Product Information
Registration Status: ActivePRAVAFEN HARD CAPSULE 40MG/160MG is approved to be sold in Singapore with effective from 2014-02-21. It is marketed by HYPHENS PHARMA PTE LTD, with the registration number of SIN14508P.
This product contains Fenofibrate 160mg, and Pravastatin 40mg in the form of CAPSULE. It is approved for ORAL use.
This product is manufactured by SMB Technology S.A. in BELGIUM.
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
Fenofibrate is a prodrug of fenofibric acid, an antilipemic agent which reduces both cholesterol and triglycerides in the blood.
Indication
For use as adjunctive therapy to diet to reduce elevated LDL-C, Total-C,Triglycerides and Apo B, and to increase HDL-C in adult patients with primary hypercholesterolemia or mixed dyslipidemia (Fredrickson Types IIa and IIb)
Mechanism of Action
Fenofibrate exerts its therapeutic effects through activation of peroxisome proliferator activated receptor a (PPARa). This increases lipolysis and elimination of triglyceride-rich particles from plasma by activating lipoprotein lipase and reducing production of apoprotein C-III. The resulting fall in triglycerides produces an alteration in the size and composition of LDL from small, dense particles, to large buoyant particles. These larger particles have a greater affinity for cholesterol receptors and are catabolized rapidly.
Pharmacokinetics
- Absorption
- Fenofibrate is well absorbed from the gastrointestinal tract. After absorption, fenofibrate is mainly excreted in the urine in the form of metabolites, primarily fenofibric acid and fenofibric acid glucuronide
- Distribution
- In healthy adults, the volume of distribution is 30 L. The volume of distribution is 95 L in individuals with moderate renal impairment and creatinine clearance of 50 to 90 mL/min [FDA Label].
- Metabolism
- Elimination
Clearance
* 1.2 L/h [Eldery]
Toxicity
LD50=1600 mg/kg (Oral, in mice); Investigated as a teratogen and reproductive hazard.
Active Ingredient/Synonyms
2-(4-(4-Chlorobenzoyl)phenoxy)-2-methylpropanoic acid 1-methylethyl ester | Fenofibrato | Fenofibratum | Finofibrate | FNF | Isopropyl (4'-(p-chlorobenzoyl)-2-phenoxy-2-methyl)propionate | Isopropyl 2-(4-(4-chlorobenzoyl)phenoxy)-2-methylpropionate | Procetofen | Fenofibrate |
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
Pravastatin is a cholesterol-lowering agent that belongs to a class of medications known as statins. It was derived from microbial transformation of mevastatin, the first statin discovered. It is a ring-opened dihydroxyacid with a 6’-hydroxyl group that does not require in vivo activation. Pravastatin is one of the lower potency statins; however, its increased hydrophilicity is thought to confer advantages such as minimal penetration through lipophilic membranes of peripheral cells, increased selectivity for hepatic tissues, and a reduction in side effects compared with lovastatin and simvastatin.
Indication
For the treatment of hypercholesterolemia and to reduce the risk of cardiovascular disease.
Mechanism of Action
Pravastatin is structurally similar to the HMG, a substituent of the endogenous substrate of HMG-CoA reductase. Unlike its parent compound, mevastatin, and statins such as lovastatin and simvastatin, pravastatin does not need to be activated in vivo. Its hydrolyzed lactone ring mimics the tetrahedral intermediate produced by the reductase allowing the agent to bind with a much greater affinity than its natural substrate. The bicyclic portion of pravastatin binds to the coenzyme A portion of the active site. Pravastatin sodium produces its lipid-lowering effect in two ways. First, as a consequence of its reversible inhibition of HMG-CoA reductase activity, it effects modest reductions in intracellular pools of cholesterol. This results in an increase in the number of LDL-receptors on cell surfaces and enhanced receptor-mediated catabolism and clearance of circulating LDL. Second, pravastatin inhibits LDL production by inhibiting hepatic synthesis of VLDL, the LDL precursor.
Pharmacokinetics
- Absorption
- Pravastatin is rapidly absorbed with peak plasma levels of the parent compound achieved 1 to 1.5 hours after administration. The average oral absorption of pravastatin is 34% and absolute bioavailability is 17%. These values however, are variable. Food decreases the systemic bioavailability but the lipid-lowering effect is not impacted. When 20 mg of pravastatin is given orally, the pharmacokinetic parameters are as follows: Cmax = 23.3-26.3 ng/mL; AUC = 54.7 to 62.2 ng•hr/mL.
- Distribution
- Metabolism
- Hepatic, there is a small amount of metabolism by P450 enzymes, but this effect is so minimal that inhibitory pharmacokinetic drug interactions have no real effect on its overall activity and elimination. An in vitro study which found moderate affinity for P450 2C9 (major), 2D6 and 3A4. Furthermore, the major degradation product is the 3α-hydroxy isomeric metabolite, which has one-tenth to one-fortieth the HMG-CoA reductase inhibitory activity of the parent compound.
- Elimination
Toxicity
Side effects include diarrhea, nausea, constipation, gas abdominal pain, myopathy, myositis, rhabdomyolysis, and hepatotoxicity. LD50= 12,000 mg/kg (orally in rat)
Active Ingredient/Synonyms
(+)-(3R,5R)-3,5-dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2-methyl-8-{[(S)-2-methylbutyryl]oxy}-1,2,6,7,8,8a-hexahydro-1-naphthyl]heptanoic acid | Pravastatin acid | Pravastatina | Pravastatine | Pravastatinum | Pravastatin |
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.