VFEND Side Effects

Generic Name: voriconazole

Please note - some side effects for VFEND may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Side Effects of VFEND - for the Consumer

Vfend

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Vfend:

Blurred vision; headache; nausea; sensitivity to light; sensitivity to the sun; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur when using Vfend:

Severe allergic reactions (rash; hives; itching; difficulty breathing or swallowing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); abnormal thoughts; black, tarry stools; bone pain; calf or leg pain, redness, swelling, or tenderness; change in the appearance of a mole; chest, jaw, or arm pain; confusion; decreased urination; fainting; fast, slow, or irregular heartbeat; fever, chills, or persistent sore throat; flushing; hallucinations; mental or mood changes (eg, depression); mouth sores; one-sided weakness; red, swollen, peeling, or blistered skin; seizures; severe or persistent dizziness or headache; shortness of breath; speech changes; sudden, severe nausea or vomiting; suicidal thoughts or actions; swelling of the arms or legs; symptoms of liver problems (eg, yellowing of the skin or eyes; dark urine; pale stools; severe or persistent nausea, vomiting, or stomach pain; loss of appetite; itching); symptoms of pancreatitis (eg, severe stomach or back pain, with or without nausea or vomiting); unusual bruising or bleeding; unusual skin change or skin growth; unusual sweating or weakness; unusual tiredness; unusual vaginal bleeding; vision changes (eg, color vision change, persistent or severe blurred vision or sensitivity to light).

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

Vfend Suspension

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Vfend Suspension:

Blurred vision; headache; nausea; sensitivity to light; sensitivity to the sun; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur when using Vfend Suspension:

Severe allergic reactions (rash; hives; itching; difficulty breathing or swallowing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); abnormal thoughts; black, tarry stools; bone pain; calf or leg pain, redness, swelling, or tenderness; change in the appearance of a mole; chest, jaw, or arm pain; confusion; decreased urination; fainting; fast, slow, or irregular heartbeat; fever, chills, or persistent sore throat; flushing; hallucinations; mental or mood changes (eg, depression); mouth sores; one-sided weakness; red, swollen, peeling, or blistered skin; seizures; severe or persistent dizziness or headache; shortness of breath; speech changes; sudden, severe nausea or vomiting; suicidal thoughts or actions; swelling of the arms or legs; symptoms of liver problems (eg, yellowing of the skin or eyes; dark urine; pale stools; severe or persistent nausea, vomiting, or stomach pain; loss of appetite; itching); symptoms of pancreatitis (eg, severe stomach or back pain, with or without nausea or vomiting); unusual bruising or bleeding; unusual skin change or skin growth; unusual sweating or weakness; unusual tiredness; unusual vaginal bleeding; vision changes (eg, color vision change, persistent or severe blurred vision or sensitivity to light).

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

Vfend Tablets

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Vfend Tablets:

Blurred vision; headache; nausea; sensitivity to light; sensitivity to the sun; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur when using Vfend Tablets:

Severe allergic reactions (rash; hives; itching; difficulty breathing or swallowing; tightness in the chest; swelling of the mouth, face, lips, or tongue; unusual hoarseness); abnormal thoughts; black, tarry stools; bone pain; calf or leg pain, redness, swelling, or tenderness; change in the appearance of a mole; chest, jaw, or arm pain; confusion; decreased urination; fainting; fast, slow, or irregular heartbeat; fever, chills, or persistent sore throat; flushing; hallucinations; mental or mood changes (eg, depression); mouth sores; one-sided weakness; red, swollen, peeling, or blistered skin; seizures; severe or persistent dizziness or headache; shortness of breath; speech changes; sudden, severe nausea or vomiting; suicidal thoughts or actions; swelling of the arms or legs; symptoms of liver problems (eg, yellowing of the skin or eyes; dark urine; pale stools; severe or persistent nausea, vomiting, or stomach pain; loss of appetite; itching); symptoms of pancreatitis (eg, severe stomach or back pain, with or without nausea or vomiting); unusual bruising or bleeding; unusual skin change or skin growth; unusual sweating or weakness; unusual tiredness; unusual vaginal bleeding; vision changes (eg, color vision change, persistent or severe blurred vision or sensitivity to light).

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

Top

VFEND Side Effects - for the Professional

Vfend

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.

Overview

The most frequently reported adverse events (all causalities) in the 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 treatment-related adverse events which most often led to discontinuation of voriconazole therapy were elevated liver function tests, rash, and visual disturbances [see Warning and Precautions (5.2, 5.3), and Adverse Reactions (6.2, 6.3)].

Clinical Trial Experience in Adults

The data described in Table 3 reflect exposure to voriconazole in 1655 patients in the therapeutic studies. This represents a heterogeneous population, including immunocompromised patients, e.g., patients with hematological malignancy or HIV and non-neutropenic patients. This subgroup does not include healthy subjects and patients treated in the compassionate use and non-therapeutic studies. This patient population was 62% male, had a mean age of 46 years (range 11–90, including 51 patients aged 12–18 years), and was 78% White and 10% Black. Five hundred sixty one patients had a duration of voriconazole therapy of greater than 12 weeks, with 136 patients receiving voriconazole for over six months. Table 3 includes all adverse events which were reported at an incidence of ≥2% during voriconazole therapy in the all therapeutic studies population, studies 307/602 and 608 combined, or study 305, as well as events of concern which occurred at an incidence of <2%.

In study 307/602, 381 patients (196 on voriconazole, 185 on amphotericin B) were treated to compare voriconazole to amphotericin B followed by other licensed antifungal therapy in the primary treatment of patients with acute invasive aspergillosis. The rate of discontinuation from voriconazole study medication due to adverse events was 21.4% (42/196 patients). In study 608, 403 patients with candidemia were treated to compare voriconazole (272 patients) to the regimen of amphotericin B followed by fluconazole (131 patients). The rate of discontinuation from voriconazole study medication due to adverse events was 19.5% out of 272 patients. Study 305 evaluated the effects of oral voriconazole (200 patients) and oral fluconazole (191 patients) in the treatment of esophageal candidiasis. The rate of discontinuation from voriconazole study medication in Study 305 due to adverse events was 7% (14/200 patients). Laboratory test abnormalities for these studies are discussed under Clinical Laboratory Values below.

Table 3: Treatment Emergent Adverse Events Rate ≥ 2% on Voriconazole or Adverse Events of Concern in All Therapeutic Studies Population, Studies 307/602-608 Combined, or Study 305. Possibly Related to Therapy or Causality Unknown*

	All Therapeutic Studies	Studies 307/602 and 608 (IV/ oral therapy)			Study 305 (oral therapy)
	Voriconazole N=1655	Voriconazole N=468	Ampho B† N=185	Ampho B→ Fluconazole N=131	Voriconazole N=200	Fluconazole N=191
	N (%)	N (%)	N (%)	N (%)	N (%)	N (%)
* Study 307/602: invasive aspergillosis; Study 608: candidemia; Study 305: esophageal candidiasis † Amphotericin B followed by other licensed antifungal therapy ‡ See Warnings and Precautions (5.3)
Special Senses‡
Abnormal vision	310 (18.7)	63 (13.5)	1 (0.5)	0	31 (15.5)	8 (4.2)
Photophobia	37 (2.2)	8 (1.7)	0	0	5 (2.5)	2 (1.0)
Chromatopsia	20 (1.2)	2 (0.4)	0	0	2 (1.0)	0
Body as a Whole
Fever	94 (5.7)	8 (1.7)	25 (13.5)	5 (3.8)	0	0
Chills	61 (3.7)	1 (0.2)	36 (19.5)	8 (6.1)	1 (0.5)	0
Headache	49 (3.0)	9 (1.9)	8 (4.3)	1 (0.8)	0	1 (0.5)
Cardiovascular System
Tachycardia	39 (2.4)	6 (1.3)	5 (2.7)	0	0	0
Digestive System
Nausea	89 (5.4)	18 (3.8)	29 (15.7)	2 (1.5)	2 (1.0)	3 (1.6)
Vomiting	72 (4.4)	15 (3.2)	18 (9.7)	1 (0.8)	2 (1.0)	1 (0.5)
Liver function tests abnormal	45 (2.7)	15 (3.2)	4 (2.2)	1 (0.8)	6 (3.0)	2 (1.0)
Cholestatic jaundice	17 (1.0)	8 (1.7)	0	1 (0.8)	3 (1.5)	0
Metabolic and Nutritional Systems
Alkaline phosphatase increased	59 (3.6)	19 (4.1)	4 (2.2)	3 (2.3)	10 (5.0)	3 (1.6)
Hepatic enzymes increased	30 (1.8)	11 (2.4)	5 (2.7)	1 (0.8)	3 (1.5)	0
SGOT increased	31 (1.9)	9 (1.9)	0	1 (0.8)	8 (4.0)	2 (1.0)
SGPT increased	29 (1.8)	9 (1.9)	1 (0.5)	2 (1.5)	6 (3.0)	2 (1.0)
Hypokalemia	26 (1.6)	3 (0.6)	36 (19.5)	16 (12.2)	0	0
Bilirubinemia	15 (0.9)	5 (1.1)	3 (1.6)	2 (1.5)	1 (0.5)	0
Creatinine increased	4 (0.2)	0	59 (31.9)	10 (7.6)	1 (0.5)	0
Nervous System
Hallucinations	39 (2.4)	13 (2.8)	1 (0.5)	0	0	0
Skin and Appendages
Rash	88 (5.3)	20 (4.3)	7 (3.8)	1 (0.8)	3 (1.5)	1 (0.5)
Urogenital
Kidney function abnormal	10 (0.6)	6 (1.3)	40 (21.6)	9 (6.9)	1 (0.5)	1 (0.5)
Acute kidney failure	7 (0.4)	2 (0.4)	11 (5.9)	7 (5.3)	0	0

