Warfarin @ - ( *** ) Coumarin and Indandione derivative
Drug Name:Warfarin @ - ( *** ) Coumarin and Indandione derivative
List Of Brands:
Indication Type Description:
Drug Interaction
Indication
Adverse Reaction
Contra-Indications
Dosages/ Overdosage Etc
Patient Information
Pharmacology/ Pharmacokinetics
Pregnancy and lactation
Drug Interaction:
Anticoagulants include- Enoxaparin, Dalteparin, Heparin, Warfarin, Anisindione
Refer - Warfarin
Interacting drugs -summary
+ Anticoagulants
Acaetaminophen / Beta blockers / Clofibrate/ Corticosteroids / Tetracylines / Dextrothyroxine/
Disulfram/ Erythromycin / Fluconazole / Fluconazole / Gemfibrozil / Glucagon/ Hydantoin /
Isoniazid / Ketaconazole / Miconazole / Propxyphene / Quinolones / Sulfonamides /
Tamoxifen / Tamoxifen / Thioamines / Thyroid hormones
these agents may increase the antocoagulant effect of
The risk of bleeding may be increased. The mechanism of is unknown or complicated
Aminoglycosides
A small rise in warfarin-induced hypoprothrombimemia may occur, possibly due to
interference in absorption of dietary Vitamin K metabolism
Amiodarone / Chloramphenicol/ Cimetidine / Ifosfamide / Lovastatin / Metronidazole /
Omeprazole / Phenyl butazone / Propafenone / Quinidine / Quinine / SMZ-TMP /
Sulfinpyrazone
these agents may increase the antocoagulant effect of warfarin or anisindione
due to inhibition of the anticoagulants hepatic metabolism.
The risk of bleeding maybe increased
Chloral hydrate/ Loop diuretics/ Nalidixic acid
these agents may increase the antocoagulant effect of warfarin or anisindionone
due to displacement from binding sites. The risk of bleeding may be increased
Aminoglycosides / Mineral oil / Tetracyclines / Vitamin E
these agents mayincrease the anticoagulant effect of warfarin or anisindione due to
interference with Vitamin K. The risk of bleeding may be increased
Cephalosporins/ Diflunisal / NSAIDs / Penicillins / Salicylates / Ascorbic acid/
Dicloxacillin / Ethanol / Ethlorvyno/ Griseofluvin / Naficillin / Sucralfate / Trazadone
these agents may increase the anticoagulant effect of warfarin and increase the risk
of bleeding due to effects on platelet function, and in the case of NSAIDs, GI irritant effects
Amioglutethimide/ Barbiturate / Carbamazapine/ Etretinate / Glutethimide / Rifampicin
these agents may decrease the anticoagulant effect of warfarin or anisindione due to
induction of the antocoagulants hepatic micrsomal enzymes
+ Anticoagulants
Hemin
hemin has exhibited transcient, mild anticoagulant effects during
clinical studies, therfore, avoidconcurrent anticoagulant therapy.
The extent and duration of hypocoagulable state has not been
established
Contraceptives Oral
OCs can increase levels of certain circulating clotting factors and
reduce antithrombin III levels, therapeutic efficacy of the anticoagulants
may be decreased by OCs. However, both an increased and
decreased effect has occurred
Epoprostenol
coadmin can increase the risk of bleeding, although this did not
occur in clinical trials
Sulfinpyrazone
anticoagulant activity of warfarin or amnisindione may be
enhanced due to anticoagulants hepatic metabolism. May
increase the risk of bleeding
Allopurinol
increased anticoagulant action of some agents may be enhanced,
but not that of warfarin
Fluvoxamine/ Paroxetine/ Sertraline + Warfarin
a pharmacodynamic interaction (increased bleeding) diathesis in the face
of unaltered prothrombin time(PT) may occur with paroxetine.
HMG Cog reductase inhibitors + warfarin
anticoagulant efect of warfarin may be increased. Monitor
prothrombin time
NSAIDs
coadm. may prolong prothrombin time (PT). Also consider the effects
of NSAIDs, have on platelet function and gastric mucosa.
Monitor PT and patients closely, and watch for signs and
symptoms of bleeding.
Corticosteroids
anticoagulant dose requirements may be reduced. Conversely,
corticosteroids may oppose the anticoagulant action.
