Acenocoumarol 4 SPM treats and prevents congestion (3 blisters x 10 tablets)

Dosage form Box of 3 blisters x 10 tablets
Specifications Acenocoumarol
Ingredient Atrial fibrillation, myocardial infarction, pulmonary artery obstruction, psoriasis, deep vein thrombosis

Ingredient

Composition information	Content
Acenocoumarol	4mg

Uses

indications

Acenocoumarol 4 mg is indicated for treatment and preventing congestion.

Pharmacological

acenocoumarol is an anti -vitamin K anti -coagulation drug. The liver synthesizes blood coagulation factors II, VII, IX and X, as well as protein C and S, requiring the presence of vitamin K. In this process, Vitamin K "active" is converted to oxidation into a "inactive" form, then activated again by vitamin K Epoxit Reductase 1 (VKORC1). Acenocoumarol is thought to be inhibited VKORC1, thus depleting functional source of vitamin K function and thus reduces the synthesis of positive coagulation factors.

After taken, vitamin K resisted to lower prothrombin in the blood for 36 to 72 hours. Treatment with anti -vitamin K drugs, after stopping the drug, anticoagulants can also last for 2-3 days. The drug restricts the development of the existing thrombosis and prevents secondary symptoms of thrombosis, although there is no direct thrombotic effect because it does not reverse the damage of ischemic tissue.

Pharmacokinetics

absorption

Acenocoumarol absorbs fast after taken, at least 60% of the dose is present in the circulatory system. The peak concentration of plasma is achieved after 1-3 hours of single -dose 10 mg and AUC value is proportional to the dose of 8 - 16mg.

Distribution

more than 98% acenocoumarol binds to protein, mainly with albumin. The distribution volume 0.16 - 0.18 l/kg for isomers R (+) and 0.22 - 0.34 l/kg for isomers s ( -).

Metabolism

Acenocoumarol is metabolized widely, the hydroxylation 6- and 7- of both isomers of acenocoumarol is the main metabolite and the Cytochrome P450 2C9 is the main place that converts into these four metabolites. Other enzymes related to metabolic (R) -acenocoumarol are CYP1A2 and CYP2C19. By reducing the keto group, two carbinol metabolites are formed.

The reduction of nitro groups forms amino metabolites. No metabolites in this group of substances have anticoagulant effects in humans, but they all work in animals. Properties can be related to CYP2C9 related gene for 14% of changes related to the meticulous response of acenocoumarol.

Elimination

About 29% are eliminated in feces and 60% in urine, with less than 0.2% of the dose excreted through the kidneys in the form of constant. The selling time of acenocoumarol from plasma is from 8 to 11 hours. The amount of plasma clearance is 3.65 hours after drinking. The total plasma removal of Acenocoumarol's isomers, has a significant higher blood coagulation activity, lower than the isomer s (-).

Special population:

Old geriatric patients: The concentration of plasma drugs is usually higher in 70 -year -old patients or higher when compared to younger patients, after using the same dose.

Renal failure: There is no clinical pharmaceutical information of acenocoumarol in patients with renal impairment. Based on the elimination of urinary tract of acenocoumarol, the ability to accumulate metabolites in patients with renal function cannot be excluded. Therefore, acenocoumarol is contraindicated in patients with severe renal impairment and must be cautious in patients with mild and medium renal impairment.

Hepatic failure: There is no clinical pharmaceutical information of acenocoumarol in patients with hepatic impairment. Based on the metabolism of acenocoumarol, and the ability to operate of reducing enzymes, CYP2C9, CYP1A2 and CYP3A4, clearly cleared clearance, thus using acenocoumarol is contraindicated in patients with severe and cautious liver failure in mild and medium -sized liver impairment patients.

Before taking Acenocoumarol 4 SPM treats and prevents congestion (3 blisters x 10 tablets)

How to use

Acenocoumarol 4 mg is the daily dose must always be used at the same time of the day. The pill must be swallowed with water.

Dosage

The dose of acenocoumarol must be personalized. If the value of PT/INR is within normal range before the beginning of treatment, the following dose schedule is recommended:

The initial dose is useful in the range of 2 mg/day to 4 mg/day, no initial dose is higher. The treatment can also start with a higher initial dose regime, usually 6 mg on the first day and the second day is 4 mg.

