Fluconazole (Fluconazole) - Side Effects and Adverse Reactions

ADVERSE REACTIONS

In Patients Receiving a Single Dose for Vaginal Candidiasis

During comparative clinical studies conducted in the United States, 448 patients with vaginal candidiasis were treated with fluconazole, 150 mg single dose. The overall incidence of side effects possibly related to fluconazole was 26%. In 422 patients receiving active comparative agents, the incidence was 16%. The most common treatment-related adverse events reported in the patients who received 150 mg single dose fluconazole for vaginitis were headache (13%), nausea (7%), and abdominal pain (6%). Other side effects reported with an incidence equal to or greater than 1% included diarrhea (3%), dyspepsia (1%), dizziness (1%), and taste perversion (1%). Most of the reported side effects were mild to moderate in severity. Rarely, angioedema and anaphylactic reaction have been reported in marketing experience.

In Patients Receiving Multiple Doses for Other Infections

Sixteen percent of over 4000 patients treated with fluconazole in clinical trials of 7 days or more experienced adverse events. Treatment was discontinued in 1.5% of patients due to adverse clinical events and in 1.3% of patients due to laboratory test abnormalities.

Clinical adverse events were reported more frequently in HIV infected patients (21%) than in non-HIV infected patients (13%); however, the patterns in HIV infected and non-HIV infected patients were similar. The proportions of patients discontinuing therapy due to clinical adverse events were similar in the two groups (1.5%).

The following treatment related clinical adverse events occurred at an incidence of 1% or greater in 4048 patients receiving fluconazole for 7 or more days in clinical trials: nausea 3.7%, headache 1.9%, skin rash 1.8%, vomiting 1.7%, abdominal pain 1.7%, and diarrhea 1.5%.

The following adverse events have occurred under conditions where a causal association is probable:

Hepatobiliary:

In combined clinical trials and marketing experience, there have been rare cases of serious hepatic reactions during treatment with fluconazole. (See WARNINGS.) The spectrum of these hepatic reactions has ranged from mild transient elevations in transaminases to clinical hepatitis, cholestasis and fulminant hepatic failure, including fatalities. Instances of fatal hepatic reactions were noted to occur primarily in patients with serious underlying medical conditions (predominantly AIDS or malignancy) and often while taking multiple concomitant medications. Transient hepatic reactions, including hepatitis and jaundice, have occurred among patients with no other identifiable risk factors. In each of these cases, liver function returned to baseline on discontinuation of fluconazole.

In two comparative trials evaluating the efficacy of fluconazole for the suppression of relapse of cryptococcal meningitis, a statistically significant increase was observed in median AST (SGOT) levels from a baseline value of 30 IU/L to 41 IU/L in one trial and 34 IU/L to 66 IU/L in the other. The overall rate of serum transaminase elevations of more than 8 times the upper limit of normal was approximately 1% in fluconazole-treated patients in clinical trials. These elevations occurred in patients with severe underlying disease, predominantly AIDS or malignancies, most of whom were receiving multiple concomitant medications, including many known to be hepatotoxic. The incidence of abnormally elevated serum transaminases was greater in patients taking fluconazole concomitantly with one or more of the following medications: rifampin, phenytoin, isoniazid, valproic acid, or oral sulfonylurea hypoglycemic agents.

Immunologic: In rare cases, anaphylaxis (including angioedema, face edema and pruritus) has been reported.

The following adverse events have occurred under conditions where a casual association is uncertain.

Cardiovascular: QT prolongation, torsade de pointes. (See PRECAUTIONS.)

Central Nervous System: Seizures.

Dermatologic: Exfoliative skin disorders including Stevens-Johnson syndrome and toxic epidermal necrolysis (see WARNINGS), alopecia.

Hematopoietic and Lymphatic: Leukopenia, including neutropenia and agranulocytosis, thrombocytopenia.

Metabolic: Hypercholesterolemia, hypertriglyceridemia, hypokalemia.

Adverse Reactions in Children

In Phase II/III clinical trials conducted in the United States and in Europe, 577 pediatric patients, ages 1 day to 17 years were treated with fluconazole at doses up to 15 mg/kg/day for up to 1,616 days. Thirteen percent of children experienced treatment related adverse events. The most commonly reported events were vomiting (5%), abdominal pain (3%), nausea (2%), and diarrhea (2%). Treatment was discontinued in 2.3% of patients due to adverse clinical events and in 1.4% of patients due to laboratory test abnormalities. The majority of treatment-related laboratory abnormalities were elevations of transaminases or alkaline phosphatase.

