Low molecular Weight Heparins

Tinazeparin, Dalteparin, Emoxaparin Refer - LMW - Heparin

Anticoagulants/platelet inhibitors

Use of LMWH ( Dalteparin, Enoxaparin, Tinazaparin ) with care in patients receiving oral anticoagulants or platelet inhibitors( eg. asprin, salicylates, NSAIDs including ketorolac, tromethamine, dypridamole, sulfinpyrazole, dextran, ticlopodine, clopidogrel) and thrombolytics because of increased risk of bleeding. Unless needed, discontinue agents that may enhance risk of haemorrhage prior to initiation of enoxaparin therapy. If co-admin. is essential use close clinical and laboratory monitoring of these patients. Aspirin unless contraindicated, is recommended in patients treated for unstable angina or non-Q-wave MI

Unstable angina/ non- Q-wave myocardial infarction ( MI ) Deep vein thrombosis

Low molecular Weight Heparins- Tinazeparin, Dalteparin, Emoxaparin                                 Refer - LMW - Heparin

Hematologic - reports of epidural or spinal hematoma formation with concurrent use of deltaparin and spinal/epidural anaesthesia or spinal puncture. Patients had postoperative indwelling epidural catheters placed for analgesia or received additional drugs affecting hemostatis.

The hematoma caused long term or permenent paralysis Miscellaneous- pain at injection siote, few cases of anaphylactoid reactions Lab test abnormalites- Asymptomatic increases in transaminase levels ( AST AND ALT levels) greater than 3 times the upper limit of normal laboratory range have been reported Because the transaminase detreminations are important in the differential diagnosis of MI, liver disease, and pilmonary emboli, interpret elevations that might be caused by LMWHs with caution.

Low molecular Weight Heparins

Tinazeparin, Dalteparin, Emoxaparin

Hypersentivity to LMWHs heparin or pork products, hypersensitivity to sulfites or benzyl alcohol ( multidose vials ) history of heparin -induced thrombocytopenia ( tinazaparin ) active major bleeding, thrombocytopenia, associted with positive in vitro tests for antiplatel body, in the presence of a LMWH.

Do not give dalteparin to patients undergoing anesthesia for unstable angina or non-Q-wave MI because of an increased risk of bleeding associated with the dosage of dalteparin recomended for unstable angina and non-Q-wave MI Special precautions- Route of administration- For subcutaneous administration only- do not administer IM or IV Interchangeability- LMWHS cannot be used interchangeably ( unit for unit ) with other LMWHs or unfracationated. Spinal /Epidural hematomas - as with other anticoagulants , rare cases of neuraxil , spinal or epidural hematomas have been reported with the concurrent use of of LMWHs and spinal /epidural anesthesia or spinal punture, resultin n long term or permanent paralysis.

The risk of these events may be higher with the use of postopertative indwelling epidural catheters or by comcomitant use of additionla drugs affecting hemostatis such as NSAIDs Hemorrhage- use LMWHSs like any other anticoagulants with extreme caution in patients, who have an incresed risk of haemorrhage, such as those with uncontrolled hypertension, bleeding diathesis, diabetic retinopathy, bacterial endocarditis, congenital or aquired bleeding disorders. Hemorrhage in some cases has been reported to result in death or permanent disability. If severe haemorrhage occurs, discontinue LMWH. Major hemorrhage including retroperitoneal bleeding have been reported. Some of these cases have been fatal. Discontinue agents that might affect hemostatis (eg. oral anticoagulants, platelet inhibitors) prior to surgery with LMWHs.Concomitant use may increase risk of haemorrhage. Monitor patients if coadmin. cannot be avoided.

Thrombocytopenia- the incidence of thrombocytopenia with platelet counts between 50000/mm2 and 100000m2 was 1.3% in patients treated with enoxaprin , 1% with tinzaparin and less than 1% with dalteparin Use extreme caution in patients with a history of heparin-induced thrombocytopenia. Do not use tinazaparin in these patients. Closely monitor thrombocytopenia of any degree Special risk patients- use with care in patients with bleedinh diathesis, uncontrolled arterial hypertension or a history of recent GI ulceration or bleeding , diabetic retinopathy, hemorrhage and severe liver or kidney insufficiency Thromboembolitic event- if a thromboembolitic event occurs despite LMWH prophylaxis, discontinue the drug and initiate appropiate therapy. Mechanical prothesis heart valves- the enoxaparin injection has not been adequately studied for thromboprophylaxis or long term use in patients with mechanical prothetic heart valves Low eight patients- an increase in exposure of enoxaparin with rophylactic dosage ( less than 45kg) and low weight men ( less than 57kg) has observed. Observe all such patients for signs and symptoms of bleeding Benzyl alcohol- multidose vials of dalteparin, enoxparin, and tinzaparin contain benzyl alcohol as a preservative . Benzyl alcohol has associated with nfatal -gasping syndrome - in premature infants. Because benzyl alcohol may cross placenta . do not use LMWHs preserved in benzyl alcohol in pregnant women. Sulfite sensitivity- Tinazaparin contains metabisulfite, a sulfite that may cause allergic-type reactions including anaphylsctic symptoms and life -threatening asthmatic episodes, in certain suseptible people. Sulfite sensitivity is seen more in asthmatic people than in nn asthmatic people. Renal/hepatic function impairment- delayed elimination of LMWHs may occur with severe liver or kidney insufficiency. Use with caution.

