Complete adverse effect profile including incidence rates and management
Important Safety Information
This is not a complete list of all possible side effects. Contact your healthcare provider if you experience any unexpected symptoms. For serious or life-threatening side effects, seek emergency medical attention immediately.
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: Serious Hypersensitivity Reactions [Warnings and Precautions ( 5.1 )].
The most common related adverse events (>1%) were paresthesia, flushing, nausea and/or vomiting, hypotension and headache.
( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact BTG at 877-377-3784 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 Clinical Trials Experience Because clinical trials are conducted under controlled but widely varying conditions, adverse reaction rates observed in clinical trials of VORAXAZE cannot be directly compared to rates in the clinical trials of other drugs and may not reflect the rates observed in practice.
The evaluation of adverse reactions in patients who received VORAXAZE was confounded, because patients had toxic plasma methotrexate concentration due to prolonged methotrexate clearance, which is associated with myelosuppression, mucositis, acute hepatitis, and renal dysfunction and failure.
The safety of VORAXAZE is based on data from 290 patients who were enrolled in Study 1 or Study 2, two single-arm, open-label, multicenter studies conducted in patients who had markedly delayed methotrexate clearance due to impaired renal function.
Patients with osteosarcoma were eligible for these studies if the plasma methotrexate concentration was >50 µmol/L at 24 hours, >5 µmol/L at 48 hours, or >2 standard deviations above the mean methotrexate elimination curve at least 12 hours after methotrexate administration;
and there was a ≥2-fold increase in serum creatinine above baseline.
All other patients were eligible for these studies if the plasma methotrexate concentration was >10 µmol/L more than 42 hours after the start of the methotrexate or the plasma methotrexate concentration was >2 standard deviations above the mean methotrexate excretion curve at least 12 hours following methotrexate;
and the serum creatinine was >1.5 times the upper limit of normal (ULN) or the creatinine clearance (CLcr) was <60 mL/min at least 12 hours following methotrexate administration.
5 WARNINGS AND PRECAUTIONS Serious Hypersensitivity Reactions: Serious hypersensitivity reactions occurred.
( 5.1 ) Monitoring Methotrexate Concentration: Measure methotrexate concentrations within 48 hours following VORAXAZE administration using a chromatographic method;
immunoassays are unreliable for samples collected within 48 hours following VORAXAZE administration.
( 5.2 ) 5.1 Serious Hypersensitivity Reactions Serious hypersensitivity reactions occurred in less than 1% of patients [ see Adverse Reactions ( 6.1 ) ].
5.2 Interference with Immunoassay Measurements of Methotrexate DAMPA (4-deoxy-4-amino-N 10 - methylpteroic acid), an inactive metabolite of methotrexate formed following VORAXAZE administration, interferes with the measurement of methotrexate concentration using immunoassays.
Like all medications, Voraxaze can cause side effects. However, not everyone who takes this medication will experience them. Many side effects are dose-dependent and may improve as your body adjusts to the medication. Others may require dose adjustment or medical attention.
Contact your healthcare provider promptly if you experience:
Seek immediate emergency medical care if you experience signs of: