Mechanism of Action
- Local fibrinolysis by binding to fibrin, converts entrapped plasminogen to plasmin
Pharmacokinetics
- Half-Life: 4 hours
- Metabolism: Renal cleared
- Time to peak: 3 to 5 hours following SC injection
Dosing – Pediatric
- Enoxaparin is used for the treatment and prevention of thrombosis.
Therapeutic dosing without renal compromise (Max dose 150 mg)
| Age 0-2 months | Age >2 months to ≤ 6 months | Age > 6 months to adult | |
| Dosing |
|
1.2 mg/kg/dose SC q12h and titrate dose to achieve anti-Xa levels of 0.5 -1.0 units/mL |
|
Prophylactic dosing without renal compromise
- For obese patient with BMI >40 (or >120 kg), then adjusted body weight should be used for starting dosing.
- Obese patients with BMI >40 or >120 kg require higher prophylactic doses with 40 mg q12h. If using higher dosing in this population, anti-factor Xa monitoring is recommended.
- If patient is part of the bariatric surgery program, please utilize their guidelines
| < 60 kg | 60 kg to < 120 kg | 120 kg or greater | |
| Dosing |
|
40 mg SC q24h or 30 mg SC q12h |
|
Dosage Adjustment for Renal Impairment +/- Dialysis
See Appendix 1.
Monitoring Therapy
- Anti-Xa levels are used to monitor enoxaparin activity.
- Anti-Xa levels are drawn from fresh venipuncture when possible. If drawn from heparinized line, waste should be drawn to avoid heparin contamination.
- Note: Levels may be underestimated in patients with very high levels of bilirubin or hemolysis.
- Anti-Xa levels are checked 4 hours after a dose is administered. When starting therapy, check the anti-Xa level after the 3rd dose or 4th dose, whichever occurs during the daytime.
- Additional anti-Xa level titrations are checked in general 4 hours after the 2nd new dose until the patient has reached their targeted anticoagulation level.
- Once the patient is at the targeted anticoagulation level on a stable dose, the anti-Xa level is monitored weekly during the hospital admission. Levels may be checked more frequently at the discretion of the prescriber.
- Trough anti-Xa is not routinely used to monitor enoxaparin. Patients on intermittent hemodialysis may use trough anti-factor Xa level to monitor enoxaparin due to inability to monitoring peak anti-Xa level as outpatient. The trough anti-factor Xa level may be helpful in determining drug-free interval in patients with high thrombosis risk(s).
- Patients with pleural catheters for chylous drainage who have changing output should be monitored at least weekly. Anticipate
- Other labs: CBC should be monitored at least weekly while on enoxaparin during hospitalization. A sudden decrease in platelet counts > 50% below baseline or below 100k should raise suspicion for heparin induced thrombocytopenia (HIT). Maintain platelet count ≥ 50K to prevent excess bleeding. Enoxaparin use is contraindicated in patients who have a history of laboratory confirmed heparin induced thrombocytopenia (HIT)
Initiating Therapy
- Prior to initiation of therapy or continuation of home therapy, but no longer than 48 hours before, the following labs should be checked: CBC, coagulation profile (PT, PTT, fibrinogen activity), CMP, urine pregnancy if applicable
- Prior to starting enoxaparin, a brain ultrasound is suggested for neonates less than 44 weeks corrected gestational age. It is also suggested that other high risk patients (i.e., patients < 1 year old, trauma patients, infants with recent history of cardiac surgery) undergo a brain ultrasound/imaging prior to starting enoxaparin.
- Infants < 3 months of age or weight < 5 kg have increased requirements per kilogram, which likely is due to a large volume of distribution and low antithrombin levels. Prior published enoxaparin dosing recommendations are often inadequate for neonates. The doses recommended in this document have been updated to reflect current practice and are more likely to achieve the therapeutic range
- Patients with chylous drainage via pleural catheter may have AT3 losses that effect enoxaparin dosing
- In obese patients (BMI >30), treatment dosing should be based on actual body weight (max starting treatment dose of 150 mg q12h) unless patient BMI >40 (or >120 kg), then adjusted body weight should be used for starting dosing.
