Dalteparin (Fragmin ® ) Anticoagulation Inpatient Management (AIM) Team 2009
Dec 17, 2015
Formulary update Understand dalteparin
Mechanism of action Indications Pharmacokinetics Dose and Monitoring Warnings/contraindications
Special considerations Obesity Renal impairment Latex allergies Bridging with warfarin
Objectives
Formulary options for VTE
Unfractionated heparin SQ IV infusion
Low molecular weight heparin Enoxaparin (Lovenox®) Dalteparin (Fragmin®)
Why the change? Dalteparin has been extensively studied as
prophylaxis and treatment for venous thromboembolism (VTE)
Data supporting its efficacy and safety suggest it has similar properties to enoxaparin
Given the comparable efficacy and safety of dalteparin with enoxaparin, a change to dalteparin will create significant cost savings without any decline in clinical outcomes
Mechanism of action
Low-molecular-weight-heparin (LMWH)
Strongly inhibits both factor Xa and factor IIa (thrombin), with a higher ratio of antifactor Xa to antifactor IIa activity (Ratio=4)
Generic name Dalteparin
Brand name Fragmin®
Manufacturer Eisai
Drug Class Low Molecular Weight Heparin
Approved by P&T March 2009 Replaces enoxaparin on formulary for VTE
prophylaxis and treatment
The Basics…
Pharmacokinetics Absorption
Bioavailability 81-93% Peak concentrations 4hrs
Distribution Vd 40-60 mL/kg
Metabolism Unknown
Excretion T1/2 2-5 hours pending ROA
Place in Therapy VTE prophylaxis VTE treatment Atrial Fibrillation
Exception Acute Coronary Syndrome patients Neonates
Dosing Guide
Prophylaxis Dalteparin 5000 international units (IU)
subcutaneously daily
Treatment Dalteparin 200 international units
(IU)/kg SQ daily Dose based on Actual Body Weight
(ABW)
Inpatient Dosing
Patient Weight (kg) Dalteparin dose (IU/day)
< 50 kg Not recommended
50.0 – 56.2 10,000
56.3 – 68.7 12,500
68.8 – 81.2 15,000
81.3 – 93.7 17,500
93.8 – 106.2 20,000
106.3 – 118.7 22,500
118.8 – 131.2 25,000
131.3 – 143.7 27,500
143.8 – 150.0 30,000
> 150.0 kgs Not recommended
Dosage formulations Multi-dose vials
Dalteparin 25,000 international units/ml Use for Treatment doses Same syringe and process as Enoxaparin—
VanishPoint Syringe
Pre-filled syringes Dalteparin 5,000 international units syringes
Use for Prophylaxis doses Sent with Cart fill
Dosing Key Points All subcutaneous injections administered at
1800 daily For both prophylaxis and treatment doses Available as 5000 international units prefilled
syringes or drawn up syringes from the IV room Weight cap Minimum 50 kg
Maximum 150 kg Doses should be rounded to the nearest 2500
international units Contraindicated in patients with CrCl <30
ml/min
How to inject Injection are
administered subcutaneously
Patient should be sitting or lying down
Sites of injection U shaped area around
the naval (preferred site)
Upper outer quadrangle of buttock
Upper outer side of thigh
How to inject With thumb and forefinger, pinch an inch at
the site of injection, if unable to do so, move on to next site
Do not expel air bubble in pre-filled syringes At a 45 to 90 degree angle, insert entire
length of needle Doses of dalteparin are drawn up in
VanishPoint syringes. http://www.vanishpoint.com/Simple4.aspx?PageID=174 Injection technique is same as the drawn up
enoxaparin syringes from Pharmacy Dispose of syringe in Biohazard box
Monitoring Monitoring is not required for most of cases For special patient populations (obesity BMI
>35, pregnancy, CrCl<30, etc), monitoring maybe considered
Hematology consult should be called to assist with monitoring and mangement of such patients
For Antifactor Xa level testing Blue top tubes should be labeled with the type of
heparin the patient is on AND must have approval from Hematology
