Lovenox

Fractionated Heparins (LMWHs)

For storage information, see specific product information within the How Supplied section.

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Enoxaparin is a clear, colorless to pale-yellow solution.
Enoxaparin cannot be used interchangeably (unit for unit) with heparin sodium or other low molecular weight heparins.
If withdrawing from the multi-dose vial, use a tuberculin or equivalent graduated syringe to ensure proper measurement of the required dose. Do not mix with other drugs or parenteral fluids.
Storage: Discard the multi-dose vial 28 days after the first use.
 
Preparation and stability of enoxaparin 20 mg/mL dilution for parenteral administration
NOTE: Enoxaparin is not FDA-approved to be prepared as a 20 mg/mL dilution. Prepare in a sterile environment, using aseptic technique.
Add the contents of 4 enoxaparin 60 mg/0.6 mL syringes and 9.6 mL preservative-free Sterile Water for Injection to a sterile glass vial.
Storage: The dilution may be stored for up to 4 weeks in the glass vial at room temperature (22 to 26 degrees C) or up to 2 weeks in tuberculin syringes with rubber stoppers at room temperature or under refrigeration (2 to 6 degrees C) without significant loss of anti-Xa activity. These stability data were determined in a class 100 environment and did not test microbiologic properties.
 
Preparation and stability of enoxaparin 8 mg/mL dilution for SUBCUTANEOUS administration
NOTE: Enoxaparin is not FDA-approved to be prepared as an 8 mg/mL dilution. Prepare in a sterile environment, using aseptic technique.
It has been suggested that an enoxaparin dilution of 8 mg/mL be used in smaller patients receiving single doses less than 8 mg/dose to ensure adequate dosing and titration. Clinicians should be aware of when to switch to a more concentrated dilution, so the patient does not receive a subcutaneous injection volume more than 1 mL/dose.
Add the contents of 1 enoxaparin 40 mg/0.4 mL syringe and 4.6 mL Sterile Water for Injection to a 10 mL sterile vial.
Storage: The dilution may be stored for up to 14 days in polypropylene syringes under refrigeration at 2 to 6 degrees C.

Use the multiple-dose vial for intravenous injection. Use a tuberculin or equivalent graduated syringe to ensure proper measurement of the required dose.
Administer via IV bolus through an intravenous line. Do not mix or coadminister with other drugs. To avoid the possible mixing with other drugs, flush the IV access port with a sufficient amount of saline or dextrose solution before and after enoxaparin administration.
May be safely administered with 0.9% Sodium Chloride Injection or 5% Dextrose Injection.

Patients should be in a supine position.
Administer by deep subcutaneous injection. Inject into the left and right anterolateral or posterolateral abdominal wall. Do not injection into skin with bruising or scars. Do not inject through clothes.
Using the thumb and forefinger, you must lift a fold of skin while giving the injection.
Insert the entire length of the needle vertically at a 90-degree angle.
Alternate the injection site with each injection. Do not rub the injection site after administration.
To avoid loss of drug when using the 30 or 40 mg prefilled syringes, do not expel the air bubble from the syringe before subcutaneous injection.
Prefilled syringes for the 30 and 40 mg doses are not graduated. Do not use these syringes to administer partial doses.
When using the prefilled syringes, after injection, a safety system to prevent inadvertent needle sticks can be activated by firmly pressing down on the plunger rod. An audible click will be heard once the protective sleeve is in place. Dispose of the syringe in a sharps container. The safety system can only be activated once the syringe is empty. Do not activate the safety system until the syringe is away from the skin.

bleeding / Early / 0-13.0
heart failure / Delayed / 1.0-1.0
intracranial bleeding / Delayed / 0.8-0.8
pulmonary edema / Early / 0.7-0.7
atrial fibrillation / Early / 0.7-0.7
retroperitoneal bleeding / Delayed / Incidence not known
spinal hematoma / Delayed / Incidence not known
ocular hemorrhage / Delayed / Incidence not known
anaphylactic shock / Rapid / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known
vasculitis / Delayed / Incidence not known
skin necrosis / Early / Incidence not known
disseminated intravascular coagulation (DIC) / Delayed / Incidence not known
thrombosis / Delayed / Incidence not known
fetal death / Delayed / Incidence not known
hyperkalemia / Delayed / Incidence not known

anemia / Delayed / 0-16.0
hematoma / Early / 0-9.0
elevated hepatic enzymes / Delayed / 5.9-6.1
peripheral edema / Delayed / 3.0-6.0
dyspnea / Early / 3.3-3.3
thrombocytopenia / Delayed / 0.1-2.8
confusion / Early / 2.2-2.2
hematuria / Delayed / 0-2.0
edema / Delayed / 2.0-2.0
bullous rash / Early / Incidence not known
erythema / Early / Incidence not known
thrombocytosis / Delayed / Incidence not known
hyperlipidemia / Delayed / Incidence not known
hypertriglyceridemia / Delayed / Incidence not known
cholestasis / Delayed / Incidence not known
osteoporosis / Delayed / Incidence not known
eosinophilia / Delayed / Incidence not known

fever / Early / 5.0-8.0
ecchymosis / Delayed / 0-3.0
nausea / Early / 2.5-3.0
diarrhea / Early / 2.2-2.2
pruritus / Rapid / Incidence not known
vesicular rash / Delayed / Incidence not known
purpura / Delayed / Incidence not known
urticaria / Rapid / Incidence not known
injection site reaction / Rapid / Incidence not known
alopecia / Delayed / Incidence not known
headache / Early / Incidence not known

Epidural or spinal hemorrhage and subsequent hematomas can occur in patients receiving enoxaparin while epidural or spinal anesthesia/analgesia or spinal puncture procedures are performed. The bleeding risk for spinal or epidural hematomas, which may result in permanent or long-term paralysis, may be greater with use of postoperative indwelling epidural catheters, in patients with a history of traumatic or repeated epidural or spinal puncture, a history of spinal deformity, a history of spinal surgery, or concomitant use of other drugs affecting hemostasis, such as NSAIDs, platelet inhibitors, or other anticoagulants. Although the optimal timing between the administration of enoxaparin and neuraxial procedures is not known, if epidural anesthesia, lumbar puncture, or spinal anesthesia is performed, it is best done when the anticoagulant effect of enoxaparin is low. The manufacturer recommends delaying the placement or removal of epidural catheters for at least 12 hours after administration in patients receiving low doses (30 mg twice daily or 40 mg once daily) and at least 24 hours after administration in patients receiving high doses (0.75 to 1 mg/kg twice daily or 1.5 mg/kg once daily). Patients receiving 0.75 mg/kg or 1 mg/kg twice daily should not receive the second enoxaparin dose in the twice daily regimen to allow a longer delay before catheter placement or removal. In patients with severe renal dysfunction (CrCl less than 30 ml/min), consider delaying the placement or removal of epidural catheters for at least 24 hours after administration in adult patients receiving low doses and 48 hours after administration in adult patients receiving high doses because of slower enoxaparin clearance. Although a specific recommendation for timing of a subsequent enoxaparin dose after catheter removal cannot be made, the manufacturer recommends considering delaying subsequent enoxaparin doses for at least 4 hours after catheter removal. If neuraxial procedures are employed, monitor patients frequently for symptoms of neurological impairment such as midline back pain, sensory and motor deficits, and bowel and/or bladder dysfunction. Consider the risk versus benefit of neuraxial intervention in patients anticoagulated or to be anticoagulated. If neurological compromise is noted, urgent treatment is necessary; however, such treatment may not prevent or reverse neurological sequelae. In addition, monitor patients closely for a fall in hematocrit and/or a fall in blood pressure, hematuria, hematemesis, and other signs or symptoms of bleeding. To minimize bleeding risk, periodic complete blood counts, including platelet count, and stool occult blood tests are recommended during the course of treatment with enoxaparin. When administered at recommended prophylaxis doses, routine coagulation tests such as prothrombin time (PT) and activated partial thromboplastin time (aPTT) are relatively insensitive measures of enoxaparin activity and, therefore, unsuitable for monitoring. Monitor anti-factor Xa concentrations to assess the anticoagulant effect of enoxaparin.

Lovenox

Rx

Low molecular weight heparin (LMWH)
Used for prophylaxis and management of systemic thromboembolism
More predictable anticoagulant response than unfractionated heparin

1 mg/kg/dose subcutaneously every 12 hours or 1.5 mg/kg/dose subcutaneously every 24 hours. Start warfarin therapy when appropriate, as early as day 1 and usually within 72 hours of initiation of enoxaparin. Continue enoxaparin for a minimum of 5 days and until a therapeutic oral anticoagulant effect has been achieved.

1 mg/kg/dose subcutaneously every 12 hours, initially. Adjust the dose to maintain an anti-factor Xa concentration of 0.5 to 1 units/mL when drawn 4 to 6 hours after the dose or 0.5 to 0.8 units/mL when drawn 2 to 6 hours after the dose.

