Product Information
Registration Status: ActiveSIN15647P
TRINOMIA HARD CAPSULES 100mg/ 20mg/ 2.5mg is approved to be sold in Singapore with effective from 2019-03-19. It is marketed by DCH AURIGA SINGAPORE, with the registration number of SIN15647P.
This product contains Acetylsalicylic Acid 100mg,Atorvastatin 20mg, and Ramipril 2.5mg in the form of CAPSULE. It is approved for ORAL use.
This product is manufactured by Ferrer Internacional S.A. in SPAIN.
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.
Product Reference
Important Note: For generic product, the SPC/PIL provided may not be brand specific.
{{/items}} {{^items}}Description
The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Acetylsalicylic acid also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. (From Martindale, The Extra Pharmacopoeia, 30th ed, p5)
Indication
For use in the temporary relief of various forms of pain, inflammation associated with various conditions (including rheumatoid arthritis, juvenile rheumatoid arthritis, systemic lupus erythematosus, osteoarthritis, and ankylosing spondylitis), and is also used to reduce the risk of death and/or nonfatal myocardial infarction in patients with a previous infarction or unstable angina pectoris.
Mechanism of Action
The analgesic, antipyretic, and anti-inflammatory effects of acetylsalicylic acid are due to actions by both the acetyl and the salicylate portions of the intact molecule as well as by the active salicylate metabolite. Acetylsalicylic acid directly and irreversibly inhibits the activity of both types of cyclooxygenase (COX-1 and COX-2) to decrease the formation of precursors of prostaglandins and thromboxanes from arachidonic acid. This makes acetylsalicylic acid different from other NSAIDS (such as diclofenac and ibuprofen) which are reversible inhibitors. Salicylate may competitively inhibit prostaglandin formation. Acetylsalicylic acid's antirheumatic (nonsteroidal anti-inflammatory) actions are a result of its analgesic and anti-inflammatory mechanisms; the therapeutic effects are not due to pituitary-adrenal stimulation. The platelet aggregation-inhibiting effect of acetylsalicylic acid specifically involves the compound's ability to act as an acetyl donor to cyclooxygenase; the nonacetylated salicylates have no clinically significant effect on platelet aggregation. Irreversible acetylation renders cyclooxygenase inactive, thereby preventing the formation of the aggregating agent thromboxane A2 in platelets. Since platelets lack the ability to synthesize new proteins, the effects persist for the life of the exposed platelets (7-10 days). Acetylsalicylic acid may also inhibit production of the platelet aggregation inhibitor, prostacyclin (prostaglandin I2), by blood vessel endothelial cells; however, inhibition prostacyclin production is not permanent as endothelial cells can produce more cyclooxygenase to replace the non-functional enzyme.
Pharmacokinetics
- Absorption
- Absorption is generally rapid and complete following oral administration but may vary according to specific salicylate used, dosage form, and other factors such as tablet dissolution rate and gastric or intraluminal pH.
- Distribution
- Metabolism
- Acetylsalicylic acid is rapidly hydrolyzed primarily in the liver to salicylic acid, which is conjugated with glycine (forming salicyluric acid) and glucuronic acid and excreted largely in the urine.
- Elimination
Toxicity
Oral, mouse: LD50 = 250 mg/kg; Oral, rabbit: LD50 = 1010 mg/kg; Oral, rat: LD50 = 200 mg/kg. Effects of overdose include: tinnitus, abdominal pain, hypokalemia, hypoglycemia, pyrexia, hyperventilation, dysrhythmia, hypotension, hallucination, renal failure, confusion, seizure, coma, and death.
Active Ingredient/Synonyms
2-Acetoxybenzenecarboxylic acid | 2-Acetoxybenzoic acid | Acetylsalicylate | Acetylsalicylsäure | acide 2-(acétyloxy)benzoïque | acide acétylsalicylique | ácido acetilsalicílico | Acidum acetylsalicylicum | ASA | Aspirin | Azetylsalizylsäure | o-acetoxybenzoic acid | O-acetylsalicylic acid | o-carboxyphenyl acetate | Polopiryna | salicylic acid acetate | Acetylsalicylic acid |
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
Atorvastatin (Lipitor) is a member of the drug class known as statins. It is used for lowering cholesterol. Atorvastatin is a competitive inhibitor of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, the rate-determining enzyme in cholesterol biosynthesis via the mevalonate pathway. HMG-CoA reductase catalyzes the conversion of HMG-CoA to mevalonate. Atorvastatin acts primarily in the liver. Decreased hepatic cholesterol levels increases hepatic uptake of cholesterol and reduces plasma cholesterol levels.
