Dalteparin (Fragmin®)

Anticoagulation Inpatient Management (AIM) Team 2009

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

All about the new agent…

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…

Clotting Cascade

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

SCM Charting—Task List

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

References:

British Journal of Haematology 2003;121:12.

Dalteparin. Package Insert. Eisai Inc. 2007

Dunn CJ, et al.Drugs 2000:60(1):203

AIM team: pager 215-312-0021