1 mg/kg/dose subcutaneously every 12 hours, initially. Adjust the dose to maintain an anti-factor Xa concentration of 0.5 to 1 units/mL when drawn 4 to 6 hours after the dose or 0.5 to 0.8 units/mL when drawn 2 to 6 hours after the dose. Alternatively, 1.2 mg/kg/dose subcutaneously every 12 hours has been recommended based on a retrospective study including 117 patients 3 months and older.

1 mg/kg/dose subcutaneously every 12 hours, initially. Adjust the dose to maintain an anti-factor Xa concentration of 0.5 to 1 units/mL when drawn 4 to 6 hours after the dose or 0.5 to 0.8 units/mL when drawn 2 to 6 hours after the dose. Alternatively, 1.5 mg/kg/dose subcutaneously every 12 hours has been recommended based on a retrospective study including 117 patients 3 months and older.

1.5 mg/kg/dose subcutaneously every 12 hours, initially. Adjust the dose to maintain an anti-factor Xa concentration of 0.5 to 1 units/mL when drawn 4 to 6 hours after the dose or 0.5 to 0.8 units/mL when drawn 2 to 6 hours after the dose. Alternatively, 1.8 mg/kg/dose subcutaneously every 12 hours has been recommended based on a retrospective study including 75 infants younger than 3 months. Patients treated with a higher initial dose achieved a therapeutic anti-factor Xa level 1 day earlier and required 1 less venipuncture on average than those treated with a standard dose (1.5 mg/kg/dose subcutaneously).

1.7 mg/kg/dose subcutaneously every 12 hours has been recommended based on several studies indicating that neonates require higher doses than older pediatric patients. Alternatively, 1.5 mg/kg/dose subcutaneously every 12 hours, initially, is recommended by guidelines for infants younger than 2 months. Adjust the dose to maintain an anti-factor Xa concentration of 0.5 to 1 units/mL when drawn 4 to 6 hours after the dose or 0.5 to 0.8 units/mL when drawn 2 to 6 hours after the dose.

2 mg/kg/dose subcutaneously every 12 hours has been recommended based on several studies indicating that premature neonates require higher doses than term neonates. Alternatively, 1.5 mg/kg/dose subcutaneously every 12 hours is recommended by guidelines for infants younger than 2 months. Adjust the dose to maintain an anti-factor Xa concentration of 0.5 to 1 units/mL when drawn 4 to 6 hours after the dose or 0.5 to 0.8 units/mL when drawn 2 to 6 hours after the dose.

1 mg/kg/dose subcutaneously every 12 hours. Start warfarin therapy when appropriate, usually within 72 hours of initiation of enoxaparin. Continue enoxaparin for a minimum of 5 days and until a therapeutic oral anticoagulant effect has been achieved.

1 mg/kg/dose subcutaneously every 12 hours or 1.5 mg/kg/dose every 24 hours throughout pregnancy and for at least 6 weeks postpartum (for a total duration of therapy of at least 3 months). Base dose on early pregnancy body weight. Discontinue enoxaparin 24 hours prior to elective induction of labor or cesarean section.

1 mg/kg/dose subcutaneously every 12 hours or 1.5 mg/kg/dose subcutaneously every 24 hours for at least 3 months.

1 mg/kg subcutaneously every 12 hours. Base dose on actual body weight.  

0.7 to 0.8 mg/kg subcutaneously every 12 hours. Base dose on actual body weight.   

1 mg/kg subcutaneously every 12 hours. Guidelines recommend LMWH in combination with oral anticoagulants until the INR is within the therapeutic range for 2 consecutive days.

40 mg subcutaneously once daily.

Guidelines suggest a dose of 3,400 anti-factor Xa International Units or less of LMWH subcutaneously once daily (equivalent to 34 mg or less per day of subcutaneous enoxaparin); 20 mg subcutaneously once daily is the dose most studied during 'low-dose' enoxaparin DVT/PE prophylaxis studies. Higher doses of 40 to 60 mg/day subcutaneously are associated with an increased risk of bleeding and the risk of bleeding may outweigh the benefit in this at moderate-risk population. Previous guidelines have suggested starting the LMWH 1 to 2 hours before surgery, followed by once daily postoperatively.

Guidelines suggest a dose more than 3,400 anti-factor Xa International Units subcutaneously once daily (equivalent to more than 34 mg subcutaneously once daily of enoxaparin); 30 mg subcutaneously every 12 hours or 40 mg subcutaneously once daily are the doses most studied during enoxaparin DVT/PE prophylaxis studies. Previous guidelines have suggested starting enoxaparin, when given in a dose of 30 mg subcutaneously every 12 hours, 8 to 12 hours preoperatively; or when given as 40 mg subcutaneously once daily, starting 1 to 2 hours preoperatively. Subsequent doses, provided hemostasis has been established, are administered beginning 24 hours after the initial preoperative dose and continued for 7 to 10 days. Continue prophylaxis throughout the period of postoperative care until the risk of DVT has diminished. In cancer surgery patients, prophylaxis for 2 to 3 weeks after surgery reduces the risk of symptomatic DVT. In all higher-risk general surgery patients, the use of mechanical prophylaxis with elastic stockings (ES) or intermittent pneumatic compression (IPC) is recommended initially. In very high-risk general surgery patients with multiple risk factors, combination of pharmacologic and mechanical (i.e., ES or IPC) prophylaxis is recommended.

40 mg subcutaneously once daily or 30 mg subcutaneously every 12 hours starting 12 hours or more before or after surgery. Continue prophylaxis for at least 10 to 14 days; up to 35 days is recommended. Low molecular weight heparin is the preferred agent for antithrombotic prophylaxis for persons undergoing total hip replacement surgery or hip fracture surgery.

30 mg subcutaneously every 12 hours. Guidelines recommend LMWH as the preferred agent for antithrombotic prophylaxis for patients undergoing total knee replacement surgery. Prophylaxis should start 12 hours or more preoperatively or postoperatively and continue for a minimum of 10 to 14 days after surgery; up to 35 days is recommended. The use of an intermittent pneumatic compression device (IPCD) during the hospital stay is encouraged.

Guidelines recommend 3,400 anti-factor Xa International Units or less of LMWH subcutaneously once daily (equivalent to 34 mg or less per day of subcutaneous enoxaparin). Continue prophylaxis until hospital discharge. Previous guidelines have suggested enoxaparin 20 mg subcutaneously 1 to 2 hours prior to surgery, then once daily.

Guidelines recommend more than 3,400 anti-factor Xa International Units of LMWH subcutaneously once daily (equivalent to more than 34 mg subcutaneously once daily of enoxaparin). For most patients, continue prophylaxis until hospital discharge; however, in patients that are considered to be at high risk (i.e., older than 60 years of age or a history of VTE), continue prophylaxis through hospitalization and for 2 to 4 weeks after discharge. Previous guidelines have suggested a dose of enoxaparin 40 mg subcutaneously 1 to 2 hours before surgery then once daily or 30 mg subcutaneously every 12 hours starting 8 to 12 hours before surgery.

20 or 40 mg subcutaneously once daily in patients that have additional risk factors for VTE. In a study, enoxaparin was started the night before surgery and continued daily through hospital admission. Patients with risk factors for VTE or weight more than 80 kg received the higher dose of 40 mg.

40 mg subcutaneously once daily in patients that have additional risk factors for VTE.

20 mg subcutaneously 1 to 2 hours prior to surgery then once daily for patients at moderate risk for VTE. For patients at highest risk, 40 mg subcutaneously 1 to 2 hours before surgery then once daily or 30 mg subcutaneously every 12 hours starting 8 to 12 hours before surgery in combination with elastic stockings (ES) with or without intermittent pneumatic compression (IPC). The optimal duration of prophylaxis is not known.

40 mg subcutaneously once daily beginning 24 hours after surgery and in combination with compression stockings, provided hemostasis has been established and no contraindications to LMWH use exist. The use of enoxaparin must be balanced with clinically important risk of intracranial bleeding; some clinicians obtain a CT scan prior to initiating LMWH to rule out an intracranial bleed. Limited data suggests that the combination of LMWH with stockings may be more effective than stockings alone in preventing VTE.

20 or 40 mg subcutaneously once daily beginning postoperatively in patients that have additional risk factors for VTE. The optimal duration of prophylaxis is unknown. In patients with multiple risk factors, the use of LMWH in combination with elastic stockings (ES) or intermittent pneumatic compression (IPC) is recommended.

30 mg subcutaneously every 12 hours usually within 36 hours of the injury, provided hemostasis has been established and no contraindications to LMWH exist. Continue VTE prophylaxis throughout hospitalization and inpatient rehabilitation. Continue prophylaxis in patients who have impaired mobility after recovery.

30 mg subcutaneously every 12 hours or 40 mg subcutaneously once daily, provided hemostasis has been established and no contraindications to LMWH use exist. Continue the LMWH throughout hospitalization and the rehabilitation phase.

40 mg subcutaneously once daily, if not contraindicated. For a patient with contraindications to antithrombotic therapy, guidelines recommend intermittent pneumatic compression (IPC) devices or elastic stockings (ES).

