openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
warnings and cautions
5 WARNINGS AND PRECAUTIONS Hepatic Toxicity : Serious hepatic reactions reported. Evaluate liver function tests at start of and during Voriconazole therapy ( 5.1 ) Arrhythmias and QT Prolongation : Correct potassium, magnesium and calcium prior to use; caution patients with proarrhythmic conditions ( 5.2 ) Infusion Related Reactions (including anaphylaxis) : Stop the infusion ( 5.3 ) Visual Disturbances (including optic neuritis and papilledema): Monitor visual function if treatment continues beyond 28 days ( 5.4 ) Severe Cutaneous Adverse Reactions: Discontinue for exfoliative cutaneous reactions ( 5.5 ) Photosensitivity : Avoid sunlight due to risk of photosensitivity ( 5.6 ) Adrenal Dysfunction: Carefully monitor patients receiving Voriconazole and corticosteroids (via all routes of administration) for adrenal dysfunction both during and after Voriconazole treatment. Instruct patients to seek immediate medical care if they develop signs and symptoms of Cushing’s syndrome or adrenal insufficiency ( 5.8 ) Embryo-Fetal Toxicity : Voriconazole can cause fetal harm when administered to a pregnant woman. Inform pregnant patients of the potential hazard to the fetus. Advise females of reproductive potential to use effective contraception during treatment with Voriconazole ( 5.9 , 8.1 , 8.3 ) Skeletal Adverse Reactions : Fluorosis and periostitis with long-term voriconazole therapy. Discontinue if these adverse reactions occur ( 5.12 ) Clinically Significant Drug Interactions : Review patient's concomitant medications ( 5.13 , 7 ) 5.1 Hepatic Toxicity In clinical trials, there have been uncommon cases of serious hepatic reactions during treatment with Voriconazole (including clinical hepatitis, cholestasis and fulminant hepatic failure, including fatalities). Instances of hepatic reactions were noted to occur primarily in patients with serious underlying medical conditions (predominantly hematological malignancy). Hepatic reactions, including hepatitis and jaundice, have occurred among patients with no other identifiable risk factors. Liver dysfunction has usually been reversible on discontinuation of therapy [see Adverse Reactions (6.1) ] . A higher frequency of liver enzyme elevations was observed in the pediatric population [see Adverse Reactions (6.1) ] . Hepatic function should be monitored in both adult and pediatric patients. Measure serum transaminase ...
openFDA text is shown for search and cross-checking; DailyMed SPL is canonical.
adverse reactions
6 ADVERSE REACTIONS The following serious adverse reactions are described elsewhere in the labeling: Hepatic Toxicity [see Warnings and Precautions (5.1) ] Arrhythmias and QT Prolongation [see Warnings and Precautions (5.2) ] Infusion Related Reactions [see Warnings and Precautions (5.3) ] Visual Disturbances [see Warnings and Precautions (5.4) ] Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.5) ] Photosensitivity [see Warnings and Precautions (5.6) ] Renal Toxicity [see Warnings and Precautions (5.7) ] Adult Patients : The most common adverse reactions (incidence ≥2%) were visual disturbances, fever, nausea, rash, vomiting, chills, headache, liver function test abnormal, tachycardia, hallucinations ( 6 ) Pediatric Patients : The most common adverse reactions (incidence ≥5%) were visual disturbances, pyrexia, vomiting, epistaxis, nausea, rash, abdominal pain, diarrhea, hypertension, hypokalemia, cough, headache, thrombocytopenia, ALT abnormal, hypotension, peripheral edema, hyperglycemia, tachycardia, dyspnea, hypocalcemia, hypophosphatemia, LFT abnormal, mucosal inflammation, photophobia, abdominal distention, constipation, dizziness, hallucinations, hemoptysis, hypoalbuminemia, hypomagnesemia, renal impairment, upper respiratory tract infection ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact UBI Pharma Inc. at pharmacovigilance@ubi-pharma.com or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in 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. Clinical Trials Experience in Adults Overview The most frequently reported adverse reactions (see Table 4 ) in the adult therapeutic trials were visual disturbances (18.7%), fever (5.7%), nausea (5.4%), rash (5.3%), vomiting (4.4%), chills (3.7%), headache (3.0%), liver function test increased (2.7%), tachycardia (2.4%), hallucinations (2.4%). The adverse reactions which most often led to discontinuation of voriconazole therapy were elevated liver function tests, rash, and visual disturbances [see Warning and Precautions (5.1 , 5.4 ) and Adverse Reactions (6.1) ] . The data described in Table 4 reflect exposure to voriconazole in 1655 patients in nine the...