Visual Disturbances

Voriconazole treatment-related visual disturbances are common. In therapeutic trials, approximately 21% of patients experienced abnormal vision, color vision change and/or photophobia. Visual disturbances may be associated with higher plasma concentrations and/or doses.

There have been post-marketing reports of prolonged visual adverse events, including optic neuritis and papilledema [see Warnings and Precautions (5.3)].

The mechanism of action of the visual disturbance is unknown, although the site of action is most likely to be within the retina. In a study in healthy subjects investigating the effect of 28-day treatment with voriconazole on retinal function, voriconazole caused a decrease in the electroretinogram (ERG) waveform amplitude, a decrease in the visual field, and an alteration in color perception. The ERG measures electrical currents in the retina. The effects were noted early in administration of voriconazole and continued through the course of study drug dosing. Fourteen days after end of dosing, ERG, visual fields and color perception returned to normal [see Warnings and Precautions (5.7)].

Dermatological Reactions

Dermatological reactions were common in the patients treated with voriconazole. The mechanism underlying these dermatologic adverse events remains unknown.

Serious cutaneous reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis and erythema multiforme have been reported during treatment with Vfend. If a patient develops an exfoliative cutaneous reaction, Vfend should be discontinued.

In addition, Vfend has been associated with photosensitivity skin reactions. Patients should avoid strong, direct sunlight during Vfend therapy. In patients with photosensitivity skin reactions, squamous cell carcinoma of the skin and melanoma have been reported during long-term therapy. If a patient develops a skin lesion consistent with squamous cell carcinoma or melanoma, Vfend should be discontinued [see Warnings and Precautions (5.13)].

Less Common Adverse Events

The following adverse events occurred in <2% of all voriconazole-treated patients in all therapeutic studies (N=1655). This listing includes events where a causal relationship to voriconazole cannot be ruled out or those which may help the physician in managing the risks to the patients. The list does not include events included in Table 5 above and does not include every event reported in the voriconazole clinical program.

Body as a Whole: abdominal pain, abdomen enlarged, allergic reaction, anaphylactoid reaction [see Warnings and Precautions (5.6)], ascites, asthenia, back pain, chest pain, cellulitis, edema, face edema, flank pain, flu syndrome, graft versus host reaction, granuloma, infection, bacterial infection, fungal infection, injection site pain, injection site infection/inflammation, mucous membrane disorder, multi-organ failure, pain, pelvic pain, peritonitis, sepsis, substernal chest pain.

Cardiovascular: atrial arrhythmia, atrial fibrillation, AV block complete, 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 prolonged, supraventricular extrasystoles, supraventricular tachycardia, syncope, thrombophlebitis, vasodilatation, ventricular arrhythmia, ventricular fibrillation, ventricular tachycardia (including torsade de pointes) [see Warnings and Precautions (5.6)].

Digestive: anorexia, cheilitis, cholecystitis, cholelithiasis, constipation, diarrhea, duodenal ulcer perforation, duodenitis, dyspepsia, dysphagia, dry mouth, esophageal ulcer, esophagitis, flatulence, gastroenteritis, gastrointestinal hemorrhage, GGT/LDH elevated, gingivitis, glossitis, gum hemorrhage, gum hyperplasia, hematemesis, hepatic coma, hepatic failure, hepatitis, intestinal perforation, intestinal ulcer, jaundice, enlarged liver, melena, mouth ulceration, pancreatitis, parotid gland enlargement, periodontitis, proctitis, pseudomembranous colitis, rectal disorder, rectal hemorrhage, stomach ulcer, stomatitis, tongue edema.

