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. Continue reading for a comprehensive list of adverse effects.

Applies to voriconazole: oral powder for suspension, oral tablet. Other dosage forms:

• intravenous powder for solution

Serious side effects of Voriconazole

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

• Black, tarry stools
• blistering, peeling, loosening of the skin
• chest pain
• chills
• cough
• diarrhea
• difficulty seeing at night
• fever
• increased sensitivity of the eyes to sunlight
• itching, rash
• joint or muscle pain
• painful or difficult urination
• red irritated eyes
• red skin lesions, often with a purple center
• sore throat
• sores, ulcers, or white spots on the lips or in the mouth
• swollen glands
• trouble breathing
• unusual bleeding or bruising
• unusual tiredness or weakness
• vision changes

Less common

• Bloating or swelling of the face, arms, hands, lower legs, or feet
• blurred vision
• chapped, red, or swollen lips
• chills
• clay-colored stools
• confusion
• dark urine
• decreased urine
• dizziness
• dry mouth
• faintness or lightheadedness when getting up suddenly from a lying or sitting position
• feeling of warmth
• increased thirst
• irregular or pounding heartbeat
• 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
• scaling, redness, burning, pain, or other signs of inflammation of the lips
• seizures
• stomach pain
• slow or fast heartbeat
• sweating
• trembling
• unpleasant breath odor
• 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

• Backache
• blindness
• blue-yellow color blindness
• bone pain
• darkening of the skin
• decreased vision
• diarrhea
• facial hair growth in females
• fainting
• fractures
• full or round face, neck, or trunk
• increased urination
• irritability
• loss of sexual desire or ability
• menstrual irregularities
• mental depression
• muscle wasting
• vomiting

Other side effects of Voriconazole

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

• Headache

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/impairment, 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 therapy included visual disturbances, rash, and elevated liver function tests.^[Ref]

Ocular

Very common (10% or more): Abnormal vision (up to 28.1%), visual disturbances/impairment (including blurred vision, chromatopsia, color vision change, photophobia, chloropsia, color blindness, cyanopsia, eye disorder, halo vision, night blindness, oscillopsia, photopsia, scintillating scotoma, decreased visual acuity, visual brightness, visual field defect, vitreous floaters, xanthopsia)

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

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

Rare (0.01% to 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, optic neuritis, retinitis, uveitis, visual field defect, alterations in color perception, decreases in electroretinogram (ERG) waveform amplitude, decreases in the visual field, transient altered perception of light, blurred vision, wavy lines on television or on going to sleep, visual disturbances (included amaurosis [partial/total blindness without visible change in the eye], asthenopia [eye strain], chromatopsia [abnormally colored vision], color blindness, diplopia, photopsia, retinal disorder, blurred vision, decreased visual acuity, visual brightness, visual impairment)

Postmarketing reports: Prolonged visual adverse events (including optic neuritis, papilledema)^[Ref]

Drug-related visual disturbances were common. In clinical trials, abnormal vision, color vision change, and/or photophobia were reported in about 21% of patients.

In clinical trials, visual impairments (including blurred vision, photophobia, chloropsia, chromatopsia, color blindness, cyanopsia, eye disorder, halo vision, night blindness, oscillopsia, photopsia, scintillating scotoma, visual acuity reduced, visual brightness, visual field defect, vitreous floaters, xanthopsia) were very common with this drug. These visual impairments were transient and fully reversible; most spontaneously resolved within 1 hour with no clinically significant long-term visual effects. Attenuation was observed with repeated doses. The visual impairments were usually mild, rarely resulted in discontinuation of therapy, and were not associated with long-term sequelae.

Visual disturbances/impairments may have been related to higher plasma levels and/or doses.

