DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Arixtra (Fondaparinux Sodium Injection) - Side Effects and Adverse Reactions

 
 



ADVERSE REACTIONS

The most serious adverse reactions reported with ARIXTRA are bleeding complications and thrombocytopenia [see Warnings and Precautions].

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The adverse reaction information below is based on data from 8,877 patients exposed to ARIXTRA in controlled trials of hip fracture, hip replacement, major knee, or abdominal surgeries, and DVT and PE treatment. These trials consisted of the following:

  • 2 peri-operative dose-response trials (n = 989)
  • 4 active-controlled peri-operative VTE prophylaxis trials with enoxaparin sodium (n = 3,616), an extended VTE prophylaxis trial (n = 327), and an active-controlled trial with dalteparin sodium (n = 1,425)
  • a dose-response trial (n = 111) and an active-controlled trial with enoxaparin sodium in DVT treatment (n = 1,091)
  • an active-controlled trial with heparin in PE treatment (n = 1,092)

Hemorrhage

During administration of ARIXTRA, the most common adverse reactions were bleeding complications [see Warnings and Precautions].

Hip Fracture, Hip Replacement, and Knee Replacement Surgery: The rates of major bleeding events reported during the hip fracture, hip replacement, or knee replacement surgery clinical trials with ARIXTRA 2.5 mg are provided in Table 2.

Table 2. Bleeding Across Randomized, Controlled Hip Fracture, Hip Replacement, and Knee Replacement Surgery Studies
Peri-Operative Prophylaxis
(Day 1 to Day 7 ± 1 post-surgery)
Extended Prophylaxis
(Day 8 to Day 28 ± 2 post-surgery)

ARIXTRA

2.5 mg SC

once daily

N = 3,616

Enoxaparin Sodiuma, b

N = 3,956

ARIXTRA

2.5 mg SC

once daily

N = 327

Placebo

SC once daily

N = 329

Major bleedingc 96 (2.7%) 75 (1.9%) 8 (2.4%) 2 (0.6%)
   Hip fracture 18/831 (2.2%) 19/842 (2.3%) 8/327 (2.4%) 2/329 (0.6%)
   Hip replacement 67/2,268 (3.0%) 55/2,597 (2.1%)
   Knee replacement 11/517 (2.1%) 1/517 (0.2%)
Fatal bleeding 0 (0.0%) 1 (<0.1%) 0 (0.0%) 0 (0.0%)
Non-fatal bleeding at critical site 0 (0.0%) 1 (<0.1%) 0 (0.0%) 0 (0.0%)
Re-operation due to bleeding 12 (0.3%) 10 (0.3%) 2 (0.6%) 2 (0.6%)
BI ≥2d 84 (2.3%) 63 (1.6%) 6 (1.8%) 0 (0.0%)
Minor bleedinge 109 (3.0%) 116 (2.9%) 5 (1.5%) 2 (0.6%)

a Enoxaparin sodium dosing regimen: 30 mg every 12 hours or 40 mg once daily.

b Not approved for use in patients undergoing hip fracture surgery.

c Major bleeding was defined as clinically overt bleeding that was fatal, bleeding at critical site (e.g. intracranial, retroperitoneal, intraocular, pericardial, spinal, or into adrenal gland), (3) associated with re-operation at operative site, or (4) with a bleeding index (BI) ≥2.

d BI ≥2: Overt bleeding associated only with a bleeding index (BI) ≥2 calculated as [number of whole blood or packed red blood cell units transfused + [(pre-bleeding) – (post-bleeding)] hemoglobin (g/dL) values].

e Minor bleeding was defined as clinically overt bleeding that was not major.

A separate analysis of major bleeding across all randomized, controlled, peri-operative, prophylaxis clinical studies of hip fracture, hip replacement, or knee replacement surgery according to the time of the first injection of ARIXTRA after surgical closure was performed in patients who received ARIXTRA only post-operatively. In this analysis, the incidences of major bleeding were as follows: <4 hours was 4.8% (5/104), 4 to 6 hours was 2.3% (28/1,196), 6 to 8 hours was 1.9% (38/1,965). In all studies, the majority (≥75%) of the major bleeding events occurred during the first 4 days after surgery.

Abdominal Surgery: In a randomized study of patients undergoing abdominal surgery, ARIXTRA 2.5 mg once daily (n = 1,433) was compared with dalteparin 5,000 IU once daily (n = 1,425). Bleeding rates are shown in Table 3.