If the thromboplastin time is normal, the treatment must be built with caution.

Elderly patients (> 65 years old), patients with liver or severe heart failure with liver congestion or malnourished patients may require lower doses during the initial and maintenance treatment.

Thromboplastin time must be done daily at the hospital starting at the second or third dose until the blood clotting is stable within the target range. The time between tests can be expanded later, depending on the stability of the results. The blood sample to perform tests in the laboratory must always be performed at the same time of the day.

Maintain treatment and blood clotting tests:

The maintenance dose of acenocoumarol changes from patients to another and must be tested separately on the basis of PT/INR value. PT/INR must be evaluated at a regular period as at least once a month.

The maintenance dose is generally in the range of 1 to 8 mg daily depending on the individual patient, other diseases in the body, clinical indications and enhance the desire to resist blood coagulation.

Depending on clinical indicators, optimize blood coagulation resistance or treatment range is aimed at generally between Inr 2.0 and 3.5 values. The Inr value is higher than 4.5 may be required for separate cases. Inr* is recommended for oral blood coagulation treatment.

Indications

IrN is recommended

2.0 - 3.0

Atrial arrhythmia

2.0 - 3.0

2.0 - 3.5

The mechanical values of the heart.

2.0 - 3.5

The response of Thromboplastin of each individual compared to international comparative standards of the World Health Organization is reflected by the international sensitive index (ISI).

"International normal ratio" (INR) is given for the purpose of standardizing PT. Inr is the ratio of the patient's blood coagulation resistance for normal plasma pt and thromboplastin in the same sword system that achieves the capacity of the value defined by the international sensitive index.

Special population

Renal failure: Acenocomarol is not recommended for patients with severe renal impairment due to increased risk of bleeding. Be cautious in patients with mild and medium renal failure.

liver failure: Acenocoumarol is not recommended for patients with severe liver failure due to increased risk of bleeding. Must be cautious in patients with mild and medium liver failure.

Population of children: Experience in oral blood coagulation drugs including acenocomarol in children are limited. Precautions and monitoring more often than prothrombin and INR are recommended.

Elderly: Lower doses are recommended, adult dose may sufficient for older patients. Precautions and monitoring more often than prothrombin and INR are recommended. ethnic group: CYP2C9 enzyme system shows many types and frequencies in the community are different. In European, North African, West Asia and India, there are CYP2C9*2 and CYP2C9*3 with frequency of 12% and 8%. Patients with one or more gene variants corresponding to this CYP2C9 reduces the clearance of S - Acenocoumarol. Patients in Africa, CYP2C9*2 and CYP2C9*3 have a corresponding gene frequency lower than 1 - 4% and 0.5 - 2.3%, compared to European, North African, Western Africa and India regions. The Japanese have a lower gene frequency of 0.1% and 1 - 6% for CYP2C9*2 and CYP2C9*3. The maintenance dose of acenocoumarol is based on genotype. Detailed information about the maintenance and medium dose is based on the CYP2C9 genotype presented in Table 1.

Table 1: Genetic genotype CYP2C9 and the maintenance dose of acenocomarol:

genotype

Expected dose (mg/week)

Average doses (mg/week)

Scope

169

17,1

8.7

15,8

2,3 - 61

14,4

6.3

13.5

3.5 - 37.5

11,0

5,1

10.5

2,3 - 22

Specific dosage depends on the condition and level of progression of the disease. For a suitable dose, you need to consult a doctor or medical specialist.

What to do when overdose?

Symptoms:

Bleeding occurs within 1-5 days after drinking, nose bleeding, hematuria, stomach bleeding, vaginal bleeding, bleeding, bleeding under the skin, gums, uterus and joints. Moreover, symptoms: tachycardia, hypotension, peripheral circulatory disorders, nausea, diarrhea, abdominal pain.

Management:

Overdose is usually based on Inr and signs of bleeding, adjustment measures must be sequentially so as not to cause thrombosis.

