GLAXO SMITH KLINE
GLAXO SMITH KLINE
Fondaparinux sodium 5mg/ml injection,
List of Related Indications:
- Prevention of DVT and PE
- Prevention of VTE
List Of Drugs:
- Fondaparinux Sodium - Selective Factor Xa Inhibitor- (Jan 2008)
Indication Type Description:
Dosages/ Overdosage Etc
Pregnancy and lactation
Fondaparinux does not markedly inhibit CYP450s ( CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1 or CYP3A4 ) in vitro Since Fondapatinaux does not bind significantly to plasma proteins other than ATIII ,
no interaction with other medicinal products by protein binding displacement are expected In other clinical studies performed with pondaparinaux the concomittant use of warfarin (oral anticoagulant ) acetylsalicylc acid (platelet inhibitor), piroxicam (non-steroidal anti-inflammatory, and digoxin ( cardiac glycoside ) did not significantly affect the pharmacokinetics or pharmacodynamics of Fondaparinaux Fondaparinaux neither influenced the INR activity of warfarin nor the bledding time under acetylsalicylic acid or piroxicam treatment not the pharmacokinetics or pharmacodynamics of digoxin at steady state.
Prevention of Venous Thromboembolic Events ( VTE) in patients undegonig major orthopedic surgery
Adverse reactions reported- Very common- ( 1/10) Common- ( 1/100, < 1/10) Uncommon (1/1000, < 1/100) Rare (1/10000, < 1/1000 ) Infections and infestations- Rare- post- operative wound disorders Blood and lymphatic system disorders- Common- Anaemia, bleeding (various including rare cases of intracranial/intracerebral & retroperitonial bleedings), purura Uncommon- Thrombocytopenia, thrombocythemia, abnormal platelets, coagulational disoder. Immune system disorders- Rare- allergic conditions Metabolism and nutrion disorders Rare- Hypokalemia Metabolism and Nutrion disorders- Rare- Hypokalemia Nervous system disorders- Uncommon- Headache Rare - Anxiety, confusion, dizziness, somnolence, vertigo Vascular disorders- Rare- Hypotension Respiratory,throaic and mediastinal disorders- Rare- Dyspnoea Gastrointestinal disorders- Uncommon- Nausea, vomiting Rare- Abdominal pain, dyspepsia, gastritis, constipation, diarrheoa Heptobiliary disorders- Uncommon- Abdominal liver function tests, hepatic enzymes increased Skin and subcutaneous tissue disorders- Uncommon- Rash, pruritis, wound secretion General disorders and administration site conditions- Common- Oedema Uncommon- Fever Rare- Reaction at injection sites, chest pain, lweg pain, fatigue, flushing, syncope Rare- Anxiety, confusion, dizziness, somnolence, vertigo
Known hyper sensitivity to or any of the components Active clinically significant bleeding Acute bacterial endocarditis Effects on ability to Drive and use Machines- No studies on the efect on the ability to drive and to use machines have been performed. Elderly ( from 75 years)- Should be used with caution in elderly patients as renal function decreases with age. Patients with body weight less than 50kg- Patients with body weight below 50 kg are at an increased risk of bleeding Renal impairment- Prevention and treatment of VTE- Should not be used in patients with a creatinine clearance of less than 30ml/min Hepatic Impairment- No dosing adjustment of is necessary SPECIAL PREACAUTIONS- Route of administration- Must not be administered intramuscularly Haemorrhage- other anticoagulants must be used with caution in conditions with an increased risk of haemorrhage (such as congenital bleeding disorders, active ulcerative gastro intestinal disease, recent intracranial haemorrhage, shortly after brain, spinal or ophthalmic surgery.) Prevention and treatment of VTE- Other medicinal products enhancing the risk of haemorrhage, with the exception of Vitamin K antagonists, used in the treatment for VTE should not be administed with the drug. If co-administration is essential, close monitoring is recomended Prevention of VTE following surgery - timing of injection The timing of the first injection requires strict adherance. The first dose should be given no earlier than 6 hours following surgical closure and only after haemostasis is established. Administration before 6 hours following has been associated with an increased risk of major bleeding. Patient groups at particular risks are those from 75 years of age, body weight of less than 50kg, or renal impairment with creatinine clearance less than 50ml/min. Spinal epidural anaesthesia/soinal puncture- Epidural or spnal haematomas that may result in long term or permanent paralysis can occur with the use of anticoagulants and spinal /epidural anaesthesia or spinal puncture The risk of rare events may be higher with post-opeative use of indwelling epidural catheters or the concomittant use of other medical products affecting haemostasis. Elderly patients- The elderly population is at increased risk of bleeding. As renal function generally decreases with age,elderly patients may show reduced elimination and increased exposure of the drug. Low body weight- Patients with low body weight less than 50 kg are at increased risk of bleeding. Elimination of fondaparinux decreases with weight decrease Fondaparinux should be used with caution in these patients
Dosages/ Overdosage Etc:
Injection - Prevention of VTE and PE Once daily 5mg for body weight less than 50kg 7.5mg for body weight 50 kg to 100kg 10mg for body weight greater than 100kg All once daily by deep sc inj . Continue for at least 5 days and until adequate oral antocogulation is established.
Preventiion of VTE- 2.5mg once daily by deep sc inj in abdominal wall stating 6 hours post-op.if hemostasis established
Pharmacology- Fondaparinax is a synthetic and selective inhibitor of activated factor X. The antithrombotic activity of fondaparinaux is theresult of antithrombin III (ATIII0 mediated selective inhibitor of Factor Xa. By binding selectively to ATIII, fondaparinaux potentiates ( about 300 times) the innate neutralization of factor XA by ATIII. Neutralization of Factor Xa interrupts the blood coagulation cascade anfd inhibits both thrombin formation and thrombus development. Fondaparinaux does not inactivate thrombin ( activated Factor II ) and has no known effect on platelet function. Pharmacodynamics- At the 2.5mg dose Fondaparinaux does not hav a clinically relevant efect on routine coagulation tests, such as activated partial thromboplastin time ( aPTT ) activated clotting time (ACT ) or prothrombin time (PT) International Normalised Ratio ( INR ) Fondapainaux does not cross-react with sera from patients with Heparin Induced Thrombocytopenia ( HIT ) type II Absoprtion- After sub-cutaneous dosing fondaparinaux is completely and rapidly absorbed ( absolute bioavailability 100% ) Following a single subcutaneous injection of ARIXTRA 2.5mg to young healthy subjects, peak plasma concentration , mean Cmax of 0.34mg/l is reached in approximately 2 hours. Elimination- Fondaparinaux is eliminated in urine as unchanged drug. In healthy individuals 64 to 77% of a single subcutaneous dose is eliminated in urine in 72 hours. The elimination half-life is about 17 hours in healthy young subjects and about 21 hours unhealthy elderly subjects. Plasma concentrations of half the mean Cmax values are reached 25 min post dosing.
Pregnancy and lactation:
Pregnancy- Limited clinical dat available on exposed pregnancies. ARIXTRA should not be prescribed to pregnant woen unless the benefit ouweighs the risk Lactation- Fondaparinaux is excreated in rat milk but is is not known whether fondaparinaux is exceted in human milk. Breast feeding is not recommended during treatment with fondaparinux Children- Safety and efficacy of fondaparinx in patients under the age of 17 has not been established.