- Patients with obesity with BMI >/=40 and/or >120 kg, those with limited subcutaneous tissue, renal insufficiency patients, and antithrombin deficient patients will likely require closer monitoring of enoxaparin dosing and anti-Xa levels.
- Doses should be rounded up to the nearest milligram
Goal anti-Xa level 0.5-1 units/mL for twice daily Therapeutic dosing, or once daily Prophylactic dosing at 4-6 hours post dose, and applies to those without bleeding. Note: Therapeutic anti-Xa levels up to 1.2 unit/mL have been targeted for patients with high risk of thrombosis
| Anti-Xa | Dose change | Repeat peak anti-Xa level |
| < 0.35 units/mL | Increase dose by 25% | 4 h after 2nd dose |
| 0.35-0.49 units/mL | Increase dose by 10% | 4 h after 2nd dose |
| 0.5-1 units/mL | None | Once per week while inpatient, one week after discharge, and then monthly (4 h after morning dose) |
| 1.1-1.5 units/mL | Decrease dose by 20% | 4 h after 2nd dose |
| 1.6-2 units/mL | Delay next dose by 3h and decrease dose by 30% | Trough prior to the next dose, then 4 h after 2nd dose |
| > 2 units/mL | Hold all doses until <0.5 units/mL, then decrease dose by 40% | Trough prior to the next dose and every 12h until <0.5 units/mL. |
Goal anti-Xa level 0.2-0.49 units/mL for twice daily Prophylactic dosing, or once daily Prophylactic dosing 12 hours post dose, and applies to those without bleeding. This table should only be applied if strict anti-Xa monitoring indicated.
| Anti-Xa | Dose change | Repeat peak anti-Xa level |
| <0.15 units/mL | Increase by 25% | 4 h after 2nd dose |
| 0.15-0.19 units/mL | Increase by 10% | 4 h after 2nd dose |
| 0.2-0.49 units/mL | None | Once per week while inpatient (4 h after morning dose) |
| 0.5-0.74 units/mL | Decrease by 20% | 4 h after 2nd dose |
| 0.75-1 units/mL | Delay next dose by 3h and decrease dose by 30% | Trough prior to the next dose, then 4 h after 2nd dose |
| >1 units/mL | Hold all doses until <0.5 units/mL, then decrease dose by 40% | Trough prior to the next dose and every 12h until <0.5 units/mL |
Goal anti-Xa level 0.1-0.3 units/mL for twice daily Prophylactic dosing. The below table applies to those without bleeding. This table should only be applied if strict anti-Xa monitoring indicated.
| Anti-Xa | Dose change | Repeat peak anti-Xa level |
| <0.1 units/mL | Increase by 10% | 4 h after 2nd dose |
| 0.1-0.3 units/mL | None | Once per week while inpatient (4 h after morning dose) |
| 0.4-0.49 units/mL | Decrease by 20% | 4 h after 2nd dose |
| 0.5-0.75 units/mL | Delay next dose by 3h and decrease dose by 30% | Trough prior to the next dose, then 4 h after 2nd dose |
| >0.75 units/mL | Hold all doses until <0.5 units/mL, then decrease dose by 40% | Trough prior to the next dose and every 12h until <0.5 units/mL |
Administration
Enoxaparin should not be administered in areas where the skin is damaged/edematous. It is recommend to NOT use an insuflon catheter for the administration of enoxaparin given the risk of hematoma.
Safety Precautions
- Renal impairment: See dose monitoring above. Use with caution and monitor patient closely. Dose adjustment and/or monitoring anti-Xa levels closely is needed when CrCl less than 30 mL/minute.
- Hepatic impairment: There are no dosage adjustments provided in the manufacturer’s labeling; use with caution.