If INR is on the treatment area but below 5, and the patient does not show signs of bleeding or does not need to quickly adjust blood clotting before surgery: 1 time to take 1 medication, then continue treatment at lower doses when he has reached the desired INR. If the Inr is very close to the desired INR, then reduce the dose without having to quit the medication.

If Inr above 5 and less than 9, the patient does not show signs of bleeding other than bleeding or nosebleeds: remove 1 or 2 times to take anticoagulant drugs, measure the Inr more often and then have the int INR desired, take the drug again at a lower doses. If the patient has other risks of bleeding, giving up the medication 1 time and giving vitamin K from 2.5 mg by oral, or 0.5 - 1mg by intravenous line slowly for 1 hour.

If Inr is over 9 without bleeding, remove 1 taken medicine and use vitamin K from 3 to 5mg by oral, or 1 - 1.5 mg by slow intravenous infusion for 1 hour allows to reduce the INR within 24 - 48 hours; Then use acenocomarol in lower doses, monitor the Inr regularly and if needed to be repeated with vitamin K.

If it is necessary to quickly adjust the anticoagulant effect in the absence of severe bleeding or severe overdose (for example, Inr above 20), taking a dose of 10 mg of vitamin K slowly intravenously and depending on the requirements of emergency, combined with fresh frozen plasma. Vitamin K may repeat every 12 hours. After high doses of vitamin K treatment, there may be a period of time before the return of vitamin K anti -vitamin K.

In case of poisoning due to an accident, it must also be evaluated according to INR and manifests bleeding complications. Must measure Inr for many days later (2-5 days), taking into account for half a long life of anticoagulant drugs.

In case of overdose, take the patient to the nearest emergency room for supportive treatment. The need for treatment by gastrointestinal, adding activated carbon and taking cholestyramine helps increase the elimination of the drug. The benefits of treatments should be balanced with the risk of bleeding of each patient.

Note:

Gastric lavage may increase the risk of stomach bleeding.

Do not use vitamin K as antagonists, especially those who request continuous anticoagulant use such as patients using artificial valve.

What to do when forgetting 1 dose? If the patient forgets the prescribed dose at the schedule, the dose must be used as soon as possible during the same day. Patients should not use the forgotten dose by double the daily dose to compensate for the forgotten doses, but must refer to the treatment doctor.

Side Effects

When using Acenocoumarol 4 mg, you may experience unwanted effects (ADR).

Common, ADR> 1/100

Body: bleeding.

central nervous system: bleeding. digestive: bleeding. Eye: bleeding.

Uncommon, 1/1000

Skin: allergies, hair loss, necrotic hemorrhage.

digestive: diarrhea, stomach - intestinal disorders.

Osteoarthritis: Individual joint pain.

blood and lymphatic system: vasculitis. liver: liver damage.

Rare, 1/10,000

Body: Hair loss.

digestive: digestive disorders, loss of appetite, nausea, vomiting. Skin: localized skin necrosis, may be due to genetically deficient C protein C or homogeneous factor is S protein, allergic skin. blood and lymphatic system: vasculitis.

Instructions on how to handle ADR:

When experiencing side effects of the drug, it is necessary to stop using and notify the doctor or go to the nearest medical facility for timely treatment.

Warnings

Before using the drug you need to read the instructions carefully and refer to the information below.

Contraindicated

Acenocoumarol 4mg contraindications in the following cases:

Hypersensitivity to acenocoumarol, the derivatives of cooumarin or the ingredients in the drug.

Pregnant women.

The elderly, alcoholism, neurological disorders or people who have no supervision.

All conditions of excessive hemorrhage may have clinical benefits such as hemorrhage and/or hemorrhagic disorder.

Right before, or after surgery on the central nervous system or eye and trauma surgery is related to the excessive exposure of the tissues.

Gastrointestinal ulcers or thick hemorrhage of the intestine - intestinal, urinary - genital or respiratory system.

Hemorrhage of brain blood vessels.

Acute pericarditis, pericardial fluid.

Inflammation of the pericardium.

Severe hypertension.

severe or severe liver failure and cases of fibrin decomposition activity increased with activities of lung, prostate or uterus.