Antifactor Xa level of 0.5 -1.5 for treatment Antifactor Xa levels may be drawn 4 hours after the
third dose
Warnings/Precautions Use with caution in patients with
increased risk of hemorrhage Bleeding diathesis, thrombocytopenia,
active ulceration/recent gastrointestinal bleeding, hemorrhagic stroke, severe liver/kidney insufficiency
Warnings/Precautions Use caution in case of history of thrombocytopenia (Plt <50,000), platelet defects or heparin-induced thrombocytopenia- refer to hematology Severe liver or kidney insufficiency Shortly after (< 48h) brain, spinal or ophthalmological surgeryNot intended for IM useActive major bleeding, or thrombocytopenia associated with positive in vitro tests for antiplatelet antibody CrCl < 30 ml/min
Contraindications Spinal or epidural hematomas Hx heparin-induced thrombocytopenia (HIT) Known hypersensitivity to heparin or pork
products Hypersensitivity to dalteparin, heparin or pork
product Spinal/epidural catheter or hematoma Do not exchange with heparin or other low
molecular weight heparins (LMWHs)
Reversal: Protamine Initial Dose
1 mg protamine for every 100 international units dalteparin given based on previous dose
Given as slow infusion not to exceed 50mg over 10 minutes
Should a second dose be given??? Measure aPTT 2-4 hours after initial infusion, if
aPTT is prolonged may administer second dose
0.5mg Protamine for every 100 international units dalteparin based on previous dose
Reversal: Protamine
aPTT may remain elevated following protamine administration
Anti-Factor Xa activity is never completely neutralized with protamine Maximum 60-75% neutralization
Other information Pregnancy Category B May use as bridge therapy to warfarin Latex Allergy
MDV and Pre-filled syringes are latex free Education materials are available on the
nursing floors and at the Family/Patient Education Center
Patient Assistance Program is available contact social worker
Outpatient insurance coverage Yes, but may require prior authorization
Key Points to Remember
Dalteparin for all indications except ACS and neonates
Dose Prophylaxis 5000
international units subcutaneous daily
Treatment 200 international units/kg subcutaneous daily
Administered @ 1800, round to nearest 2500 international units
Weights 50-150 kg Contraindicated in CrCl
<30 ml/min
Use caution in pt at high risk of bleeding
Contraindicated in pts with epidurals
Protamine may be used as reversal, but not complete
Latex Free Education materials
and patient assistance program available
Patient Education Education available as
Dalteparin teaching kit from Patient Education Department
DVD/video on ON-DEMAND channel Consults for AIM team may be requested
if the patient requires further education
Discharge Dosing Inpatient dosing different from
Outpatient dosing due to the availability of multi-dose vials
Available Outpatient Pre-filled syringes 2500 IU 5000 IU 7500 IU 10,000 IU 12,5000 IU 15,000 IU 18,000 IU
Outpatient DosingWeight (kg) Dalteparin pre-filled syringe
ONCE daily dosing
50.0 – 56.2 10,000 IU
56.3 – 68.7 12,500 IU
68.8 – 81.2 15,000 IU
81.3 – 93.7 18,000 IU
93.8 – 112.5 20,000 IU
112.6 –137.5 25,000 IU
137.6 –150.0 30,000 IU
Outpatient dosing adjusted to commmercially available pre-filled syringes
When will this change happen?
Effective DECEMBER 1, 2009 Enoxaparin Dalteparin conversion
Pharmacist receive reports of patients on enoxaparin and will notify MDs the morning of 12/1/09 There is no issue with patients on q12hr
dosing and they receive the 0900 dose. The Dalteparin dose will begin at 1800 that day
MDs have until 2pm to change the order to Dalteparin
Please contact MDs if changes are not in by 2pm