40 mg subcutaneously for 1 dose 2 to 4 hours before travel, although a higher dose of 1 mg/kg subcutaneously for 1 dose has also been used.

0.5 mg/kg/dose subcutaneously every 12 hours; adjust dose to maintain an anti-factor Xa concentration of 0.1 to 0.3 International Units/mL.

0.75 mg/kg/dose subcutaneously every 12 hours; adjust dose to maintain an anti-factor Xa concentration of 0.1 to 0.3 International Units/mL.

0.75 mg/kg/dose subcutaneously every 12 hours; adjust dose to maintain an anti-factor Xa concentration of 0.1 to 0.3 International Units/mL.

40 mg subcutaneously once daily for 6 weeks postpartum; clinical surveillance is recommended antepartum. May consider adjusting dose to maintain anti-factor Xa concentration of 0.2 to 0.6 International Units/mL. Low-risk of recurrent VTE is defined as a single episode of VTE associated with a transient risk factor unrelated to pregnancy or use of estrogen.

40 mg subcutaneously once daily throughout pregnancy and continued for 6 weeks postpartum. May consider adjusting dose to maintain anti-factor Xa concentration of 0.2 to 0.6 International Units/mL. Moderate- to high-risk of recurrent VTE is defined as a single, unprovoked VTE, pregnancy- or estrogen-related VTE, or multiple unprovoked VTE, and not receiving long-term anticoagulation.

40 mg subcutaneously once daily for 6 weeks postpartum; clinical surveillance is recommended antepartum. May consider adjusting dose to maintain anti-factor Xa concentration of 0.2 to 0.6 International Units/mL.

40 mg subcutaneously once daily throughout pregnancy and continued for 6 weeks postpartum. May consider adjusting dose to maintain anti-factor Xa concentration of 0.2 to 0.6 International Units/mL.

40 mg subcutaneously once daily for 6 weeks postpartum; clinical surveillance is recommended antepartum. May consider adjusting dose to maintain anti-factor Xa concentration of 0.2 to 0.6 International Units/mL.

40 mg subcutaneously every 12 hours throughout pregnancy and continued for 6 weeks postpartum. May consider adjusting dose to maintain anti-factor Xa concentration of 0.2 to 0.6 International Units/mL.

40 mg subcutaneously once daily or every 12 hours throughout pregnancy and continued for 6 weeks postpartum. May consider adjusting dose to maintain anti-factor Xa concentration of 0.2 to 0.6 International Units/mL.

1 mg/kg subcutaneously every 12 hours with resumption of long-term anticoagulation postpartum.

1 mg/kg/dose subcutaneously every 12 hours throughout pregnancy, or alternately, from weeks 6 to 12, followed by warfarin (INR 2.5 to 3.5) until the middle of the third trimester, and then enoxaparin for the remainder of the pregnancy. Adjust dose to maintain anti-factor Xa concentration of 0.8 to 1.2 International Units/mL. In persons who are at especially high risk, the addition of low-dose aspirin is recommended.

40 mg subcutaneously once daily for up to 3 months as an alternative to IV heparin for continuation of anticoagulation beyond 48 hours of an AMI. All acute MI patients should receive at least LMWH or low-dose heparin until the patient is ambulatory for prevention of DVT.

1 mg/kg subcutaneously every 12 hours or 1.5 mg/kg subcutaneously once daily at presentation for patients without contraindications. For patients with atrial fibrillation of known duration less than 48 hours, cardioversion can be performed without anticoagulation.

0.5 mg/kg subcutaneously once or twice daily. Anti-factor Xa concentrations may be monitored with dosage adjustments considered to achieve an anti-factor Xa concentration of 0.2 to 0.5 International Units/mL. Although previous guidelines recommended weight-based dosing for VTE prophylaxis in obese patients, current guidelines do not provide specific dosing recommendations but suggest an increased dose may be required. Among obese, medically ill patients (n = 28, BMI 35 kg/m2 or more), the mean anti-factor Xa concentration after 1 to 2 doses of enoxaparin 0.5 mg/kg subcutaneously once daily was 0.25 International Units/mL (range 0.08 to 0.59 International Units/mL). Another small prospective study of obese, medically ill patients (n = 31, BMI 40 kg/m2 or more) compared enoxaparin 40 mg, 0.4 mg/kg, and 0.5 mg/kg subcutaneously once daily for 3 days or less in most patients. Patients receiving 0.5 mg/kg once daily achieved goal anti-factor Xa concentrations more often (p less than 0.001). Further, 82% of patients in the 40 mg group had anti-factor Xa concentrations below goal compared to 36% and 13% in the 0.4 mg/kg and 0.5 mg/kg groups, respectively (p less than 0.001). There were no observed bleeding or thrombosis complications. A retrospective study evaluated enoxaparin 0.5 mg/kg subcutaneously twice daily in obese surgical ICU patients (n = 23, mean BMI = 46.4 kg/m2). Among these patients, 91% achieved goal anti-factor Xa concentrations with a mean concentration of 0.34 International Units/mL (range 0.2 to 0.59 International Units/mL) after the third or fourth dose. Subsequent dose adjustments of +/- 10 mg were allowed based on anti-factor Xa results. DVT and minor bleeding were each reported in 1 patient.

0.5 to 0.75 mg/kg IV bolus.

0.3 mg/kg IV bolus if subcutaneous enoxaparin given 8 to 12 hours earlier; do not administer additional enoxaparin if subcutaneous enoxaparin given within previous 8 hours.

1 mg/kg subcutaneously every 12 hours until discharge or revascularization. The usual duration of enoxaparin therapy is 2 to 8 days. Administer in combination with aspirin. An initial 30 mg IV bolus has been used in select patients.

30 mg IV bolus plus 1 mg/kg subcutaneously, followed by 1 mg/kg subcutaneously every 12 hours (Max: 100 mg for the first 2 doses only) until hospital discharge, for up to 8 days or revascularization. Administer an additional 0.3 mg/kg IV bolus at the time of PCI if subcutaneous enoxaparin given more than 8 hours earlier; do not administer additional enoxaparin if subcutaneous enoxaparin given within previous 8 hours. If administered with a thrombolytic, administer enoxaparin between 15 minutes before and 30 minutes after initiation of fibrinolytic therapy. Administer in combination with aspirin.

0.75 mg/kg subcutaneously every 12 hours (Max: 75 mg for the first 2 doses only) until hospital discharge, for up to 8 days or revascularization. If administered with a thrombolytic, administer enoxaparin between 15 minutes before and 30 minutes after initiation of fibrinolytic therapy. Administer in combination with aspirin.

The ACCP guidelines recommend treatment with enoxaparin during the acute phase, even in the presence of hemorrhagic infarction. Then, treat with a vitamin k antagonist for 3—6 months. A specific dose of enoxaparin has not been suggested.

The ACCP guidelines recommend treatment with LMWH initially, followed by warfarin or continued treatment with enoxaparin for 3 months, even if a localized hemorrhagic infarct is present. In a small, pilot study, children with sinovenous thrombosis were randomized to unfractionated heparin (n = 10), enoxaparin (n = 12), or no treatment (n = 8). In children >= 2 months of age the initial dose of enoxaparin was 1 mg/kg subcutaneously every 12 hours adjusted to maintain a goal anti-factor Xa concentration of 0.5—1 anti-factor Xa International Units/mL. The majority of patients received warfarin after the initial treatment; however, 4 patients received enoxaparin for the entire treatment period of 3 months. Recurrent thrombosis was not reported in patients taking enoxaparin or heparin; however, 1 patient in the heparin group experienced clinically silent bleeding. Three patients that did not receive an anticoagulant died versus zero patients that did receive anticoagulant therapy.

The ACCP guidelines recommend LMWH for 3 months as long as the there is no large ischemic infarct or an intracranial hemorrhage. In a small, pilot study, children with sinovenous thrombosis were randomized to unfractionated heparin (n = 10), enoxaparin (n = 12), or no treatment (n = 8). In children < 2 months of age the initial dose of enoxaparin was 1.5 mg/kg subcutaneously every 12 hours adjusted to maintain a goal anti-factor Xa concentration of 0.5—1 anti-factor Xa International Units/ml. The majority of patients received warfarin after the initial treatment; however, 4 patients received enoxaparin for the entire treatment period of 3 months. Recurrent thrombosis was not reported in patients taking enoxaparin or heparin; however, 1 patient in the heparin group experienced clinically silent bleeding. Three patients that did not receive an anticoagulant died versus zero patients that did receive anticoagulant therapy.

40 mg subcutaneously once daily throughout pregnancy in combination with low-dose aspirin. May consider adjusting dose to maintain anti-factor Xa concentration of 0.2 to 0.6 International Units/mL.

40 mg subcutaneously once daily or 30 mg subcutaneously twice daily may be sufficient. DOACs have short half-lives; hence, alternative anticoagulation during temporary interruption is not needed in the majority of situations.