Caution when using

transformation from heparin treatment

In clinical states that require fast blood coagulation, the initial treatment with heparin is more preferred because the blood coagulation effect of acenocoumarol is slow. The conversion to acenocoumarol can start simultaneously with heparin treatment or may slow down depending on the clinical state.

To ensure continued blood clotting resistance, it is recommended to continue prescribing heparin treatments in at least 4 days after starting acenocoumarol treatment and continuing heparin treatment until the INR is in the target range for at least two consecutive days. During the conversion phase, closely monitoring the effect of anticoagulants is necessary.

Dental treatment and surgery

Patients who use acenocoumarol, who undergo surgery or invasion requires strict exploration of their blood clotting status. Under the definite conditions, such as when the surgery position is limited and accessible, it is allowed to effectively use the local processes for hemostasis, very small dental and surgical processes can be performed during the continued blood coagulation resistance, without excessive hemorrhage.

The decision to stop acenocoumarol, even in a short time, must carefully consider the risks and individual benefits. The introduction of the northern bridge to treat blood coagulation, such as heparin must be based on careful evaluation of the risk of embolism and bleeding.

Hepatic failure

Be cautious in patients with mild and medium liver failure because of the synthesis of coagulation factors may be impaired or may have abnormal activity of platelets.

kidney failure

Due to the ability to accumulate metabolites when impaired renal function, be cautious in patients with mild and medium renal impairment.

heart failure

In severe heart failure, the expression of extremely cautious dose must be done, as congestion can reduce the activity of gamma - carboxylation of blood clotting factors. However, with the recovery of liver congestion, it is necessary to increase the dose.

Hematology

Be cautious with patients who have known or suspected abnormal bleeding after injury, deficiency of protein C or protein s.

Special population

In patients with children and older (> 65 years old), caution and monitoring more often than prothrombin and INR are recommended.

Other forms:

Strict medical monitoring must be performed in cases or conditions that can reduce the protein bonds of acenocoumarol (such as: hyperthyroidism, tumor, kidney disease, inflammation and infection).

Disorders affecting the absorption of the stomach - intestines may change the anticoagulant effect of acenocoumarol.

During treatment with anti -coagulation drugs, injecting in muscle can cause tumors and must be avoided.

subcutaneous injection and intravenous injection can be performed without causing this complication.

Careful care must be done is necessary to shorten PT/INR (Thromboplastin time) for the diagnosis or treatment process (such as X -ray, spinal teasing, very small surgery, tooth extraction ...).

Patients with rare genetic problems in galactose tolerance, Lapp lactase deficiency or malposure - Galactose are not allowed to use this drug.

The ability to drive and operate machinery

does not affect the ability to drive and use machines.

Pregnancy

There was a statistics of about 4% of the fetal deformity when the mother took this medication in the first quarter of pregnancy. In the next quarters, there is still risk (including miscarriage). So only use the drug when it is impossible for heparin.

Breastfeeding period

Avoid breastfeeding. If you have to breastfeed, you should compensate for vitamin K for the child.

Interactive drug

A lot of drugs can interact with anti -vitamin K drugs, so they need to monitor patients 3-4 days after adding or removing combination drugs

Contraindications for coordination:

Aspirin (especially with high doses of over 3 g/day) increases anticoagulant effects and the risk of bleeding due to platelet aggregation inhibits and transferring anticoagulant drugs from bonding with plasma proteins.

Miconazole: Surprisingly hemorrhage can be severe due to increased blood in the blood and inhibiting metabolism of anti -vitamin K drugs.

phenylbutazon increases anticoagulants combined with irritation of the gastrointestinal mucosa.

Pyrazol nonsteroidal anti -inflammatory drugs: Increased risk of bleeding due to platelet inhibition and gastrointestinal mucosa.

Do not coordinate:

Aspirin with a dose of less than 3 g/day.

Non -steroid anti -inflammatory drugs, including selective inhibition COX - 2.

Chloramphenicol: Increases the effect of anticoagulant oral medications due to reducing the metabolism of this drug in the liver. If it is not possible to avoid coordination, you must check the Inr more often, adjust the dose in and after 8 days of stopping chloramphenicol.