adverse reactions table
Table 4: Adverse Reactions Rate ≥ 2% on Voriconazole or Adverse Reactions of Concern in Therapeutic Studies Population, Studies 307/602–608 Combined, or Study 305. Possibly Related to Therapy or Causality Unknown Study 307/602: IA; Study 608: candidemia; Study 305: ECTherapeutic Studies Studies 303, 304, 305, 307, 309, 602, 603, 604, 608Studies 307/602 and 608 (IV/ oral therapy) Study 305 (oral therapy) Voriconazole N=1655 Voriconazole N=468 Ampho B Amphotericin B followed by other licensed antifungal therapy N=185 Ampho B→ Fluconazole N=131 Voriconazole N=200 Fluconazole N=191 N (%)N (%)N (%)N (%)N (%)N (%)Special Senses See Warnings and Precautions (5.4)Abnormal vision310 (18.7)63 (13.5)1 (0.5)031 (15.5)8 (4.2)Photophobia37 (2.2)8 (1.7)005 (2.5)2 (1.0)Chromatopsia20 (1.2)2 (0.4)002 (1.0)0Body as a WholeFever94 (5.7)8 (1.7)25 (13.5)5 (3.8)00Chills61 (3.7)1 (0.2)36 (19.5)8 (6.1)1 (0.5)0Headache49 (3.0)9 (1.9)8 (4.3)1 (0.8)01 (0.5)Cardiovascular SystemTachycardia39 (2.4)6 (1.3)5 (2.7)000Digestive SystemNausea89 (5.4)18 (3.8)29 (15.7)2 (1.5)2 (1.0)3 (1.6)Vomiting72 (4.4)15 (3.2)18 (9.7)1 (0.8)2 (1.0)1 (0.5)Liver function tests abnormal45 (2.7)15 (3.2)4 (2.2)1 (0.8)6 (3.0)2 (1.0)Cholestatic jaundice17 (1.0)8 (1.7)01 (0.8)3 (1.5)0Metabolic and Nutritional SystemsAlkaline phosphatase increased59 (3.6)19 (4.1)4 (2.2)3 (2.3)10 (5.0)3 (1.6)Hepatic enzymes increased30 (1.8)11 (2.4)5 (2.7)1 (0.8)3 (1.5)0SGOT increased31 (1.9)9 (1.9)01 (0.8)8 (4.0)2 (1.0)SGPT increased29 (1.8)9 (1.9)1 (0.5)2 (1.5)6 (3.0)2 (1.0)Hypokalemia26 (1.6)3 (0.6)36 (19.5)16 (12.2)00Bilirubinemia15 (0.9)5 (1.1)3 (1.6)2 (1.5)1 (0.5)0Creatinine increased4 (0.2)059 (31.9)10 (7.6)1 (0.5)0Nervous SystemHallucinations39 (2.4)13 (2.8)1 (0.5)000Skin and AppendagesRash88 (5.3)20 (4.3)7 (3.8)1 (0.8)3 (1.5)1 (0.5)UrogenitalKidney function abnormal10 (0.6)6 (1.3)40 (21.6)9 (6.9)1 (0.5)1 (0.5)Acute kidney failure7 (0.4)2 (0.4)11 (5.9)7 (5.3)00