Product Information
Registration Status: ActiveCOSYREL FILM-COATED TABLET 5 mg/ 10 mg is approved to be sold in Singapore with effective from 2017-12-28. It is marketed by SERVIER (S) PTE LTD, with the registration number of SIN15399P.
This product contains Bisoprolol 5mg, and Perindopril 10mg in the form of TABLET, FILM COATED. It is approved for ORAL use.
This product is manufactured by Les Laboratoires Servier Industrie [LSI] in FRANCE.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Description
Bisoprolol is a cardioselective β1-adrenergic blocking agent used for secondary prevention of myocardial infarction (MI), heart failure, angina pectoris and mild to moderate hypertension. Bisoprolol is structurally similar to metoprolol, acebutolol and atenolol in that it has two substituents in the para position of the benzene ring. The β1-selectivity of these agents is thought to be due in part to the large substituents in the para position. At lower doses (less than 20 mg daily), bisoprolol selectively blocks cardiac β1-adrenergic receptors with little activity against β2-adrenergic receptors of the lungs and vascular smooth muscle. Receptor selectivity decreases with daily doses of 20 mg or greater. Unlike propranolol and pindolol, bisoprolol does not exhibit membrane-stabilizing or sympathomimetic activity. Bisoprolol possesses a single chiral centre and is administered as a racemic mixture. Only l-bisoprolol exhibits significant β-blocking activity.
Indication
For management of heart failure, angina pectoris, and mild to moderate hypertension and for secondary prevention of myocardial infarction (MI).
Mechanism of Action
Bisoprolol selectively blocks catecholamine stimulation of β1-adrenergic receptors in the heart and vascular smooth muscle. This results in a reduction of heart rate, cardiac output, systolic and diastolic blood pressure, and possibly reflex orthostatic hypotension. At higher doses (e.g. 20 mg and greater) bisoprolol may competitively block β2-adrenergic receptors in bronchial and vascular smooth muscle causing bronchospasm and vasodilation.
Pharmacokinetics
- Absorption
- Well absorbed. Bioavailability > 80%. Absorption is not affected by food. Peak plasma concentrations occur within 2-4 hours.
- Distribution
- Metabolism
- Approximately 50% of the dose is metabolized primarily metabolized by CYP3A4 to inactive metabolites. In vitro studies have shown that bisoprolol is also metabolized by CYP2D6 though this does not appear to be clinically significant. Approximately half the administered dose is excreted in unchanged in urine.
- Elimination
Toxicity
Oral, mouse: LD50 = 100 mg/kg; Skin, rabbit: LD50 = 200 mg/kg; Skin, rat: LD50 = 500 mg/kg. Symptoms of overdose include congestive heart failure (marked by sudden weight gain, swelling of the legs, feet, and ankles, fatigue, and shortness of breath), difficult or labored breathing, low blood pressure, low blood sugar, and slow heartbeat.
Active Ingredient/Synonyms
(+-)-1-((alpha-(2-Isopropoxyethoxy)-P-tolyl)oxy)-3-(isopropylamino)-2-propanol | (RS)-1-(4-(2-isopropoxyethoxymethyl)phenoxy)-3-(isopropylamino)-2-propanol | Bisoprolol | Bisoprololum | Bisoprolol |
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.
Description
Perindopril is a nonsulfhydryl prodrug that belongs to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is rapidly metabolized in the liver to perindoprilat, its active metabolite, following oral administration. Perindoprilat is a potent, competitive inhibitor of ACE, the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Perindopril may be used to treat mild to moderate essential hypertension, mild to moderate congestive heart failure, and to reduce the cardiovascular risk of individuals with hypertension or post-myocardial infarction and stable coronary disease.
Indication
For the treatment of mild to moderate essential hypertension, mild to moderate congestive heart failure, and to reduce the cardiovascular risk of individuals with hypertension or post-myocardial infarction and stable coronary disease.
Mechanism of Action
There are two isoforms of ACE: the somatic isoform, which exists as a glycoprotein comprised of a single polypeptide chain of 1277; and the testicular isoform, which has a lower molecular mass and is thought to play a role in sperm maturation and binding of sperm to the oviduct epithelium. Somatic ACE has two functionally active domains, N and C, which arise from tandem gene duplication. Although the two domains have high sequence similarity, they play distinct physiological roles. The C-domain is predominantly involved in blood pressure regulation while the N-domain plays a role in hematopoietic stem cell differentiation and proliferation. ACE inhibitors bind to and inhibit the activity of both domains, but have much greater affinity for and inhibitory activity against the C-domain. Perindoprilat, the active metabolite of perindopril, competes with ATI for binding to ACE and inhibits and enzymatic proteolysis of ATI to ATII. Decreasing ATII levels in the body decreases blood pressure by inhibiting the pressor effects of ATII as described in the Pharmacology section above. Perindopril also causes an increase in plasma renin activity likely due to a loss of feedback inhibition mediated by ATII on the release of renin and/or stimulation of reflex mechanisms via baroreceptors.
Pharmacokinetics
- Absorption
- Rapidly absorbed with peak plasma concentrations occurring approximately 1 hour after oral administration. Bioavailability is 65-75%. Following absorption, perindopril is hydrolyzed to perindoprilat, which has an average bioavailability of 20%. The rate and extent of absorption is unaffected by food. However, food decreases the extent of biotransformation to peridoprilat and reduces its bioavailability by 35%.
- Distribution
- Metabolism
- Extensively metabolized, with only 4-12% of the dose recovered in urine following oral administration. Six metabolites have been identified: perindoprilat, perindopril glucuronide, perindoprilat glucuronide, a perindopril lactam, and two perindoprilat lactams. Only perindoprilat is pharmacologically active. Peridoprilat and perindoprilat glucuronide are the two main circulating metabolites.
- Elimination
Clearance
* 219 - 362 mL/min [oral administration]
Toxicity
The most likely symptom of overdose is severe hypotension. The most common adverse effects observed in controlled clinical trials include cough, digestive symptoms, fatigue, headache, and dizziness.
Active Ingredient/Synonyms
(2S,3AS,7as)-1-[(2S)-2-{[(2S)-1-ethoxy-1-oxopentan-2-yl]amino}propanoyl]octahydro-1H-indole-2-carboxylic acid | Perindoprilum | Perindopril |
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.