Arixtra


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fondaparinux sodium

Arixtra

Pharmacologic class: Selective factor Xa inhibitor

Therapeutic class: Anticoagulant, antithrombotic

Pregnancy risk category B

Action

Selectively inhibits factor Xa, disrupting blood coagulation and inhibiting thrombin formation and thrombus development

Availability

Injection: 2.5 mg/0.5 ml in single-dose syringe

Indications and dosages

Prevention of deep-vein thrombosis after hip fracture surgery or hip or knee replacement surgery

Adults: 2.5 mg subcutaneously 6 to 8 hours after surgery, once hemostasis occurs; usual duration is 5 to 9 days (up to 11 days) given daily. After hip fracture surgery, extended prophylactic course of up to 24 additional days is recommended; some patients have tolerated a total course of 32 days.

Deep-vein thrombosis and pulmonary emboli

Adults: 5 mg subcutaneously once daily for patients weighing less than 50 kg (110 lb), 7.5 mg subcutaneously for patients weighing 50 to 100 kg (110 to 220 lb) or 10 mg subcutaneously for patients weighing more than 100 kg (220 lb) for 5 days and until therapeutic oral anticoagulant effect occurs (as shown by International Normalized Ratio of 2 to 3). Usual duration of therapy is 5 to 9 days, but may continue for up to 26 days.

Dosage adjustment

• Renal impairment

Contraindications

• Hypersensitivity to drug
• Bacterial endocarditis
• Severe renal disease
• Active major bleeding
• Patients weighing less than 50 kg (110 lb) who have undergone hip fracture, hip replacement, or knee replacement surgery

Precautions

Use cautiously in:
• diabetic retinopathy, hepatic disease, blood dyscrasias, heparin-induced thrombocytopenia, severe hypertension, alcoholism
• patients older than age 75
• pregnant or breastfeeding patients
• children (safety and efficacy not established).

Administration

Withhold for at least 6 to 8 hours after surgery, to minimize risk of major bleeding.

Give by subcutaneous injection only. Don't give I.M.
• Rotate injection sites among fatty tissue areas on left and right anterolateral and posterolateral abdominal walls.
• Don't expel air bubble from syringe; doing so may reduce amount of drug delivered.
• Listen for slight click when plunger is fully released. After drug has been injected, needle retracts and white safety indicator is visible.
• Don't mix with other injections or infusions.
• Know that when drug is used to treat deep-vein thrombosis and pulmonary emboli, concomitant warfarin treatment should begin as soon as possible (usually within 72 hours).

Adverse reactions

CNS: depression, dizziness, asthenia, headache, abnormal thinking, confusion, insomnia, neuropathy

CV: hypotension

GI: nausea, vomiting, diarrhea, constipation, abdominal pain, dyspepsia, dry mouth, anorexia

GU: urinary retention, urinary tract infection

Hematologic: anemia, hematoma, purpura, minor bleeding, major bleeding, thrombocytopenia, retroperitoneal hemorrhage, postoperative hemorrhage

Metabolic: hypokalemia

Skin: bullous eruption

Other: increased wound drainage, injection site bleeding, pain, edema, fever

Interactions

Drug-drug.Anticoagulants: increased risk of bleeding

Drug-herbs.Anise, astragalus, bilberry, black currant, bladder wrack, bogbean, boldo, borage, buchu, capsaicin, cat's claw, celery, chaparral, cinchona, clove oil, dandelion, dong quai, fenugreek, feverfew, garlic, ginger, ginkgo, papaya, red clover, rhubarb, safflower oil, skullcap, tan-shen: additive anticoagulant effect

St. John's wort: reduced anticoagulant effect

Patient monitoring

• Monitor CBC, platelet count, creatinine level, and renal function tests. Assess stools for occult blood.
• Monitor vital signs, temperature, and fluid intake and output.

Stay alert for bleeding tendency, especially postoperative hemorrhage.
• Check for increased wound drainage after surgery.

In patient undergoing concomitant neuraxial anesthesia or spinal puncture, watch for neurologic impairment (indicating possible spinal or epidural hematoma).

Discontinue drug if severe renal impairment occurs.

