What Is Indapamide?

Indapamide is a sulfa diuretic, with diuretic and calcium antagonistic effects, and is a powerful and long-acting antihypertensive drug. It is also used clinically for the treatment of water and sodium retention in congestive heart failure.

Indapamide is a sulfa diuretic, with diuretic and calcium antagonistic effects, and is a powerful and long-acting antihypertensive drug. It is also used clinically for the treatment of water and sodium retention in congestive heart failure.

Chinese name

Indapamide

English name

indapamide

nickname

Indamine; indura furosemide; indenesulfenamide

Chemical formula

C16H16ClN3O3S

Molecular weight

365.8345

CAS Registry Number

26807-65-8

Water soluble

Almost insoluble in water.

Density

1.51g / cm3

Exterior

White or off-white powder

Melting point

162-167

Introduction to indapamide compounds

Indapamide Basic Information

Chinese name: indapamide ^[1]

Chinese alias: N- (2-methyl-2,3-dihydro-1H-indolyl)-; 3-sulfamoyl-4-chloro-benzamide; indanamine; indan furosemide; indene Sulfonamide; indapamide; indapam; long-acting hypotensive tablets; sulfonamide indole; meriba; nano-ionization; sodium-ionization;

English name: indapamide

English alias: N- (4-CHLORO-3-SULFAMOYLBENZAMIDO) -2-METHYLINDOLINE; N- [4-CHLORO-3-SULFAMOYL-BENZAMIDOL] -2-METHYLINDOLINE INDAPAMIDE; 1- (4-chloro-3-sulfamoylbenzamido)- 2-methylindoline; 3-dihydro-2-methyl-1h-indol-1-yl) -benzamid; 3- (aminosulfonyl) -4-chloro-n- (2,3-dihydro-2-methyl-1h-indol- 1-yl) benzamide; 4-chloro-n- (2-methyl-1-indolinyl) -3-sulfamoyl-benzamid; 4-chloro-n- (2-methyl-1-indolinyl) -3-sulfamoylbenzamide; bajaten; damide; fludex; indaflex; indamol; ipamix; lozol; natrilix; noranat; s1520; se-1520; tandix; INDAPAMID; Indapamidum; 4-chloro-N- (2-methyl-2,3-dihydro-1H-indol-1 -yl) -3-sulfamoylbenzamide

Indapamide

CAS number: 26807-65-8

EINECS number: 248-012-7

Molecular formula: C ₁₆ H ₁₆ ClN ₃ O ₃ S

Molecular weight: 365.8345

Exact mass: 365.06000

PSA: 100.88000

LogP: 4.32040 ^[2]

Physicochemical properties of indapamide

Traits: white or off-white powder.

Solubility: Almost insoluble in water.

Content: 99% 102%

Melting point: 162-167 ° C

Density: 1.51g / cm ³

Refractive index: 1.693

Stability: stable under normal temperature and pressure

Storage conditions: storeroom ventilated, low temperature and dry

Indapamide Safety Information

Customs Code: 29350009090

WGK Germany: 2

RTECS number: CV2451200 ^[2]

Indapamide Pharmacopoeia Standard

Source (name), content (potency) of indapamide

This product is N- (2-methyl-2,3-dihydro-1H-indolyl) -3-sulfamoyl-4-chloro-benzamide. Calculated on dry basis, containing C16H16ClN3O3S shall not be less than 98.5%.

Indapamide traits

This product is almost white needle-like crystal or crystalline powder; odorless and tasteless.

This product is easily soluble in acetone, glacial acetic acid, soluble in ethanol or ethyl acetate, slightly soluble in chloroform or ether, almost insoluble in water; almost insoluble in dilute hydrochloric acid.

Melting point

The melting point of this product (Appendix VIC of Part Two of the 2010 Pharmacopoeia) is 162 to 167 ° C (the temperature at which the meniscus is formed is taken as the full melting temperature).

Indapamide identification

(1) Take about 50mg of this product, add 3ml of water, shake, add 0.5ml of hydrogen peroxide test solution, shake, heat slightly to near boiling, let cool, filter, add 3 drops of ferric chloride test solution to the filtrate, Shake well, add 1-2 drops of sodium hydroxide test solution, and produce brown-red precipitate.

(2) Take about 50mg of this product, add about 1 ~ 2ml of sodium hydroxide solution (0.4 100) dropwise to make a saturated solution, filter, and add 1 drop of copper sulfate test solution to the filtrate, which will produce a yellow or brown precipitate .

(3) In the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution.

(4) The infrared light absorption spectrum of this product should be the same as that of the control ("Infrared Spectra of Drugs" 192).