1 mg/kg/dose subcutaneously twice daily or 1.5 mg/kg/dose subcutaneously once daily. Alternatively, 30 mg subcutaneously twice daily or 40 mg subcutaneously once daily (low-dose prophylactic regimen) or 40 mg subcutaneously twice daily (intermediate-dose regimen) has been used. Stop warfarin approximately 5 days prior to procedure and initiate LMWH 24 hours or more after the first missed dose of warfarin. Guidelines recommend starting LMWH when INR is less than 2 in those with nonvalvular atrial fibrillation, or if INR is not measured, after omitting 2 to 3 doses of warfarin. Administer the last dose of LMWH approximately 24 hours before procedure, potentially longer in those with renal dysfunction. If necessary, residual anticoagulation can be assessed by checking antifactor Xa concentrations. In most cases, warfarin can be restarted in the first 12 to 24 hours after the procedure at the patient’s usual therapeutic dose; post-procedural bridging can be considered in patients with moderate or high risk of stroke or thromboembolic events.

0.5 mg/kg/dose (Max: 30 mg/dose) subcutaneous every 12 hours.

1 mg/kg/dose subcutaneous every 12 hours. Adjust dose to maintain anti-factor Xa concentration of 0.5 to 1 units/mL. Patients with coronary artery aneurysms and a maximal z-score of 10 or more should be treated with low dose aspirin and therapeutic anticoagulation with enoxaparin for at least 2 weeks before transitioning to warfarin. Patients with an ejection fraction (EF) less than 35% should receive low dose aspirin and therapeutic anticoagulation (enoxaparin or warfarin) until EF exceeds 35%. Patients with documented thrombosis should receive low dose aspirin and therapeutic anticoagulation (enoxaparin or warfarin) for 3 months, pending thrombosis resolution.[65707]

†Indicates off-label use

Enoxaparin therapy has not been studied in patients with hepatic impairment; exposure to enoxaparin in this patient population is unknown.

Adults
The following initial dosage adjustments have been recommended. While some have recommended monitoring anti-factor Xa serum concentrations, others do not recommend using serum concentrations to guide dosage adjustment in patients with a CrCl less than 30 mL/minute. Instead, the recommendation is to use the manufacturer's renal dose adjustment or switch to an alternative anticoagulant with lower renal clearance. Although no dosage adjustment is recommended for 30 to 80 mL/min, observe these patients frequently for signs and symptoms of bleeding.
CrCl 30 mL/minute or more: No dosage adjustment needed.
CrCl less than 30 mL/minute:
Thrombosis prophylaxis in abdominal or hip or knee replacement surgery or acute medical illness: 30 mg subcutaneously once daily
Prophylaxis of ischemic complications of unstable angina or non-Q-wave myocardial infarction plus aspirin: 1 mg/kg subcutaneously once daily
Treatment of deep vein thrombosis with or without pulmonary embolism plus warfarin: 1 mg/kg subcutaneously once daily
Treatment of acute ST-segment elevation myocardial infarction in patients younger than 75 years plus aspirin: 30 mg IV bolus plus 1 mg/kg subcutaneously then 1 mg/kg subcutaneously once daily
Treatment of acute ST-segment elevation myocardial infarction in patients 75 years and older plus aspirin: 1 mg/kg subcutaneously once daily
 
Pediatric patients
The following initial dosage adjustments have been recommended for pediatric patients. Adjust dose further based on anti-factor Xa concentrations. Although no dosage adjustment is recommended for 30 to 80 mL/min, observe these patients frequently for signs and symptoms of bleeding.
CrCl 30 mL/minute/1.73 m2 or more: No dosage adjustment needed.
CrCl 10 to 29 mL/minute/1.73 m2: Reduce initial dose by 30%.
CrCl less than 10 mL/minute//1.73 m2: Reduce initial dose by 50% and administer every 24 hours.
 
Intermittent hemodialysis and Peritoneal dialysis
Reduce the initial dose by 50%.
 
Continuous renal replacement therapy (CRRT)
Reduce the initial dose by 30% (assuming a dialysis dose of 2,000 mL/minute/1.73 m2).

