Wednesday, February 14, 2018

Dalteparin Anticoagulant Drug

INTRODUCTION
Dalteparin is an anticoagulant that helps prevent the formation of blood clots.
Dalteparin is used together with aspirin to prevent blood vessel complications in people with certain types of angina (chest pain) or heart attack.
Dalteparin is also used to prevent a type of blood clot called deep vein thrombosis (DVT), which can lead to blood clots in the lungs (pulmonary embolism). A DVT can occur after certain types of surgery, or in people who are bed-ridden due to a prolonged illness.
Dalteparin is also used long-term to treat a type of blood clot called venous thromboembolism (VTE) in people with cancer.

THERAPEUTIC USES:
 Dalteparin is used as a blood thinner for the prevention of blood clots in patients with unstable angina and non-Q-wave heart attack. It is used for preventing blood clots called deep venous thrombosis (DVT) that can occur after abdominal surgery, hip replacement surgery, or in sick patients who are unable to be mobile. In cancer patients, it may be used to treat blood clots and prevent further clot formation. It may also be used to treat blood clots in non-cancer patients.
Dalteparin is used to treat the following conditions:
• Angina, Deep Vein Thrombosis Prophylaxis after Abdominal Surgery,
•Deep Vein Thrombosis Prophylaxis after Hip Replacement Surgery,
•  Deep Vein Thrombosis Prophylaxis after Orthopedic Surgery,
• Deep Vein Thrombosis, Prophylaxis, Heart Attack, Venous Thromboembolism.

SIDE EFFECTS
More common:
• Deep, dark purple bruise, pain, or swelling at the injection site
Less common:
• Bleeding of the gums
• coughing up blood
• difficulty with breathing or swallowing
• Dizziness
• headache
• increased menstrual flow or vaginal bleeding
• nosebleeds
• paralysis
• prolonged bleeding from cuts
• red or black, tarry stools
 red or dark brown urine
• unexplained pain, swelling, or discomfort, especially in the chest, abdomen or stomach, joints, or muscles
• unusual bruising
• vomiting of blood or material that looks like coffee grounds
• weakness
Rare:
• Back pain
• bleeding from mucous membranes
• bluish or black discoloration, flushing, or redness of the skin
• burning, pricking, tickling,

MECHANISM OF ACTION:
Dalteparin is a low molecular weight heparin with antithrombotic properties. It acts by enhancing the inhibition of Factor Xa and thrombin by antithrombin. In humans, dalteparin potentiates preferentially the inhibition of coagulation Factor Xa, while only slightly affecting the activated partial thromboplastin time (APTT).

PRECAUTIONS:
Before using dalteparin injection,
• tell your doctor and pharmacist if you are allergic to dalteparin, heparin, pork products, any other medications, or any of the ingredients in dalteparin injection. Ask your pharmacist for a list of the ingredients.
• tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take. Be sure to mention the medications listed in the IMPORTANT WARNING section. Your doctor may need to change the doses of your medications or monitor you carefully for side effects.
• tell your doctor if you have heavy bleeding anywhere in your body that cannot be stopped or if you have or have ever had a low level of platelets (type of blood cells needed for normal clotting) in your blood. Your doctor may tell you not to use dalteparin.
• tell your doctor if you have or have ever had a bleeding disorder such as hemophilia (condition in which the blood does not clot normally), ulcers in your stomach or intestines, high blood pressure, endocarditis (an infection in the heart), a stroke or ministroke (TIA), eye disease due to diabetes, or liver or kidney disease. Also tell your doctor if you have recently had brain or eye surgery.
• tell your doctor if you are pregnant, plan to become pregnant, or are breastfeeding. If you become pregnant while using dalteparin injection, call your doctor.
• if you are having surgery, including dental surgery, tell the doctor or dentist that you are using dalteparin injection.

PHARMACODYNAMICS 
Doses of dalteparin Injection of up to 10,000 anti-Factor Xa IU administered subcutaneously as a single dose or two 5000 IU doses 12 hours apart to healthy subjects did not produce a significant change in platelet aggregation, fibrinolysis, or global clotting tests such as prothrombin time (PT), thrombin time (TT) or APTT. Subcutaneous administration of doses of 5000 IU twice daily of FRAGMIN for seven consecutive days to patients undergoing abdominal surgery did not markedly affect APTT, Platelet Factor 4 (PF4), or lipoprotein lipase.

PHARMACOKINETICS
Mean peak levels of plasma anti-Factor Xa activity following single subcutaneous doses of 2500, 5000 and 10,000 IU were 0.19 ± 0.04, 0.41 ± 0.07 and 0.82 ± 0.10 IU/ml, respectively, and were attained in about 4 hours in most subjects. Absolute bioavailability in healthy volunteers, measured as the anti-Factor Xa activity, was 87 ± 6%. Increasing the dose from 2500 to 10,000 IU resulted in an overall increase in anti-Factor Xa AUC that was greater than proportional by about one-third.
Peak anti-Factor Xa activity increased more or less linearly with dose over the same dose range. There appeared to be no appreciable accumulation of anti-Factor Xa activity with twice-daily dosing of 100 IU/kg subcutaneously for up to 7 days.
The volume of distribution for dalteparin anti-Factor Xa activity was 40 to 60 mL/kg. The mean plasma clearances of dalteparin anti-Factor Xa activity in normal volunteers following single intravenous bolus doses of 30 and 120 anti-Factor Xa IU/kg were 24.6 ± 5.4 and 15.6 ± 2.4 mL/hr/kg, respectively. The corresponding mean disposition half-lives were 1.47 ± 0.3 and 2.5 ± 0.3 hours.
Following intravenous doses of 40 and 60 IU/kg, mean terminal half-lives were 2.1 ± 0.3 and 2.3 ± 0.4 hours, respectively.

DRUG-DRUG INTERACTIONS:
• Using antithrombin III +dalteparin = increase the risk of bleeding, including severe and sometimes fatal hemorrhage
• abciximab +dalteparin= may increase the risk of bleeding, including severe and sometimes fatal hemorrhage
• Dalteparin +aspirin= increase bleeding complications, vomiting,brusing.
• dalteparin +argatroban= may increase the risk of bleeding, including severe and sometimes fatal hemorrhage
• dalteparin +ibuprofen=can increase the risk of bleeding complications

REFERENCE: Tripathi K.D; "Essentials of medical pharmacology"; Page no- 619

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