- Drug-Drug interactions:
- Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.) may enhance the anticoagulant effect of Anticoagulants.
- Drug-Food Interactions: None
- Long term use (≥1 year) of heparin or LMWH may increase the risk of osteoporosis.
- Heparin Induced Thrombocytopenia (HIT) – Though rare, HIT does occur in children. This should be suspected in any patient on heparin, UFH or LMWH, with unexplained drop in platelet count > 50% from baseline or with thrombocytopenia.
Ordering Enoxaparin
- Doses should be rounded up to the nearest WHOLE MILLIGRAM
- Enoxaparin can be ordered as a multidose vial 300 mg/3mL.
- Most patients prefer to use an insulin syringe with a 31 gauge, 5/16” needle with the dose drawn from the multiple dose vial.
- Insulin syringes are marked in units and were made for use with insulin. Enoxaparin is given in mg, not units. However, because 1 mg of enoxaparin is the same volume as 1 unit of insulin, the insulin syringe can be used. A 1 unit measurement in an insulin syringe is equivalent to 1 mg of enoxaparin.
- You must order a syringe if ordering a multiple dose vial. Either choose the insulin syringe (30 units/0.3mL, 50 units/0.5 mL or 100 units/1 mL) or a standard needle. Be sure the family is educated prior to discharge to use the needle you prescribe for home use.
- Some pharmacies prepare syringes (pre-drawn syringes)
- TB syringe with TB ultra fine (for neonates/small children) with 30 gauge needle also available and most often comes attached and don’t need to order separately if ordering through well-known retail pharmacy or PMCH/St. Vincent.
- Manufacturer’s pre-filled syringes. The concentration is 100 mg/1 mL. The needle is 27gauge, ½ inch length and is attached to the syringe.
- 30 mg/0.3 mL and 40 mg/0.4 mL syringes have NO graduation marks on the syringe barrel. They are ordered specifically for a dose that is fixed/not changing.
- 60 mg/0.6 mL, 80 mg/0.8 mL and 100 mg/1 mL syringes – all are graduated; consequently some drug can be squirted out to achieve the ordered dose i.e. using a 60 mg prefilled syringe, for ordered dose of 48 mg, a patient could squirt out 12 mg prior to administering the injection.
- Rarely used in pediatric patients are Manufacturer’s pre-filled syringes at a concentration of 150 mg/1 mL. This information is included here for completeness and in the event that a morbidly obese patient requires an enoxaparin dose > 100 mg.
- 120 mg/0.8 mL and 150 mg/1mL syringes both have 27 gauge, ½ inch needles attached
- Insulin syringes are marked in units and were made for use with insulin. Enoxaparin is given in mg, not units. However, because 1 mg of enoxaparin is the same volume as 1 unit of insulin, the insulin syringe can be used. A 1 unit measurement in an insulin syringe is equivalent to 1 mg of enoxaparin.