5-Aminosalicylates: (Moderate) Coadministration of 5-aminosalicylates and low molecular weight heparins may result in an increased risk of bleeding (i.e., hematomas) following neuraxial anesthesia. Discontinue 5-aminosalicylates prior to the initiation of a low molecular weight heparins. If this is not possible, it is recommended to monitor patients closely for bleeding.
Abciximab: (Moderate) The use of abciximab within 7 days of use an oral anticoagulant is contraindicated unless the patient's prothrombin time is less than or equal to 1.2 times the control value. Because abciximab inhibits platelet aggregation, additive effects may be seen when abciximab is given in combination with other agents that affect hemostasis such as other platelet inhibitors (e.g., aspirin, ASA, clopidogrel, dipyridamole, ticlopidine), thrombolytic agents (e.g., alteplase, reteplase, streptokinase), and anticoagulants (e.g., heparin, warfarin). However, in clinical trials with abciximab, aspirin and heparin were administered concomitantly. The bleeding risk is significantly increased with concurrent abciximab and thrombolytic therapy; the risks of combination therapy should be weighed against the potential benefits. The GUSTO V study evaluated reduced-dose reteplase in combination with full dose abciximab, in comparison to full dose reteplase alone in patients with acute myocardial infarction (MI); all patients received concurrent aspirin and heparin therapy. The combination regimen was associated with a two-fold increase in moderate to severe non-intracranial bleeding complications, including spontaneous GI bleeding. In addition, large doses of salicylates (>= 3 to 4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. Although NSAIDs lacks platelet inhibitory effects, an increased risk for GI bleeding is possible when NSAIDs are administered during abciximab therapy.
Acetaminophen; Ibuprofen: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Ado-Trastuzumab emtansine: (Moderate) Use caution if coadministration of anticoagulants with ado-trastuzumab emtansine is necessary due to reports of severe and sometimes fatal hemorrhage, including intracranial bleeding, with ado-trastuzumab emtansine therapy. Consider additional monitoring when concomitant use is medically necessary. While some patients who experienced bleeding during ado-trastuzumab therapy were also receiving anticoagulation therapy, others had no known additional risk factors.
Alteplase: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including thrombolytic agents, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Altretamine: (Moderate) Due to the thrombocytopenic effects of altretamine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Amlodipine; Celecoxib: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Anagrelide: (Moderate) Although anagrelide inhibits platelet aggregation at high doses, there is a potential additive risk for bleeding if anagrelide is given in combination with other agents that effect hemostasis such as other anticoagulants. In addition, large doses of salicylates (>= 3 to 4 g/day) can cause hypoprothrombinemia, an additional risk factor for bleeding. An in vivo interaction study in humans demonstrated that a single 1 mg dose of anagrelide administered concomitantly with a single dose of aspirin 900 mg was well tolerated; there was no effect on bleeding time, PT, or PTT. However, aspirin alone produced a marked inhibition of platelet aggregation ex vivo; anagrelide enhanced the platelet inhibition effects of aspirin slightly. Patients may be at increased risk of bleeding if anagrelide is administered with aspirin.
Antithrombin III: (Major) As a regulator of hemostasis, antithrombin III (AT III) may increase bleeding risk in patients receiving low molecular weight heparins (LMWHs) concomitantly. The anticoagulant effect of LMWHs is enhanced by concurrent treatment with AT III in patients with hereditary AT III deficiency. In addition, the half-life of AT III may be altered during concomitant administration with anticoagulants. Thus, in order to avoid bleeding, the LMWH dosage may need to be reduced during treatment with AT III. Coagulation tests (aPTT and anti-Factor Xa, when appropriate) should be performed regularly and especially in the first hours following the start or withdrawal of AT III therapy to ensure appropriate anticoagulation.
Apixaban: (Major) Avoid concomitant use of apixaban with low molecular weight heparins due to the increased risk for bleeding. Short-term overlaps in anticoagulation therapy may be necessary for patients transitioning from one anticoagulant to another. Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if the use of multiple anticoagulants is necessary.
Argatroban: (Moderate) An additive risk of bleeding may be seen in patients receiving enoxaparin in combination with other anticoagulants. If coadministration of 2 or more anticoagulants is necessary, patients should be closely monitored for evidence of bleeding.
Aspirin, ASA; Dipyridamole: (Moderate) Because dipyridamole is a platelet inhibitor, there is a potential additive risk for bleeding if dipyridamole is given in combination with other agents that affect hemostasis.
Betrixaban: (Major) Avoid concurrent use of betrixaban with enoxaparin due to the increased bleeding risk. Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if betrixaban and other anticoagulants are used concomitantly. Coadministration of betrixaban and other anticoagulants may increase the risk of bleeding. Long-term concomitant treatment with betrixaban and other anticoagulants is not recommended; short-term use may be necessary for patients transitioning to or from betrixaban.
Bivalirudin: (Major) An additive risk of bleeding may be seen in patients receiving enoxaparin in combination with other anticoagulants. If coadministration of 2 or more anticoagulants is necessary, patients should be closely monitored for evidence of bleeding.
Bupivacaine; Meloxicam: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Caplacizumab: (Major) Avoid concomitant use of caplacizumab and anticoagulants when possible. Assess and monitor closely for bleeding if use together is necessary. Interrupt use of caplacizumab if clinically significant bleeding occurs.
Celecoxib: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Celecoxib; Tramadol: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Chlorambucil: (Moderate) Due to the thrombocytopenic effects of chlorambucil, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Cilostazol: (Moderate) The safety of cilostazol has not been established with concomitant administration of anticoagulants. Because cilostazol is a platelet aggregation inhibitor, concomitant administration with similar acting drugs could theoretically result in an increased risk of bleeding due to additive pharmacodynamic effects, and combinations of these agents should be approached with caution. Patients on anticoagulants should be monitored for changes in response to anticoagulation therapy if cilostazol is administered concurrently.
Clofarabine: (Moderate) Due to the thrombocytopenic effects of clofarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Clopidogrel: (Moderate) Because clopidogrel inhibits platelet aggregation, a potential additive risk for bleeding exists if clopidogrel is given in combination with other agents that affect hemostasis such as anticoagulants.
Collagenase: (Moderate) Cautious use of injectable collagenase by patients taking anticoagulants is advised. The efficacy and safety of administering injectable collagenase to a patient taking an anticoagulant within 7 days before the injection are unknown. Receipt of injectable collagenase may cause an ecchymosis or bleeding at the injection site.
Cytarabine, ARA-C: (Moderate) Due to the thrombocytopenic effects of pyrimidine analogs, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Dabigatran: (Major) Avoid use of dabigatran with enoxaparin due to the increased bleeding risk. Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if dabigatran and other anticoagulants are used concomitantly. Coadministration of dabigatran and other anticoagulants may increase the risk of bleeding. Long-term concomitant treatment with dabigatran and other anticoagulants is not recommended; short-term use may be necessary for patients transitioning to or from dabigatran.
Dalteparin: (Major) An additive risk of bleeding may be seen in patients receiving other anticoagulants in combination with enoxaparin. Monitor clinical and laboratory response closely when enoxaparin is coadministered with drugs known to increase the risk of bleeding.
Danazol: (Major) Danazol can decrease hepatic synthesis of procoagulant factors, increasing the possibility of bleeding when used concurrently with anticoagulants.
Dasatinib: (Moderate) Monitor for evidence of bleeding if coadministration of dasatinib and anticoagulants is necessary. Dasatinib can cause serious and fatal bleeding. Concomitant anticoagulants may increase the risk of hemorrhage.
Deferasirox: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including anticoagulants.
Defibrotide: (Contraindicated) Coadministration of defibrotide with antithrombotic agents like anticoagulants is contraindicated. The pharmacodynamic activity and risk of hemorrhage with antithrombotic agents are increased if coadministered with defibrotide. If therapy with defibrotide is necessary, discontinue systemic antithrombotic agents (not including use for routine maintenance or reopening of central venous catheters) prior to initiation of defibrotide therapy. Consider delaying the onset of defibrotide treatment until the effects of the antithrombotic agent have abated.
Desirudin: (Moderate) Any agent which may enhance the risk of hemorrhage (e.g., enoxaparin) should generally be discontinued before initiating desirudin therapy. If coadministration cannot be avoided, close clinical and laboratory monitoring should be conducted.
Desvenlafaxine: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including serotonin norepinephrine reuptake inhibitors (SNRIs), before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Dextran: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Diclofenac: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Diclofenac; Misoprostol: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Diflunisal: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Diphenhydramine; Ibuprofen: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Diphenhydramine; Naproxen: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Dipyridamole: (Moderate) Because dipyridamole is a platelet inhibitor, there is a potential additive risk for bleeding if dipyridamole is given in combination with other agents that affect hemostasis.
Duloxetine: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including serotonin norepinephrine reuptake inhibitors (SNRIs), before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Edoxaban: (Major) Avoid concurrent use of edoxaban with low molecular weight heparins due to the increased bleeding risk. Monitor patients closely and promptly evaluate any signs or symptoms of bleeding if edoxaban and other anticoagulants are used concomitantly. Coadministration of edoxaban and other anticoagulants may increase the risk of bleeding. Long-term concomitant treatment with edoxaban and other anticoagulants is not recommended; short-term use may be necessary for patients transitioning to or from edoxaban.
Eltrombopag: (Moderate) Use caution when discontinuing eltrombopag in patients receiving anticoagulants (e.g., warfarin, enoxaparin, dabigatran, rivaroxaban). The risk of bleeding and recurrent thrombocytopenia is increased in patients receiving these drugs when eltrombopag is discontinued.
Epoprostenol: (Moderate) When used concurrently with anticoagulants, epoprostenol may increase the risk of bleeding.
Eptifibatide: (Moderate) Concomitant use of eptifibatide and other agents that may affect hemostasis, such as anticoagulants, may be associated with an increased risk of bleeding.
Esterified Estrogens; Methyltestosterone: (Moderate) Methyltestosterone can increase the effects of anticoagulants through reduction of procoagulant factor. Patients receiving oral anticoagulant therapy should be closely monitored, especially when methyltestosterone treatment is initiated or discontinued.
Etodolac: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Fenoprofen: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Fish Oil, Omega-3 Fatty Acids (Dietary Supplements): (Moderate) Drug interactions with fish oil, omega-3 fatty acids (Dietary Supplements) or fish oil, omega-3 fatty acids (FDA-approved) are unclear at this time. However, because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 3-6 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant fish oil therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly.
Flurbiprofen: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Fondaparinux: (Major) Discontinue enoxaparin before starting fondaparinux due to the increased bleeding risk, unless these agents are essential. If coadministration is necessary, monitor patients closely and promptly evaluate any signs or symptoms of bleeding.
Garlic, Allium sativum: (Moderate) Garlic produces clinically significant antiplatelet effects so additive risk of bleeding may occur if anticoagulants are given in combination. Avoid concurrent use of herbs which interact with anticoagulants when possible. If garlic dietary supplements are taken, monitor the INR or other appropriate parameters to attain clinical and anticoagulant endpoints. In regard to warfarin, published data are limited to a random case report; however, the product labeling for warfarin includes garlic as having potential for interaction due to additive pharmacologic activity. A case of spontaneous spinal epidural hematoma, attributed to dysfunctional platelets from excessive garlic use in a patient not receiving concomitant anticoagulation, has been reported.
