In Summary

Commonly reported side effects of voriconazole include: blurred vision, vision color changes, visual disturbance, and enhanced visual perception. Other side effects include: fever, nausea, skin rash, vomiting, and chills. See below for a comprehensive list of adverse effects.

For the Consumer

Applies to voriconazole: oral powder for suspension, oral tablet

Other dosage forms:

• intravenous powder for solution

Along with its needed effects, voriconazole may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking voriconazole:

More common

• Difficulty seeing at night
• increased sensitivity of the eyes to sunlight
• rash
• vision changes

Less common

• Bloating or swelling of the face, arms, hands, lower legs, or feet
• blurred vision
• chills
• clay-colored stools
• confusion
• convulsions
• dark urine
• decreased urine
• dizziness
• dry mouth
• faintness or lightheadedness when getting up suddenly from a lying or sitting position
• feeling of warmth
• fever
• increased thirst
• irregular or pounding heartbeat
• itching
• loss of appetite
• muscle pain or cramps
• muscle spasms or twitching
• nausea
• nervousness
• numbness or tingling in the hands, feet, or lips
• pounding in the ears
• rapid weight gain
• rash with flat lesions or small raised lesions on the skin
• redness of the face, neck, arms, and occasionally, the upper chest
• stomach pain
• slow or fast heartbeat
• sweating
• trembling
• unpleasant breath odor
• unusual tiredness or weakness
• vomiting of blood
• yellow eyes or skin

Rare

• Agitation
• blistering, peeling, or loosening of the skin
• hostility or anger
• increased sensitivity of the skin to sunlight
• irritability
• redness or other discoloration of the skin
• seeing things that are not there
• severe sunburn

Incidence not known

• Bone pain

Some side effects of voriconazole may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

Less common

• Diarrhea
• headache
• vomiting

For Healthcare Professionals

Applies to voriconazole: intravenous powder for injection, oral powder for reconstitution, oral tablet

General

The most frequently reported side effects in clinical trials were visual disturbances, fever/pyrexia, nausea, rash, vomiting, diarrhea, chills, headache, increased/abnormal liver function test, peripheral edema, respiratory distress, abdominal pain, tachycardia, and hallucinations. Side effects that most frequently led to the discontinuation of voriconazole treatment included visual disturbances, rash, and elevated liver function tests.

Ocular

Very common (10% or more): Abnormal vision (up to 28.1%), visual disturbances/impairment (including altered/enhanced visual perception, blurred vision, chromatopsia, color vision change, photophobia)

Common (1% to 10%): Photophobia, chromatopsia, retinal hemorrhage

Uncommon (0.1% to 1%): Papilledema, optic nerve disorder, optic neuritis, scleritis, blepharitis, diplopia, oculogyric crisis/oculogyration

Rare (less than 0.1%): Optic atrophy, corneal opacity

Frequency not reported: Eye hemorrhage, abnormality of accommodation, color blindness, conjunctivitis, eye pain, dry eyes, keratitis, keratoconjunctivitis, mydriasis, night blindness, retinitis, uveitis, visual field defect, transient altered perception of light, blurred vision, wavy lines on television or on going to sleep

Postmarketing reports: Prolonged visual adverse events (including optic neuritis and papilledema)

The visual disturbances were usually mild and rarely resulted in the discontinuation of therapy.

Ocular side effects have been reported frequently and have included abnormal vision, altered/enhanced visual perception, blurred vision, color vision change, and/or photophobia in about 21% of patients. These visual disturbances were transient and fully reversible; most spontaneously resolving within 1 hour with no clinically significant long-term visual effects. Attenuation was observed with repeated doses. Visual disturbances may be related to higher plasma voriconazole levels and/or doses. The mechanism has not been fully identified; however, the site of action is most likely within the retina. In a 28-day study of the effect of voriconazole on retinal activity in healthy subjects, alterations in color perception, decreases in electroretinogram waveform amplitude, and diminished visual field measurements were linked to the administration of voriconazole. Within 14 days of stopping the drug, each indicator of visual function had returned to baseline.