Barbiturates
barbiturate can increase metabolism of anticoagulants resulting in a
decreased response. Patients stabilised on anticoagulants may require
dosage adjustments if barbiturates are added to or withdrawn
Valproic acid
the potential exists for valproate to displace warfarin from protein binding
sites. Monitor coagulation tests
Carbamazepine
Carbamazepine may increase metabolism of these agents due to
induction of microsomal enzyme induction. Hypoprothrombinemic effect
of the anticoagulants may be decreased
Sucralfate
a decrease in the hypoprothrombinemic effect of warfarin may occur
Sulfonamides + anticoagulants
warfarins anticoagulation action may be enhanced. Haemorrhage
could occur
Thyroid Hormones
anticoagulant action is increased, a decreased dose may be necessary
Thiazide diuretics
anticoagulant effcts may be diminished
Loop diuretics
anticoagulant activity may be enhanced
Quinidine
anticoagulation may be potetiated, hemorrhage may occur.
Omeprazole
increases anticoagulant effect of warfarin or anisindione due to
anticoagulants hepatic metabolism. Risk of bleeding may be increased
Cisapride + Anticoagulants
since coagulation times may be increased, it is advisable to check .
them after 1 week after the start and discontinuation of cisapride therapy.
Adjust the anticoagulant dose if necessary
Penicillins parentral
Large IV doses of penicillin can increase bleeding risks of
anticoagulants by prolonging bleeding time. Conversely,
Nafcillin has been associated with warfarin resistence
Fluroquinolones + Anticoagulants
the effects of the anticoagulant may be increased. Monitor prothrombin
time
Tetracycline
increase the hypoprothrombinenic effect of concurrent anticoagulants
Monitor prothrombin activity
Azithromycin + Warfarin
azithromycin did not affect the prothrombin time (PT) response to single dose
of warfarin. However concurent use of macrolides and warfarin, associated
with increased anticoagulant effects. Carefully monitor PT in patients
treated with azithromycin and warfarin concomittantly
Metronidazole
may increase the anticoagulant effect of Warfarin oranisindione
due to anticoagulants hepatic metabolism. Risk of bleeding may
be increased
Fluconazole
May increase the anticoagulant effect of warfarin or anisindione
Risk of bleeding may be increased. Mechanism of action not
known or complicated
Itraconazole
anticoagulant of warfarin may be enhanced.Monitor prothrombin
time
TMP+ SMZ
prothrombin time of warfarin may be prolonged. Monitor coagulation
tests and adjust dosage as required
Typhoid Vaccine
as with other drugs administered by IM injection, give polysaccharide
vaccine with caution to persons receiving anticoagulant therapy
Influenza virus Vaccine
although influenza vaccination reportedly inhibits the clearance of these
agents further studies have failed to show any adverse effects of
influenza vaccination among patients taking these drugs
Hepatitis B vaccine
as with drugs admministered by IM injection give hepatitis B vaccine
with caution to persons receiving anticoagulant therapy
Alprostadil
Patients on anticoagulants such as heparin or warfarin may have increased
propensity for bleeding after intracavernosal injection
Indication:
Anticoagulant
Anticoagulants include- Enoxaparin, Dalteparin, Heparin, Warfarin, Anisindione Refer - Warfarin
Adverse Reaction:
Haemorrhage- is the principal adverse effect of oral anticoagulant. Skin necrosis has occured rarely.Consider the posiblity of of hemorrhage in evaluating the condition of any anticoaguated patient with complaint does that do not indicate an obiuos diagnosis.
Others include- nausea, diarrhoea, pyrexia, dermatitis,urticaria,alopecia,sore mouth,mouth ulcers,red-orange urine, paralytic ileus,intestinal obstruction from submucosal or intramural haemorrhage.
Necrosis or gangrene of the skin and other tissues,vomiting,anorexia,abdominal cramps,
hepatotoxicity, cholestic jaundice.
Anisindione- dermatitis has been the only reported reactrin consistently associated with anisinione.
The following reactions have been reported with anisindione.-
Headache, sore throat, blurred vision, paralysis of accomodation, steatorrhea, heptitis, liver damage,renal tuibular necrosis, albunineria, anuria, myleoid immaturity, lecuocyttes aagglutins, red cell aplasia,atypical monocellular cells, leukopenia, leukocytosis, anemia, thrombocytopenia, eosinophollia, agranulocytosis, jaundice, nephropathy.