Ginger, Zingiber officinale: (Moderate) Additive bleeding may occur if anticoagulants are given in combination with ginger, zingiber officinale. Ginger inhibits thromboxane synthetase (platelet aggregation inducer) and is a prostacyclin agonist. Patients taking ginger and an anticoagulant should be monitored closely for bleeding.
Ginkgo, Ginkgo biloba: (Moderate) Monitor for signs or symptoms of bleeding with coadministration of ginkgo biloba and low molecular weight heparins as an increased bleeding risk may occur. Although data are mixed, ginkgo biloba is reported to inhibit platelet aggregation and several case reports describe bleeding complications with ginkgo biloba, with or without concomitant drug therapy.
Green Tea: (Moderate) Green tea has demonstrated antiplatelet and fibrinolytic actions in animals. It is possible that the use of green tea may increase the risk of bleeding if co-administered with anticoagulants (e.g., enoxaparin, heparin, warfarin, and others), thrombolytic agents, or platelet inhibitors (e.g., aspirin, clopidogrel, cilostazol and others). Caution and careful monitoring of clinical and/or laboratory parameters are warranted if green tea is coadministered with any of these agents. Exogenous administration or occult sources of vitamin K may decrease or reverse the activity of warfarin; stability of the diet can be an important factor in maintaining anticoagulation goals. Occult sources of vitamin K include green tea and green tea dietary supplements. Published data are limited in regard to this interaction. A patient with previous INRs of 3.2 and 3.79 on a dose of 7.5mg daily of warfarin (goal INR 2.5 to 3.5) had an INR of 1.37. One month later, the patient's INR was 1.14. The patient admitted that he had started consuming 0.51 gallon of green tea daily approximately one week prior to the INR of 1.37. The patient denied noncompliance and other changes in diet, medications, or health. The patient discontinued green tea and one week later his INR was 2.55. While the amount of vitamin K in a single cup of brewed green tea may not be high (0.03 mcg/100 g), the actual amount may vary from cup to cup depending on the amount of tea leaves used, the length of time the tea bags are allowed to brew, and the volume of tea consumed. Additionally, if a patient drinks multiple cups of tea per day, the amount of vitamin K could reach significance. It is recommended that patients on warfarin maintain a stable intake of green tea.
Hemin: (Major) Because hemin has exhibited transient, mild anticoagulant effects during clinical studies, concurrent use of anticoagulants should be avoided. The extent and duration of the hypocoagulable state induced by hemin has not been established.
Heparin: (Major) An additive risk of bleeding may be seen in patients receiving enoxaparin in combination with other anticoagulants. If coadministration of 2 or more anticoagulants is necessary, patients should be closely monitored for evidence of bleeding.
Hydrocodone; Ibuprofen: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Ibritumomab Tiuxetan: (Major) During and after therapy, avoid the concomitant use of Yttrium (Y)-90 ibrutumomab tiuxetan with drugs that interfere with coagulation such as anticoagulants; the risk of bleeding may be increased. If coadministration with anticoagulants is necessary, monitor platelet counts more frequently for evidence of thrombocytopenia.
Ibrutinib: (Moderate) The concomitant use of ibrutinib and anticoagulant agents such as enoxaparin may increase the risk of bleeding; monitor patients for signs of bleeding. Severe bleeding events have occurred with ibrutinib therapy including intracranial hemorrhage, GI bleeding, hematuria, and post procedural hemorrhage; some events were fatal. The mechanism for bleeding with ibrutinib therapy is not well understood.
Ibuprofen: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Ibuprofen; Famotidine: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Ibuprofen; Oxycodone: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Ibuprofen; Pseudoephedrine: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Icosapent ethyl: (Moderate) Icosapent ethyl is an ethyl ester of the omega-3 fatty acid eicosapentaenoic acid (EPA). Because omega-3 fatty acids inhibit platelet aggregation, caution is advised when icosapent ethyl is used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 36 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant icosapent ethyl therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly.
Iloprost: (Moderate) When used concurrently with anticoagulants, inhaled iloprost may increase the risk of bleeding.
Indomethacin: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Inotersen: (Moderate) Use caution with concomitant use of inotersen and anticoagulants due to the potential risk of bleeding from thrombocytopenia. Consider discontinuation of anticoagulants in a patient taking inotersen with a platelet count of less than 50,000 per microliter.
Intravenous Lipid Emulsions: (Moderate) Drug interactions with fish oil, omega-3 fatty acids (Dietary Supplements) or fish oil, omega-3 fatty acids (FDA-approved) are unclear at this time. However, because fish oil, omega-3 fatty acids inhibit platelet aggregation, caution is advised when fish oils are used concurrently with anticoagulants, platelet inhibitors, or thrombolytic agents. Theoretically, the risk of bleeding may be increased, but some studies that combined these agents did not produce clinically significant bleeding events. In one placebo-controlled, randomized, double-blinded, parallel study, patients receiving stable, chronic warfarin therapy were administered various doses of fish oil supplements to determine the effect on INR determinations. Patients were randomized to receive a 4-week treatment period of either placebo or 3 or 6 grams of fish oil daily. Patients were followed on a twice-weekly basis for INR determinations and adverse reactions. There was no statistically significant difference in INRs between the placebo or treatment period within each group. There was also no difference in INRs found between groups. One episode of ecchymosis was reported, but no major bleeding episodes occurred. The authors concluded that fish oil supplementation in doses of 3-6 grams per day does not have a statistically significant effect on the INR of patients receiving chronic warfarin therapy. However, an increase in INR from 2.8 to 4.3 in a patient stable on warfarin therapy has been reported when increasing the dose of fish oil, omega-3 fatty acids from 1 gram/day to 2 grams/day. The INR decreased once the patient decreased her dose of fish oil to 1 gram/day. This implies that a dose-related effect of fish oil on warfarin may be possible. Patients receiving warfarin that initiate concomitant fish oil therapy should have their INR monitored more closely and the dose of warfarin adjusted accordingly.
Ketoprofen: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Ketorolac: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Levomilnacipran: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including serotonin norepinephrine reuptake inhibitors (SNRIs), before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Lomustine, CCNU: (Moderate) Due to the bone marrow suppressive and thrombocytopenic effects of lomustine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Meclofenamate Sodium: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Mefenamic Acid: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Meloxicam: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Methoxsalen: (Minor) Agents, such as anticoagulants, that decrease clotting could decrease the efficacy of photosensitizing agents used in photodynamic therapy.
Methylsulfonylmethane, MSM: (Moderate) Increased effects from concomitant anticoagulant drugs such as increased bruising or blood in the stool have been reported in patients taking methylsulfonylmethane, MSM. Although these effects have not been confirmed in published medical literature or during clinical studies, clinicians should consider using methylsulfonylmethane, MSM with caution in patients who are taking anticoagulants such as warfarin until data confirming the safety of MSM in patients taking these drugs are available. During one of the available, published clinical trials in patients with osteoarthritis, those patients with bleeding disorders or using anticoagulants or antiplatelets were excluded from enrollment. Patients who choose to consume methylsulfonylmethane, MSM while receiving warfarin should be observed for increased bleeding.
Methyltestosterone: (Moderate) Methyltestosterone can increase the effects of anticoagulants through reduction of procoagulant factor. Patients receiving oral anticoagulant therapy should be closely monitored, especially when methyltestosterone treatment is initiated or discontinued.
Mifepristone: (Contraindicated) When mifepristone is used for the termination of pregnancy, concurrent use of anticoagulants is contraindicated due to the risk of serious bleeding.
Milnacipran: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including serotonin norepinephrine reuptake inhibitors (SNRIs), before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Miltefosine: (Moderate) Caution is advised when administering miltefosine with anticoagulants, as use of these drugs together may increase risk for bleeding. Miltefosine, when administered for the treatment of visceral leishmaniasis, has been associated with thrombocytopenia; monitor platelet counts in patients receiving treatment for this indication. In addition, monitor closely for increased bleeding if use in combination with an anticoagulant.
Mycophenolate: (Moderate) Mycophenolate may causes thrombocytopenia and increase the risk for bleeding. Agents which may lead to an increased incidence of bleeding in patients with thrombocytopenia include anticoagulants.
Nabumetone: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Naproxen: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Naproxen; Esomeprazole: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Naproxen; Pseudoephedrine: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Nelarabine: (Moderate) Due to the thrombocytopenic effects of nelarabine, an additive risk of bleeding may be seen in patients receiving concomitant anticoagulants.
Nintedanib: (Moderate) Nintedanib is a VEGFR inhibitor and may increase the risk of bleeding. Monitor patients who are taking anticoagulants closely and adjust anticoagulation therapy as necessary. Use nintedanib in patients with known risk of bleeding only if the anticipated benefit outweighs the potential risk.
Nonsteroidal antiinflammatory drugs: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Obinutuzumab: (Moderate) Fatal hemorrhagic events have been reported in patients treated with obinutuzumab; all events occured during cycle 1. Monitor all patients for thrombocytopenia and bleeding, and consider withholding concomitant medications which may increase bleeding risk (i.e., anticoagulants, platelet inhibitors), especially during the first cycle.
Omacetaxine: (Major) Avoid the concomitant use of omacetaxine and anticoagulants when the platelet count is less than 50,000 cells/microliter due to an increased risk of bleeding.
Omidubicel: (Moderate) Because of the potential effects of certain dextran formulations on bleeding time, use with caution in patients on anticoagulants concurrently.
Orlistat: (Moderate) Patients on chronic stable doses of anticoagulants, like enoxaparin, should be monitored closely for changes in coagulation parameters when orlistat is prescribed. Reports of decreased prothrombin, increased INR, and unbalanced anticoagulant treatment resulting in change of hemostatic parameters have been reported in patients treated concomitantly with orlistat and anticoagulants.
Oxandrolone: (Moderate) An increased effect of anticoagulants may occur with oxandrolone; the anticoagulant dosage may need adjustment downward with oxandrolone initiation or adjustment upward with oxandrolone discontinuation to maintain the desired clinical effect. Oxandrolone suppresses clotting factors II, V, VII, and X, which results in an increased prothrombin time. An increase in plasminogen-activator activity, and serum concentrations of plasminogen, protein C, and antithrombin III have occurred with several 17-alpha-alkylated androgens. For example, concurrent use of oxandrolone and warfarin may result in unexpectedly large increases in the INR or prothrombin time (PT). A multidose study of oxandrolone (5 or 10 mg PO twice daily) in 15 healthy individuals concurrently treated with warfarin resulted in significant increases in warfarin half-life and AUC; a 5.5-fold decrease in the mean warfarin dosage from 6.13 mg/day to 1.13 mg/day (approximately 80 to 85% dose reduction) was necessary to maintain a target INR of 1.5. According to the manufacturer, if oxandrolone therapy is initiated in a patient already receiving warfarin, the dose of warfarin may need to be decreased significantly to reduce the potential for excessive INR elevations and associated risk of serious bleeding events. The patient should be closely monitored with frequent evaluation of the INR and clinical parameter, and the dosage of warfarin should be adjusted as necessary until a stable target INR is achieved. Careful monitoring of the INR and necessary adjustment of the warfarin dosage are also recommended when the androgen therapy is changed or discontinued.
