Friday, July 21, 2023

HEPARINS (LOW MOLECULAR WEIGHT) dalteparin (dal-te-pa-rin) Fragmin enoxaparin (e-nox-a-pa-rin) Lovenox

 Indications

Enoxaparin and dalteparin: Prevention of venous

thromboembolism (VTE) (deep vein thrombosis [DVT]

and/or pulmonary embolism [PE]) in surgical or medical

patients. Dalteparin only: Extended treatment of

symptomatic DVT and/or PE in patients with cancer.

Enoxaparin only: Treatment of DVT with or without

PE (with warfarin). Enoxaparin and dalteparin:

Prevention of ischemic complications (with aspirin)

from unstable angina and non-ST-segment-elevation

MI. Enoxaparin only: Treatment of acute ST-segmentelevation

MI (with thrombolytics or percutaneous coronary

intervention).

Action

Potentiate the inhibitory effect of antithrombin on factor

Xa and thrombin. Therapeutic Effects: Prevention

of thrombus formation.

Pharmacokinetics

Absorption: Well absorbed after subcut administration

(87% for dalteparin, 92% for enoxaparin). 

Distribution: Unknown.

Metabolism and Excretion: Dalteparin—unknown;

enoxaparin—primarily eliminated renally.

Half-life: Dalteparin—2.1–2.3 hr; enoxaparin—

3–6 hr (all areqin renal insufficiency).

TIME/ACTION PROFILE (anticoagulant effect)

ROUTE ONSET PEAK DURATION

Dalteparin

subcut

rapid 4 hr up to 24 hr

Enoxaparin

subcut

unknown 3–5 hr 12 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity to specific

agents or pork products; cross-sensitivity may occur;

Some products contain sulfites or benzyl alcohol and

should be avoided in patients with known hypersensitivity

or intolerance; Active major bleeding; History of

heparin-induced thrombocytopenia; Dalteparin—regional

anesthesia during treatment for unstable angina/

non–Q-wave MI.

Use Cautiously in: Severe hepatic or renal disease

(adjust dose of enoxaparin if CCr 30 mL/min);

Women 45 kg or men 57 kg; Retinopathy (hypertensive

or diabetic); Untreated hypertension; Geri: May

haveqrisk of bleeding due to age-relatedpin renal

function; Dalteparin—Geri:qmortality in patients

70 yrs with renal insufficiency; Recent history of ulcer

disease; History of congenital or acquired bleeding disorder;

OB, Lactation, Pedi: Safety not established;

should not be used in pregnant patients with prosthetic

heart valves without careful monitoring.

Exercise Extreme Caution in: Spinal/epidural

anesthesia (qrisk of spinal/epidural hematomas, especially

with concurrent NSAIDs, repeated or traumatic

epidural puncture, or indwelling epidural catheter); Severe

uncontrolled hypertension; Bacterial endocarditis;

Bleeding disorders.

Adverse Reactions/Side Effects

CNS: dizziness, headache, insomnia. CV: edema. GI:

constipation,qliver enzymes, nausea, vomiting. GU:

urinary retention. Derm: alopecia, ecchymoses, pruritus,

rash, urticaria. Hemat: BLEEDING, anemia, eosinophilia,

thrombocytopenia. Local: erythema at injection

site, hematoma, irritation, pain. MS: osteoporosis.

Misc: fever.

Interactions

Drug-Drug: Risk of bleeding may beqby concurrent

use of drugs that affect platelet function and

coagulation, including warfarin, aspirin, NSAIDs,

dipyridamole, clopidogrel, abciximab, eptifibatide,

tirofiban, and thrombolytics.

Drug-Natural Products:qbleeding risk with arnica,

chamomile, clove, feverfew, garlic, ginger,

ginkgo, Panax ginseng, and others.

Route/Dosage

Dalteparin

Subcut (Adults): Prophylaxis of DVT following abdominal

surgery—2500 units 1–2 hr before surgery,

then once daily for 5–10 days; Prophylaxis of VTE in

high-risk patients undergoing abdominal surgery—

5000 units evening before surgery, then once daily for

5–10 days or in patients with malignancy, 2500 units

1–2 hr before surgery, another 2500 units 12 hr later,

then 5000 units once daily for 5–10 days; Prophylaxis

of VTE in patients undergoing hip replacement surgery—

2500 units within 2 hr before surgery, then

2500 units 4–8 hr after surgery, then 5000 units once

daily (start at least 6 hr after postsurgical dose) for 5–

10 days or 5000 units evening before surgery (10–14

hr before surgery), then 5000 units 4–8 hr after surgery,

then 5000 units once daily for 5–10 days or 2500

units 4–8 hr after surgery, then 5000 units once daily

(start at least 6 hr after postsurgical dose); Prophylaxis

of VTE in medical patients with severely restricted

mobility during acute illness: 5000 units once daily

for 12 to 14 days. Unstable angina/non–ST-segmentelevation

MI—120 units/kg (not to exceed 10,000

units) q 12 hr for 5–8 days with concurrent aspirin;

