华法林（华法林）
1. 概述
2. 药理机制
3. 药代动力学
12.3 Pharmacokinetics Warfarin sodium is a racemic mixture of the R – and S -enantiomers of warfarin. The S -enantiomer exhibits 2 to 5 times more anticoagulant activity than the R -enantiomer in humans, but generally has a more rapid clearance. Absorption Warfarin is essentially completely absorbed after oral administration, with peak concentration generally attained within the first 4 hours. Distribution Warfarin shows a volume of distribution of about 0.14 L/kg. Approximately 99% of the drug is bound to plasma proteins. Metabolism
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4. 临床应用
- 其他特指的动脉或小动脉疾病
- 静脉血栓栓塞症
- 栓塞性闭塞引起的脑缺血性卒中
- 心房颤动
可用剂型
- 口服 > 固体 > 片剂：5毫克（有刻痕）（钠盐）；1毫克（有刻痕）（钠盐）；2毫克（有刻痕）（钠盐）；0.5毫克（有刻痕）（钠盐）；3毫克（有刻痕）（钠盐）
- 口服 > 固体 > 片剂：5毫克（有刻痕）（钠盐）；1毫克（有刻痕）（钠盐）；2毫克（有刻痕）（钠盐）；0.5毫克（有刻痕）（钠盐）；3毫克（有刻痕）（钠盐）
备注
- 备注：补充目录 — 需要专门的诊断或监测设施，和/或专科医疗护理，和/或专业培训。
- 首次列入世界卫生组织基本药物标准清单：1977年
- 电子版基本药物标准清单条目：
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来源：世界卫生组织基本药物标准清单（第23版，2023年）
5. 剂量信息
Individualize dosing regimen for each patient, and adjust based on INR response. ( 2.1 , 2.2 ) Knowledge of genotype can inform initial dose selection. ( 2.3 ) Monitoring: Obtain daily INR determinations upon initiation until stable in the therapeutic range. Obtain subsequent INR determinations every 1 to 4 weeks. ( 2.4 ) Review conversion instructions from other anticoagulants. ( 2.8 ) 2.1 Individualized Dosing The dosage and administration of warfarin sodium tablets must be individualized for each patient according to the patient’s International Normalized Ratio (INR) response to the drug. Adjust the dose based on the patient’s INR and the condition being treated. Consult the latest evidence-based clinical practice guidelines regarding the duration and intensity of anticoagulation for the indicated conditions. 2.2 Recommended Target INR Ranges and Durations for Individual Indications An INR of greater than 4 appears to provide no additional therapeutic benefit in most patients and is associated with a higher risk of bleeding. Venous Thromboembolism (including deep venous thrombosis [DVT] and PE) Adjust the warfarin dose to maintain a target INR of 2.5 (INR range, 2 to 3) for all treatment durations. The duration of treatment is based on the indication as follows: For patients with a DVT or PE secondary to a transient (reversible) risk factor, treatment with warfarin for 3 months is recommended. For patients with an unprovoked DVT or PE, treatment with warfarin is recommended for at least 3 months. After 3 months of therapy, evaluate the risk-benefit ratio of long-term treatment for the individual patient. For patients with two episodes of unprovoked DVT or PE, long-term treatment with warfarin is recommended. For a patient receiving long-term anticoagulant treatment, periodically reassess the risk-benefit ratio of continuing such treatment in the individual patient. Atrial Fibrillation In patients with non-valvular AF, anticoagulate with warfarin to target INR of
[Truncated — see full prescribing information for complete dosing data]
6. 不良反应与风险
The following serious adverse reactions to warfarin sodium are discussed in greater detail in other sections of the labeling: Hemorrhage Tissue Necrosis Calciphylaxis Acute Kidney Injury Systemic Atheroemboli and Cholesterol Microemboli Limb Ischemia, Necrosis, and Gangrene in Patients with HIT and HITTS Other Clinical Settings with Increased Risks Other adverse reactions to warfarin sodium include: Immune system disorders: hypersensitivity/allergic reactions (including urticaria and anaphylactic reactions) Vascular disorders: vasculitis Hepatobiliary disorders: hepatitis, elevated liver enzymes. Cholestatic hepatitis has been associated with concomitant administration of warfarin sodium and ticlopidine. Gastrointestinal disorders: nausea, vomiting, diarrhea, taste perversion, abdominal pain, flatulence, bloating Skin disorders: rash, dermatitis (including bullous eruptions), pruritus, alopecia Respiratory disorders: tracheal or tracheobronchial calcification General disorders: chills Most common adverse reactions to warfarin sodium are fatal and nonfatal hemorrhage from any tissue or organ. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Teva at 1-888-838-2872 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
7. 戒断与依赖
8. 药物相互作用
Concomitant use of drugs that increase bleeding risk, antibiotics, antifungals, botanical (herbal) products, and inhibitors and inducers of CYP2C9, 1A2, or 3A4. ( 7 ) Consult labeling of all concurrently used drugs for complete information about interactions with warfarin sodium or increased risks for bleeding. ( 7 ) 7.1 General Information Drugs may interact with warfarin sodium through pharmacodynamic or pharmacokinetic mechanisms. Pharmacodynamic mechanisms for drug interactions with warfarin sodium are synergism (impaired hemostasis, reduced clotting factor synthesis), competitive antagonism (vitamin K), and alteration of the physiologic control loop for vitamin K metabolism (hereditary resistance). Pharmacokinetic mechanisms for drug interactions with warfarin sodium are mainly enzyme induction, enzyme inhibition, and reduced plasma protein binding. It is important to note that some drugs may interact by more than one mechanism. More frequent INR monitoring should be performed when starting or stopping other drugs, including botanicals, or when changing dosages of other drugs, including drugs intended for short-term use (e.g., antibiotics, antifungals, corticosteroids) [ see Boxed Warning ]. Consult the labeling of all concurrently used drugs to obtain further information about interactions with warfarin sodium or adverse reactions pertaining to bleeding. 7.2 CYP450 Interactions CYP450 isozymes involved in the metabolism of warfarin include CYP2C9, 2C19, 2C8, 2C18, 1A2, and 3A4. The more potent warfarin S -enantiomer is metabolized by CYP2C9 while the R -enantiomer is metabolized by CYP1A2 and 3A4. Inhibitors of CYP2C9, 1A2, and/or 3A4 have the potential to increase the effect (increase INR) of warfarin by increasing the exposure of warfarin. Inducers of CYP2C9, 1A2, and/or 3A4 have the potential to decrease the effect (decrease INR) of warfarin by decreasing the exposure of warfarin. Examples of inhibitors and inducers of CYP2C9, 1A2, and 3A4 are below in Tabl
[Truncated — see full prescribing information for complete interaction data]
9. 相关化合物
- CAS Number: 81-81-2
- Molecular Formula: C19H16O4
- Molecular Weight: 308.3 g/mol
- IUPAC Name: 4-hydroxy-3-(3-oxo-1-phenylbutyl)chromen-2-one
作用机制
12.1 Mechanism of Action Warfarin acts by inhibiting the synthesis of vitamin K-dependent clotting factors, which include Factors II, VII, IX, and X, and the anticoagulant proteins C and S. Vitamin K is an essential cofactor for the post ribosomal synthesis of the vitamin K-dependent clotting factors. Vitamin K promotes the biosynthesis of γ-carboxyglutamic acid residues in the proteins that are essential for biological activity. Warfarin is thought to interfere with clotting factor synthesis by inhibition of the C1 subunit of vitamin K epoxide reductase (VKORC1) enzyme complex, thereby reducing the regeneration of vitamin K 1 epoxide .