Indapamide test

relative substance

Take this product, add an appropriate amount of mobile phase, shake and dissolve it in a hot water bath, and dilute with mobile phase to make a solution containing about 0.5mg per 1ml as a test solution; take an appropriate amount of precision, and dilute with A solution containing about 5 g per 1 ml was prepared as a control solution. According to the chromatographic conditions under the content determination item, take 20 l of the control solution, inject it into the liquid chromatograph, adjust the detection sensitivity, so that the peak height of the main component chromatographic peak is about 20% of the full range, and then accurately measure the test solution and the control. 20l of each solution were injected into the liquid chromatograph respectively, and the retention time of the chromatogram to the peak of the main component was recorded three times. If there is an impurity peak in the chromatogram of the test solution, the area of a single impurity peak should not be greater than 0.5 times the area of the main peak of the control solution ( 0.5%), the sum of the peak areas of each impurity must not be greater than the main peak area of the control solution (1.0%). Any chromatographic peak in the test solution that is less than 0.02 times the area of the main peak of the control solution can be ignored.

Loss on drying

Take this product and dry it at 105 ° C to constant weight, and the weight loss shall not exceed 2.4% (Appendix L of the Pharmacopoeia Part II of the 2010 edition).

Residue on ignition

Take 1.0g of this product and check it according to law (Appendix N of Part Two of the 2010 Pharmacopoeia). The residual residue shall not exceed 0.1%.

Heavy metal

Take the residue left under the burning residue and inspect it according to law (Appendix H of the 2010 edition of the Pharmacopoeia, the second method). The heavy metal must not exceed 10 parts per million.

Determination of indapamide

It was determined by high performance liquid chromatography (Appendix VD of Part Two of the Pharmacopoeia, 2010 Edition).

Chromatographic conditions and system suitability tests

Octadecylsilane-bonded silica gel was used as the filler; methanol-water-glacial acetic acid (45: 55: 0.1) was used as the mobile phase; the detection wavelength was 240nm. Take about 20mg of indapamide reference substance, accurately weigh it, place it in a 100ml volumetric flask, add 5ml of methanol to dissolve, dilute to the mark with mobile phase, shake well, take 5ml of the above solution, add 2ml of 1mol / L sodium hydroxide solution, Shake well, heat in a water bath for 1 hour, let it cool, adjust to neutrality with 1mol / L hydrochloric acid solution, dilute to 50ml with mobile phase, shake well, take 20l, and inject liquid chromatography to make the indapamide peak The retention time is about 12 minutes, and the resolution of the indapamide peak from the degradation product peak with a relative retention time of about 1.26 should be greater than 6.0.

Assay

Take about 20mg of this product, accurately weigh it, put it in a 100ml measuring bottle, add 5ml of methanol to dissolve it, dilute to the mark with mobile phase, shake well, and use it as a stock solution for the test; take a precise amount of 10ml, put it in a 50ml measuring bottle, use The mobile phase was diluted to the mark, shaken, and 20 l was taken, injected into a liquid chromatograph, and the chromatogram was recorded. Another indapamide reference substance was taken and measured in the same way. Calculate the peak area according to the external standard method, and get ^[3] .

Indapamide Category

Antihypertensive drugs.

Indapamide storage

Shaded and sealed.

Indapamide preparation

Indapamide tablets

Indapamide drug description

Indapamide Classification

Circulatory Drugs> Antihypertensive Drugs> Diuretic Antihypertensive Drugs

Indapamide dosage form

Tablet: 2.5mg

Pharmacological effects of indapamide

This drug is a thiazide-like diuretic and an indole derivative ^[1] , which has a diuretic effect and a calcium antagonistic effect. (1) It can relax vascular smooth muscle by blocking calcium inflow, reducing peripheral vascular resistance, and producing a hypotensive effect (while its diuretic effect cannot explain the hypotensive effect, because the dose when the hypotensive effect occurs is much smaller than the diuretic effect The dose). (2) This medicine has little or no effect on cardiac output, heart rate and heart rhythm during hypotension. Long-term medication rarely affects glomerular filtration rate or renal blood flow. (3) This drug exerts a diuretic effect by inhibiting the reabsorption of water and electrolytes in the diluted renal tubular cortex.

Indapamide pharmacokinetics

Oral absorption is fast and complete. The blood concentration reaches 1-2 hours, and the bioavailability is 93%. It is not affected by food. The maximum antihypertensive effect was reached in about 24 hours after a single oral dose; the maximum antihypertensive effect was reached in about 8-12 weeks after repeated administration, and the effect was maintained for 8 weeks. This drug is metabolized in the liver and produces 19 metabolites. The plasma protein binding rate is 71% -79%. This drug also binds to elastin in vascular smooth muscle. The half-life is 14-18 hours. About 70% are excreted by the kidney (of which 7% are prototypical), and 23% are excreted by the gastrointestinal tract.

Indapamide dosage

adult

Oral administration

1. Hypertension: (1) The recommended initial dose is 1.25 mg each time, once a day, taken in the morning. If the effect is not good after 4 weeks, it can be increased to 2.5mg once a day. If the effect is still not good, it can be increased to 5mg once a day after 4 weeks. Generally speaking, for congestive heart failure or hypertension, a daily dose of more than 5 mg will not increase the efficacy. (2) The drug is now available in a low-dose (1.5mg) sustained release dosage form. According to several studies, 1.5 mg slow-release (SR) and 2.5 mg immediate-release (IR) have the same statistical and clinical antihypertensive effect, and both are superior to placebo. However, the incidence of hypokalemia caused by slow-release agents is more than 50% lower than that of immediate-release agents.

2. Edema: The recommended initial dose is 2.5 mg per day in the morning. If the effect is not satisfactory after 1 week, the daily dose can be increased to 5 mg.

Renal insufficiency dose

Although only 5% of this drug is excreted from the urine in its original form, azotemia can be aggravated by a decrease in blood volume, so patients with impaired renal function should use this drug with caution. If progressive renal impairment occurs during treatment, drug withdrawal should be considered. The diuretic effect of this drug decreases with decreasing renal function.

Hepatic insufficiency dose

This drug is extensively metabolized in the liver, and patients with liver disease should consider reduction.

Elderly dose

Elderly patients can well tolerate the regular dose of 2.5 mg daily. After a single daily dose stabilizes arterial blood pressure, a maintenance dose of 2.5 mg can be taken once every other day.

Indapamide precautions

1. Contraindications (1) Severe renal insufficiency. (2) Hepatic encephalopathy or severe liver dysfunction. (3) Hypokalemia. (4) Allergic to this medicine and sulfa drugs (foreign data).

2. Use with caution (1) Diabetes. (2) Liver insufficiency. (3) Gout or hyperuricemia. (4) The elderly. (5) Electrolyte disorders (such as hyponatremia and hypercalcemia) (foreign data). (6) Systemic lupus erythematosus (foreign data).

3. The effects of drugs on children have not been studied.

4. The effects of the drug on the elderly The elderly are more sensitive to antihypertensive effects and changes in electrolytes, and often have changes in renal function. Pay attention when using this medicine.

5. Effects of drugs on pregnancy No problems have been found in animal studies and human studies are still lacking.

6. Effects of the drug on breastfeeding Whether this drug is excreted into breast milk is unclear, but no problems have been found in human application.

7. The effect of the drug on the test value or diagnosis (1) Plasma renin activity and uric acid can be increased when the drug is used, but the latter is usually within the normal range. (2) Serum calcium, protein-bound iodine, blood potassium, and blood sodium can be reduced, but the changes of the latter two are usually within the normal range. (3) This medicine can make athletes doping test positive.

8. Check and monitor the blood glucose, urea nitrogen, uric acid, blood pressure and blood electrolytes regularly before and after the medication and during the medication.

Indapamide adverse reactions

1. Digestive system is less common with diarrhea, loss of appetite, nausea, and occasionally dry mouth, nausea, constipation, etc.

2. Orthostatic hypotension, palpitations, and arrhythmias are rare in the cardiovascular system.

3. Less nervous system headache, insomnia, occasional dizziness, paresthesia and so on.

4. Rarely metabolized hyponatremia, hypokalemia, hypochloric alkalosis.

5. Rare skin, itching and other allergic reactions.

[Reference of adverse reactions abroad]

1. Blood system in vitro experiments show that the drug can inhibit platelet aggregation.

2. Cardiac arrhythmias, ventricular palpitations and orthostatic hypotension are common in the cardiovascular system.

3. There are reports of dizziness, headache, dizziness, paresthesia and fatigue in the central nervous system.

4. Endocrine system This drug can cause a significant increase in blood uric acid levels and worsening gout. It has been reported that this drug can aggravate impaired glucose tolerance in uncontrolled diabetic patients. This drug has been reported to cause hyperosmolar non-ketogenic diabetic coma.

5. Metabolism This medicine can cause hypokalemia, and the plasma potassium level should be monitored during treatment and potassium supplementation if necessary. The drug can also cause hyponatremia and hypochloremia, and even metabolic encephalopathy (clinical manifestations of vomiting, drowsiness, stiffness, coma and seizures, etc.).

6. The gastrointestinal tract can cause nausea, vomiting, anorexia, abdominal pain, constipation, diarrhea and other gastrointestinal discomforts.

