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

Interacting drugs - summary

Cephalosporin + Heparin                                                                                                  additive effect of heparin -increased risk of bleeding

Nitroglycerin    +  Heparin                                                                                        decreased pharmcol. effect of heparin

Penicillins   +  Heparin                                                                                                     additive effect - increased risk of bleedding

Salicylates  + Heparin                                                                                               increased risk of bleeding

Platletet inhibitors with Heparin  eg. ibuprofen, indomethicin,  hydroxychloroquinine NSAIDs ,ticloodine,phenylbutazone, aspirin, dextran                                                                                                                                  increased risk of bleeding

Digitalis, tetracyline, nicotine, antihistamines with Heparin                                          counteract anticoagulant effect of heparin

Streptokinase +  Heparin                                                                                         decreased anticoagulant effect

Cephalosporin with

Heparin                                                                                                                           several parentral cephalosporins have caused coagulopathies,
  this might be additive with heparin, possibly increasing the                                                       risk of  bleeding

Nitroglycerin with

Heparin                                                                                                                                  the pharmacologic effects of heparin may be decreased, although
 the information on the interaction is conflicting

Penicillins with

Heparin                                                                                                                           parentral penicillins can produce alterations in platelet aggregation
  and coagulation tests. These effects might be additive with                                                    heparin possibly increasing the risk of bleeding
 

Digitalis, tetracyline,nicotine,antihistamines with

Heparin                                                                                                                                may partialy counteract anticoagulant action of heparin sodium

Streptokinase +

Heparin                                                                                                                              relative resistence to heparin anticoagulation following admin. of
streptokinase as a systemic throbolytic agent may occur
 

Thembosis/ embolism
Coagulopathies
Deep vein thrombosis


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

 

Haemorrhage-

is the chief complication < 10% Local- avoid IM use. local irritation ,ertythema, mild pain, hematoria or ulceration may follow deep SC use, but more common with IM use.

Hypersensitivity-

Most common- chills, fever, urticaria. Rare- asthma, rhinitis, lacrimation, headache, nausea, vomiting, shock, anaphyloid reactions, Allergic vasospastic reactions with painful, ischemic cyanotic limbs may develop 6 to 10 days after starting therapy and last 4 to 6 hrs .

Whether these are identical to thrombocytopenia - associated complications is undetermined

Hypersentivity to heparin,

severe thrombocytopenia, uncontrolled bleeding ( except when it is due to DIC), any patient from whom suitable blood coagulation tests cannot be performed at the apropiate intervals ( there is usually no need to monitor coagulation parameters in patients receiving low dose
heparin

Warnings-
IM admin should be avoided

Haemorrhage can occur at any site in patients receiving heparin.

Adrenal hemorrhage resulting in acute adrenal insufficiency has occured. Discontinue therapy.

Ovarian ( corpus luteum ) hemorrhage developed in number of women of reproductive age
receiving antocoagulants. It unrecognized this may be fatal

Germinal matrix -intraventricular haemorrhage occurs fourfold higher in low-birth weight infants
receiving heparin thearpy.
Use heparin with extreme caution in disease states in which there is increased danger of
haemorrhage. These include-

Cardiovascular -subacute bacterial endocarditis, aterial sclerosis, dissecting aneurysm,
increased capillarry permeability, severe hypertension.    
CNS- during and immediately following spinal tap, spinal anesthesia or major surgery,
espcially of the brain, spinal cord or eye.

Hematologic-

hemophilia, som vascular purpuras, thrombocytopenia
GI- ulcerative lesions, diverticulitis or ulcerative colitis, continuous tube drainage of the stomach
or small intestine

Obstertic- threatened abortion, menstruation.  
Other- liver disease with impaired hemostatis, severe renal disease

Hyperlipidemia- heparin may increase free fatty acid serum levels by induction of lipoprotein
lipase.

Benzyl alcohol- contained in some products as preservative, has been associated with fatal
- gasping syndrome - in premature infants

Resistence - increased resitence to the drug frequently encounterd in fever, thrombosis,
thrombophlebitis, infections with thrombosing tendencies, MI, cancer and post operative
states.

Hypersentivity- heparin is derived from animal tissue, use caution in patients with a history of
allergy. Before a therapeutic dose is given, a trial dose may be advisable.

Elderly- a higher incidence of bleedng has occured in women > 60 years of age.

Pregnancy-
Use with caution during pregnancy especially during the last trimester and during the immediate
postpartum period, because of the risk of maternal haemorrhage

Lactation- heparin is not excreted in breast milk.

Children- safety and efficacy have not been determined in new borns, germinal matrix intraventricular
hemorrhage occurs more often in low birth weight infants receiving heparin.

Precautions-
Monitoring - common test used to monitor heparins effect is activated partial thromboplastin time
APTT . APTT is widely used quick easily done and reproducible
Perform periodic platelet counts hemotocrit and tests for occult blood in stool during the entire
course of therapy, regardless of the route of administration

Hyperkalemia

may develop probably due to induced hypoaldosteronism.
Use with caution in patients with diabetes or renal insufficiency. Monitor patients closely

Drug/Lab interactions-
Significant elevation in aminotransferase AST and ALT have occurred in high percentage of
patients. Cautiously interpret aminotransferase increases that might be caused by heparin.

 

Date of Approval       2002

Indication-

Thembosis/ embolism Coagulopathies Deep vein thrombosis Given by intermittant IV injection, continuous IV infusion or deep SC ( above the oliac crest of abdominal fat layer ) injection.

Dosage-

Avoid IM injection.

Adjust dosage according to coagulation test prior to,each injection. Dosage is adequate when WBCT is approximately 2-5 to 3 times control value or when APTT is 1.5 to 2 times normal

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. Other medicines- Tell your doctor if in case you are taking over -the counter ( OTC ) medicines ,
   even aspirin, laxatives, vitamins or antacids

12. Other medical problems- Tel 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 bleedin
      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-

Commercial preparations of heparin are derived from bovine lung or porcine intestinal mucosa, although chemical and biological differnces exist, there is no clincal differnce in thev antithrombotic effects.
Heparin calcium is reported to cause lower incidence of hematoma than heparin sodium, however difference inside effects or efficacy have not been documented

Pharmacokinetics-

Heparin is absorbed from the GI tract and must be given IV or SC.
Peak plasma levels of heparin are acheived in 2 to 4 hours following SC use, although there is considerable individual variation.

Once absorbed heparin is distributed in plasma and is extensively protein bound.
Heparin is rapidly cleared from plasma   with an average half life of 30 to 180 minutes
Heparin is excreted in urine as unchanged drug ( upto 50% ) particularly after large doses.

Elderly- a higher incidence of bleedng has occured in women > 60 years of age.

Pregnancy-

Use with caution during pregnancy especially during the last trimester and during the immediate
postpartum period, because of the risk of maternal haemorrhage

Lactation-

heparin is not excreted in breast milk.

Children- safety and efficacy have not been determined in new borns, germinal matrix intraventricular
hemorrhage occurs more often in low birth weight infants receiving heparin.