fondaparinux (fon-da-par-i-nux) Arixtra

 Indications

Prevention and treatment of deep vein thrombosis and

pulmonary embolism. Unlabeled Use: Systemic anticoagulation

for other diagnoses.

Action

Binds selectively to antithrombin III (AT III). This binding

potentiates the neutralization (inactivation) of active

factor X (Xa). Therapeutic Effects: Interruption of

the coagulation cascade resulting in inhibition of

thrombus formation. Prevention of thrombus formation

decreases the risk of pulmonary emboli.

Pharmacokinetics

Absorption: 100% absorbed following subcutaneous

administration.

Distribution: Distributes mainly throughout the intravascular

space.

Metabolism and Excretion: Eliminated mainly

unchanged in urine.

Half-life: 17–21 hr.

TIME/ACTION PROFILE (anticoagulant effect)

ROUTE ONSET PEAK DURATION

Subcut rapid 3 hr 24 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Severe renal

impairment (CCr 30 mL/min;qrisk of bleeding);

Body weight 50 kg (for prophylaxis) (markedlyq

risk of bleeding); Active major bleeding; Bacterial endocarditis;

Thrombocytopenia due to fondaparinux antibodies.

Use Cautiously in: Mild-to-moderate renal impairment

(CCr 30–50 mL/min); Untreated hypertension;

Recent history of ulcer disease; Body weight 50 kg

(for treatment of DVT or PE) (mayqrisk of bleeding);

Geri: Patients 65 yr (qrisk of bleeding); Malignancy;

History of heparin-induced thrombocytopenia; OB: Use

during pregnancy only if clearly needed; Lactation,

Pedi: Safety not established.

Exercise Extreme Caution in: History of congenital

or acquired bleeding disorder; Severe uncontrolled

hypertension; Hemorrhagic stroke; Recent CNS or ophthalmologic

surgery; Active GI bleeding/ulceration; Retinopathy

(hypertensive or diabetic); Neuroaxial spinal anesthesia or spinal puncture, especially if concurrent

with an indwelling epidural catheter, drugs affecting hemostasis,

history of traumatic/repeated spinal puncture

or spinal deformity (qrisk of spinal/epidural hematoma

that may lead to long-term or permanent paralysis).

Adverse Reactions/Side Effects

CNS: confusion, dizziness, headache, insomnia. CV:

edema, hypotension. GI: constipation, diarrhea, dyspepsia,

qliver enzymes, nausea, vomiting. GU: urinary

retention. Derm: bullous eruption, hematoma, purpura,

rash. Hemat: bleeding, thrombocytopenia. F

and E: hypokalemia. Misc: hypersensitivity reactions

including ANGIOEDEMA, fever,qwound drainage.

Interactions

Drug-Drug: Risk of bleeding may beqby concurrent

use of warfarin or drugs that affect platelet

function, including aspirin, NSAIDs, dipyridamole,

some cephalosporins, valproates, clopidogrel,

abciximab, eptifibatide, tirofiban, and dextran.

Drug-Natural Products:qrisk of bleeding with

arnica, chamomile, clove, dong quai, feverfew,

garlic, ginger, gingko, Panax ginseng, and others.

Route/Dosage

Treatment of DVT/PE

Subcut (Adults): 50 kg—5 mg once daily for at

least 5 days until therapeutic anticoagulation with warfarin

is achieved (INR 2 for 2 consecutive days); warfarin

may be started within 72 hr of fondaparinux (has

been used for up to 26 days); 50–100 kg—7.5 mg

once daily for at least 5 days until therapeutic anticoagulation

with warfarin is achieved (INR 2 for 2 consecutive

days);100 kg—10 mg once daily for at least 5

days until therapeutic anticoagulation with warfarin is

achieved (INR 2 for 2 consecutive days); warfarin

may be started within 72 hr of fondaparinux.

Prevention of DVT/PE

Subcut (Adults): 2.5 mg once daily, starting 6–8 hr

after surgery, continuing for 5–9 days (up to 11 days)

following abdominal surgery or knee/hip replacement

or continuing for 24 days following hip fracture surgery

(up to 32 days).

Availability (generic available)

Solution for subcut injection (prefilled syringes):

2.5 mg/0.5 mL, 5 mg/0.4 mL, 7.5 mg/0.6 mL, 10 mg/

0.8 mL.