Voriconazole Side Effects

It is possible that some side effects of voriconazole may not have been reported. These can be reported to the FDA here. Always consult a healthcare professional for medical advice.

For the Consumer

Applies to voriconazole: oral powder for suspension, oral tablet

As well as its needed effects, voriconazole may cause unwanted side effects that require medical attention.

If any of the following side effects occur while taking voriconazole, check with your doctor immediately:

More common
  • Difficulty seeing at night
  • increased sensitivity of the eyes to sunlight
  • rash
  • vision changes
Less common
  • Abdominal or stomach pain
  • 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
  • fever
  • flushing
  • 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
  • shortness of breath
  • 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 voriconazole side effects may not need any medical attention. As your body gets used to the medicine these side effects may disappear. Your health care professional may be able to help you prevent or reduce these side effects, but do check with them if any of the following side effects continue, or if you are concerned 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 liver function test, peripheral edema, 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

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.

Very common (10% or more): Abnormal vision (up to 28.1%), visual disturbances (including altered/enhanced visual perception, blurred vision, chromatopsia, color vision change, photophobia)
Common (1% to 10%): Photophobia, chromatopsia
Uncommon (0.1% to 1%): Papilledema, optic nerve disorder, optic neuritis, scleritis, blepharitis, diplopia
Rare (less than 0.1%): Optic atrophy, retinal hemorrhage, oculogyric crisis/oculogyration, 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)

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
Uncommon (0.1% to 1%): Increased blood cholesterol, hypercholesterolemia, hyponatremia, hypomagnesemia
Frequency not reported: Decreased glucose tolerance, hypercalcemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hyperuricemia, hypocalcemia, hypophosphatemia, anorexia, hyperinsulinemia

Renal

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
Rare (less than 0.1%): Renal tubular necrosis
Frequency not reported: Decreased CrCl, hydronephrosis, kidney pain, nephrosis, uremia

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.

Hepatic

Very common (10% or more): Elevated AST (up to 20.3%), elevated total bilirubin (up to 19.4%), elevated ALT (up to 18.9%)
Common (1% to 10%): Abnormal liver function tests, increased hepatic enzymes, cholestatic jaundice, bilirubinemia, elevated GGT, elevated LDH, jaundice
Uncommon (0.1% to 1%): Hepatic failure, hepatitis, hepatomegaly/enlarged liver, cholecystitis, cholelithiasis
Rare (less than 0.1%): Serious hepatic reactions (including clinical hepatitis, cholestasis, fulminant hepatic failure including fatalities), hepatic coma

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 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.

Dermatologic

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.

Very common (10% or more): Rash (up to 19%)
Common (1% to 10%): Alopecia, exfoliative dermatitis, phototoxic reaction, maculopapular rash, macular rash, papular rash, photosensitivity skin reaction, pruritus, erythema, purpura
Uncommon (0.1% to 1%): Fixed drug eruption, Stevens-Johnson syndrome, angioedema/angioneurotic edema, allergic dermatitis, urticaria, psoriasis, eczema
Rare (less than 0.1%): Toxic epidermal necrolysis, erythema multiforme, 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

Nervous system

Very common (10% or more): Headache
Common (1% to 10%): Dizziness, paresthesia, tremor
Uncommon (0.1% to 1%): Ataxia, brain edema, vertigo, hypertonia, hypoesthesia, nystagmus, syncope, dysgeusia/altered taste perception/taste perversion
Rare (less than 0.1%): Convulsion, encephalopathy, Guillain-Barre syndrome, extrapyramidal syndrome, somnolence during infusion, peripheral neuropathy, hypoacusis, tinnitus
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

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

Very common (10% or more): Fever/pyrexia, peripheral edema
Common (1% to 10%): Chills (up to 3.7%), influenza-like illness, asthenia, face edema, flu syndrome
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)

Gastrointestinal

Very common (10% or more): Abdominal pain, nausea, vomiting, diarrhea
Common (1% to 10%): Cheilitis, gastroenteritis, dry mouth
Uncommon (0.1% to 1%): Pancreatitis, peritonitis, duodenitis, gingivitis, glossitis, tongue edema, swollen tongue, dyspepsia, constipation
Rare (less than 0.1%): 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

Cardiovascular

Common (1% to 10%): Tachycardia, hypotension, phlebitis, thrombophlebitis
Uncommon (0.1% to 1%): Atrial arrhythmia, ventricular arrhythmia, ventricular fibrillation, supraventricular arrhythmia, supraventricular tachycardia, bradycardia, ECG QT prolonged, vasodilatation
Rare (less than 0.1%): Ventricular tachycardia, 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, bone marrow depression
Uncommon (0.1% to 1%): Disseminated intravascular coagulation, agranulocytosis, lymphadenopathy, eosinophilia
Rare (less than 0.1%): Lymphangitis
Frequency not reported: Hemolytic anemia, bleeding time increased, cyanosis, ecchymosis, hypervolemia, petechiae, enlarged spleen, thrombotic thrombocytopenic purpura

Respiratory

Common (1% to 10%): Acute respiratory distress syndrome, pulmonary edema, respiratory distress, chest pain, sinusitis
Frequency not reported: Increased cough, dyspnea, epistaxis, hemoptysis, hypoxia, pharyngitis, pleural effusion, pneumonia, respiratory disorder, respiratory tract infection, rhinitis, 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 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.

Common (1% to 10%): Hallucinations, confusion/confusional state, anxiety, depression, agitation
Rare (less than 0.1%): Insomnia
Frequency not reported: Abnormal dreams, depersonalization, psychosis, suicidal ideation, musical hallucinations

Musculoskeletal

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

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

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

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.

Uncommon (0.1% to 1%): Allergic reaction, anaphylactoid reaction, hypersensitivity, drug hypersensitivity
Rare (less than 0.1%): Anaphylactoid-type reactions (including flushing, fever, sweating, tachycardia, chest tightness, dyspnea, faintness, nausea, pruritus, rash)

Endocrine

Uncommon (0.1% to 1%): Adrenal cortex insufficiency
Rare (less than 0.1%): Hyperthyroidism, hypothyroidism
Frequency not reported: Diabetes insipidus

Oncologic

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

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

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