Adult: As an adjunct to diet and exercise: 10-40 mg once daily, preferably taken in the evening. Adjust the dose according to response at intervals of at least 4 weeks. Alternatively, 40-80 mg daily. Dosage recommendations may vary among individual products or between countries (refer to detailed product guidelines).
Oral Heterozygous familial hypercholesterolaemia
Child: 8-13 years 20 mg once daily; 14-18 years 40 mg once daily.
Oral Cardiovascular risk reduction
Adult: As primary prevention to reduce the risk of CV events in patients with hypercholesterolaemia, and as secondary prevention to reduce the risk of MI, myocardial revascularisation, stroke and TIA in patients with history of MI or unstable angina: 40 mg once daily.
Oral Posttransplant hyperlipidaemia
Adult: Reduction of posttransplantation hyperlipidaemia in patients receiving immunosuppressive treatment after solid organ transplantation: Initially, 20 mg once daily, may be increased to 40 mg daily depending on the patient's response. Close medical supervision is needed during dose increases.
Các sản phẩm có chứa hoạt chất Pravastatin tại Việt Nam?
Patients taking ciclosporin: Initially, 10 mg or 20 mg once daily, then titrate to higher doses with caution. Max: 20 mg or 40 mg once daily. Dosage recommendations may vary among individual products or between countries (refer to detailed product guidelines).
Patients taking clarithromycin or erythromycin: Max: 40 mg once daily.
Pharmacogenomics:
The SLCO1B1 gene encodes OATP1B1, an influx transporter which mediates the hepatic uptake of statins and other exogenous or endogenous compounds into hepatocytes for subsequent clearance. Certain SLCO1B1 polymorphisms (e.g. 521T>C [rs4149056] polymorphism) can produce a less active form of OATP1B1 enzyme. Individuals with genetic variation in SLCO1B1 may have an altered systemic exposure to statins which may increase the risk for statin-associated musculoskeletal symptoms (SAMS). Genetic testing may be considered to help optimise new or existing statin treatments to decrease the risk of SAMS.
Clinical Pharmacogenetics Implementation Consortium (CPIC) Guideline as of January 2022:
Genotype and Phenotype
Implications
Recommendations
SLCO1B1 decreased function
Patients carrying 1 normal or increased functional allele and 1 non-functional allele e.g. *1/*5, *1/*15
Increased pravastatin exposure as compared with normal function; usual risk for myopathy with ≤40 mg doses.
Initiate therapy at the desired starting dose and then adjust according to disease-specific guidelines. There is an increased risk for myopathy particularly with >40 mg daily doses.
SLCO1B1 possible decreased function
Patients carrying 1 non-functional allele and 1 uncertain or unknown function allele e.g. *5/*6, *15/*10, *5/*43
Increased pravastatin exposure as compared with normal function; usual risk for myopathy with ≤40 mg doses.
Initiate therapy at the desired starting dose and then adjust according to disease-specific guidelines. There is an increased risk for myopathy particularly with >40 mg daily doses.
SLCO1B1 poor function
Patients carrying 2 non-functional alleles e.g. *5/*5, *5/*15, *15/*15
Increased pravastatin exposure as compared with normal and decreased function; usual risk for myopathy with ≤40 mg doses.
Initiate therapy at a dose of ≤40 mg and then adjust according to disease-specific guidelines. If the patient has tolerated a 40 mg dose but higher potency is necessary, may consider a higher dose (>40 mg) or an alternative statin or combination therapy (with a non-statin guideline-directed medical treatment).
Suy thận
Primary hypercholesterolaemia; Mixed hyperlipidaemia; Posttransplant hyperlipidaemia; Cardiovascular risk reduction:
Moderate to severe: Initially, 10 mg once daily, may be adjusted according to response.
Cách dùng
Pravastatin May be taken with or without food.
Chống chỉ định
Active liver disease, decompensated cirrhosis, unexplained persistent elevations of serum transaminases (>3 times the ULN). Pregnancy and lactation.