Oxaprozin: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Palifermin: (Moderate) The co-administration of palifermin and unfractionated heparin may result in a 4 to 5-fold increase in palifermin exposure; however, this interaction does not appear to affect the pharmacodynamics of either drug. If heparin is used to maintain an IV line, rinse the line with saline prior to and after palifermin administration. The palifermin AUC value was increased by 5-fold and the mean clearance was decreased by 80% after a single 60 mcg/kg dose of palifermin was administered with therapeutic levels of unfractionated heparin compared with no heparin in 27 healthy subjects. The activated partial thromboplastin time (aPTT) was not affected by this interaction. The palifermin AUC value was increased by 425% and the palifermin clearance, volume of distribution, and half-life was decreased by 76.5%, 73.1%, and 38.8%, respectively, following the administration of palifermin 40 mcg/kg/day for 3 days in combination with therapeutic levels of unfractionated heparin compared with no heparin in 31 healthy subjects. Palifermin administration results in a dose-dependent epithelial cell proliferation that may be assessed by Ki67 immunohistochemical staining. In this study, the pharmacokinetics of palifermin did not affect Ki67 expression in buccal biopsies. The co-administration of palifermin and low-molecular weight heparins (LMWHs), such as enoxaparin and dalteparin, is expected to have a similar interaction.
Pentosan: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including pentosan, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring. Pentosan is a weak anticoagulant, having one-fifteenth the anticoagulant activity of heparin.
Piperacillin; Tazobactam: (Moderate) Some penicillins (e.g., piperacillin) can inhibit platelet aggregation, which may increase the risk of bleeding with any anticoagulants. Clinically important bleeding of this type, however, is relatively rare. The concomitant use of warfarin with many classes of antibiotics, including penicillins, may result in an increased INR thereby potentiating the risk for bleeding. Inhibition of vitamin K synthesis due to alterations in the intestinal flora may be a mechanism; however, concurrent infection is also a potential risk factor for elevated INR. Monitor patients for signs and symptoms of bleeding. Additionally, increased monitoring of the INR, especially during initiation and upon discontinuation of the antibiotic, may be necessary in patients receiving warfarin.
Piroxicam: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Prasterone, Dehydroepiandrosterone, DHEA (Dietary Supplements): (Major) Prasterone (DHEA) is contraindicated for use in patients with active deep vein thrombosis, pulmonary embolism or history of these conditions. Prasterone is also contraindicated in patients with active arterial thromboembolic disease (for example, stroke and myocardial infarction), or a history of these conditions. Thus, patients receiving anticoagulation due to a history of these conditions are not candidates for prasterone treatment. DHEA is converted to androgens and estrogens within the human body and thus may affect hemostasis via androgenic or estrogenic effects. Estrogens increase the production of clotting factors VII, VIII, IX, and X. Androgens, such as testosterone, increase the synthesis of several anticoagulant and fibrinolytic proteins. Because of the potential effects on coagulation, patients receiving prasterone or DHEA concurrently with preventative anticoagulants (e.g., warfarin or heparin) or other platelet inhibitors, including aspirin, ASA should be monitored for side effects or the need for dosage adjustments.
Prasterone, Dehydroepiandrosterone, DHEA (FDA-approved): (Major) Prasterone (DHEA) is contraindicated for use in patients with active deep vein thrombosis, pulmonary embolism or history of these conditions. Prasterone is also contraindicated in patients with active arterial thromboembolic disease (for example, stroke and myocardial infarction), or a history of these conditions. Thus, patients receiving anticoagulation due to a history of these conditions are not candidates for prasterone treatment. DHEA is converted to androgens and estrogens within the human body and thus may affect hemostasis via androgenic or estrogenic effects. Estrogens increase the production of clotting factors VII, VIII, IX, and X. Androgens, such as testosterone, increase the synthesis of several anticoagulant and fibrinolytic proteins. Because of the potential effects on coagulation, patients receiving prasterone or DHEA concurrently with preventative anticoagulants (e.g., warfarin or heparin) or other platelet inhibitors, including aspirin, ASA should be monitored for side effects or the need for dosage adjustments.
Prasugrel: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including prasugrel, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Reteplase, r-PA: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including thrombolytic agents, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Rivaroxaban: (Major) Avoid concurrent administration of rivaroxaban and enoxaparin due to increased bleeding risk unless the benefits outweigh the risks. In a drug interaction study, single doses of enoxaparin (40 mg subcutaneous) and rivaroxaban (10 mg) given concomitantly resulted in an additive effect on anti-factor Xa activity. Enoxaparin did not affect the pharmacokinetic parameters of rivaroxaban.
Salicylates: (Moderate) An additive risk of bleeding may be seen in patients receiving a low molecular weight heparin in combination with other agents known to increase the risk of bleeding such as salicylates. Monitor clinical and laboratory response closely during concurrent use.
Selective serotonin reuptake inhibitors: (Moderate) Monitor for signs and symptoms of bleeding during concomitant low molecular weight heparin and selective serotonin reuptake inhibitor (SSRI) use due to increased risk for bleeding. Serotonin release by platelets plays an important role in hemostasis. Epidemiological studies have demonstrated an association between use of psychotropic drugs that interfere with serotonin reuptake and the occurrence of upper gastrointestinal bleeding. Altered anticoagulant effects, including increased bleeding, have been reported when SSRIs are coadministered with another anticoagulant.
Serotonin norepinephrine reuptake inhibitors: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including serotonin norepinephrine reuptake inhibitors (SNRIs), before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Sodium Iodide: (Moderate) Anticoagulants may alter sodium iodide I-131 pharmacokinetics and dynamics for up to 1 week after administrations.
Spironolactone: (Moderate) Monitor serum potassium during concomitant low molecular weight heparin (LMWH) and spironolactone use due to the risk for hyperkalemia. Cases of hyperkalemia have been reported with coadministration of LMWH and spironolactone.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Monitor serum potassium during concomitant low molecular weight heparin (LMWH) and spironolactone use due to the risk for hyperkalemia. Cases of hyperkalemia have been reported with coadministration of LMWH and spironolactone.
Sulindac: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Sumatriptan; Naproxen: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Telavancin: (Moderate) Telavancin has no effect on coagulation or platelet aggregation; however, caution is advised when administering telavancin concurrently with anticoagulants as telavancin may interfere with laboratory tests used in monitoring these medications. The coagulation tests affected by telavancin include prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), activated clotting time, and coagulation based factor Xa tests. When measured shortly after completion of a telavancin infusion, the results of these tests are increased; however, the effects of telavancin on these tests dissipate over time as plasma concentrations of telavancin decrease. Therefore, when administering telavancin in conjunction with anticoagulants ensure that blood samples for these coagulation tests are collected as close as possible to the patient's next telavancin dose.
Tenecteplase: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including thrombolytic agents, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Thrombolytic Agents: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including thrombolytic agents, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Ticagrelor: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including ticagrelor, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Ticlopidine: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including ticlopidine, before initiation of enoxaparin therapy. If a patient is switched from an anticoagulant to ticlopidine, discontinue the anticoagulant prior to ticlopidine administration. If coadministration is essential, conduct close clinical and laboratory monitoring.
Tipranavir: (Moderate) Caution should be used when administering tipranavir to patients receiving anticoagulants. In clinical trials, there have been reports of intracranial bleeding, including fatalities, in HIV infected patients receiving tipranavir as part of combination antiretroviral therapy. In many of these reports, the patients had other medical conditions (CNS lesions, head trauma, recent neurosurgery, coagulopathy, hypertension, or alcoholism/alcohol abuse) or were receiving concomitant medications, including anticoagulants, that may have caused or contributed to these events.
Tirofiban: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including tirofiban, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Tolmetin: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Trazodone: (Moderate) Patients should be instructed to monitor for signs and symptoms of bleeding while taking trazodone concurrently with anticoagulants and to promptly report any bleeding events to the practitioner. Serotonergic agents may increase the risk of bleeding when combined with anticoagulants via inhibition of serotonin uptake by platelets; however, the absolute risk is not known. It would be prudent for clinicians to monitor the INR and patient's clinical status closely if trazodone is added to or removed from the regimen of a patient stabilized on anticoagulant therapy.
Treprostinil: (Moderate) When used concurrently with anticoagulants, treprostinil may increase the risk of bleeding.
Valdecoxib: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including nonsteroidal antiinflammatory drugs, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Venlafaxine: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including serotonin norepinephrine reuptake inhibitors (SNRIs), before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.
Verteporfin: (Moderate) Use caution if coadministration of verteporfin with anticoagulants is necessary due to the risk of decreased verteporfin efficacy. Verteporfin is a light-activated drug. Once activated, local damage to neovascular endothelium results in a release of procoagulant and vasoactive factors resulting in platelet aggregation, fibrin clot formation, and vasoconstriction. Concomitant use of drugs that decrease clotting could decrease the efficacy of verteporfin therapy.
Vilazodone: (Moderate) Patients should be instructed to monitor for signs and symptoms of bleeding while taking vilazodone concurrently with anticoagulants and to promptly report any bleeding events to the practitioner. Serotonergic agents may increase the risk of bleeding when combined with anticoagulants via inhibition of serotonin uptake by platelets; however, the absolute risk is not known. In addition, both vilazodone and warfarin are highly protein bound, which may result in displacement of warfarin from protein binding sites and an increased anticoagulant effect. It would be prudent for clinicians to monitor the INR and clinical status of the patient closely if vilazodone is added to or removed from the regimen of a patient stabilized on warfarin.
Vorapaxar: (Major) Avoid concomitant use of vorapaxar and warfarin or other anticoagulants. Because vorapaxar inhibits platelet aggregation, a potential additive risk for bleeding exists if vorapaxar is given in combination with other agents that affect hemostasis such as anticoagulants.
Vortioxetine: (Moderate) Platelet aggregation may be impaired by vortioxetine due to platelet serotonin depletion, possibly increasing the risk of a bleeding complication (e.g., gastrointestinal bleeding, ecchymoses, epistaxis, hematomas, petechiae, hemorrhage) in patients receiving anticoagulants. Bleeding events related to drugs that inhibit serotonin reuptake have ranged from ecchymosis to life-threatening hemorrhages. Patients should be instructed to monitor for signs and symptoms of bleeding while taking vortioxetine concurrently with anticoagulants and to promptly report any bleeding events to the practitioner. Co-administration of vortioxetine and warfarin has not been shown to significantly affect the pharmacokinetics of either agent.
Warfarin: (Major) Whenever possible, discontinue agents which may enhance the risk of hemorrhage, including warfarin, before initiation of enoxaparin therapy. If coadministration is essential, conduct close clinical and laboratory monitoring.