Patient teaching

Instruct patient to immediately report bleeding.
• Caution patient to avoid activities that can cause injury. Tell him to use soft toothbrush and electric razor to avoid gum and skin injury.
• Tell patient that he'll undergo regular blood testing during therapy.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and herbs mentioned above.

fondaparinux

(fon-da-par-i-nux) ,

Arixtra

(trade name)

Classification

Therapeutic: anticoagulants
Pharmacologic: active factor x inhibitors
Pregnancy Category: B

Indications

Prevention and treatment of deep vein thrombosis and pulmonary embolism.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)

ROUTEONSETPEAKDURATION
Subcutrapid3 hr24 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity;Severe renal impairment (CCr <30 mL/min; ↑ risk of bleeding);Body weight <50 kg (for prophylaxis) (markedly ↑ 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) (may ↑ risk of bleeding); Geriatric: Patients >65 yr (↑ risk of bleeding);Malignancy;History of heparin-induced thrombocytopenia; Obstetric / Lactation / Pediatric: Safety not established; use during pregnancy only if clearly needed.
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);Spinal/epidural anesthesia or spinal puncture (↑ risk of spinal/epidural hematoma that may lead to long-term or permanent paralysis).

Adverse Reactions/Side Effects

Central nervous system

  • confusion
  • dizziness
  • headache
  • insomnia

Cardiovascular

  • edema
  • hypotension

Gastrointestinal

  • constipation
  • diarrhea
  • dyspepsia
  • ↑ liver enzymes
  • nausea
  • vomiting

Genitourinary

  • urinary retention

Dermatologic

  • bullous eruption
  • hematoma
  • purpura
  • rash

Hematologic

  • bleeding (most frequent)
  • thrombocytopenia

Fluid and Electrolyte

  • hypokalemia

Miscellaneous

  • hypersensitivity reactions including angioedema (life-threatening)
  • fever
  • ↑ wound drainage

Interactions

Drug-Drug interaction

Risk of bleeding may be ↑ by concurrent use of warfarin or drugs that affect platelet function, including aspirin, NSAIDs, dipyridamole, some cephalosporins, valproates, clopidogrel, ticlopidine, abciximab, eptifibatide, tirofiban, and dextran.↑ risk of bleeding with arnica, chamomile, clove, dong quai, feverfew, garlic, ginger, gingko, Panax ginseng, and others.

Route/Dosage

Treatment of DVT/PE

Subcutaneous (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

Subcutaneous (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: 2.5 mg/0.5 mL in prefilled syringes, 5 mg/0.4 mL in prefilled syringes, 7.5 mg/0.6 mL in prefilled syringes, 10 mg/0.8 mL in prefilled syringes

Nursing implications

Nursing assessment

  • Assess for signs of bleeding and hemorrhage (bleeding gums; nosebleed; unusual bruising; black, tarry stools; hematuria; fall in hematocrit; sudden drop in BP; guaiac positive stools); bleeding from surgical site. Notify health care professional if these occur.
  • Assess for evidence of additional or increased thrombosis. Symptoms will depend on area of involvement. Monitor neurological status frequently for signs of impairment, especially in patients with indwelling epidural catheters for administration of analgesia or with concomitant use of drugs affecting hemostasis (NSAIDs, platelet inhibitors, other anticoagulants). Risk is increased by traumatic or repeated epidural or spinal puncture. May require urgent treatment.
  • Lab Test Considerations: Monitor platelet count closely; may cause thrombocytopenia. If platelet count is <100,000/mm3, discontinue fondaparinux.
    • Fondaparinux is not accurately measured by prothrombin time (PT), activated thromboplastin time (aPTT), or international standards of heparin or low-molecular-weight heparins. If unexpected changes in coagulation parameters or major bleeding occurs, discontinue fondaparinux.
    • Monitor CBC, serum creatinine levels, and stool occult blood tests routinely during therapy.
    • May cause asymptomatic ↑ in AST and ALT. Elevations are fully reversible and not associated with ↑ in bilirubin.
    • May cause ↑ aPTT temporally associated with bleeding with or without concomitant administration of other anticoagulants and thrombocytopenia with thrombosis similar to heparin-induced thrombocytopenia, with or without exposure to heparin or low-molecular-weight heparins.

Potential Nursing Diagnoses

Ineffective tissue perfusion (Indications)
Risk for injury (Side Effects)

Implementation

  • Fondaparinux cannot be used interchangeably with heparin, low-molecular-weight heparins, or heparinoids as they differ in manufacturing process, anti-Xa and anti-IIa activity, units, and dose. Each of these medications has its own instructions for use.
    • Initial dose should be administered 6-8 hr after surgery. Administration before 6 hr after surgery has been associated with risk of major bleeding.
  • Subcutaneous: Administer subcut only into fatty tissue, alternating sites between right and left anterolateral or posterolateral abdominal wall. Inject entire length of needle at a 45° or 90° angle into a skin fold held between thumb and forefinger; hold skin fold throughout injection. Do not aspirate or massage. Rotate sites frequently. Do not administer IM because of danger of hematoma formation. Solution should be clear; do not inject solution containing particulate matter. Do not mix with other injections.
    • Fondaparinux is provided in a single-dose prefilled syringe with an automatic needle protection system. Do not expel air bubble from prefilled syringe before injection to prevent loss of drug.

Patient/Family Teaching

  • Advise patient to report any symptoms of unusual bleeding or bruising, dizziness, itching, rash, fever, swelling, or difficulty breathing to health care professional immediately.
  • Instruct patient not to take aspirin or NSAIDs without consulting health care professional during therapy.

Evaluation/Desired Outcomes

  • Prevention and treatment of deep vein thrombosis and pulmonary embolism.

Arixtra

A selective factor-Xa-inhibiting synthetic heparin anticoagulant, which is a pentasaccharide that covers the active site of heparin specific for antithrombin III.

Indications
Prophylaxis of deep vein thrombosis (DVT) and PEs in hospitalised patients, including those with hip fractures and injuries, or patients undergoing total hip or total knee replacement surgery; it may be used to manage heparin-induced thrombocytopaenia (HIT).  

Adverse effects
Bleeding, thrombocytopaenia, local reactions, increased aminotransferases.

Arixtra

A brand name for FONDAPARINUX.
References in periodicals archive ?
The US patents on Arixtra expired in 2002, the year before the drug was launched in the US.
Annual sales of Arixtra, which prevents deep vein thrombosis in patients undergoing surgery, were smaller at 24 million euros (pounds 15.
Diosynth is synthesizing the complex molecule to be used in Organon's new antithrombotic drug, Arixtra.
Arixtra is indicated for the prophylaxis of deep vein thrombosis (DVT), which may cause pulmonary embolism (PE) in patients going through hip fracture surgery, including extended prophylaxis, hip replacement surgery, knee replacement surgery or abdominal surgery who are at risk for thromboembolic complications.
Prof Alexander Turpie was speaking of the launch of research into the effects of Arixtra, an inhibitor drug which is being developed in order to prevent deep vein thromboses after serious surgery as well as in general medical patients.
commercialization, marketing and intellectual property rights relating to Arixtra (fondaparinux sodium) Injection and the authorized generic (AG) of Arixtra from Aspen Global Incorporated (Aspen).
Arixtra is indicated for the prophylaxis of deep vein thrombosis (DVT), which might lead to pulmonary embolism (PE) in patients undergoing hip fracture surgery, also to include extended prophylaxis, hip replacement surgery, knee replacement surgery or abdominal surgery who are at risk for thromboembolic complications.
This study forecasts revenues of ten leading drugs in the antithrombotic agents market, including Plavix, Lovenox, Pletal, Fragmin, Asasantin, Arixtra and Aspirin Cardio.
Elsewhere in the Regional Portfolio, shares in GlaxoSmithKline closed 17p higher amid positive comments regarding Glaxo's anticoagulant, Arixtra.
Indeed, the report findings reveal that GlaxoSmithKline's currently marketed Arixtra (fondaparinux) is significantly limited in Europe as only about 12 percent of ACS patients who have an ICU stay are treated with this drug.
commercialization, marketing and intellectual property rights to Arixtra injection from Aspen Global Incorporated for $225 million (initial payment).
Pharmaceutical stock Glaxo SmithKline gained 17p to 1458p after the FDA granted a priority review for Arixtra.