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

 

Prophylaxis of thromboembolic dis orders of various origin

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

Cardiovascular - artial fibrillation, heart failure

Hematologic - epidural or spinal hematoma formation with concurrent use of enoxaparin and spinal/ epidural anesthesia or spinal puncture
rare cases of hypersensitivity, cutaneous vasculitis, purpura, thrombocytosis, and thrombocytopenia,with thrombosis have occured

Local - injection site hemorrhage, injection site pain, injection site reactions ( eg. inflammation,nodules, skin necrosis, oozing )

Respiratory- Lung edema, pneumonia

Miscellaneous- very rare cases of hyperlipidemia have beeb reported with 1 case of hyperlipidemia with marked hypertriglyceridemia reported in a diabetic patient, 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.
 

 

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 concomitant 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 weight 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.

 Dosage - 20 to 40mg depending on the degree of risk of thromboembolism given
subcutaneously once a day.

1. Allergies- Tell your doctor if you have ever had any unusual or allergic reactions to enoxaparin or
    to heparin or other related medicines. Also tell your doctor  if your are allergic to any other
    substances such as foods, preservatives or dyes.

2. Pregnancy-  it has been shown to cause birth defects or  other problems in animal studies.  
   
3. Breast feeding-  mothers who are using this medicine and who wish to breast feef should discuss     this with their doctor.  
       
4. Children-  no specific information comparing use of enoxaparin in children with use in other age   groups  
   
5. Elderly- this medicine has not been to cause different side effects or problems in older people   than it does  in younger adults.

13. Other medicines- tell your doctor if you are taking any of the following-
    
      Aspirin or
      Divalproex or
      Inflammation or pain medicine , except narcotics or
      Plicamycin or
      Sulfinpyrazone or
      Thrombolytic agents or
      Ticlopidine or
      Valproic acid - using any of these medicines together with enoxaparin may increase the risk  of bleeding
    
14. Other medical problems -
     
       Blood disease or bleeding problems or
       Blood vessel problems or
       High infection or
       High blood pressure or
       Kidney disease or
       Liver disease or
       Threatened miscarriage - the risk of bleeding may be increased


15. Missed dose-
    If you miss a dose of this medicine take it as soon as possible. However if it is almost            time for  your next dose go back to your regular dosing schedule.
     Do not double doses.

Pharmacology:
Enoxaparin  exerts its anticoagulant activity in two ways. The more important action is reduction of thrombin generation, while the second is inhibition of thrombin ( factor IIa) itself. Reduction  of thrombin levels is acheived by inhibiting the prothrombinase enzyme complex which includes factor Xa catalysing the conversion of prothrombin to thrombin.

Pharmacokinetics:
Enoxaparin is rapidly and completely absorbed after subcutaneous injection and maximum
antifactor Xa and antithrombin activites occur after 3- 5 hrs after SC injection. The small part of the dose is metabolised in the liver. Elimination half-life is about 4-5 hr.

 

Pregnancy-

Use during only when 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.