Enoxaparin Sodium (Porcine)/Lovenox Intravenous Inj Sol: 1mL, 100mg
Enoxaparin Sodium (Porcine)/Lovenox Subcutaneous Inj Sol: 0.3mL, 0.4mL, 0.6mL, 0.8mL, 1mL, 30mg, 40mg, 60mg, 80mg, 100mg, 120mg, 150mg

Enoxaparin has a narrow therapeutic index, specific for the patient population and indication. The maximum dosage is individualized based on anti-factor Xa concentrations and assessment of efficacy and safety parameters.

Enoxaparin exerts its antithrombotic activity by binding to and accelerating the activity of antithrombin III (AT III). The interaction with antithrombin is mediated by a unique pentasaccharide sequence distributed along the heparin chains. Only 15% to 25% of the chains of enoxaparin contain this pentasaccharide sequence, compared with about one-third of the chains of unfractionated heparin (UFH). By activating antithrombin, coagulation factor Xa and factor IIa (thrombin) are inhibited. Enoxaparin and other low molecular weight heparins (LMWHs) are more selective inhibitors of factor Xa than UFH. Although any pentasaccharide chain can inhibit factor Xa, only those at least 18 saccharide units long can inactivate thrombin, since a long chain is required to form a ternary complex between heparin, antithrombin, and thrombin. Although most of the chains of UFH are at least 18 saccharide units long, less than 50% of those of enoxaparin and other LMWHs are of adequate length to bind both antithrombin and thrombin (factor IIa). Therefore, the anti-factor Xa:anti-factor IIa inhibitory ratio of enoxaparin is 2 to 4:1, compared to 1:1 for UFH. Ultimately, thrombin inhibition prevents the formation of fibrin clots. At recommended doses, enoxaparin does not significantly affect platelet activity, prothrombin time (PT) or activated partial thromboplastin time (aPTT).

Enoxaparin is administered by subcutaneous or intravenous (IV) injection. Enoxaparin pharmacokinetics appear to be linear over the recommended dosage ranges. A significant route of elimination for enoxaparin is renal, which appears to be dose-independent. After IV radiolabeled enoxaparin, 40% of total radioactivity and 8% to 20% of anti-Factor Xa is recovered in the urine within 24 hours.
 
Affected cytochrome P450 isoenzymes and drug transporters: none

A 30 mg IV bolus immediately followed by 1 mg/kg subcutaneously every 12 hours provides initial peak anti-factor Xa concentrations of 1.16 International Units/mL and average exposure corresponding to 84% of steady-state concentrations. After IV dosing, the total body clearance of enoxaparin in adults is 26 mL/minute. Results of a small (n = 7) retrospective study in critically ill pediatric patients indicates the peak anti-factor Xa concentrations may occur sooner after IV dosing (1 to 2 hours) vs. subcutaneously dosing (4 to 6 hours).

Based on anti-factor Xa activity, mean absolute bioavailability in adults after 1.5 mg/kg subcutaneously is approximately 100%. Peak plasma anti-factor Xa activity occurs 3 to 5 hours after subcutaneous injection. After repeated subcutaneous administration of 40 mg once daily and 1.5 mg/kg once daily regimens in healthy adult volunteers, steady-state is reached on day 2 with an average exposure ratio about 15% higher than after a single dose. Steady-state enoxaparin activity levels are well predicted by single-dose pharmacokinetics. After repeated subcutaneous administration of the 1 mg/kg twice daily regimen in adults, steady-state is reached from day 4 with mean exposure about 65% higher than after a single dose and mean peak and trough serum concentrations of about 1.2 and 0.52 International Units/mL, respectively. Based on enoxaparin pharmacokinetics, this difference in steady-state is expected, and is within the therapeutic range. The elimination half-life of enoxaparin in adults based on anti-factor Xa activity is 4.5 hours after a single subcutaneous dose, and may increase to 7 hours after repeated dosing. Following a 40 mg subcutaneous dose of enoxaparin in adults, significant anti-factor Xa activity persists in plasma for about 12 hours; the apparent clearance of subcutaneous enoxaparin is 15 mL/minute.

Benzyl alcohol can cross the placenta, thus multiple-dose vials of enoxaparin (contain 1.5% benzyl alcohol) should be used with caution during pregnancy, and only if clearly needed. It is recommended to use preservative-free enoxaparin when possible in pregnant women. No well-controlled studies exist in pregnant women. Enoxaparin was found to cross the placenta in animal studies. The rate of major congenital anomalies in a retrospective, cohort study involving 693 live births was 2.5%; similar to estimated background risk in the general population. Sixty-three women experienced 72 hemorrhagic events; 11 were classified as serious. In addition, there were 14 neonatal, hemorrhagic cases. Several reports have described the use of enoxaparin during pregnancy without fetal or maternal complications.[25683] There have been reports of congenital anomalies including cerebral anomalies, limb anomalies, hypospadias, peripheral vascular malformation, fibrotic dysplasia, and cardiac defect, when women received enoxaparin during pregnancy. A cause and effect relationship has not been established nor has the incidence been shown to be higher than in the general population. Fetal death has been reported with post-marketing use of enoxaparin in pregnant women; causality for these cases has not been determined. Pregnant women, similar to other patient populations, receiving anticoagulants, including enoxaparin, are at increased risk for bleeding. Hemorrhage can occur at any site and may lead to death of mother and/or fetus. Pregnant women receiving enoxaparin should be carefully monitored, especially women with lupus anticoagulant or antiphospholipid antibody syndrome who have a history of fetal loss. According to the manufacturer, it is not known if dosage adjustment or anti-factor Xa monitoring is needed during general pregnancy (in pregnant women without prosthetic valves). Pregnant women and women of child-bearing potential should be apprised of the potential hazard to the fetus and the mother if enoxaparin is administered during pregnancy. In addition, one case of hyperlipidemia with hypertriglyceridemia in a diabetic pregnant woman receiving enoxaparin has been reported; causality is uncertain. In a clinical study of pregnant women with prosthetic heart valves given enoxaparin (1 mg/kg twice daily) to reduce the risk of thromboembolism, 2 of 8 women developed clots resulting in blockage of the valve and leading to maternal and fetal death. There are post-marketing reports of prosthetic valve thrombosis in pregnant women with prosthetic heart valves while receiving enoxaparin for thromboprophylaxis. These events resulted in maternal death or surgical interventions. Enoxaparin has not been adequately studied for thromboprophylaxis in pregnant women with prosthetic heart valves; however, the 2004 ACCP guidelines do recommend using LMWH in pregnant women with prosthetic heart valves requiring anticoagulation therapy.[32598] Pregnant women with prosthetic heart valves may be at higher risk for thromboembolism, and have a higher rate of fetal loss from stillbirth, spontaneous abortion, and premature delivery. Frequent monitoring of peak and trough anti-factor Xa levels, and follow up enoxaparin dosage adjustments may be needed for patients with mechanical valves, especially pregnant women. Compared with unfractionated heparin, low molecular weight heparins (LMWHs) may have advantages in pregnant women because they cause less heparin-induced thrombocytopenia and may be less likely to produce osteoporosis; the 2004 ACCP guidelines indicate that because of these reasons, LMWH are the preferred drugs for the treatment of acute venous thromboembolism (VTE) in pregnancy. The treatment of acute venous thromboembolism in pregnancy requires weight-adjusted dosing, but optimal dose regimens have not been established; however, because the half-life of enoxaparin is decreased in pregnancy, twice daily dosing is preferred for acute VTE treatment.[32598] Teratogenic effects have not been demonstrated in animals.[25683]

According to the manufacturer, it is unknown if enoxaparin is excreted into breast milk. The manufacturer recommends caution when using enoxaparin in women who are breast-feeding. However, because of the relatively high molecular weight of enoxaparin, excretion is expected to be minimal. Also, because of inactivation by the GI tract on oral ingestion, any potential risk to a nursing infant posed by enoxaparin should be negligible. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.