very rarely
–
Aplastic anemia
Very rarely
–
Hemolytic anemia
Very rarely
–
From the immune system
Allergic reactions
–
Very rarely
Metabolism and nutrition
Hypokalemia
Often
In clinical studies, hypokalemia (plasma potassium levels <3.4 mmol/L) was observed in 10% of patients and levels <3.2 mmol/L in 4% of patients after 4–6 weeks of treatment. After 12 weeks of treatment, the average decrease in plasma potassium levels was 0.23 mmol/l (see section "Special Instructions") - Hyperglycemia - Very rarely Hypercalcemia Very rarely - Hyponatremia with hypovolemia1 Frequency unknown - Mental disorders Insomnia - Uncommon Mood changes (including anxiety) - Uncommon Depression - Uncommon Confusion - Rarely From the nervous system Drowsiness - Often (especially at the beginning of treatment) Dizziness - Often (especially at the beginning of treatment) Headache Rarely Often (especially at the beginning of treatment) Tremor - Uncommon Taste changes - Uncommon Fainting Frequency unknown Uncommon Decreased sensitivity - Uncommon Paresthesia Rarely Uncommon Vertigo Rarely - Hypertonicity - Very rarely Peripheral neuropathy - Very rarely From the side of the organ of vision Visual impairment (including diplopia) - Uncommon Myopia Frequency unknown - Blurred vision Frequency unknown - Decreased visual acuity Frequency unknown - Hearing and labyrinth disorders Tinnitus - Uncommon From the side of the heart Heartbeat - Often Myocardial infarction - Very rarely Arrhythmia (including bradycardia, ventricular tachycardia and atrial fibrillation) Very rarely Very rarely Torsade de pointes (potentially fatal) tachycardia Frequency unknown (see sections "Drug interactions" and "Special instructions") - From the side of blood vessels Rush of blood to the skin of the face - Often Arterial hypotension Very rarely Uncommon Vasculitis - Very rarely From the respiratory system Dyspnea - Uncommon Rhinitis - Uncommon Cough - Very rarely From the digestive system Abdominal pain - Often Nausea Rarely Often Vomit Uncommon Uncommon Dyspepsia - Uncommon Changes in bowel function (including diarrhea and constipation) - Uncommon Dry mouth Rarely Uncommon Pancreatitis Very rarely Very rarely Gastritis - Very rarely Gingival hyperplasia - Very rarely Constipation Rarely Uncommon From the liver and biliary tract Hepatitis Frequency unknown Very rarely Jaundice - Very rarely Increased liver enzyme activity Frequency unknown Very rarely2 Liver dysfunction Very rarely - Possible development of hepatic encephalopathy in case of liver failure Frequency unknown (see sections "Contraindications" and "Special instructions") - From the skin and subcutaneous tissue Maculopapular rash Often - Purpura Uncommon Uncommon Alopecia - Uncommon Change in skin color - Uncommon Hyperhidrosis - Uncommon Itching - Uncommon Skin rash - Uncommon Exanthema - Uncommon Angioedema Very rarely Very rarely Hives Very rarely Very rarely Toxic epidermal necrolysis Very rarely - Stevens-Johnson syndrome Very rarely Very rarely Erythema multiforme - Very rarely Exfoliative dermatitis - Very rarely Quincke's edema - Very rarely Photosensitivity Cases of photosensitivity reactions have been described (see section "Special instructions") Very rarely Possible exacerbation of existing acute SLE Frequency unknown - From the musculoskeletal and connective tissue side Swelling of the legs - Often Arthralgia - Uncommon Myalgia - Uncommon Muscle spasms - Uncommon Back pain - Uncommon From the urinary system Urinary dysfunction - Uncommon Nocturia - Uncommon Increased frequency of urination - Uncommon Kidney failure Very rarely - From the genital organs and breast Impotence - Uncommon Gynecomastia - Uncommon Common disorders and symptoms Edema - Often Increased fatigue Rarely Often Chest pain - Uncommon Asthenia - Uncommon Pain - Uncommon Malaise - Uncommon Laboratory and instrumental data Weight gain - Uncommon Weight loss - Uncommon Prolongation of the QT interval on the electrocardiogram Frequency unknown (see sections "Drug interactions" and "Special instructions") - Increased uric acid and blood glucose levels during treatment Frequency unknown
The appropriateness of these diuretics in patients with gout or diabetes mellitus should be carefully evaluated.
–

1 leads to dehydration and orthostatic hypotension. Concomitant loss of chlorine ions can lead to secondary compensatory metabolic alkalosis: the frequency and severity of this effect are insignificant.