Pregnancy- Use during pregnancy only if needed. Cases of cleft palate, optic nerve hypoplasia, Downs syndrome, and cutis aplasia of the scalp in infants of women who received Tinzaparin during during pregnancy, have been reported A cause- and- effect relationship has not been established Lactation- Not known whether these drugs are excreted in brast milk. In studies where Tinzaparin was administered to lsactaing rats , very low levels of tinzaparin were found in breast milk. Excercise caution while administeting to a nursing woman.

Children- Safety and efficacy have not been established Elderly- Delayed elimination of enoxaparin and tinzaparin may occur. use with caution.

Unstable angina/ non- Q-wave myocardial infarction ( MI ) Deep vein thrombosis Unstable angina Dosage- in patients with with unstable angina or non-Q-wave MI, the recommended dose of dalteparin is 120 units /kg of body weight but not more tan 10000 units ,subcutaneously every 12 hours with concurrent oral aspirin ( 75 to 165mg/day ) therapy Treatment should be continued until the patient is clinically stabilized.

The usual duration of administration is 5 to 8 days. Concurrent aspirin therapy is recommended except when contraindicated Deep vein thrombosis- Hip replacement surgery- Preoperative start evening 10 to 14 hours before surgery- 5000 units 4 to 8 hours after surgery 5000 units Preoperative - start day of surgery - within 2 hours before surgery 2500 units 4 to 8 hours after surgery 2500 units Postoperative 4 to 8 hours after surgery 2500 units Postoperative period daily 5000 units

Low molecular Weight Heparins- Tinazeparin, Dalteparin, Emoxaparin

Instruct patient to contact the physician if they experience bleeding , bruising, dizziness, lightheadedness, itching, rash, fever, swelling, or difficulty breathing. Instruct patients to notify physician if pregnant, planning to become pregnant, or if breast feeding Instruct patients to change the injection technique site daily Instruct patients to use proper injection technique, inject under the skin, not into mucle

To minimze bruising, advice patients not to rub the injection site after completion of injection.

Low molecular Weight Heparins- Tinazeparin, Dalteparin, Emoxaparin

Pharmacology

Enoxaparin ( average molecular weight is approx. 2000 to 8000 daltons ) Tinzaparin ( average molecular weight is approx. 5500 to 7000 daltons ) Daltaparin ( average molecular weight is approx. 2000 to 9000 daltons ) These LMWHs are obtained by depolymerization of unfractionated porcine heparin.

They have antithrombiotic properties. These agents enhance the inhibition factor of Factor Xa and thrombin binding to and accelrating antithrombin activity They preferentially potentiate the inhibition factor of Xa while only slightly effecting the thrombin and clotting time ( eg. thrombin time TT or activated partial prothrobin time aPTT )

Pharmacokinetics

Metabolism- LMWHs are primarily metabolised in the liver by desulfation and/ or deolymerization with much reduced biological potency. Total renal clearance of active and non-active enoxaparin fragments represents 40% of the dose with 10% being active fragments Special population- Renal function impairment- Dalteparin- in patients with chronic renal requiring hemodialysis, the mean half-life of anti Factor Xa activity may be considerably longer , therfore greater accumulation can be expected in these patients Enoxaparin- in psatients with severe renal impairment (Ccr less than 30 mL/min ) the AUC is significantly increased on a average by 65%. Tinzaparin- clearance reduced in moderate ( Ccr 30 to 50 mL/min ) and severe ( less than 30 mL/min ) renal impairment. Patients with severe renal impairment exhibited a 24% reduction in tinzaparin clearance

Low molecular Weight Heparins- Tinazeparin, Dalteparin, Emoxaparin

Pregnancy

Use during pregnancy only if needed. Cases of cleft palate, optic nerve hypoplasia, Downs syndrome, and cutis aplasia of the scalp in infants of women who received Tinzaparin during during pregnancy, have been reported A cause- and- effect relationship has not been established Lactation- Not known whether these drugs are excreted in brast milk.

In studies where Tinzaparin was administered to lsactaing rats , very low levels of tinzaparin were found in breast milk. Excercise caution while administeting to a nursing woman. Children- Safety and efficacy have not been established Elderly- Delayed elimination of enoxaparin and tinzaparin may occur. use with caution.