Table 3. Bleeding in the Abdominal Surgery Study

ARIXTRA

2.5 mg SC once daily

Dalteparin Sodium

5,000 IU SC once daily

N = 1,433 N = 1,425
Major bleedinga 49 (3.4%) 34 (2.4%)
Fatal bleeding 2 (0.1%) 2 (0.1%)
Non-fatal bleeding at critical site 0 (0.0%) 0 (0.0%)
Other non-fatal major bleeding
   Surgical site 38 (2.7%) 26 (1.8%)
   Non-surgical site 9 (0.6%) 6 (0.4%)
Minor bleedingb 31 (2.2%) 23 (1.6%)

a Major bleeding was defined as bleeding that was (1) fatal, (2) bleeding at the surgical site leading to intervention, (3) non-surgical bleeding at a critical site (e.g. intracranial, retroperitoneal, intraocular, pericardial, spinal, or into adrenal gland), or leading to an intervention, and/or with a bleeding index (BI) ≥2.

b Minor bleeding was defined as clinically overt bleeding that was not major.

The rates of major bleeding according to the time interval following the first ARIXTRA injection were as follows: <6 hours was 3.4% (9/263) and 6 to 8 hours was 2.9% (32/1112).

Treatment of Deep Vein Thrombosis and Pulmonary Embolism: The rates of bleeding events reported during the DVT and PE clinical trials with the ARIXTRA injection treatment regimen are provided in Table 4.

Table 4. Bleedinga in Deep Vein Thrombosis and Pulmonary Embolism Treatment Studies

ARIXTRA

N = 2,294

Enoxaparin Sodium

N = 1,101

Heparin

aPTT adjusted IV

N = 1,092

Major bleedingb 28 (1.2%) 13 (1.2%) 12 (1.1%)
Fatal bleeding 3 (0.1%) 0 (0.0%) 1 (0.1%)
Non-fatal bleeding at a critical site 3 (0.1%) 0 (0.0%) 2 (0.2%)
Intracranial bleeding 3 (0.1%) 0 (0.0%) 1 (0.1%)
Retro-peritoneal bleeding 0 (0.0%) 0 (0.0%) 1 (0.1%)
Other clinically overt bleedingc 22 (1.0%) 13 (1.2%) 10 (0.9%)
Minor bleedingd 70 (3.1%) 33 (3.0%) 57 (5.2%)

a Bleeding rates are during the study drug treatment period (approximately 7 days). Patients were also treated with vitamin K antagonists initiated within 72 hours after the first study drug administration.

b Major bleeding was defined as clinically overt: –and/or contributing to death – and/or in a critical organ including intracranial, retroperitoneal, intraocular, spinal, pericardial, or adrenal gland – and/or associated with a fall in hemoglobin level ≥2 g/dL – and/or leading to a transfusion ≥2 units of packed red blood cells or whole blood.

c Clinically overt bleeding with a 2 g/dL fall in hemoglobin and/or leading to transfusion of PRBC or whole blood ≥2 units.

d Minor bleeding was defined as clinically overt bleeding that was not major.

Local Reactions

Local irritation (injection site bleeding, rash, and pruritus) may occur following subcutaneous injection of ARIXTRA.

Elevations of Serum Aminotransferases

In the peri-operative prophylaxis randomized clinical trials of 7 ± 2 days, asymptomatic increases in aspartate (AST) and alanine (ALT) aminotransferase levels greater than 3 times the upper limit of normal were reported in 1.7% and 2.6% of patients, respectively, during treatment with ARIXTRA 2.5 mg once daily versus 3.2% and 3.9% of patients, respectively, during treatment with enoxaparin sodium 30 mg every 12 hours or 40 mg once daily enoxaparin sodium. These elevations are reversible and rarely associated with increases in bilirubin. In the extended prophylaxis clinical trial, no significant differences in AST and ALT levels between ARIXTRA 2.5 mg and placebo-treated patients were observed.

In the DVT and PE treatment clinical trials, asymptomatic increases in AST and ALT levels greater than 3 times the upper limit of normal of the laboratory reference range were reported in 0.7% and 1.3% of patients, respectively, during treatment with ARIXTRA. In comparison, these increases were reported in 4.8% and 12.3% of patients, respectively, in the DVT treatment trial during treatment with enoxaparin sodium 1 mg/kg every 12 hours and in 2.9% and 8.7% of patients, respectively, in the PE treatment trial during treatment with aPTT adjusted heparin.

Since aminotransferase determinations are important in the differential diagnosis of myocardial infarction, liver disease, and pulmonary emboli, elevations that might be caused by drugs like ARIXTRA should be interpreted with caution.

