IRBESARTAN-HYDROCHLOROTHIAZIDE ACTAVIS FILM-COATED TABLET 150/12.5mg

Irbesartan
Hydrochlorothiazide

Source of information: Drugbank (External Link). Last updated on: 3rd July 18
*Trade Name used in the content below may not be the same as the HSA-registered product.

Active Ingredient / Synonyms

2-butyl-3-{[2'-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1,3-diazaspiro[4.4]non-1-en-4-one | Irbesartan | Irbesartan |

Description

Irbesartan is an angiotensin receptor blocker (ARB) used mainly for the treatment of hypertension. It competes with angiotensin II for binding at the AT1 receptor subtype. Unlike ACE inhibitors, ARBs do not have the adverse effect of dry cough. The use of ARBs is pending revision due to findings from several clinical trials suggesting that this class of drugs may be associated with a small increased risk of cancer.

Indication

For the treatment of hypertension, as well as diabetic nephropathy with an elevated serum creatinine and proteinuria (>300 mg/day) in patients with type 2 diabetes and hypertension. Irbesartan is also used as a second line agent in the treatment of congestive heart failure.

Mechanism of Action

Irbesartan is a nonpeptide tetrazole derivative and an angiotensin II antagonist that selectively blocks the binding of angiotensin II to the AT1 receptor. In the renin-angiotensin system, angiotensin I is converted by angiotensin-converting enzyme (ACE) to form angiotensin II. Angiotensin II stimulates the adrenal cortex to synthesize and secrete aldosterone, which decreases the excretion of sodium and increases the excretion of potassium. Angiotensin II also acts as a vasoconstrictor in vascular smooth muscle. Irbesartan, by blocking the binding of angiotensin II to the AT1 receptor, promotes vasodilation and decreases the effects of aldosterone. The negative feedback regulation of angiotensin II on renin secretion is also inhibited, but the resulting rise in plasma renin concentrations and consequent rise in angiotensin II plasma concentrations do not counteract the blood pressure–lowering effect that occurs. The action of ARBs is different from ACE inhibitors, which block the conversion of angiotensin I to angiotensin II, meaning that the production of angiotensin II is not completely inhibited, as the hormone can be formed via other enzymes. Also, unlike ACE inhibitors, irbesartan and other ARBs do not interfere with response to bradykinins and substance P, which allows for the absence of adverse effects that are present in ACE inhibitors (eg. dry cough).

Pharmacodynamics

Angiotensin II, the principal pressor agent of the renin-angiotensin system, is responsible for effects such as vasoconstriction, stimulation of synthesis and release of aldosterone, cardiac stimulation, and renal reabsorption of sodium. Irbesartan is a specific competitive antagonist of AT1 receptors with a much greater affinity (more than 8500-fold) for the AT1 receptor than for the AT2 receptor and no agonist activity. Irbesartan's inhibition of angiotensin II binding to the AT1 receptor leads to multiple effects including vasodilation, a reduction in the secretion of vasopressin, and reduction in the production and secretion of aldosterone. The resulting effect is a decrease in blood pressure.

Pharmacokinetics

Absorption:

Rapid and complete with an average absolute bioavailability of 60-80%. Food has no affect on bioavailability.

Distribution:

* 53 to 93 L

Metabolism:

Hepatic. Irbesartan is metabolized via glucuronide conjugation and oxidation. In vitro studies of irbesartan oxidation by cytochrome P450 isoenzymes indicated irbesartan was oxidized primarily by 2C9; metabolism by 3A4 was negligible.

Elimination:

Irbesartan is metabolized via glucuronide conjugation and oxidation. Irbesartan and its metabolites are excreted by both biliary and renal routes. Irbesartan is excreted in the milk of lactating rats.

Half-life

11-15 hours

Clearance

* 157-176 mL/min

Toxicity

Hypotension and tachycardia; bradycardia might also occur from overdose, LD50=mg/kg(orally in rat)

Source of information: Drugbank (External Link). Last updated on: 3rd July 18
*Trade Name used in the content below may not be the same as the HSA-registered product.

Active Ingredient / Synonyms

HCTZ | Hydrochlorothiazide |

Description

A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It has been used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism. [PubChem]

Indication

For the treatment of high blood pressure and management of edema.

Mechanism of Action

Hydrochlorothiazide, a thiazide diuretic, inhibits water reabsorption in the nephron by inhibiting the sodium-chloride symporter (SLC12A3) in the distal convoluted tubule, which is responsible for 5% of total sodium reabsorption. Normally, the sodium-chloride symporter transports sodium and chloride from the lumen into the epithelial cell lining the distal convoluted tubule. The energy for this is provided by a sodium gradient established by sodium-potassium ATPases on the basolateral membrane. Once sodium has entered the cell, it is transported out into the basolateral interstitium via the sodium-potassium ATPase, causing an increase in the osmolarity of the interstitium, thereby establishing an osmotic gradient for water reabsorption. By blocking the sodium-chloride symporter, hydrochlorothiazide effectively reduces the osmotic gradient and water reabsorption throughout the nephron.

