Enoxaparin (Lovenox) - Home DVT Treatment Program Model Guidelines for Implementation   Recent literature has suggested that using subcutaneous low-molecular-weight heparin (LMWH) at home for the treatment of deep venous thrombosis (DVT) is as effective as using continuous infusion of unfractionated heparin (UH) in the hospital(1,2). The use of LMWH provides an opportunity to enhance patients' satisfaction by allowing patients to be treated at home, and to reduce hospitalization expenses. However, a comprehensive treatment program must be in place to ensure the safety and efficacy of such therapy. The following information is adapted from programs established at the Kenmore Health Center of HCD and in the Greater Rhode Island Region, and is intended to guide clinicians who are interested in developing such a program. It is important for interested clinicians to tailor these guidelines to meet their needs and communicate plans with affected hospitals prior to implementation. Indication Treatment of uncomplicated proximal DVT (thrombosis in the popliteal vein or a more proximal vein) in patients who may be managed at home. Dose and Administration Enoxaparin (Lovenox) 1 mg/kg subcutaneously twice daily for at least 5 days and warfarin (Coumadin) maintenance therapy to reach an INR 2.0 - 3.0; discontinue enoxaparin when INR is > 2.0 for two consecutive days. Exclusion Criteria symptoms of pulmonary embolism (shortness of breath, chest pain, pleurisy) high risk for bleeding complications (e.g., coagulopathy, active peptic ulcer disease, liver disease) active bleeding (e.g., heavy menses, OB+ stools) history of pulmonary embolism or > 2 DVTs known hypercoaguable state (e.g., AT III, protein C or protein S deficiency) pregnancy risk for falls history of non-compliance allergy to enoxaparin, heparin or pork products other coexisting condition(s) that may complicate outpatient LMWH treatment (e.g., certain patients with active cancer, infection, or recent stroke) Baseline documentation Document DVT by appropriate studies (e.g. IPG, ultrasound,venography). Document absence of exclusion criteria. Obtain initial blood work (CBC, PT/PTT, platelets, LFTs). Obtain baseline EKG. Procedure Day 1 Establish patient eligibility for home DVT treatment program. Complete baseline documentation. Administer first dose of enoxaparin in controlled setting. Provide a prescription for the remaining course of enoxaparin and a prescription for warfarin (no need to provide enoxaparin prescription if patient will be coming into clinic for injections twice daily). Provide patient education on drug(s), administration technique, and disease. Establish follow-up mechanism. Day 2-5 (or 6,7) Follow patient and adjust warfarin dose based on INR results. Discontinue enoxaparin after 5 days and INR > 2.0. Important Considerations Estimate the number of patients who may be treated at home in order to allocate appropriate resources. Work cooperatively with affected areas to identify and enroll patients (e.g., ER staff). Plan for off hour enrollment (evenings, weekends). Establish a contact person (group) to which questions regarding the program can be directed. Have designated clinician(s) (e.g., patient's primary care physician, patient's primary nurse) to assume responsibility for each patient while in the program and after completion. Identify a pharmacy or home care service that can provide prefilled syringes of enoxaparin. The manufacturer of enoxaparin has data on file that suggest prefilled syringes are stable for at least 5 days at room temperature. Identify a home care service or visiting nurse for patients who may require assistance in administering enoxaparin and obtaining necessary laboratory work. References 1.Koopman MM, Prandoni P, Piovella R, et al. Treatment of venous thrombosis with intravenous unfractionated heparin administered in the hospital as compared with subcutaneous low-molecular-weight heparin administered at home. N Engl J Med 1996;334:682-7. 2.Levine M, Gent M Hirsh J, et al. A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep-vein thrombosis. N Engl J Med 1996;334:677-81. Brief Review* of Enoxaparin's Safety and Efficacy for the Treatment of Deep Vein Thrombosis Overview Low-Molecular-Weight Heparins (LMWHs) are fragments of heparin produced by either chemical or enzymatic depolymerization. LMWHs exert their anticoagulant effect mainly through inactivation of factor Xa. LMWHs do not affect the aPTT because of their limited effect on thrombin. They also have a more predictable pharmacokinetic profile than unfractionated heparin and less interpatient variability. These properties allow for subcutaneous, once or twice daily dosing of LMWHs without laboratory