Diflunisal: Increasing the effect of anticoagulant oral medications due to competition associated with plasma proteins.

Should take other painkillers, such as paracetamol.

Caution when coordinating:

Allopurinol, aminoglutethimid, amiodaron, Androgen, anti -depression drugs Serotonin, Benzbromaron, Bosentan, Carbamazepin, Cephalosporin, Cimetidin (over 800 mg/day), Cisaprid, Cholestyramin, Corticoid (except Hydrocortison used in Addisane) Cyclin, cytotoxic drugs, fibrates, fungal Azols, fluoroquinolones, heparin, thyroid hormones, enzyme induction drugs, statins, macrolids (except for spiramycin), neviparin, efavirenz, imidazol group, orlistat, pentoxifylin, phenytoin, propafenon, propafenon, propafenon Ritonavir, Lopinavir, some sulfamids (sulfamethoxazol, sulfafurazol, sulfamethizol), sucraflate, cancer medicine (Tamoxifen, Raloxifen), Tibolon, Vitamin E above 500 mg/day, alcohol, anti -thrombotic drugs, blood pepper, ... also change anti -coagulation effect.

Acenocoumarol's anticoagulant effects:

allurinol; Anabolic steroids; Androgen.

Anti -arrhyths (such as amiodarone, quinidine).

Antibiotics, broad -spectrum antibiotics (such as amoxicillin, coamoxiclav) macrolid (such as erythromycin, clarithromycin).

Cephalosporin for the second and third generation.

metronidazole; Quinolone (such as ciprofloxacin, norfloxacin, ofloxacin); Tetracyclines; Neomycin; Chloramphenicol; Fibrates (like clofibric acid).

Fibrates derivatives or have the same structure (such as gemfibrozil, fenofibrate). Disulfiram; Etacrynic acid; Glucagon; Anti -H2 (such as cimetidine).

Imidazole derivatives (Econazole, Fluconazole, Ketoconazole, Miconazole).

paracetamol; Sulfonamides (including co-trimoxazole); Antidiabetic (Glibenclamide).

Dextrothyroxine.

sulfinyrazone; SulphonylueS (Tolbutamide and Chlopropamide).

Statin (Atorvastatin, Fluvastatin, Simvastatin).

Selective Serotonin reabsorption inhibitors (fluoxetine, paroxetine); Tamoxifen; 5-Fluorouracil; Tramadol.

corticosteroid (methylprednisolone, prednisone).

Inhibitors of CYP2C9, hemostatic drugs include heparin, platelograph inhibitors (clopidogrel, dipyridamole), salicylic acid and derivatives such as acetylsalicylic acid, para - aminosalicylic acid; diflunisal, phenylbutazone and pyrazolone derivatives (sulfinpyrazone); Non -steroid anti -inflammatory (NSAIDs) includes COX - 2 inhibitors (Celecoxib) and methylprednisolone. They can increase the risk of bleeding. In case of simultaneous use is inevitable, blood clotting tests should be done regularly.

Drugs that reduce the anticoagulant effect of acenocoumarol:

Aminoglutethimide.

anti-cancer drugs (Azathioprine, 6-Mercaptopurine); Barbiturates (phenobarbital); Carbamazepine.

cholestyramine; Griseofulvin; Birth control pills; Rifampicin.

Diuretics, induction agents: CYP2C19, CYP2C9 or CYP3A4.

In addition, Protease inhibitors (Indinavir, Nelfinavir, Ritonavir, Saquinavir) also affects the anticoagulant effect of the drug and has no reports on increased or decreased anticoagulants of the drug.

Serum levelin concentration may increase when treated simultaneously with Hytantoin's derivatives (such as phenytoin).

Acenocoumarol may increase hypoglycemia when using sulphonylurea derivatives (such as glibenclamide, Glimepiride).

Patients with liver dysfunction when treated with acenocoumarol should limit drinking.

When treated with acenocoumarol, patients should avoid drinking juice. Strengthen monitoring and monitoring of INR for patients often using kumquat juice.

Storage

In a dry place, avoid light, temperatures below 30 ° C.

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