Metabolic

Elevated alkaline phosphatase (greater than 3 times ULN; up to 22.6%) and decreased potassium (less than 0.9 times lower limit of normal; up to 16.7%) have been reported.

Very common (10% or more): Elevated alkaline phosphatase (up to 22.6%), decreased potassium (up to 16.7%)

Common (1% to 10%): Hypokalemia, hypoglycemia, hyponatremia

Uncommon (0.1% to 1%): Increased blood cholesterol, hypercholesterolemia, hypomagnesemia

Frequency not reported: Decreased glucose tolerance, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hyperuricemia, hypocalcemia, hypophosphatemia, anorexia, hyperinsulinemia

Renal

Increased creatinine (greater than 1.3 times ULN) has been reported in up to 21.4% of patients.

Acute renal failure has been reported in severely ill patients.

Very common (10% or more): Increased blood creatinine (up to 21.4%)

Common (1% to 10%): Acute renal failure, abnormal kidney function

Uncommon (0.1% to 1%): Increased BUN, nephritis, renal tubular necrosis, increased blood urea

Frequency not reported: Decreased CrCl, hydronephrosis, kidney pain, nephrosis, uremia

Hepatic

The overall incidence of clinically significant transaminase abnormalities during clinical studies was 13.5% of patients treated with voriconazole. Increased incidence of abnormal liver function tests may be related to higher plasma levels and/or doses. Most abnormal liver function tests resolved during therapy without dose adjustment or after dose adjustment (including therapy discontinuation).

Elevated AST (greater than 3 times upper limit of normal [ULN]; up to 20.3%), total bilirubin (greater than 1.5 times ULN; up to 19.4%), and ALT (greater than 3 times ULN; up to 18.9%) have been reported.

Very common (10% or more): Elevated AST (up to 20.3%), elevated total bilirubin (up to 19.4%), elevated ALT (up to 18.9%), abnormal liver function test (including AST, ALT, alkaline phosphatase, GGT, LDH, bilirubin)

Common (1% to 10%): Increased hepatic enzymes, cholestatic jaundice, bilirubinemia, elevated GGT, elevated LDH, jaundice, hepatitis

Uncommon (0.1% to 1%): Hepatic failure, hepatomegaly/enlarged liver, cholecystitis, cholelithiasis

Rare (less than 0.1%): Serious hepatic reactions (including clinical hepatitis, cholestasis, fulminant hepatic failure including fatalities), hepatic coma

Dermatologic

Very common (10% or more): Rash (up to 19%)

Common (1% to 10%): Alopecia, exfoliative dermatitis, phototoxic reaction, maculopapular rash, photosensitivity skin reaction, pruritus, erythema, purpura

Uncommon (0.1% to 1%): Fixed drug eruption, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, angioedema/angioneurotic edema, allergic dermatitis, urticaria, psoriasis, eczema, phototoxicity, macular rash, papular rash

Rare (less than 0.1%): Discoid lupus erythematosus, pseudoporphyria

Frequency not reported: Serious exfoliative cutaneous reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme), phototoxicity (including bullous erythema, lentigines, keratosis, pseudoporphyria, photoaging), photocarcinogenesis, contact dermatitis, furunculosis, herpes simplex, melanoma, melanosis, skin discoloration, skin disorder, dry skin, squamous cell carcinoma, sweating, blistering eruptions/bullous lesions, worsening of psoriasis

Postmarketing reports: Cutaneous lupus erythematosus

Most rashes were of mild to moderate severity.

A photosensitivity reaction (manifested as facial edema and cheilitis) was reported in ambulatory patients (n=5) receiving voriconazole 200 mg twice daily for chronic invasive Aspergillus 4 weeks after starting therapy. Symptoms resolved shortly after stopping the drug. Plasma and serum levels of all-trans retinol and 13-cis retinol were elevated in all the cases (n=3) measured supporting a hypothesis that voriconazole inhibits a step in the breakdown of all-trans retinoic acid.