The mechanism of action of the visual disturbances is unknown; however, the site of action is most likely within the retina. In a study in healthy subjects examining the effect of this drug on retinal function, this drug caused alterations in color perception, decreases in ERG waveform amplitude, and decreases in the visual field; the ERG changes did not progress over 29 days of therapy. At 14 days after the last dose, color perception, ERG, and visual fields returned to baseline.^[Ref]

Other

Very common (10% or more): Elevated alkaline phosphatase (up to 22.6%), decreased potassium (up to 16.7%), fever/pyrexia, peripheral edema

Common (1% to 10%): Chills, asthenia, face edema (included periorbital edema, lip edema, mouth edema), chest pain

Uncommon (0.1% to 1%): Increased blood cholesterol, influenza-like illness

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), mucosal inflammation, hypothermia, lethargy, flushing^[Ref]

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

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

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%): Nephritis, renal tubular necrosis, increased blood urea

Frequency not reported: Increased BUN, decreased CrCl, hydronephrosis, kidney pain, nephrosis, uremia, renal impairment, renal failure^[Ref]

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

Acute renal failure has been reported in severely ill patients treated with this drug.^[Ref]

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%), abnormal liver function test

Common (1% to 10%): Increased hepatic enzymes, cholestatic jaundice, bilirubinemia, jaundice, hepatitis (included drug-induced liver injury, toxic hepatitis, hepatocellular injury, hepatotoxicity)

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

Frequency not reported: Serious hepatic reactions (including clinical hepatitis, cholestasis, fulminant hepatic failure including fatalities), hepatic coma, elevated GGT/LDH, abnormal ALT, hyperbilirubinemia^[Ref]

The overall incidence of transaminase increases greater than 3 x ULN (not necessarily comprising a side effect) during clinical studies was 18% in adult patients and 25.8% in pediatric patients treated with this drug. Increased incidence of abnormal liver function tests may have been related to higher plasma levels and/or doses. Most abnormal liver function tests resolved during therapy without dose adjustment or resolved after dose adjustment (including therapy discontinuation).

Elevated AST (greater than 3 x ULN; up to 20.3%), total bilirubin (greater than 1.5 x ULN; up to 19.4%), and ALT (greater than 3 x ULN; up to 18.9%) have been reported.^[Ref]

Dermatologic

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

Common (1% to 10%): Alopecia, exfoliative dermatitis, maculopapular rash, pruritus, erythema

Uncommon (0.1% to 1%): Stevens-Johnson syndrome, allergic dermatitis, purpura, urticaria, eczema, phototoxicity, photosensitivity reaction, macular rash, papular rash

Rare (0.01% to 0.1%): Toxic epidermal necrolysis, drug reaction with eosinophilia and systemic symptoms (DRESS), erythema multiforme, angioedema, pseudoporphyria, psoriasis, drug eruption

Frequency not reported: Severe cutaneous adverse reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis, DRESS), phototoxicity (including bullous erythema, lentigines, keratosis, pseudoporphyria, photoaging), photocarcinogenesis, contact dermatitis, discoid lupus erythematosus, fixed drug eruption, furunculosis, herpes simplex, melanoma, melanosis, skin discoloration, skin disorder, dry skin, squamous cell carcinoma, sweating, blistering eruptions/bullous lesions, worsening of psoriasis, photosensitivity-related skin reactions (e.g., pseudoporphyria, cheilitis, cutaneous lupus erythematosus), generalized rash, pruritic rash, dermatitis, phototoxic reaction

Postmarketing reports: Cutaneous lupus erythematosus, ephelides, lentigo, DRESS, actinic keratosis^[Ref]

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 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 this drug inhibits a step in the breakdown of all-trans retinoic acid.

A 65-year-old patient experienced pseudoporphyria after minimal sun exposure coincident with use of this drug. After pseudoporphyria was diagnosed and because the drug could not be stopped, the patient was instructed to avoid the sun and use sunscreens with ultraviolet A and B 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 use of this drug. 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 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 the start of this drug 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.^[Ref]

Nervous system

Very common (10% or more): Headache

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

Uncommon (0.1% to 1%): Ataxia, brain edema, vertigo, hypoesthesia, dysgeusia/altered taste perception/taste perversion, encephalopathy (included hypoxic-ischemic encephalopathy, metabolic encephalopathy), extrapyramidal syndrome/disorder (included akathisia, parkinsonism), peripheral neuropathy, hypoacusis, tinnitus