Indication
May be used as primary prevention in individuals with multiple risk factors for coronary heart disease (CHD) and as secondary prevention in individuals with CHD to reduce the risk of myocardial infarction (MI), stroke, angina, and revascularization procedures. May be used to reduce the risk of cardiovascular events in patients with acute coronary syndrome (ACS). May be used in the treatment of primary hypercholesterolemia and mixed dyslipidemia, homozygous familial hypercholesterolemia, primary dysbetalipoproteinemia, and/or hypertriglyeridemia as an adjunct to dietary therapy to decrease serum total and low-density lipoprotein cholesterol (LDL-C), apolipoprotein B (apoB), and triglyceride concentrations, while increasing high-density lipoprotein cholesterol (HDL-C) levels.
Mechanism of Action
Atorvastatin selectively and competitively inhibits the hepatic enzyme HMG-CoA reductase. As HMG-CoA reductase is responsible for converting HMG-CoA to mevalonate in the cholesterol biosynthesis pathway, this results in a subsequent decrease in hepatic cholesterol levels. Decreased hepatic cholesterol levels stimulates upregulation of hepatic LDL-C receptors which increases hepatic uptake of LDL-C and reduces serum LDL-C concentrations.
Pharmacokinetics
- Absorption
- Atorvastatin is rapidly absorbed after oral administration with maximum plasma concentrations achieved in 1 to 2 hours. The absolute bioavailability of atorvastatin (parent drug) is approximately 14% and the systemic availability of HMG-CoA reductase inhibitory activity is approximately 30%. The low systemic bioavailability is due to presystemic clearance by gastrointestinal mucosa and first-pass metabolism in the liver.
- Distribution
- 381 L
- Metabolism
- Atorvastatin is extensively metabolized to ortho- and parahydroxylated derivatives and various beta-oxidation products. In vitro inhibition of HMG-CoA reductase by ortho- and parahydroxylated metabolites is equivalent to that of atorvastatin. Approximately 70% of circulating inhibitory activity for HMG-CoA reductase is attributed to active metabolites. CYP3A4 is also involved in the metabolism of atorvastatin.
- Elimination
Toxicity
Generally well-tolerated. Side effects may include myalgia, constipation, asthenia, abdominal pain, and nausea. Other possible side effects include myotoxicity (myopathy, myositis, rhabdomyolysis) and hepatotoxicity. To avoid toxicity in Asian patients, lower doses should be considered.
Active Ingredient/Synonyms
atorvastatina | atorvastatine | atorvastatinum | Atorvastatin |
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
Ramipril is a prodrug belonging to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is metabolized to ramiprilat in the liver and, to a lesser extent, kidneys. Ramiprilat 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). Ramipril may be used in the treatment of hypertension, congestive heart failure, nephropathy, and to reduce the rate of death, myocardial infarction and stroke in individuals at high risk of cardiovascular events.
Indication
For the management of mild to severe hypertension. May be used to reduce cardiovascular mortality following myocardial infarction in hemodynamically stable individuals who develop clinical signs of congestive heart failure within a few days following myocardial infarction. To reduce the rate of death, myocardial infarction and stroke in individuals at high risk of cardiovascular events. May be used to slow the progression of renal disease in individuals with hypertension, diabetes mellitus and microalubinuria or overt nephropathy.
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. Ramiprilat, the principle active metabolite of ramipril, 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. Ramipril 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
- The extent of absorption is at least 50-60%. Food decreases the rate of absorption from the GI tract without affecting the extent of absorption. The absolute bioavailabilities of ramipril and ramiprilat were 28% and 44%, respectively, when oral administration was compared to intravenous administration.
- Distribution
- Metabolism
- Hepatic metabolism accounts for 75% of total ramipril metabolism. 25% of hepatic metabolism produces the active metabolite ramiprilat via liver esterase enzymes. 100% of renal metabolism converts ramipril to ramiprilat. Other metabolites, diketopiperazine ester, the diketopiperazine acid, and the glucuronides of ramipril and ramiprilat, are inactive.
- Elimination
Toxicity
Symptoms of overdose may include excessive peripheral vasodilation (with marked hypotension and shock), bradycardia, electrolyte disturbances, and renal failure. The most likely adverse reactions are symptoms attributable to its blood-pressure lowing effect. May cause headache, dizziness, asthenia, chest pain, nausea, peripheral edema, somnolence, impotence, rash, arthritis, and dyspnea. LD50 = 10933 mg/kg (orally in mice).
Active Ingredient/Synonyms
(2S-(1(R*(r*)),2alpha,3abeta,6abeta))-1-(2-((1-(ethoxycarbonyl)-3-phenylpropyl)amino)-1-oxopropyl)octahydrocyclopenta(b)pyrrole-2-carboxylic acid | Altace (tn) | Ramipril | Ramiprilum | Tritace | Ramipril |
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.