Voriconazole Side Effects

Some side effects of voriconazole may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

For the Consumer

Applies to voriconazole: oral powder for reconstitution, oral tablet

Get emergency medical help if you have any of these signs of an allergic reaction while taking voriconazole: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have any of these serious side effects:

• sudden behavior changes, problems with thinking or speech;

• upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes);

• urinating less than usual or not at all;

• bone pain, swelling;

• uneven heart rate, chest pain, general ill feeling; or

• severe skin reaction -- fever, sore throat, swelling in your face or tongue, burning in your eyes, skin pain, followed by a red or purple skin rash that spreads (especially in the face or upper body) and causes blistering and peeling.

Less serious side effects of voriconazole may include:

• vision problems such as blurred vision, eyes being more sensitive to light;

• fever;

• mild nausea, vomiting, or diarrhea;

• headache; or

• swelling in your hands, ankles, or feet.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects.

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, nausea, rash, vomiting, chills, headache, increased liver function test, tachycardia, and hallucinations. Side effects that most frequently led to the discontinuation of voriconazole treatment included visual disturbances, rash, and elevated liver function tests.

Hepatic

The overall incidence of clinically significant transaminase abnormalities during clinical studies was 12.4% of patients treated with voriconazole. Increased incidence of abnormal liver function tests may be related to higher plasma concentrations and/or doses.

Very common (10% or more): Elevated alkaline phosphatase (greater than 3 times ULN; up to 22.6%), elevated AST (greater than 3 times ULN; up to 20.3%), elevated total bilirubin (greater than 1.5 times ULN; up to 19.4%), elevated ALT (greater than 3 times ULN; up to 18.9%)
Common (1% to 10%): Increased alkaline phosphatase (up to 5%), increased SGOT (up to 4%), abnormal liver function tests (up to 3.2%), increased SGPT (up to 3%), increased hepatic enzyme (up to 2.4%), cholestatic jaundice (up to 1.7%), bilirubinemia (up to 1.1%); Less than 2%: Increased GGT/LDH, hepatic failure, hepatitis, jaundice, enlarged liver, hepatic coma
Rare (less than 0.1%): Serious hepatic reactions (including clinical hepatitis, cholestasis, and fulminant hepatic failure, including fatalities)

Ocular

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, color vision change, and/or photophobia in about 21% of patients. Visual disturbances may be related to higher plasma voriconazole concentrations and/or doses. The mechanism responsible for producing this side effect 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 medication, each indicator of visual function had returned to baseline.

Very common (10% or more): Abnormal vision (up to 18.7%)
Common (1% to 10%): Photophobia (up to 2.5%), chromatopsia (up to 1.2%); Less than 2%: Eye hemorrhage, abnormality of accommodation, blepharitis, color blindness, conjunctivitis, corneal opacity, eye pain, dry eyes, keratitis, keratoconjunctivitis, mydriasis, night blindness, optic atrophy, optic neuritis, papilledema, retinal hemorrhage, retinitis, scleritis, uveitis, visual field defect
Frequency not reported: 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)

Dermatologic

The majority of rashes were of mild to moderate severity.

A photosensitivity reaction manifested as facial edema and cheilitis is reported in a group of ambulatory patients (n=5) receiving voriconazole 200 mg twice daily for chronic invasive aspergillus 4 weeks from the start of therapy. Symptoms resolved shortly after stopping the drug treatment. Plasma and serum concentrations 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. It is recommended that patients avoid strong, direct sunlight during voriconazole treatment.

A 65-year-old patient experienced pseudoporphyria after minimal sun exposure coincident with voriconazole therapy. Following the diagnosis of pseudoporphyria 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 treatment, 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 treatment. 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, voriconazole therapy was discontinued. The blistering resolved within 2 weeks with no further episodes.

Common (1% to 10%): Rashes (up to 7%); Less than 2%: Alopecia, angioedema, contact dermatitis, discoid lupus erythematosus, eczema, erythema multiforme, exfoliative dermatitis, fixed drug eruption, furunculosis, herpes simplex, maculopapular rash, melanoma, melanosis, photosensitivity skin reaction, pruritus, pseudoporphyria, psoriasis, skin discoloration, skin disorder, dry skin, Stevens-Johnson syndrome, squamous cell carcinoma, sweating, toxic epidermal necrolysis, urticaria
Rare (less than 0.1%): Blistering eruptions/bullous lesions (at least 2 cases), worsening of psoriasis (at least 1 case)
Frequency not reported: Serious exfoliative cutaneous reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme), phototoxicity (including bullous erythema, erythema, lentigines, keratosis, pseudoporphyria, photoaging), photocarcinogenesis

Gastrointestinal

Common (1% to 10%): Nausea (up to 5.4%), vomiting (up to 4.4%); Less than 2%: Diarrhea, dry mouth, anorexia, cheilitis, cholecystitis, cholelithiasis, constipation, duodenal ulcer perforation, duodenitis, dyspepsia, dysphagia, esophageal ulcer, esophagitis, flatulence, gastroenteritis, gastrointestinal hemorrhage, gingivitis, glossitis, gum hemorrhage, gum hyperplasia, hematemesis, intestinal perforation, intestinal ulcer, melena, mouth ulceration, pancreatitis, parotid gland enlargement, periodontitis, proctitis, pseudomembranous colitis, rectal disorder, rectal hemorrhage, stomach ulcer, stomatitis, tongue edema

Metabolic

Very common (10% or more): Decreased potassium (less than 0.9 times LLN; up to 16.7%)
Common (1% to 10%): Hypokalemia (up to 1.6%); Less than 2%: Increased creatine phosphokinase, decreased glucose tolerance, hypercalcemia, hypercholesterolemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hyperuricemia, hypocalcemia, hypoglycemia, hypomagnesemia, hyponatremia, hypophosphatemia
Frequency not reported: Hyperinsulinemia

Renal

Very common (10% or more): Increased creatinine (greater than 1.3 times ULN; up to 21.4%)
Common (1% to 10%): Abnormal kidney function (up to 1.3%); Less than 2%: Increased blood urea nitrogen, decreased creatinine clearance, hydronephrosis, kidney pain, nephritis, nephrosis, kidney tubular necrosis, uremia
Uncommon (0.1% to 1%): Increased creatinine (up to 0.5%), acute kidney failure (up to 0.4%)
Frequency not reported: Acute renal failure

Acute renal failure has been reported in severely ill patients.

