·        TREATMENT:  Standardized weight adjusted dosing of enoxaparin by pharmacy will be used for treatment of DVT, unstable angina, Non-Q Wave MI and other indications requiring 1 mg/kg (LMWH during transition to or from oral anticoagulation). Weight adjusted dosing will decrease the potential for incorrect dosages and wastage.  Pharmacists will write an order in the chart when adjusting the dose.

·        The pharmacy will carry the following sizes of Lovenoxâ 30 mg, 40 mg, and 60 mg syringes.

·        Nurses should combine the contents of multiple Lovenox syringes into one syringe before injecting the patient.

Renal adjustment for creatinine clearance less than 30 ml/min

Prophylaxis in abdominal or hip- or knee-replacement surgery, 30 mg by subcutaneous (s.c.) injection once daily,

Prophylaxis in medical patients with severely restricted mobility during an acute illness, 30 mg by s.c. injection once daily,

Prophylaxis of the ischemic complications of unstable angina and non-Q-wave myocardial infarction, 1 mg/kg by s.c. injection once daily plus aspirin therapy,

Inpatient treatment of acute deep venous thrombosis, 1 mg/kg by s.c. injection once daily plus warfarin therapy, and

Outpatient treatment of acute deep vein thrombosis without pulmonary embolism, 1 mg/kg by s.c. injection once daily plus warfarin therapy.

Anticoagulation in Neuraxial Blockade

• The following medications must receive approval of the anesthesiologist prior to administration in patients with epidural catheters:
  • Low molecular weight heparins, including, [Lovenox (enoxaparin), Fragmin (Dalteparin)]
  • Factor Xa inhibitors: Arixtra (fondaparinux)
  • Direct thrombin Inhibitors: Angiomax (bivalirudin), argatroban, Refludan (lepirudin)
  • 2b/3a platelet inhibitors: Integrilin (eptifibatide), ReoPro (abciximab), Aggrastat (tirofiban)
  • Full dose or continuous infusion heparin (not low dose heparin, 5000 units SC q12h)
  • Platelet inhibitors: Ticlid (Ticlopidine), Plavix (Clopidogrel)
  • IV Thrombolytics (not catheter clearance protocols), Activase (alteplase), TNK (tenecteplase), streptokinase
• Pharmacy will enter the pharmacy computer system that will print on the MAR for all patients with epidural catheters: Do not administer the following medications without approval of anesthesia to patients with epidural catheters: Lovenox (enoxaparin), Fragmin (dalteparin), Arixtra (fondaparinux), Angiomax (bivalirudin), argatroban, Refludan (lepirudin), Integrilin (eptifibatide), ReoPro (abciximab), Aggrastat (tirofiban), therapeutic dose heparin, Ticlid (ticlopidine), Plavix (clopidogrel), Activase (alteplase), TNK (tenecteplase), streptokinase or other anticoagulants unless approved by the anesthesiologist on call. Minidose subcutaneous heparin (5000 units Q12 hours), Celebrex, and NSAID may be administered.  The SMS note is EPID. 

Specific Recommendations from The American Society of Regional Anesthesia and Pain Medicine Consensus Conference on Neuraxial Anesthesia and Anticoagulation include:

• Preoperative Warfarin
  • Chronic warfarin therapy should be stopped 4-5 days prior to neuraxial anesthesia.
    • Normal range INR values are associated with normal hemostasis when discontinuing chronic warfarin therapy.
  • INR should be measured prior to initiation of neuraxial block
• Postoperative Warfarin
  • The analgesic solution used for neuraxial block should be tailored to minimize the degree of sensory and motor block.
  • INRs < 1.5 are associated with normal hemostasis on initial of warfarin
    • INR should be < 1.5 when the epidural catheter is pulled
  • Warfarin should be withheld or reduced in patients with indwelling neuraxial catheters when the INR is > 3.
• Preoperative LMWH
  • Needle placement should be no sooner than
    • 24 hours after therapeutic doses of Lovenox (DVT/PE treatment)
    • 10-12 hours after prophylaxis with single daily dose of LMWH
• Postoperative LMWH
  • Lovenox should be given no sooner than 2 hours after catheter removal and should be delayed 24 hours postoperatively if blood is present during needle or catheter placement.
  • LMWH (twice daily dosing prophylaxis regimens,)
    • Initiated postoperatively should start no earlier than 24 hours postoperatively
    • If continuous technique used, remove catheter at least 2 hours before 1^st dose of LMWH
  • LMWH (Single daily dosing prophylaxis regimens)
    • First dose 6-8 hours postoperatively
    • Second dose of LWMH should be given no sooner than 24 hours after the first dose.
    • Catheter should be removed a minimum of 10-12 hours after the last dose of LMWH
    • Lovenox should be given no sooner than 2 hours after catheter removal and should be delayed 24 hours postoperatively if blood is present during needle or catheter placement.
• Antiplatelet Medications
  • Plavix (Clopidogrel) should be discontinued 7 days prior to neuraxial blockage.
  • Ticlid (Ticlopidine) should be discontinued 10-14 days prior neuraxial blockage.
• 2b/3a Inhibitors:
  • 2b/3a inhibitors (Integrilin, Aggrastat) should be discontinued 8 hours prior to neuraxial blockage
  • Reopro (abciximab) should be discontinued 24-48 hours prior to neuraxial blockage.
• Heparin
  • Heparin intravenous
    • Start heparin > 1 hour after neuraxial technique
    • Remove catheter 2-4 hours after heparin infusion stopped, assess coagulation status prior to neuraxial catheter removal
  • Combining neuraxial techniques with intraoperative anticoagulation with heparin during vascular surgery seems acceptable with the following cautions:
    • Avoid this technique in patients with other coagulopathies
    • Heparin administration should be delayed for 1 hour after needle placement
    • Indwelling neuraxial catheters should be removed 2-4 hours after the last heparin dose and the patients coagulation status is evaluated and re-heparinization should occur 1 hour after catheter removal
    • Monitor the patient postoperatively to provide early detection of motor block and consider use of minimal concentration of local anesthetics to enhance the early detection of a spinal hematoma
  • Cardiopulmonary bypass
    • Full dose heparin should be discontinued 2-4 hours prior to neuraxial catheter remove.
    • Neuraxial blocks should be avoided in patients with known coagulopathy from any cause
    • Surgery should be delayed 24 hours in the event of a traumatic tap
    • Time from instrumentation to systemic heparinization should exceed 60 minutes
    • Epidural catheters should be removed when normal coagulation is restored
  • Subcutaneously Heparin
    • Low dose heparin 5000 units subcutaneously q12 hours may be used. If therapy last longer than 4 days, platelets should be monitored prior to neuraxial block and catheter removal.
• Systemic Thrombolytics
  • Patients receiving fibrinolytic and thrombolytic drugs should be cautioned against receiving spinal or epidural anesthetics except in highly unusual circumstances. Data are not available to clearly outline the length of time neuraxial puncture should be avoided after discontinuation of these drugs.

Epoetin P&T Review

Chemotherapy Induced anemia

• Epoetin 40,000 units once a week will be converted to approximately 150 units/kg three times a week or 225 units twice a week depending on patient weight (see chart below) as less total epoetin is required to achieve similar results. Randomized controlled trials utilized weight based dosing.

·        The rate of rise in: Hgb, reticulocyte count, and RBCs is the same for 150 units/kg three times a week or 40,0000 units once a week.

·        The pharmacodynamic responses of the three times weekly and once weekly dosing regimens are similar. Although the serum erythropoietin AUC for every week dosing is larger than that of three times a week dosing the AUC (reticulocytes), AUC (Hgb) and the AUC (RBC) are comparable.  Serum erythropoietin levels for every week dosing drop below three times a week dosing 4 days post injection.