2 most often in combination with cholestasis.

Exceptionally rare cases of extrapyramidal syndrome have been observed with the use of amlodipine.

Interaction

Amlodipine

Dantrolene (IV administration): Ventricular fibrillation and cardiovascular collapse with a fatal outcome were observed in animals due to hyperkalemia after administration of verapamil and IV administration of dantrolene. Due to the risk of hyperkalemia, it is recommended to avoid the concomitant use of calcium channel blockers such as amlodipine in patients with a predisposition to malignant hyperthermia, as well as in the treatment of malignant hyperthermia.

Taking amlodipine with grapefruit or grapefruit juice is not recommended as the bioavailability of amlodipine may be increased in some patients, resulting in increased blood pressure lowering effects.

Cytochrome CYP3A4 inhibitors: Concomitant use of amlodipine with strong or moderate CYP3A4 inhibitors (protease inhibitors, azole antifungals, macrolides such as erythromycin or clarithromycin, verapamil or diltiazem) may lead to a significant increase in amlodipine concentrations. Clinical manifestations of these pharmacokinetic abnormalities may be more pronounced in elderly patients. Monitoring of clinical status and dose adjustment may be required.

CYP3A4 inducers: There is no information on the effect of CYP3A4 inducers on amlodipine. Concomitant use of CYP3A4 inducers (for example, rifampicin, St. John’s wort) may lead to a decrease in the plasma concentration of amlodipine. Amlodipine should be used with caution in combination with CYP3A4 inducers.

Effect of amlodipine on other drugs

Amlodipine has an additional hypotensive effect when taken simultaneously with other drugs that have antihypertensive effects.

In clinical drug interaction studies, amlodipine did not affect the pharmacokinetics of atorvastatin, digoxin, warfarin or cyclosporine.

Simvastatin: Concomitant use of multiple doses of amlodipine 10 mg and simvastatin 80 mg resulted in a 77% increase in simvastatin concentrations compared to simvastatin monotherapy. In patients receiving amlodipine, the dose of simvastatin should not exceed 20 mg/day.

Indapamide

Combinations of drugs whose use is not recommended

Lithium preparations

With the simultaneous use of indapamide and lithium preparations, an increase in the level of lithium in the blood plasma may be observed with signs of overdose, as with a salt-free diet (reduced excretion of lithium in the urine). However, if the use of diuretics is necessary, careful monitoring of plasma lithium and dosage adjustment is required.

Combinations that require precautions when using

Drugs that cause tachycardia of the “pirouette” type:

class IA antiarrhythmic drugs (quinidine, hydroquinidine, disopyramide);
class III antiarrhythmic drugs (amiodarone, sotalol, dofetilide, ibutilide);
some antipsychotic drugs: phenothiazines (chlorpromazine, cyamemazine, levomepromazine, thioridazine, trifluoroperazine), benzamides (amisulpride, sulpiride, sultopride, tiapride), butyrophenones (droperidol, haloperidol);
others: bepridil, cisapride, difemanil, erythromycin for intravenous administration, halofantrine, mizolastine, pentamidine, sparfloxacin, moxifloxacin, vincamycin for intravenous administration.

Increased risk of ventricular arrhythmias, especially torsade de pointes (hypokalemia as a risk factor)

Before prescribing drugs that cause tachycardia of the “pirouette” type while taking the drug Arifam®, a study should be conducted to identify hypokalemia and make correction if necessary. Monitoring of clinical status, plasma electrolytes and ECG is required.

In the presence of hypokalemia, drugs that do not cause torsade de pointes should be used.

NSAIDs (systemic use), including selective COX-2 inhibitors, salicylic acid in high doses (≥3 g/day)

Possible reduction in the antihypertensive effect of indapamide. The risk of developing acute renal failure in patients with dehydration (reduced glomerular filtration). At the beginning of treatment, hydration and monitoring of renal function should be carried out.

ACE inhibitors

Risk of sudden hypotension and/or acute renal failure at the start of treatment with an ACE inhibitor against the background of an already existing decrease in sodium levels (especially in patients with renal artery stenosis).