Endocrine: adrenal cortex insufficiency, diabetes insipidus, hyperthyroidism, hypothyroidism.

Hemic and Lymphatic: agranulocytosis, anemia (macrocytic, megaloblastic, microcytic, normocytic), aplastic anemia, hemolytic anemia, bleeding time increased, cyanosis, DIC, ecchymosis, eosinophilia, hypervolemia, leukopenia, lymphadenopathy, lymphangitis, marrow depression, pancytopenia, petechia, purpura, enlarged spleen, thrombocytopenia, thrombotic thrombocytopenic purpura.

Metabolic and Nutritional: albuminuria, BUN increased, creatine phosphokinase increased, edema, glucose tolerance decreased, hypercalcemia, hypercholesteremia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hyperuricemia, hypocalcemia, hypoglycemia, hypomagnesemia, hyponatremia, hypophosphatemia, peripheral edema, uremia.

Musculoskeletal: arthralgia, arthritis, bone necrosis, bone pain, leg cramps, myalgia, myasthenia, myopathy, osteomalacia, osteoporosis.

Nervous System: abnormal dreams, acute brain syndrome, agitation, akathisia, amnesia, anxiety, ataxia, brain edema, coma, confusion, convulsion, delirium, dementia, depersonalization, depression, diplopia, dizziness, encephalitis, encephalopathy, euphoria, Extrapyramidal Syndrome, grand mal convulsion, Guillain-Barré syndrome, hypertonia, hypesthesia, insomnia, intracranial hypertension, libido decreased, neuralgia, neuropathy, nystagmus, oculogyric crisis, paresthesia, psychosis, somnolence, suicidal ideation, tremor, vertigo.

Respiratory System: cough increased, dyspnea, epistaxis, hemoptysis, hypoxia, lung edema, pharyngitis, pleural effusion, pneumonia, respiratory disorder, respiratory distress syndrome, respiratory tract infection, rhinitis, sinusitis, voice alteration.

Skin and Appendages: alopecia, angioedema, contact dermatitis, discoid lupus erythematosis, 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, skin dry, Stevens-Johnson syndrome, squamous cell carcinoma, sweating, toxic epidermal necrolysis, urticaria.

Special Senses: abnormality of accommodation, blepharitis, color blindness, conjunctivitis, corneal opacity, deafness, ear pain, eye pain, eye hemorrhage, dry eyes, hypoacusis, keratitis, keratoconjunctivitis, mydriasis, night blindness, optic atrophy, optic neuritis, otitis externa, papilledema, retinal hemorrhage, retinitis, scleritis, taste loss, taste perversion, tinnitus, uveitis, visual field defect.

Urogenital: anuria, blighted ovum, creatinine clearance decreased, dysmenorrhea, dysuria, epididymitis, glycosuria, hemorrhagic cystitis, hematuria, hydronephrosis, impotence, kidney pain, kidney tubular necrosis, metrorrhagia, nephritis, nephrosis, oliguria, scrotal edema, urinary incontinence, urinary retention, urinary tract infection, uterine hemorrhage, vaginal hemorrhage.

Clinical Laboratory Values

The overall incidence of clinically significant transaminase abnormalities in all therapeutic studies was 12.4% (206/1655) of patients treated with voriconazole. Increased incidence of liver function test abnormalities may be associated with higher plasma concentrations and/or doses. The majority of abnormal liver function tests either resolved during treatment without dose adjustment or following dose adjustment, including discontinuation of therapy.

Voriconazole has been infrequently associated with cases of serious hepatic toxicity including cases of jaundice and rare cases of hepatitis and hepatic failure leading to death. Most of these patients had other serious underlying conditions.

Liver function tests should be evaluated at the start of and during the course of Vfend therapy. Patients who develop abnormal liver function tests during Vfend therapy should be monitored for the development of more severe hepatic injury. Patient management should include laboratory evaluation of hepatic function (particularly liver function tests and bilirubin). Discontinuation of Vfend must be considered if clinical signs and symptoms consistent with liver disease develop that may be attributable to Vfend [see Warnings and Precautions (5.2)].