Appendix 1: Enoxaparin Guidelines for Patients with Renal Insufficiency or Failure
Dosage Adjustment for Renal Impairment
Algorithm 1: CrCl < 30 mL/min +/- peritoneal dialysis
- Dose 1: normal weight based dosing
- Dose 2: based on initial dose and CrCl (give 12 hours after initial dose)
- CrCl 10-30 mL/min: decrease dose by 30% and maintain interval of 12 h
- CrCl < 10 mL/min: decrease dose by 50% and maintain interval of 12 h
- Dose 3+: based on result of anti-Xa levels 4 h after Dose 2
Table 1. Nomogram for adjusting enoxaparin dose based on peak anti-Xa level
| Anti-Factor Xa | Dose change | Time to Repeat Anti-Factor Xa Level |
| < 0.35 units/mL | Increase by 25% | 4 h after 2nd dose |
| 0.35-0.49 units/mL | Increase by 10% | 4 h the 2nd dose |
| 0.5-1 units/mL | None | Once level is within target range, then check anti-Xa every 3 days for at least 2 levels, then weekly. |
| 1.1-1.5 units/mL | Decrease dose by 20% | 4 h after 2nd dose |
| 1.6-2 units/mL | Delay next dose by 3h and decrease dose by 30% | 4 h after 2nd dose |
| > 2 units/mL | Hold dose | Measure every 12 h until anti-Xa level is < 0.5 units/mL. Then resume at 40% dose and recheck 4 h after 2nd dose |
Algorithm 2: patients on intermittent hemodialysis
- Dose 1 and 2: 1 mg/kg every 24 h; time dosing such that daily dose is given ~2 hours after dialysis and trough can be drawn prior to dialysis when indicated
- Dose 3+: based on result of anti-Xa levels 4 h after Dose 2, with subsequent doses every 24 h based Tables 2 and 3
Table 2. Nomogram for adjusting enoxaparin dose based on peak anti-Xa level
| Anti-Factor Xa | Dose change | Time to Repeat Anti-Factor Xa Level |
| < 0.35 units/mL | Increase by 25% | 4 h after 2nd dose |
| 0.35-0.49 units/mL | Increase by 10% | 4 h after 2nd dose |
| 0.5-1 units/mL | None | Once level is within target range, then check anti-Xa trough 20-24 hours after last dose and adjust dose based on Table 3 and give every 24 hours |
| 1.1-1.5 units/mL | Decrease dose by 20% | 4 h after 2nd dose |
| 1.6-2 units/mL | Delay next dose by 3h and decrease dose by 30% | 4 h after 2nd dose |
| > 2 units/mL | Hold dose | Measure every 12 h until anti-Xa level is < 0.5 units/mL. Then resume at 40% dose and recheck 4 h after 2nd dose |
Table 3. Nomogram for adjusting enoxaparin dose for trough anti-Xa level in patients with renal impairment as outpatient (20-24 h after dose)
| Trough Anti-Xa Level | Peak Anti-Xa Level | Dose change | Time to Repeat Anti-Xa Level |
| < 0.1 units/mL | 0.5-0.75 units/mL | Increase by 10% | 4 h after 2nd dose |
| > 0.75 units/mL | Discuss with clinical pharmacy | ||
| 0.1-0.3 units/mL | 0.5-1 units/mL | None | Once levels are in the target range, check peak and trough every 3 days for at least 2 levels, then weekly |
| >0.3 units/mL | 0.5-0.75 units/mL | Recheck both peak and trough within 48 h. If repeat peak and trough are similar to initial peak and trough, then adjust/monitoring according to peak recommendation. If different, then use nomogram for adjusting based on trough. | |
| >0.75-1 units/mL | Decrease by 10% | 4h after the 2nd dose | |
| >1 units/mL | Discuss with clinical pharmacy | ||
Monitoring Anti-Xa for Renal Impairment
- For patients with renal impairment (CrCl < 30 mL/min) or on peritoneal dialysis, follow anti-Xa peak:
- Inpatient: Send anti-Xa peak after 2nd (or 3rd dose) and follow usual anti-Xa titrating goals. Once at goal, obtain anti-Xa every 3-4 days while inpatient for at least 2 levels, then weekly for at least 4 levels, then every 2 weeks
- Outpatient: anti-Xa weekly for at least 2 levels, then every 2 weeks for at least 3 levels, then monthly
- For patients on intermittent hemodialysis (all age), follow anti-Xa peak and trough: Send anti-Xa peak after 2nd (or 3rd dose) and adjust anti-Xa with usual anti-Xa titrating goals until within goal. When peak anti-Xa is within goal, send a trough level prior to the next dose. Adjust dose to the trough level range 0.1-0.3 unit/mL.
- Inpatient: peak or trough every 3-4 days for at least 2 levels, then weekly for at least 4 levels, then every 2 weeks
- Outpatient: weekly
- 20% enoxaparin is removed by HD