Warfarin- other side effects which are infrequent include
Cutaneous- necrosis or gangrene, of thge skin and other tissue
GI- vomiting, anirexia, abdominal cramping, diarrhea, hepatotoxicity,cholestatic jaundice
Miscellaneous- fever,symetic cholestrerol micromicroembolism, -purple toe- syndrome, hypersentivity reactions, compressive neuropathy, secondary to hemorrhage adjacent to a nerve (rare)
Contra-Indications:
Pregnancy,maemorrhagic tendencies,hemophillia,thrombocyto-penic purpura,leukemia,recent or contemplated surgry of eyeor CNS,major regional lumbar block,anesthesia,or surgery resulting in large open surfaces,patients bleeding from GI,respisratory or GU tract,threatened aborption,aneurysm ascorbic acid deficiency, history of bleeding diasthesis.
Special precautions:
Monitor prothrombin time. Most serious risks associated with anticoagulant therapy are hemorrhage in any tissue or organ and less frequently necrosis or gangrene of skin and other tissues.This has resulted in death or permanent disability. Haemorrhagic tendency may be manifested by haematuria,skin petechiae,haemorrhage into or from a wound or ulcerating lesion
.Caution patients to report any sign of bleeding, bruising, red or dark brown urine or black
or red stools.
Hemorrhage/necrosis- the most serious risks associated with anticaogulant therapy are hemorrhage in any tissue or organ and less frequently necrosis of skin and tissues, this has resulted in death and permanent disability. Diagnose carefully to determine when anticoagilants are suspected by an underlying disease. Discontinue therapy when antocaogulants are suspected, consider heparin therapy.
Purple toe syndrome- anticoagulant therapy amy enhance the release of artheromatous plaque emboli thereby increasig the risk of complications from systemic cholesterol microembolization including the -purple toe syndrome-. discontinuation of therapy is recommemded when such phenomena are observed.
Adrenal hemorrhage- with resultant acute adrenal insufficiency has ocurred. discontinue therapy if signs and symptoms of acute adrenal hemorrhage or insufficiency develop.
Special risk patients- there is an increased risk with the use of anticoagulants in the following conditions-
Trauma, infection (concomittant with antibiotic therapy may alter internal florea) renal
insufficiency, prolonged dietary insufficiencies,severe to moderate hypertension etc.
Throughly evaluate the benefits vs the enhanced risk of hemorrhage.
Protein C deficiency- tissue necrosis occur in absence of protein C deficiency. Suspect this condition if threre is a history of recurrent episodes of thromboembolic disoredrrs. in the patient or the family.
Agranucytosis and hepatitis- have been associated with anisondione use. Test urine periodically for albumin whenever anisindione is used because of renal damage.
Rebound hypercoagulability- was thought to oiccur upon sudden anticoagulant withdrawal, but has not been reproducible. Therefore tappering the dose over 3 to 4 weeks is recommended if possible.
Hypersensitivity- discontinue the medication at the first sign of hyperersentivity reactions.
Renal.hepatic function impairment- use with caution.
Elderly- may be more sensitive to these agents.
Pregnancy- if a patient becomes pregnant during therapy, apparise her of the potential risks to the fetus and discuss the possibility of terminating the pregancy.
Lactation- effects on premature infants have not been establshed.
Children- safety for use in children < 18 years have not been estabished.
Dosages/ Overdosage Etc:
Indications:
Anticoagulant
Dosage:
Initiate with 10 mg/day for 2 to 4 days. Adjust daily dose according to PT or INR determinations.
Use lower dose in elderly patients. Bioequivalence problems known with different brands.
Brand interchange is not recommended.
Overdosage
Symptoms-
Early microscopic hematuria, ecessive menstrual bleeding, melena petichiae, oozing form of superficial injuries(eg. nicks made by shaving, bleeding from gums after brushing teeth, excessive bruising)
Treatment
1. Excessive anticoagulation with or without bleeding, is readilycontrolled by discontinuing
therapy and if necessary, by administration of oral or parentral phytonadione
Missed dose-
1. If you miss a dose of this medicine, take it as soon as possible, then go back to yourregular dosing schedule.
2. If you do not remember until the next day, do not take the missed dose at all, do not double the next dose.
3. Doubling the dose may cause bleeding.
4. Instead goback to your regular dosing schedule.
5. It is best to keep a record of each dose as you use it to avoid mistakes.
6. Also, be sure to give your doctor a record of any doses you miss.
6. If you have any questions about this, check with your doctor.
Patient Information:
Anticoagulants include- Enoxaparin, Dalteparin, Heparin, Warfarin, Anisindione
1. Dosing is highly individual and may have to be adjusted based on lab test results. Strict
adherence to prescribed dosage schedule is necessary.
2. Do not take or discontinue any other medication, except on advice of physician or pharmacist.
Avoid alcohol, salicylates and drastic changes in dietary habits.
3. Oral anticoagulants may cause a red-orange discolouration of alkaline urine.
4. Notify physician if unusual bleeding or bruising, red or dark brown urine (blood), red or tar
black stools or diarrhea occurs
5. Do not change brands without consulting a physician or pharmacist.
6. Consult physician before undergoing dental work or elective surgery.
7. Pregnancy- anticoagulants may cause birth defects- do not begin this medicine during pregnancy and do not become pregnant while taking it.
8. Breast feeding- warfarin is not likely to cause problems in nursing babies. A bood test can be done if unwaranted effects are occuring in the nursing baby.
9.Children- very young basbies may be sensitive to anticoagulants. May increase the chance of bleeding during treatment.
10. Elderly- may increase the chance of bleeding.
11. Instruct patients to avoid alcohol consumption
12. Instruct patient to avoid any activity or sport that may result in traumatic injury
13. Advice patients that PT tests and regular visits to their health care provider or clinic are needed to monitor therapy
14. Instruct patients to carry identification stating that warfarin is being taken
15. If the prescribed dose of warfarin is forgotten, instruct patients to notify their health care
provider immediatly. Instruct patients to take the dose as soon as possible on the same
day, but do not take a double dose of warfarin the next day to make up for the missed
doses.
16. The amout of vitamin K in food may affect therapy with warfarin. Advice patients to eat healthy balanced diet maintaing a consistent amount of vitamin K. Instruct patients to avoid drastic changes in dietary habits, such as eating large amounts of green leafy vegetables. Instruct patients to avoid intake of cranberry juice or any other cranberry products.
Encourge patients to notify healthcare provider if any of these products are part of their
diet
17. Instruct patients to contact their health care provider to report any illness, such as diarrhea, infection or fever.
18. Advice patients to notify their health care provider immediately if any unusual bleeding or
symptoms occur. Signs and symptoms of bleeding include pain, swelling, or discomfort,
prolonged bleeding from cuts, increased menstrual flow or vaginal bleeding of gums from
brushing , unusual bleeding or bruising, red or dark brown urine, red or tar black stools,
headache, dizziness, or weakness.
19. If therapy of warfain is discontinued, caution patients that the anticoagulant effects of
warfarin may persist for about 2 to 5 days.
20. Inform patients that all warfarin products represent the same medication and should not
taken concomitantly as overdosage may result.
21. Other medicines- Tell your doctor if in case you are taking over -the counter ( OTC )
medicines, even aspirin, laxatives, vitamins or antacids
22. Other medical problems- Tell your doctor if you have had any of the following conditions recently-
Childbirth or Falls or blows to the body or head or Fever lasting more than a couple of days
Heavy or unusual menstrual bleeding , Insertion of interuterine disc (IUD) or
Medical or dental surgery or Severe or continuing diarrhea or Spinal anesthesia or
X-ray (radiation ) treatment- risk of serious bleeding is increased.
Pharmacology/ Pharmacokinetics:
Pharmacology:
Coumarins (warfarin) and indandiones (anisindione) interfere with the hepatic synthesis of Vitamin K dependent clotting factors which results in an vivo depletion of clotting factors VII, IX, X and II (prothrombin)
Pharmacokinetics:
Oral anticoagulants are generally rapidly and completely absorbed. Although serum levels are easily attained therapeutic effect is more dependent on depletion of clotting factors; duration of effect may vary more in relation to their half-lives. Anticoagulants are metabolised by hepatic microsomal enzymes and are excreted primarily in the urine and feces as inactive metabolites
Pregnancy and lactation:
Pregnancy:
If oral anticoagulants are used in pregnant women, do not administer during first trimeater, and discontinue prior to labor and delivery
Lactation:
Warfarin appears in breast milk in an inactive form. Infants nursed by warfarin treated mothers had no change in PT. Effects in premature infants have not been evaluated.
Children-
S afety for use in children < 18 years have not been estabished.