Acute renal failure has been observed in severely ill patients undergoing treatment with Vfend. Patients being treated with voriconazole are likely to be treated concomitantly with nephrotoxic medications and have concurrent conditions that may result in decreased renal function. It is recommended that patients are monitored for the development of abnormal renal function. This should include laboratory evaluation, particularly serum creatinine.

Tables 4 to 6 show the number of patients with hypokalemia and clinically significant changes in renal and liver function tests in three randomized, comparative multicenter studies. In study 305, patients with esophageal candidiasis were randomized to either oral voriconazole or oral fluconazole. In study 307/602, patients with definite or probable invasive aspergillosis were randomized to either voriconazole or amphotericin B therapy. In study 608, patients with candidemia were randomized to either voriconazole or the regimen of amphotericin B followed by fluconazole.

Table 4: Protocol 305 – Patients with Esophageal Candidiasis Clinically Significant Laboratory Test Abnormalities

	Criteria*	Voriconazole	Fluconazole
		n/N (%)	n /N (%)
n = number of patients with a clinically significant abnormality while on study therapy
N = total number of patients with at least one observation of the given lab test while on study therapy
ULN = upper limit of normal
* Without regard to baseline value
T. Bilirubin	>1.5× ULN	8/185 (4.3)	7/186 (3.8)
AST	>3.0× ULN	38/187 (20.3)	15/186 (8.1)
ALT	>3.0× ULN	20/187 (10.7)	12/186 (6.5)
Alk phos	>3.0× ULN	19/187 (10.2)	14/186 (7.5)

Table 5: Protocol 307/602 – Primary Treatment of Invasive Aspergillosis Clinically Significant Laboratory Test Abnormalities

	Criteria*	Voriconazole	Amphotericin B†
		n/N (%)	n/N (%)
n = number of patients with a clinically significant abnormality while on study therapy
N = total number of patients with at least one observation of the given lab test while on study therapy
ULN = upper limit of normal
LLN = lower limit of normal
* Without regard to baseline value † Amphotericin B followed by other licensed antifungal therapy
T. Bilirubin	>1.5× ULN	35/180 (19.4)	46/173 (26.6)
AST	>3.0× ULN	21/180 (11.7)	18/174 (10.3)
ALT	>3.0× ULN	34/180 (18.9)	40/173 (23.1)
Alk phos	>3.0× ULN	29/181 (16.0)	38/173 (22.0)
Creatinine	>1.3× ULN	39/182 (21.4)	102/177 (57.6)
Potassium	<0.9× LLN	30/181 (16.6)	70/178 (39.3)

Table 6: Protocol 608 – Treatment of Candidemia Clinically Significant Laboratory Test Abnormalities

	Criteria*	Voriconazole	Amphotericin B followed by Fluconazole
		n/N (%)	n/N (%)
n = number of patients with a clinically significant abnormality while on study therapy
N = total number of patients with at least one observation of the given lab test while on study therapy
ULN = upper limit of normal
LLN = lower limit of normal
* Without regard to baseline value
T. Bilirubin	>1.5× ULN	50/261 (19.2)	31/115 (27.0)
AST	>3.0× ULN	40/261 (15.3)	16/116 (13.8)
ALT	>3.0× ULN	22/261 (8.4)	15/116 (12.9)
Alk phos	>3.0× ULN	59/261 (22.6)	26/115 (22.6)
Creatinine	>1.3× ULN	39/260 (15.0)	32/118 (27.1)
Potassium	<0.9× LLN	43/258 (16.7)	35/118 (29.7)

Postmarketing Experience

The following adverse reactions have been identified during post approval use of voriconazole. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Skeletal: fluorosis and periostitis have been reported during long-term voriconazole therapy [see Warnings and Precautions (5.14)].

Top

Side Effects by Body System - for Healthcare Professionals

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

Hepatic side effects have included abnormal liver function tests (up to 3.2%), increased alkaline phosphatase (up to 5%), increased hepatic enzyme (up to 2.4%), increased SGOT (up to 4%), increased SGPT (up to 3%), cholestatic jaundice (up to 1.7%), and bilirubinemia (up to 1.1%). Cases of serious hepatic reactions (including clinical hepatitis, cholestasis, and fulminant hepatic failure, including fatalities) have rarely been reported. Increased GGT/LDH, hepatic failure, hepatitis, jaundice, enlarged liver, and hepatic coma have been reported in less than 2% of patients. Elevated total bilirubin (greater than 1.5 times ULN; up to 19.4%), AST (greater than 3 times ULN; up to 20.3%), ALT (greater than 3 times ULN; up to 18.9%), and alkaline phosphatase (greater than 3 times ULN; up to 22.6%) have also been reported.