Extended treatment of symptomatic VTE in cancer

patients—200 units/kg (not to exceed 18,000 units)

once daily for first 30 days, followed by 150 units/kg

(not to exceed 18,000 units) once daily for mo 2–6.

Renal Impairment

Subcut (Adults): Cancer patients receiving extended

treatment of symptomatic VTE with CCr30

mL/min—Monitor anti-Xa levels (target 0.5–1.5 IU/

mL).

Enoxaparin

Subcut (Adults): VTE prophylaxis in patients undergoing

knee replacement surgery—30 mg q 12 hr

starting 12–24 hr postop for 7–10 days; VTE prophylaxis

in patients undergoing hip replacement surgery—

30 mg q 12 hr starting 12–24 hr postop or 40

mg once daily starting 12 hr before surgery (either

dose may be continued for 7–14 days; continued prophylaxis

with 40 mg once daily may be continued for up

to 3 wk); VTE prophylaxis following abdominal surgery—

40 mg once daily starting 2 hr before surgery

and then continued for 7–12 days or until ambulatory

(up to 14 days); VTE prophylaxis in medical patients

with acute illness—40 mg once daily for 6–14 days;

Treatment of DVT/PE (outpatient)—1 mg/kg q 12

hr. Warfarin should be started within 72 hr; enoxaparin

may be continued for a minimum of 5 days and until therapeutic anticoagulation with warfarin is achieved

(INR 2 for 2 consecutive days); Treatment of DVT/PE

(inpatient)—1 mg/kg q 12 hr or 1.5 mg/kg once

daily. Warfarin should be started within 72 hr; enoxaparin

may be continued for a minimum of 5 days and

until therapeutic anticoagulation with warfarin is

achieved (INR 2 for two consecutive days); Unstable

angina/non–ST-segment-elevation MI—1 mg/kg q

12 hr for 2–8 days (with aspirin).

IV, Subcut (Adults 75 yr): Acute ST-segment-elevation

MI—Administer single IV bolus of 30 mg plus 1

mg/kg subcut dose (maximum of 100 mg for first 2

doses only), followed by 1 mg/kg subcut q 12 hr. The

usual duration of treatment is 2–8 days. In patients undergoing

percutaneous coronary intervention, if last

subcut dose was 8 hr before balloon inflation, no additional

dosing needed; if last subcut dose was 8 hr

before balloon inflation, administer single IV bolus of

0.3 mg/kg.

Subcut (Adults 75 yr): Acute ST-segment-elevation

MI—0.75 mg/kg every 12 hr (no IV bolus

needed) (maximum of 75 mg for first 2 doses only; no

initial bolus). The usual duration of treatment is 2–8

days.

Renal Impairment

Subcut (Adults CCr 30 mL/min): VTE prophylaxis

for abdominal or knee/hip replacement surgery—

30 mg once daily. Treatment of DVT/PE—1 mg/kg

once daily. Unstable angina/non-ST-segment-elevation

MI—1 mg/kg once daily. Acute ST-segment-elevation

MI (patients75 yr)—Single IV bolus of 30

mg plus 1 mg/kg subcut dose, followed by 1 mg/kg subcut

once daily. Acute ST-segment-elevation MI (patients

75 yr)—1 mg/kg once daily (no initial bolus).

Availability

Dalteparin

Solution for injection (prefilled syringes): 2500

units/0.2 mL, 5000 units/0.2 mL, 7500 units/0.3 mL,

10,000 units/1 mL, 12,500 units/0.5 mL, 15,000 units/

0.6 mL, 18,000 units/0.72 mL. Solution for injection

(multidose vials): 25,000 IU/mL.

Enoxaparin (generic available)

Solution for injection (prefilled syringes): 30 mg/

0.3 mL, 40 mg/0.4 mL, 60 mg/0.6 mL, 80 mg/0.8 mL,

100 mg/1 mL, 120 mg/0.8 mL, 150 mg/mL.

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