Pharmacodynamics

Thiazides such as hydrochlorothiazide promote water loss from the body (diuretics). They inhibit Na+/Cl- reabsorption from the distal convoluted tubules in the kidneys. Thiazides also cause loss of potassium and an increase in serum uric acid. Thiazides are often used to treat hypertension, but their hypotensive effects are not necessarily due to their diuretic activity. Thiazides have been shown to prevent hypertension-related morbidity and mortality although the mechanism is not fully understood. Thiazides cause vasodilation by activating calcium-activated potassium channels (large conductance) in vascular smooth muscles and inhibiting various carbonic anhydrases in vascular tissue.

Pharmacokinetics

Absorption:

50-60%

Distribution:

Not Available

Metabolism:

Hydrochlorothiazide is not metabolized.

Elimination:

Hydrochlorothiazide is not metabolized but is eliminated rapidly by the kidney. Hydrochlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.

Half-life

5.6 and 14.8 hours

Clearance

Not Available

Toxicity

The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias. The oral LD50 of hydrochlorothiazide is greater than 10 g/kg in the mouse and rat.

References

  1. Health Science Authority of Singapore - Reclassified POM
  2. Drugbank

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Approval Information

IRBESARTAN-HYDROCHLOROTHIAZIDE ACTAVIS FILM-COATED TABLET 150/12.5mg was registered with Health Science Authority of Singapore by DRUG HOUSES OF AUSTRALIA PTE LTD. It is marketed with the registration number of SIN15029P with effective from 2016-06-06.

This product contains 150mg of Irbesartan, and 12.5mg of Hydrochlorothiazide in the form of ORAL TABLET, FILM-COATED.

The medicine was manufactured by Actavis ehf. in ICELAND, and BALKANPHARMA DUPNITSA AD in BULGARIA

It is a Presciption Only Medicine which can only be obtained from a doctor or a dentist, or from a pharmacist with a prescription from a Singapore-registered doctor or dentist.

Anatomical Therapeutic Chemical (ATC) Classification

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1DEXTROMETHORPHAN LINCTUS 15mg/5mlDextromethorphanP OnlyDRUG HOUSES OF AUSTRALIA PTE LTDActive
22ZENMOLIN SYRUP 2mg/5mlSalbutamolP OnlyDRUG HOUSES OF AUSTRALIA PTE LTDActive
41APO-PROPRANOLOL TABLET 40mgPropranololPOMPHARMAFORTE SINGAPORE PTE LTDActive
42APO-DIAZEPAM TABLET 2mgDiazepamPOMPHARMAFORTE SINGAPORE PTE LTDActive
44APO-DIAZEPAM TABLET 5mgDiazepamPOMPHARMAFORTE SINGAPORE PTE LTDActive
45APO-DIAZEPAM TABLET 10mgDiazepamPOMPHARMAFORTE SINGAPORE PTE LTDActive
46APO-PROPRANOLOL TABLET 10mgPropranololPOMPHARMAFORTE SINGAPORE PTE LTDActive
55APO-ISDN TABLET 10mgIsosorbide DinitratePOMPHARMAFORTE SINGAPORE PTE LTDActive
63DIAPO TABLET 10mgDiazepamPOMBEACONS PHARMACEUTICALS PTE LTDActive
64FURMIDE TABLET 40mgFurosemidePOMBEACONS PHARMACEUTICALS PTE LTDActive

Products Containing as Mixture Ingredient

Drug IDTrade NameActive IngredientsForensic ClassRegistrantStatus
4DIPHENHYDRAMINE EXPECTORANTAmmonium Chloride|Diphenhydramine|Sodium CitrateP OnlyDRUG HOUSES OF AUSTRALIA PTE LTDActive
5DIPHENHYDRAMINE EXPECTORANT PAED.Ammonium Chloride|Diphenhydramine|Sodium CitrateP OnlyDRUG HOUSES OF AUSTRALIA PTE LTDActive
400FAKTU SUPPOSITORYCinchocaine|PolicresulenP OnlyTAKEDA PHARMACEUTICALS (ASIA PACIFIC) PTE LTDActive
407TRIMAXAZOLE TABLETSulfamethoxazole|TrimethoprimPOMBEACONS PHARMACEUTICALS PTE LTDActive
435APO-SULFATRIM TABLETSulfamethoxazole|TrimethoprimPOMPHARMAFORTE SINGAPORE PTE LTDActive
508APO-SULFATRIM PEDIATRIC TABLETSulfamethoxazole|TrimethoprimPOMPHARMAFORTE SINGAPORE PTE LTDActive
526B.S. SUSPENSIONSulfamethoxazole|TrimethoprimPOMAPEX PHARMA MARKETING PTE LTDActive
583CO-TRIMEXAZOLE SUSPENSIONSulfamethoxazole|TrimethoprimPOMBEACONS PHARMACEUTICALS PTE LTDActive
676BANEOCIN OINTMENTBacitracin|NeomycinPOMNOVARTIS (SINGAPORE) PTE LTDActive
678BANEOCIN POWDERBacitracin|NeomycinPOMNOVARTIS (SINGAPORE) PTE LTDActive