monitoring. Enoxaparin (Lovenox) is a LMWH which is effective in both prophylaxis and treatment of deep vein thrombosis (DVT). Dose and Administration of Enoxaparin DVT Treatment: enoxaparin, 1 mg/kg subcutaneously twice daily for 5-7 days Efficacy: Summary of Clinical Trials Enoxaparin was compared with unfractionated heparin (UH) in a randomized trial of 134 patients with proximal DVT. Patients received enoxaparin 1 mg/kg subcutaneously twice daily or UH by continuous infusion with the rate adjusted to keep the aPTT 1.5-2.5x control. A significant difference in efficacy in favor of enoxaparin was noted (35 patients had improved venography, 24 unchanged and one worsened vs 18 improved, 34 unchanged and 5 worsened). Levine et al conducted a randomized, controlled trial in 500 patients with acute proximal DVT. Patients were treated with either enoxaparin 1 mg/kg subcutaneously twice daily, administered primarily at home without laboratory monitoring, or with a continuous infusion of UH adjusted to keep the aPTT between 60-85 seconds in the hospital. Main outcome measures were recurrent thromboembolism, major bleeding, and number of days in the hospital. The mean duration of treatment was similar in both groups (5.8 days-enoxaparin vs 5.5 days-UH). Five patients (2%) receiving enoxaparin had major bleeding complications as compared to 3 patients (1.2%) receiving UH (p=0.50). Patients treated with enoxaparin spent an average of 1. 1 days in the hospital as compared to 6.5 days with UH. Forty-nine percent of patients assigned to enoxaparin were never hospitalized. Three meta-analyses have found that treatment with LMWHs is superior to treatment with UH. Each analysis pooled the results of various LMWHs versus UH and included between 10-16 studies. These analyses suggested that LMWHs decrease thrombus extension on venography, recurrent thromboembolic events, and may also reduce major bleeding and mortality in patients with acute venous thromboembolism. Adverse Effects Bleeding: Meta-analyses comparing LMWH to UH showed that the incidence of major bleeding ranged from 0.9% to 2.4% and from 2.2% to 4.7%, respectively. Individual clinical trials comparing enoxaparin to UH for the treatment of acute DVT have not detected a significant difference in the incidence of hemorrhagic complications. Thrombocytopenia: Heparin-induced thrombocytopenia (HIT) can also occur in patients receiving LMWHs, although it is thought to be less common than with UH. HIT was reported in 9 of 332 patients treated with UH and none of 333 patients treated with enoxaparin in a randomized, double-blind clinical trial. However, there is considerable cross-sensitivity between UH and LMWHs. In patients with HIT, cross-sensitivity with enoxaparin has been reported in approximately 34% of cases. Therefore, the potential for cross-sensitivity should be assessed using platelet aggregometry in patients with HIT before initiating enoxaparin. Summary Enoxaparin is as effective as unfractioned heparin and may have a lower incidence of bleeding for the treatment of acute DVT. Its long half-life and ability to be administered subcutaneously twice daily without laboratory monitoring make it a valuable option for outpatient treatment in selected patients. As of July 1, 1997, neither Enoxaparin nor any other LMWH has recieved FDA approval for treatment of DVT. References: 1.Simonneau G, Charbonnier B, Decousus H, et al. Subcutaneous low-molecular-weight heparin compared with intravenous unfractionated heparin in the treatment of proximal deep vein thrombosis. Arch Intern Med 1993:153:1541-6. 2.Levine M, Gent M, Hirsh J, et al. A comparison of low-molecular-weight heparin administered primarily at home with unfractionated heparin administered in the hospital for proximal deep vein thrombosis. N Engl J Med 1996;334:677-81. 3.Leizorovicz A, Simonneau G, Decousus K, Boissel JP. Comparison of efficacy and safety of low molecular weight heparins and unfractionated heparin in initial treatment of deep venous thrombosis: a meta-analysis. BMJ 1994;309:299-304. 4.Lensing AWA, Prins MH, Davidson BL, Hirsh J. Treatment of deep venous thrombosis with low-molecular weight heparins. Arch Intern Med 1995; 155-601-7. 5.Siragusa S, Cosmi B, Piovella F, et al. Low-molecular-weight heparins and unfractionated heparin in the treatment of patients with acute venous thromboembolism: results of a meta-analysis. Am J Med 1996; 100:267-77. 6.Kikta MJ, Keller MP, Humphrey PW, Silver D. Can low molecular weight heparins and heparinoids be safely given to patients with heparin-induced thrombocytopenia syndrome? Surgery 1993; 1 14:705-10. 