Rare (0.01% to 0.1%): Hepatic encephalopathy, Guillain-Barre syndrome, nystagmus

Frequency not reported: Acute brain syndrome, akathisia, amnesia, coma, deafness, dementia, ear pain, encephalitis, grand mal convulsion, intracranial hypertension, neuralgia, neuropathy, otitis externa, taste loss, somnolence during infusion^[Ref]

Gastrointestinal

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

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

Uncommon (0.1% to 1%): Pancreatitis, peritonitis, duodenitis, gastroenteritis, glossitis, 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, tongue edema, abdominal distention, upper abdominal pain, abdominal tenderness^[Ref]

There have been postmarketing reports of pancreatitis in pediatric patients.^[Ref]

Respiratory

Very common (10% or more): Respiratory distress (included dyspnea, exertional dyspnea)

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

Frequency not reported: Increased cough, dyspnea, epistaxis, influenza syndrome, hemoptysis, hypoxia, pharyngitis, pleural effusion, pneumonia, respiratory disorder, respiratory tract infection, rhinitis, voice alteration, upper respiratory tract infection, bronchospasm, nasal congestion, respiratory failure, tachypnea^[Ref]

Metabolic

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

Uncommon (0.1% to 1%): Hypercholesterolemia, hypomagnesemia

Frequency not reported: Decreased glucose tolerance, hypercalcemia, hypercholesterolemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hyperuricemia, hypocalcemia, hypophosphatemia, anorexia, hyperinsulinemia, hypoalbuminemia, hyperphosphatemia^[Ref]

Cardiovascular

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

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

Rare (0.01% to 0.1%): Torsade de pointes, complete atrioventricular block, bundle branch block, nodal rhythm

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

Hematologic

Common (1% to 10%): Thrombocytopenia (included immune thrombocytopenic purpura), anemia, leukopenia, pancytopenia, agranulocytosis (included febrile neutropenia, neutropenia)

Uncommon (0.1% to 1%): Lymphadenopathy, eosinophilia, lymphangitis, bone marrow failure

Rare (0.01% to 0.1%): Disseminated intravascular coagulation

Frequency not reported: Anemia (macrocytic, megaloblastic, microcytic, normocytic), aplastic anemia, hemolytic anemia, bleeding time increased, cyanosis, ecchymosis, hypervolemia, marrow depression, petechiae, enlarged spleen, thrombotic thrombocytopenic purpura^[Ref]

Psychiatric

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

Frequency not reported: Abnormal dreams, delirium, depersonalization, euphoria, decreased libido, psychosis, suicidal ideation, musical hallucinations, auditory hallucination, visual hallucination, affect lability^[Ref]

A 78-year-old man diagnosed with acute myelogenous leukemia experienced musical hallucinations coincident with use of this drug. 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.^[Ref]

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^[Ref]

Fluorosis and periostitis have been reported with long-term therapy.^[Ref]

Genitourinary

Common (1% to 10%): Hematuria

Uncommon (0.1% to 1%): Proteinuria

Frequency not reported: Albuminuria, 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^[Ref]

Local

Uncommon (0.1% to 1%): Infusion site reaction

Frequency not reported: Injection site pain, injection site infection/inflammation, catheter site pain^[Ref]

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, with symptoms appearing immediately upon starting the infusion.^[Ref]

Uncommon (0.1% to 1%): Hypersensitivity

Rare (0.01% to 0.1%): Anaphylactoid reaction

Frequency not reported: Allergic reaction, anaphylactoid-type reactions (including flushing, fever, sweating, tachycardia, chest tightness, dyspnea, faintness, nausea, pruritus, rash), drug hypersensitivity^[Ref]

Endocrine

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

Rare (0.01% to 0.1%): Hyperthyroidism

Frequency not reported: Diabetes insipidus^[Ref]

Oncologic

Melanoma and squamous cell carcinoma of the skin have been reported during long-term therapy in patients with photosensitivity skin reactions. Squamous cell carcinoma has also been reported during postmarketing experience.^[Ref]

Frequency not reported: Melanoma, squamous cell carcinoma of the skin^[Ref]