A 65-year-old patient experienced pseudoporphyria after minimal sun exposure coincident with voriconazole therapy. After pseudoporphyria was diagnosed and because the drug could not be stopped, the patient was instructed to avoid the sun and use sunscreens with UVA and UVB protection. The drug was stopped after a year of therapy, but the patient continued to be extremely photosensitive for several months.

A 45-year-old female with a history of non-Hodgkin's lymphoma 3 years post allogeneic bone marrow transplant experienced blistering eruptions coincident with voriconazole therapy. Her posttransplant course had been complicated by chronic, grade 2, cutaneous graft versus host disease requiring therapy. The patient had no history of bullous skin lesions. She was started on voriconazole 200 mg twice daily as prophylactic antifungal therapy. One week later, tense blisters were observed on the hips and later on the hands. There were prodromal burning sensations, but no associated pruritus or pain. The lesions resolved over 5 to 7 days without scarring. She experienced recurrent episodes involving her legs and feet. A biopsy obtained from the knee showed moderate hyperkeratosis, striking atrophy, and extensive basal vacuolization and colloid body formation. The temporal association of voriconazole initiation and onset of the eruption raised suspicion that it was the etiologic factor; thus, the drug was discontinued. The blistering resolved within 2 weeks with no further episodes.

Nervous system

Very common (10% or more): Headache

Common (1% to 10%): Dizziness, paresthesia, tremor, convulsion, hypertonia, somnolence, syncope

Uncommon (0.1% to 1%): Ataxia, brain edema, vertigo, hypoesthesia, nystagmus, dysgeusia/altered taste perception/taste perversion, encephalopathy, extrapyramidal syndrome/disorder, peripheral neuropathy, hypoacusis, tinnitus

Rare (less than 0.1%): Hepatic encephalopathy, Guillain-Barre syndrome, somnolence during infusion

Frequency not reported: Acute brain syndrome, akathisia, amnesia, coma, decreased libido, deafness, delirium, dementia, ear pain, encephalitis, euphoria, grand mal convulsion, intracranial hypertension, neuralgia, neuropathy, otitis externa, taste loss

Other

Very common (10% or more): Fever/pyrexia, peripheral edema

Common (1% to 10%): Chills, influenza-like illness, asthenia, face edema, flu syndrome, chest pain

Frequency not reported: Enlarged abdomen, ascites, cellulitis, edema, flank pain, graft versus host reaction, granuloma, infection, bacterial infection, fungal infection, mucous membrane disorder, multi-organ failure, pain, pelvic pain, sepsis, substernal chest pain, infusion-related side effects (including immediate anaphylactoid-type reactions)

Infusion-related side effects have included immediate anaphylactoid-type reactions (including flushing, fever, sweating, tachycardia, chest tightness, dyspnea, faintness, nausea, pruritus, rash).

Gastrointestinal

Very common (10% or more): Abdominal pain, nausea, vomiting, diarrhea

Common (1% to 10%): Cheilitis, gastroenteritis, dry mouth, gingivitis, dyspepsia, constipation

Uncommon (0.1% to 1%): Pancreatitis, peritonitis, duodenitis, glossitis, tongue edema, swollen tongue, pseudomembranous colitis

Frequency not reported: Duodenal ulcer perforation, dysphagia, esophageal ulcer, esophagitis, flatulence, gastrointestinal hemorrhage, gum hemorrhage, gum hyperplasia, hematemesis, intestinal perforation, intestinal ulcer, melena, mouth ulceration, parotid gland enlargement, periodontitis, proctitis, rectal disorder, rectal hemorrhage, stomach ulcer, stomatitis

Respiratory

Very common (10% or more): Respiratory distress

Common (1% to 10%): Acute respiratory distress syndrome, pulmonary edema, sinusitis

Frequency not reported: Increased cough, dyspnea, epistaxis, hemoptysis, hypoxia, pharyngitis, pleural effusion, pneumonia, respiratory disorder, respiratory tract infection, rhinitis, voice alteration

Cardiovascular

Common (1% to 10%): Tachycardia, hypotension, phlebitis, thrombophlebitis, supraventricular arrhythmia, bradycardia