Other

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

Common (1% to 10%): Fever (up to 5.7%), chills (up to 3.7%); Less than 2%: Abdominal pain, chest pain, enlarged abdomen, ascites, asthenia, back pain, cellulitis, edema, face edema, flank pain, flu syndrome, graft versus host reaction, granuloma, infection, bacterial infection, fungal infection, mucous membrane disorder, multi-organ failure, pain, pelvic pain, peripheral edema, peritonitis, sepsis, substernal chest pain
Frequency not reported: Infusion related side effects (including immediate anaphylactoid-type reactions)

Nervous system

Common (1% to 10%): Headache (up to 3%), hallucinations (up to 2.8%); Less than 2%: Dizziness, acute brain syndrome, agitation, akathisia, amnesia, ataxia, brain edema, coma, confusion, convulsion, decreased libido, deafness, delirium, dementia, diplopia, ear pain, encephalitis, encephalopathy, euphoria, extrapyramidal syndrome, grand mal convulsion, Guillain-Barre syndrome, hypoacusis, hypertonia, hypesthesia, insomnia, intracranial hypertension, neuralgia, neuropathy, nystagmus, oculogyric crisis, otitis externa, paresthesia, somnolence, taste loss, taste perversion, tinnitus, tremor, vertigo

Cardiovascular

Common (1% to 10%): Tachycardia (up to 2.4%); Less than 2%: Atrial arrhythmia, atrial fibrillation, complete AV block, bigeminy, bradycardia, bundle branch block, cardiomegaly, cardiomyopathy, cerebral hemorrhage, cerebral ischemia, cerebrovascular accident, congestive heart failure, deep thrombophlebitis, endocarditis, extrasystoles, heart arrest, hypertension, hypotension, myocardial infarction, nodal arrhythmia, palpitation, phlebitis, postural hypotension, pulmonary embolus, QT interval prolongation, supraventricular extrasystoles, supraventricular tachycardia, syncope, thrombophlebitis, vasodilatation, ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia (including torsade de pointes)
Frequency not reported: Abnormalities in ECG

Hypersensitivity

Common (1% to 10%): Less than 2%: Allergic reaction, anaphylactoid reaction
Rare (less than 0.1%): Anaphylactoid-type reactions (including flushing, fever, sweating, tachycardia, chest tightness, dyspnea, faintness, nausea, pruritus, and rash)

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

Hematologic

Common (1% to 10%): Less than 2%: Thrombocytopenia, anemia (macrocytic, megaloblastic, microcytic, normocytic), leukopenia, pancytopenia, agranulocytosis, aplastic anemia, hemolytic anemia, bleeding time increased, cyanosis, disseminated intravascular coagulation, ecchymosis, eosinophilia, hypervolemia, lymphadenopathy, lymphangitis, marrow depression, petechiae, purpura, enlarged spleen, thrombotic thrombocytopenic purpura

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

Genitourinary

Common (1% to 10%): Less than 2%: Albuminuria, anuria, blighted ovum, dysmenorrhea, dysuria, epididymitis, glycosuria, hemorrhagic cystitis, hematuria, impotence, metrorrhagia, oliguria, scrotal edema, urinary incontinence, urinary retention, urinary tract infection, uterine hemorrhage, vaginal hemorrhage

Musculoskeletal

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

Common (1% to 10%): Less than 2%: Arthralgia, arthritis, bone necrosis, bone pain, leg cramps, myalgia, myasthenia, myopathy, osteomalacia, osteoporosis
Rare (less than 0.1%): Periostitis deformans (at least 1 case)
Postmarketing reports: Fluorosis, periostitis

Endocrine

Common (1% to 10%): Less than 2%: Adrenal cortex insufficiency, diabetes insipidus, hyperthyroidism, hypothyroidism

Respiratory

Common (1% to 10%): Less than 2%: Increased cough, dyspnea, epistaxis, hemoptysis, hypoxia, lung edema, pharyngitis, pleural effusion, pneumonia, respiratory disorder, respiratory distress syndrome, respiratory tract infection, rhinitis, sinusitis, voice alteration

Psychiatric

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 following the initiation of voriconazole therapy (300 mg orally twice daily) for prevention of fungal infection. Following discontinuation of voriconazole, the music had become sporadic after 2 days and by the third day the music had ceased.

Common (1% to 10%): Less than 2%: Abnormal dreams, anxiety, depersonalization, depression, psychosis, suicidal ideation
Rare (less than 0.1%): Musical hallucinations (at least 1 case)

Local

Common (1% to 10%): Less than 2%: Injection site pain, injection site infection/inflammation

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date, and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This information does not endorse drugs, diagnose patients, or recommend therapy. This drug information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug of drug combination is safe, effective, or appropriate for any given patient. Drugs.com does not assume any responsibility for any aspect of healthcare administered with the aid of information provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse, or pharmacist.