For arterial hypertension, if previous treatment with diuretics could cause a decrease in sodium levels, it is necessary:

3 days before starting treatment with an ACE inhibitor, stop taking diuretics. In the future, if necessary, diuretics can be resumed;
or prescribe an ACE inhibitor at a low initial dose and gradually increase the dose.

In chronic heart failure, treatment with ACE inhibitors should begin with low doses with a possible preliminary reduction in the doses of diuretics.

In all cases, renal function (plasma creatinine level) should be monitored during the first weeks of treatment with an ACE inhibitor.

Other drugs that cause hypokalemia: amphotericin B (iv), gluco- and mineralocorticoids (systemic), tetracosactide, laxatives that stimulate intestinal motility

Increased risk of hypokalemia (additive effect). Plasma potassium concentrations should be monitored and, if necessary, corrected. This is especially true with concomitant treatment with cardiac glycosides. Laxatives that do not stimulate intestinal motility should be used.

Cardiac glycosides

Hypokalemia enhances the toxic effects of cardiac glycosides. Plasma potassium concentrations and ECG parameters should be monitored, as well as treatment adjustments if necessary.

Baclofen

Strengthening the antihypertensive effect. At the beginning of treatment, hydration and monitoring of renal function should be carried out.

Allopurinol

Concomitant use with indapamide may increase the risk of hypersensitivity reactions to allopurinol.

Combinations of drugs requiring attention

Potassium-sparing diuretics (amiloride, spironolactone, triamterene)

Although the combination is appropriate in some patients, hypokalemia or hyperkalemia may occur (especially in patients with renal failure and diabetes mellitus). Plasma potassium concentrations and ECG readings should be monitored and treatment reconsidered if necessary.

Metformin

Functional renal failure, which can occur against the background of diuretics, especially loop diuretics, with simultaneous administration of metformin increases the risk of developing lactic acidosis. Metformin should not be used if plasma creatinine levels exceed 15 mg/L (135 µmol/L) in men and 12 mg/L (110 µmol/L) in women.

Iodinated contrast agents

With dehydration caused by diuretics, there is an increased risk of developing acute renal failure, especially when using iodinated contrast agents in high doses. Before administering an iodine-containing drug, fluid loss should be compensated.

Tricyclic antidepressants, antipsychotics

There is an increased risk of orthostatic hypotension and increased antihypertensive effect (additive effect).

Calcium salts

Due to decreased urinary calcium excretion, there is a risk of hypercalcemia.

Cyclosporine, tacrolimus

There is a risk of increased plasma creatinine levels without any change in circulating cyclosporine concentrations, even in the absence of water/sodium loss.

Corticosteroids, tetracosactide (systemic use)

Decreased antihypertensive effect (water/sodium retention due to corticosteroids).

Overdose

There is no information on overdose of Arifam®.

Amlodipine

Information on intentional overdose in humans is limited.

Available data demonstrate that significant overdose can lead to excessive peripheral vasodilation and possibly reflex tachycardia. There have been cases of severe and possibly prolonged systemic hypotension up to the development of shock with a fatal outcome.

In case of clinically significant hypotension due to amlodipine overdose, active support for the functioning of the cardiovascular system is necessary, including frequent monitoring of cardiac and respiratory functions, limb elevation, control of blood volume and diuresis.

To restore vascular tone and blood pressure, the use of vasoconstrictors can be effective in the absence of contraindications to their use. IV administration of calcium gluconate can help reverse calcium channel blockade.

In some cases, gastric lavage may be appropriate. In healthy volunteers, the use of activated charcoal within 2 hours after taking 10 mg of amlodipine led to a decrease in the rate of absorption of amlodipine.

Since amlodipine is highly protein bound, dialysis is unlikely to be effective.

Indapamide

Indapamide did not exhibit toxicity when used in doses up to 40 mg, i.e. 27 times higher than the therapeutic dose.

Signs of acute poisoning are mainly water and electrolyte disturbances (hyponatremia, hypokalemia). The clinical picture may include nausea, vomiting, hypotension, muscle spasms, vertigo, drowsiness, confusion, polyuria or oliguria, possibly even anuria (due to hypovolemia).

Initial emergency measures include rapid elimination of the ingested substance(s) by gastric lavage and/or administration of activated charcoal, followed by restoration of fluid and electrolyte balance to normal in a specialized department.

Storage conditions

The drug should be stored out of the reach of children at a temperature not exceeding 30°C.

Shelf life

2 years.

Manufacturer

Servier Industry Laboratories, France