7.Ramakrishna R, Manoharan A, Kwan YL, Kyle PW. Heparin-induced thrombocytopenia: cross-reactivity between standard heparin, low molecular weight heparin, dalteparin (Fragmin) and heparinoid, danaparoid (Orgaran). Br J Haematol 1995;91:736-8. 8.Slocum MM, Adams JG, Teel R, et al. Use of enoxaparin in patients with heparin-induced thrombocytopenia syndrome. J Vasc Surg 1996;23:839-43. 9.Warkentin TE, Levine MN, Hirsh J, et al. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med 1995;332:1330-5. * Adapted from the October 1996 BPHC Pharmacy and Therapeutic Committee Review of low-molecular-weight heparins by Amy Santoro, PharmD. For a copy of the complete review, please call Maida Gerrin at (617)731-7543. Deep Vein Thrombosis (DVT) - Home Treatment Program Patient Information Sheet Welcome to the DVT home treatment program. In the past, DVT had to be treated in the hospital. However, with the development of a new medication, DVT may now be treated safely at home. It is extremely important that you review this information sheet in order to determine if this program is right for you. What is DVT? Deep vein thrombosis (DVT) is the formation of a blood clot within one of the veins in your leg. When DVT is not treated appropriately, the blood clot can detach from the wall of the vein and travel within the blood supply to the heart and lungs resulting in a serious medical condition. In addition, untreated DVT may cause chronic pain and swelling of the affected leg. How will I be treated for this condition? You will receive two daily subcutaneous (underneath the skin) injections of enoxaparin (Lovenox) for 5-7 days along with a longer course of an oral medication called warfarin (Coumadin). Both medications belong to a class of drugs known as anticoagulants. Anticoagulants do not dissolve existing clots; instead they prevent existing clots from getting larger and new clots from forming. Your body's own defense system will dissolve existing clots. How is enoxaparin (Lovenox) given? Enoxaparin is given subcutaneously twice daily. Many patients can give the injections to themselves at home, and you can be given instructions to learn how to give yourself these injections if this is an appropriate plan for you. It is important to give the medication exactly as directed. How is warfarin (Coumadin) given? Warfarin is given orally once daily. You will be getting regular blood tests to measure how well this medication is working. The dose of warfarin may be adjusted according to the results of the blood tests. What should I do if I miss a dose of enoxaparin or warfarin? You should contact __________________ as soon as you notice that you have missed a dose. What are some of the side effects of enoxaparin? Approximately 2% of patients may experience bleeding. Please notify __________________ immediately if you experience any of the following symptoms: unusual bleeding or bruising (e.g., bleeding gums, red spots on the skin, nose bleeds) heavy menstrual bleeding blood in urine or stool; black tarry stools back pain or stomach pain cold, blue, or painful feet Other minor side effects include skin irritation, pain, and bruises at the injection site. What are some of the side effects of warfarin? Like enoxaparin the major complication of warfarin is bleeding. Therefore, you should notify __________________ if you experience any of the symptoms listed in the previous answer. Please check with your doctor for more information on warfarin. Should I be aware of other signs and symptoms? You should notify __________________ immediately if you experience chest pain, shortness of breath, a feeling of passing out, or palpitation (heart racing). What medications do I need to avoid while on these medications? You should avoid taking medications that contain aspirin, medications such as ibuprofen (Advil, Motrin, Nuprin), naproxen (Aleve), ketoprofen (Orudis KT, Actron Caplets), or any other non-steroidal anti-inflammatory drugs (NSAIDs). You should always check with your doctor before starting any new prescription or over-the-counter medication. Moreover, alcohol and various food may also interact with warfarin. Please check with your doctor, nurse or pharmacist for more information. Can I maintain daily activities while taking these medications? Bed rest with leg elevation as much as possible for at least the first 24 hours is recommended. You may get more leg pain and swelling if you are on your feet all the time. What other precautions do I need to take while on these medications? Monitor signs and symptoms of bleeding. Be careful while brushing or flossing your teeth. Avoid injuries. Keep enoxaparin syringes at room temperature. Do not refrigerate or freeze enoxaparin. Store away from heat and direct light. Keep all medications out of the reach of children.