• Epoetin 60,000 units once a week will be converted to approximately 225 units/kg three times a week (see chart below)
• A conservative estimate of cost saving per year by converting to protocol dosing is $ 76,021.

Anemia of Chronic Kidney Disease

• Epoetin will be administered two to three times a week by the subcutaneous route. (National Kidney Foundation/DOQI Clinical Practice Guideline for Anemia of Chronic Kidney Disease: Update 2000)
• The subcutaneous route of administration will be used, as it is 30-50% more efficient than intravenous administration. The National Kidney Foundation recommends subcutaneous administration for dialysis patients and virtually all studies in oncology patients employed subcutaneous administration. Typically, a patient requires 50% more epoetin to maintain the same Hgb when epoetin is administered by the IV route as compared to the subcutaneous route.
• Epoetin doses will be rounded to the closest vial size or combination of vials that results in a injection volume of < 2ml. (2,000, 4000, 6,000, 8,000, 10,000, 12,000, and 14,000 units)

Surgery Patients

• One dose, 600 units/kg on the day of surgery may be dispensed, further doses if ordered will be converted per the tables below. Please note in the SMS aux sig for the 600 units/kg order that it is a surgery patient. The FDA approved dose is on the day of surgery only.  

Erythropoiesis Stimulating Agents: FDA Warning

CMS has determined that there is sufficient evidence to conclude that erythropoiesis stimulating agent (ESA) treatment is not reasonable and necessary for beneficiaries with certain clinical conditions, either because of a deleterious effect of the ESA on their underlying disease or because the underlying disease increases their risk of adverse effects related to ESA use. These conditions include:

1. any anemia in cancer or cancer treatment patients due to folate deficiency, B-12 deficiency, iron deficiency, hemolysis, bleeding, or bone marrow fibrosis;
2. the anemia associated with the treatment of acute and chronic myelogenous leukemias (CML, AML), or erythroid cancers;
3. the anemia of cancer not related to cancer treatment;
4. any anemia associated only with radiotherapy;
5. prophylactic use to prevent chemotherapy-induced anemia;
6. prophylactic use to reduce tumor hypoxia;
7. patients with erythropoietin-type resistance due to neutralizing antibodies; and
8. anemia due to cancer treatment if patients have uncontrolled hypertension.

CMS have also determined that ESA treatment for the anemia secondary to myelosuppressive anticancer chemotherapy in solid tumors, multiple myeloma, lymphoma and lymphocytic leukemia is only reasonable and necessary under the following specified conditions:

1. The hemoglobin level immediately prior to initiation or maintenance of ESA treatment is < 10 g/dL (or the hematocrit is < 30%).
2. The starting dose for ESA treatment is the recommended FDA label starting dose, no more than 150 U/kg/three times weekly for epoetin and 2.25 mcg/kg/weekly for darbepoetin alpha. Equivalent doses may be given over other approved time periods.
3. Maintenance of ESA therapy is the starting dose if the hemoglobin level remains below 10 g/dL (or hematocrit is < 30%) 4 weeks after initiation of therapy and the rise in hemoglobin is > 1g/dL (hematocrit > 3%).
4. For patients whose hemoglobin rises <1 g/dl (hematocrit rise <3%) compared to pretreatment baseline over 4 weeks of treatment and whose hemoglobin level remains <10 g/dL after the 4 weeks of treatment (or the hematocrit is <30%), the recommended FDA label starting dose may be increased once by 25%. Continued use of the drug is not reasonable and necessary if the hemoglobin rises <1 g/dl (hematocrit rise <3 %) compared to pretreatment baseline by 8 weeks of treatment.
5. Continued administration of the drug is not reasonable and necessary if there is a rapid rise in hemoglobin > 1 g/dl (hematocrit > 3%) over 2 weeks of treatment unless the hemoglobin remains below or subsequently falls to < 10 g/dL (or the hematocrit is < 30%). Continuation and reinstitution of ESA therapy must include a dose reduction of 25% from the previously administered dose.
6. ESA treatment duration for each course of chemotherapy includes the 8 weeks following the final dose of myelosuppressive chemotherapy in a chemotherapy regimen.