7. Urogenital system can cause or aggravate azotemia (renal insufficiency). There are also reports of frequent urination, nocturia and impotence caused by this drug.

8. Respiratory system can cause runny nose.

9. Skin rashes such as urticaria, itching, nodular vasculitis, and skin redness are common. Cases of severe erythema polymorphic drug eruption and toxic epidermolysis and necrosis have been reported.

Indapamide drug interactions

1. Combination with amiodarone can cause arrhythmia due to low potassium. It should not be used in combination with antiarrhythmic drugs such as quinidine, propidamine, amiodarone, benzyl bromide, and sotalol.

2. Combined with digitalis, it can cause digitalis poisoning due to potassium loss.

3. Combined with dopamine, the diuretic effect of this medicine is enhanced.

4. The antihypertensive effect is enhanced when combined with other antihypertensive drugs.

5. Combined with baclofen can increase antihypertensive effect.

6. Combined with lithium agent, can increase blood lithium concentration and appear excessive signs.

7. In combination with large doses of salicylate, patients with dehydration may develop acute renal failure.

8. Combined with amphotericin B (intravenous) or laxatives can increase the risk of hypokalemia.

9. When combined with angiotensin-converting enzyme inhibitors (ACEI), patients with hyponatremia (especially those with renal artery stenosis) may develop sudden hypotension and / or acute renal failure and should be discontinued. This medicine will be used again after 3 days. If necessary, reuse potassium-releasing diuretics or give a small dose of ACEI.

10. Combining with metformin is prone to lactic acidosis.

11. Combination with iodine contrast agent can increase the risk of acute renal failure.

12. Combined with tricyclic antidepressants (such as imipramine) or sedatives, it can enhance the antihypertensive effect and increase the risk of orthostatic hypotension.

13. Combined with cyclosporine, it may lead to an increase in serum creatinine concentration.

Cyclosporine

14. Combined with corticosteroids or teicotaxin, the pharmacological effect of this medicine is weakened.

15. The antihypertensive effect is weakened when combined with sympathomimetic drugs.

16. The anticoagulant effect of oral anticoagulants can be weakened.

17. Non-steroidal anti-inflammatory analgesics can reduce the natriuretic effect of this drug.

18. Arrhythmia can be caused by combination with the following drugs: astemizole, benzprodil, erythromycin (intravenous administration), haloflurane, pentamidine, sutopril, terfenadine, vincamine.

Indapamide poisoning

Indapamide (Suphan, Indapamine, Indamine) is a non-thiazide diuretic and antihypertensive drug with calcium antagonistic and diuretic effects. Clinically, it is mainly used to treat water and sodium retention and pregnancy edema caused by congestive heart failure. It is also used to treat hypertension. The usual amount is 2.5mg each time, 1 / d. Mainly affect water and salt metabolism, cause water and electrolyte imbalance, and produce hypokalemia.

Clinical manifestation

Adverse reaction performance:

Central nervous system

Dizziness, fatigue, weakness, dizziness, irritability, anxiety, insomnia or drowsiness, blurred vision, numbness of the limbs, convulsions, etc.

2. Digestive system

Nausea, vomiting, anorexia, indigestion, diarrhea or constipation, abdominal pain, cholestatic jaundice and salivary glanditis.

3. Circulatory system

Orthostatic hypotension, palpitations, arrhythmias (such as pre-ventricular contractions), vasculitis, etc.

4. Urinary system

Frequent urination, polyuria, etc.

5. Metabolic abnormalities

Taking large doses can cause hypokalemia, hypochloremia, hyperuricemia, hyperglycemia, elevated serum urea nitrogen, increased creatinine, and diabetes.

6. Blood system

Granulocytosis, leukopenia, thrombocytopenia, megaloblastic anemia, etc.

7. Allergic reactions

Can appear rash, urticaria, pruritus, drug fever, photosensitive dermatitis, erythema polymorpha.

8. Other

Cough, sinusitis, conjunctivitis, yellow vision, low libido, impotence, etc.

treatment

The main points of treatment of indapamide poisoning are:

Proper chlorine and potassium supplementation, correction of water and electrolyte balance disorders, and the remaining symptomatic treatment ^[4] .

Indapamide preparation

Indapamide tablets 2.5mg.

Storage method: shading and sealed.

Indapamide capsule 2.5mg.

Storage method: shading and sealed.

Indapamide sustained-release tablets 1.5mg.

Storage method: Store below 30 .

Indapamide Expert Reviews

Indapamide has a reliable antihypertensive effect, is convenient to take, has few adverse reactions, and has stable blood pressure. It is an ideal drug for mild to moderate hypertension and can be used as a first-line drug for antihypertensive drugs.