Uncommon (0.1% to 1%): Atrial arrhythmia, ventricular arrhythmia, ventricular fibrillation, supraventricular tachycardia, ECG QT prolonged, vasodilatation, ventricular extrasystoles, ventricular tachycardia

Rare (less than 0.1%): Torsade de pointes, complete atrioventricular block, bundle branch block, nodal rhythm, nodal arrhythmia

Frequency not reported: Atrial fibrillation, bigeminy, cardiomegaly, cardiomyopathy, cerebral hemorrhage, cerebral ischemia, cerebrovascular accident, congestive heart failure, deep thrombophlebitis, endocarditis, extrasystoles, heart arrest, hypertension, myocardial infarction, postural hypotension, pulmonary embolus, supraventricular extrasystoles, palpitation, abnormalities in ECG

Hematologic

Common (1% to 10%): Thrombocytopenia, anemia (including macrocytic, megaloblastic, microcytic, normocytic, aplastic), leukopenia, pancytopenia, agranulocytosis

Uncommon (0.1% to 1%): Disseminated intravascular coagulation, lymphadenopathy, eosinophilia, lymphangitis, bone marrow failure

Frequency not reported: Hemolytic anemia, bleeding time increased, cyanosis, ecchymosis, hypervolemia, petechiae, enlarged spleen, thrombotic thrombocytopenic purpura

Psychiatric

Common (1% to 10%): Hallucinations, confusion/confusional state, anxiety, depression, agitation, insomnia

Frequency not reported: Abnormal dreams, depersonalization, psychosis, suicidal ideation, musical hallucinations

A 78-year-old man diagnosed with acute myelogenous leukemia experienced musical hallucinations coincident with voriconazole therapy. The musical hallucinations began acutely and almost immediately after starting therapy (300 mg orally twice daily) for prevention of fungal infection. After therapy was discontinued, the music became sporadic after 2 days and by the third day the music had ceased.

Musculoskeletal

Fluorosis and periostitis have been reported with long-term therapy.

Common (1% to 10%): Back pain

Uncommon (0.1% to 1%): Arthritis

Frequency not reported: Arthralgia, increased creatine phosphokinase, bone necrosis, bone pain, leg cramps, myalgia, myasthenia, myopathy, osteomalacia, osteoporosis, periostitis deformans

Postmarketing reports: Fluorosis, periostitis

Genitourinary

Common (1% to 10%): Hematuria

Uncommon (0.1% to 1%): Albuminuria, proteinuria

Frequency not reported: Anuria, blighted ovum, dysmenorrhea, dysuria, epididymitis, glycosuria, hemorrhagic cystitis, impotence, metrorrhagia, oliguria, scrotal edema, urinary incontinence, urinary retention, urinary tract infection, uterine hemorrhage, vaginal hemorrhage

Local

Common (1% to 10%): Injection site reaction/inflammation

Frequency not reported: Injection site pain, injection site infection/inflammation

Hypersensitivity

Common (1% to 10%): Hypersensitivity

Uncommon (0.1% to 1%): Allergic reaction, anaphylactoid reaction, drug hypersensitivity

Rare (less than 0.1%): Anaphylactoid-type reactions (including flushing, fever, sweating, tachycardia, chest tightness, dyspnea, faintness, nausea, pruritus, rash)

During infusion of the IV formulation in healthy subjects, anaphylactoid-type reactions (including flushing, fever, sweating, tachycardia, chest tightness, dyspnea, faintness, nausea, pruritus, rash) have been reported rarely, with symptoms appearing immediately upon starting the infusion.

Endocrine

Uncommon (0.1% to 1%): Adrenal cortex insufficiency, hypothyroidism

Rare (less than 0.1%): Hyperthyroidism

Frequency not reported: Diabetes insipidus

Oncologic

Melanoma and squamous cell carcinoma of the skin have been reported during long-term therapy in patients with photosensitivity skin reactions.

Frequency not reported: Melanoma, squamous cell carcinoma of the skin