·        Levaquin or (ceftriaxone plus azithromycin) will be recommended by the pharmacist to the physician in place of ertapenem for community-acquired pneumonia. Ertapenem is not recommended for community-acquired pneumoniae as it has little activity against highly-penicillin-resistant pneumococci and does not cover atypical pathogens.

·        Levaquin will be automatically substituted for ertapenem when ordered for urinary tract infections.

Invanz is not recommended for the treatment of hospital acquired intra-abdominal infections by Infectious Diseases Society of America or the Surgical Infection Society. It may be used for mild to moderate community acquired intra-abdominal infections.

Dosage Equivalents:

Azithromycin                             Erythromycin               

500 mg IV q24h                         250-500 mg q6h                       

 Chemotherapy Induced anemia

• Epoetin 40,000 units once a week will be converted to approximately 150 units/kg three times a week or 225 units twice a week depending on patient weight (see chart below) as less total epoetin is required to achieve similar results. Randomized controlled trials utilized weight based dosing. Use the subcutaneous route.

• Epoetin 60,000 units once a week will be converted to approximately 225 units/kg three times a week (see chart below). Use the Subcutaneous route.

Anemia of Chronic Kidney Disease

• Epoetin will be administered two to three times a week by the subcutaneous route. (National Kidney Foundation/DOQI Clinical Practice Guideline for Anemia of Chronic Kidney Disease: Update 2000)
• Epoetin doses will be rounded to the closest vial size or combination of vials that results in a injection volume of < 2ml. (2,000, 4000, 6,000, 8,000, 10,000, 12,000, and 14,000 units)

FDA Warning Against Use of Erythropoiesis Stimulating Agents in Anemia in Cancer Patients Not Receiving Chemotherapy

·        Pantoprazole (Protonix), injection and oral, is the proton pump inhibitor of choice, with automatic substitution for omeprazole (Prilosecâ), rabeprazole (Aciphexâ),  Lansoprazole (Prevacidâ), and other oral proton pump inhibitors unless the physician has checked the dispense as written block.

Lanoprazole Solutabs, 15 mg or 30 mg, may be mixed with water and placed down a very small bore pediatric feeding tube. The granules do not clump or adhere to the tube.

Pantoprazole IV Criteria for use

·        Criteria for use of IV Proton Pump Inhibitors (PPIs) are list below.  If a patient does not meet criteria the pharmacist will call the physician and/or leave a chart note recommending conversion to oral therapy.

• Initial treatment of patients with active upper GI tract bleeding, until they can tolerate oral therapy, usually after three days of therapy.
• Initial treatment of patients with Zollinger-Ellison syndrome, until they can tolerate oral therapy
• Stress-ulcer prophylaxis for critical care patients
• Patients who require PPI therapy who can not tolerate oral or NG PPI therapy

·        Patients on IV proton pump inhibitors will have an order entered for the oral route allowing the nurse to use the oral route when the patient is tolerating oral therapy. Proton pump inhibitors may be given by the oral route if the patient does not have active gastrointestinal bleeding, malabsorption syndrome, short bowel syndrome, severe diarrhea, uncontrolled nausea and vomiting, continuous nasogastric suctioning, and is not at risk for aspiration. 

• Initiation of therapy in Byetta naive patients in the hospital is not recommended due to the high initial rate of nausea and vomiting.
• Patients using Byetta at home may continue to use their medication from home while in the hospital.
  • Patients still experiencing nausea and/or vomiting secondary to Byetta should not continue Byetta in the hospital as it may complicate their clinical picture.