Other Adverse Reactions

Other adverse reactions that occurred during treatment with ARIXTRA in clinical trials with patients undergoing hip fracture, hip replacement, or knee replacement surgery are provided in Table 5.

Table 5. Adverse Reactions Across Randomized, Controlled, Hip Fracture Surgery, Hip Replacement Surgery, and Knee Replacement Surgery Studies
Adverse Reactions Peri-Operative Prophylaxis
(Day 1 to Day 7 ± 1 post-surgery)
Extended Prophylaxis
(Day 8 to Day 28 ± 2 post-surgery)

ARIXTRA

2.5 mg SC

once daily

Enoxaparin Sodiuma, b

ARIXTRA

2.5 mg SC

once daily

Placebo

SC once daily

N = 3,616 N = 3,956 N = 327 N = 329
Anemia 707 (19.6%) 670 (16.9%) 5 (1.5%) 4 (1.2%)
Insomnia 179 (5.0%) 214 (5.4%) 3 (0.9%) 1 (0.3%)
Wound drainage increased 161 (4.5%) 184 (4.7%) 2 (0.6%) 0 (0.0%)
Hypokalemia 152 (4.2%) 164 (4.1%) 0 (0.0%) 0 (0.0%)
Dizziness 131 (3.6%) 165 (4.2%) 2 (0.6%) 0 (0.0%)
Purpura 128 (3.5%) 137 (3.5%) 0 (0.0%) 0 (0.0%)
Hypotension 126 (3.5%) 125 (3.2%) 1 (0.3%) 0 (0.0%)
Confusion 113 (3.1%) 132 (3.3%) 4 (1.2%) 1 (0.3%)
Bullous eruptionc 112 (3.1%) 102 (2.6%) 0 (0.0%) 1 (0.3%)
Hematoma 103 (2.8%) 109 (2.8%) 7 (2.1%) 1 (0.3%)
Post-operative hemorrhage 85 (2.4%) 69 (1.7%) 2 (0.6%) 2 (0.6%)

a Enoxaparin sodium dosing regimen: 30 mg every 12 hours or 40 mg once daily.

b Not approved for use in patients undergoing hip fracture surgery.

c Localized blister coded as bullous eruption.

Adverse reactions in the abdominal surgery study and in the VTE treatment trials generally occurred at lower rates than in the hip and knee surgery trials described above. The most common adverse reaction in the abdominal surgery trial was post-operative wound infection (4.9%), and the most common adverse reaction in the VTE treatment trials was epistaxis (1.3%).

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of ARIXTRA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Isolated occurrences of thrombocytopenia with thrombosis that manifested similar to heparin-induced thrombocytopenia have been reported in the postmarketing experience and isolated cases of elevated aPTT temporally associated with bleeding events have been reported following administration of ARIXTRA (with or without concomitant administration of other anticoagulants) [see Warnings and Precautions].



REPORTS OF SUSPECTED ARIXTRA SIDE EFFECTS / ADVERSE REACTIONS

Below is a sample of reports where side effects / adverse reactions may be related to Arixtra. The information is not vetted and should not be considered as verified clinical evidence.

Possible Arixtra side effects / adverse reactions in 83 year old male

Reported by a health professional (non-physician/pharmacist) from France on 2011-10-06

Patient: 83 year old male

Reactions: Aplastic Anaemia, Intentional Drug Misuse

Suspect drug(s):
Arixtra



Possible Arixtra side effects / adverse reactions in 70 year old female

Reported by a consumer/non-health professional from United States on 2011-10-14

Patient: 70 year old female

Reactions: Thrombosis, Blood Pressure Increased, Heart Rate Decreased, Oedema Peripheral, Dizziness, Injection Site Pain, Injection Site Swelling

Adverse event resulted in: hospitalization

Suspect drug(s):
Arixtra

Other drugs received by patient: Amlodipine; Benazepril Hydrochloride; Metoprolol Tartrate; Lovaza; Coumadin; Prevacid



Possible Arixtra side effects / adverse reactions in 65 year old male

Reported by a pharmacist from United States on 2011-10-19

Patient: 65 year old male weighing 130.9 kg (288.0 pounds)

Reactions: Blood Calcium Decreased, Renal Failure, Haemorrhage, Drug Administration Error, Underdose

Adverse event resulted in: life threatening event, hospitalization

Suspect drug(s):
Arixtra

Other drugs received by patient: Potassium Chloride; Aldactone; Lisinopril; Coreg; Lasix



See index of all Arixtra side effect reports >>

Drug label data at the top of this Page last updated: 2012-01-23

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2015