Thận trọng
Patient with myasthenia gravis, predisposing factors for muscular disorders (e.g. hypothyroidism, history of muscular toxicity with a statin or fibrate, personal or family history of hereditary muscular disorders); history of liver disease or heavy alcohol intake. Patients at risk for diabetes mellitus or those undergoing surgery. Patients with SLCO1B1 gene polymorphism. Concomitant use with fibrates (e.g. gemfibrozil), systemic fusidic acid, ciclosporin, erythromycin, and clarithromycin. Renal impairment. Children and elderly.
Tác dụng không mong muốn
Significant: Increased HbA1c and fasting blood glucose levels; hepatotoxicity (e.g. increased serum transaminase levels); myalgia, myopathy; interstitial lung disease (prolonged use). Rarely, immune-mediated necrotising myopathy (IMNM); new-onset or exacerbation of pre-existing myasthenia gravis or ocular myasthenia. Eye disorders: Visual disturbances, including blurred vision. Gastrointestinal disorders: Dyspepsia, diarrhoea, abdominal pain, nausea, vomiting, constipation. General disorders and administration site conditions: Fatigue, chest pain. Investigations: Increased creatine phosphokinase. Nervous system disorders: Dizziness, headache. Psychiatric disorders: Sleep disturbance, insomnia. Renal and urinary disorders: Dysuria, nocturia. Respiratory, thoracic and mediastinal disorders: Cough, URTI. Skin and subcutaneous tissue disorders: Pruritus, rash, urticaria. Potentially Fatal: Rarely, hepatic failure; rhabdomyolysis (with or without secondary renal insufficiency).
Exclude the secondary causes of hypercholesterolaemia before treatment initiation. Obtain lipid profile (fasting or non-fasting) at baseline, within 4-12 weeks after treatment initiation, and then every 3-12 months thereafter. Monitor LFTs prior to starting treatment and as clinically indicated; creatine phosphokinase at baseline (particularly in patients with symptoms suggestive of myopathy and family history of statin intolerance or muscle disease) and regularly during treatment. Monitor for new-onset diabetes mellitus; signs and symptoms of myopathy or rhabdomyolysis during treatment.
Tương tác
Decreased bioavailability with bile acid sequestrants (e.g. colestyramine, colestipol); administer pravastatin at least 1 hour before or 4 hours after the bile acid sequestrant. Potentially Fatal: Increased risk of myopathy or rhabdomyolysis with systemic fusidic acid, fibrates (e.g. gemfibrozil, fenofibrate), ciclosporin, erythromycin, clarithromycin, and colchicine.
Tác dụng
Description: Mechanism of Action: Pravastatin is a competitive inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, an enzyme that catalyses the rate-limiting step involved in cholesterol synthesis. The inhibition of HMG-CoA reductase decreases intracellular cholesterol synthesis, resulting in increased low-density lipoprotein (LDL) receptors on cell surfaces and enhanced receptor-mediated catabolism and clearance of circulating LDL-cholesterol (LDL-C). Pharmacokinetics: Absorption: Rapidly but incompletely absorbed from the gastrointestinal tract. Absolute bioavailability: 17%. Time to peak plasma concentration: 1-1.5 hours. Distribution: Crosses the placenta; enters breast milk (small amounts). Volume of distribution: 0.46 L/kg. Plasma protein binding: Approx 50%. Metabolism: Metabolised in the liver to form 3-α-hydroxy-iso-pravastatin (primary metabolite); undergoes extensive first-pass metabolism. Excretion: Via faeces (70%); urine (approx 20%). Elimination half-life: Approx 1.5-2 hours.
Đặc tính
Pravastatin Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 54687, Pravastatin. https://pubchem.ncbi.nlm.nih.gov/compound/Pravastatin. Accessed June 26, 2024.
Bảo quản
Store between 15-30°C. Protect from light and moisture.
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