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.

Ocular

Ocular side effects have been reported frequently and have included abnormal vision, color vision change, and/or photophobia in about 21% of patients. Abnormal vision (up to 18.7%), photophobia (up to 2.5%), chromatopsia (up to 1.2%), blurred vision, and wavy lines on television or on going to sleep have been reported. 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, and visual field defect have been reported in less than 2% of patients. Transient altered perception of light has also been reported. Prolonged visual adverse events, including optic neuritis and papilledema, have been reported during postmarketing experience.

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

Ocular side effects 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.

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.

Dermatologic side effects have included rashes (up to 7%). Serious cutaneous reactions (including Stevens-Johnson syndrome, toxic epidermal necrolysis, and erythema multiforme) have been reported rarely. 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, and urticaria have been reported in less than 2% of patients. At least two cases of blistering eruptions have been reported.

Gastrointestinal

Gastrointestinal side effects have included nausea (up to 5.4%) and vomiting (up to 4.4%). 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, and tongue edema have been reported in less than 2% of patients.

Metabolic

Metabolic side effects have included hypokalemia (up to 1.6%). Increased creatine phosphokinase, decreased glucose tolerance, hypercalcemia, hypercholesterolemia, hyperglycemia, hyperkalemia, hypermagnesemia, hypernatremia, hyperuricemia, hypocalcemia, hypoglycemia, hypomagnesemia, hyponatremia, and hypophosphatemia have been reported in less than 2% of patients. Decreased potassium (less than 0.9 times LLN) has been reported in up to 16.7% of patients.

Renal

Renal side effects have included abnormal kidney function (up to 1.3%), acute kidney failure (up to 0.4%), and increased creatinine (up to 0.5%). Increased blood urea nitrogen, decreased creatinine clearance, hydronephrosis, kidney pain, nephritis, nephrosis, kidney tubular necrosis, and uremia have been reported in less than 2% of patients. 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.

Other

Other side effects have included fever (up to 5.7%) and chills (up to 3.7%). 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, and substernal chest pain have been reported in less than 2% of patients. Infusion related side effects have included immediate anaphylactoid-type reactions (including flushing, fever, sweating, tachycardia, chest tightness, dyspnea, faintness, nausea, pruritus, and rash).

Nervous system

Nervous system side effects have included headache (up to 3%) and hallucinations (up to 2.8%). 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, and vertigo have been reported in less than 2% of patients.

Cardiovascular

Cardiovascular side effects have included tachycardia (up to 2.4%) and abnormalities in ECG. 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, and ventricular tachycardia (including torsade de pointes) have been reported in less than 2% of patients.

Hypersensitivity

Hypersensitivity side effects have included allergic reaction and anaphylactoid reaction in less than 2% of patients. 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

Hematologic side effects have included 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, and thrombotic thrombocytopenic purpura in less than 2% of patients.

Oncologic

Oncologic side effects have included melanoma and squamous cell carcinoma of the skin during long-term therapy in patients with photosensitivity skin reactions.

Genitourinary

Genitourinary side effects have included 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, and vaginal hemorrhage in less than 2% of patients.

Musculoskeletal

Musculoskeletal side effects have included arthralgia, arthritis, bone necrosis, bone pain, leg cramps, myalgia, myasthenia, myopathy, osteomalacia, and osteoporosis in less than 2% of patients. Fluorosis and periostitis have been reported with long-term therapy during postmarketing experience.

Endocrine

Endocrine side effects have included adrenal cortex insufficiency, diabetes insipidus, hyperthyroidism, and hypothyroidism in less than 2% of patients.

Respiratory

Respiratory side effects have included increased cough, dyspnea, epistaxis, hemoptysis, hypoxia, lung edema, pharyngitis, pleural effusion, pneumonia, respiratory disorder, respiratory distress syndrome, respiratory tract infection, rhinitis, sinusitis, and voice alteration in less than 2% of patients.

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.

Psychiatric side effects have included abnormal dreams, anxiety, depersonalization, depression, psychosis, and suicidal ideation in less than 2% of patients. At least one case of musical hallucinations has been reported.

Local

Local side effects have included injection site pain and injection site infection/inflammation in less than 2% of patients.

Top

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.