Percentage of Patients With Treatment-Related Side Effects

	Fluconazole	Comparative Agents
	(N=577)	(N=451)
With any side effect	13.0	9.3
Vomiting	5.4	5.1
Abdominal pain	2.8	1.6
Nausea	2.3	1.6
Diarrhea	2.1	2.2

REPORTS OF SIDE EFFECTS / ADVERSE REACTIONS RELATED TO FLUCONAZOLE

Possible Fluconazole side effects / adverse reactions in 54 year old male

Reported by a consumer/non-health professional from United Kingdom on 2007-01-08

Patient: 54 year old male

Reactions: Toxic Epidermal Necrolysis

Suspect drug(s):
Amoxicillin
    Dosage: 1g three times per day
    Indication: Drug USE FOR Unknown Indication

Actrapid
    Indication: Drug USE FOR Unknown Indication

Alfentanil
    Indication: Drug USE FOR Unknown Indication

Aquasept
    Indication: Drug USE FOR Unknown Indication

Bactroban
    Indication: Drug USE FOR Unknown Indication

Calcium Chloride
    Indication: Drug USE FOR Unknown Indication

Calcium Gluconate
    Indication: Drug USE FOR Unknown Indication

Ceftriaxone
    Indication: Drug USE FOR Unknown Indication

Clexane
    Dosage: 20mg per day
    Indication: Drug USE FOR Unknown Indication

Dobutamine HCL
    Indication: Drug USE FOR Unknown Indication

Fluconazole
    Dosage: 200mg per day
    Indication: Drug USE FOR Unknown Indication

Fragmin
    Dosage: 2500iu per day
    Indication: Drug USE FOR Unknown Indication

Furosemide
    Dosage: 20mg twice per day
    Indication: Drug USE FOR Unknown Indication

Furosemide
    Dosage: 20mg per day
    Administration route: Oral

Hydrocortisone
    Dosage: 100mg single dose
    Indication: Drug USE FOR Unknown Indication

Lactulose
    Indication: Drug USE FOR Unknown Indication

Lansoprazole
    Indication: Drug USE FOR Unknown Indication

Lorazepam
    Indication: Drug USE FOR Unknown Indication

Magnesium Sulfate
    Indication: Drug USE FOR Unknown Indication

Noradrenaline
    Indication: Drug USE FOR Unknown Indication

Omeprazole
    Indication: Drug USE FOR Unknown Indication

Acetaminophen
    Indication: Drug USE FOR Unknown Indication

Piriton
    Dosage: 10mg four times per day
    Indication: Drug USE FOR Unknown Indication

Potassium Chloride
    Indication: Drug USE FOR Unknown Indication

Potassium Phosphates
    Indication: Drug USE FOR Unknown Indication

Propofol
    Indication: Drug USE FOR Unknown Indication

Ventolin
    Indication: Drug USE FOR Unknown Indication

Sando-K
    Indication: Drug USE FOR Unknown Indication

Silver Sulphadiazine
    Administration route: Topical
    Indication: Drug USE FOR Unknown Indication

Simvastatin
    Dosage: 40mg per day
    Indication: Drug USE FOR Unknown Indication

Sodium Bicarbonate
    Indication: Drug USE FOR Unknown Indication

Sodium Chloride 0.9%
    Indication: Drug USE FOR Unknown Indication

Thiamin
    Dosage: 100mg per day
    Administration route: Oral
    Indication: Drug USE FOR Unknown Indication

Tinzaparin
    Dosage: 3500mcl per day
    Indication: Drug USE FOR Unknown Indication

Vitamin K
    Indication: Drug USE FOR Unknown Indication

Other drugs received by patient: Amoxicillin; Aspirin; Atrovent; Ciprofloxacin; Amoxicillin + Clavulanate Potassium; Erythromycin; Metoclopramide; Midodrine; Pantoprazole Sodium; Piperacillin and Tazobactam; Vancomycin; Zopiclone

Possible Fluconazole side effects / adverse reactions in 54 year old male

Reported by a consumer/non-health professional from United Kingdom on 2007-01-09

Patient: 54 year old male

Reactions: Toxic Epidermal Necrolysis

Suspect drug(s):
Rocephin
    Indication: Drug USE FOR Unknown Indication

Actrapid
    Indication: Drug USE FOR Unknown Indication

Vitamin K
    Indication: Drug USE FOR Unknown Indication

Tinzaparin
    Indication: Drug USE FOR Unknown Indication

Thiamin
    Administration route: Oral
    Indication: Drug USE FOR Unknown Indication

Sodium Chloride
    Indication: Drug USE FOR Unknown Indication

Sodium Bicarbonate
    Indication: Drug USE FOR Unknown Indication

Simvastatin
    Indication: Drug USE FOR Unknown Indication

Silver Sulphadiazine
    Administration route: Topical
    Indication: Drug USE FOR Unknown Indication

Sando-K
    Indication: Drug USE FOR Unknown Indication

Ventolin
    Indication: Drug USE FOR Unknown Indication

Propofol
    Indication: Drug USE FOR Unknown Indication

Potassium Phosphates
    Indication: Drug USE FOR Unknown Indication

Potassium Chloride
    Indication: Drug USE FOR Unknown Indication

Piriton
    Indication: Drug USE FOR Unknown Indication

Acetaminophen
    Indication: Drug USE FOR Unknown Indication

Omeprazole
    Indication: Drug USE FOR Unknown Indication

Noradrenaline
    Indication: Drug USE FOR Unknown Indication

Magnesium Sulfate
    Indication: Drug USE FOR Unknown Indication

Lorazepam
    Indication: Drug USE FOR Unknown Indication

Lansoprazole
    Indication: Drug USE FOR Unknown Indication

Lactulose
    Indication: Drug USE FOR Unknown Indication

Hydrocortisone
    Indication: Drug USE FOR Unknown Indication

Furosemide
    Administration route: Oral
    Indication: Drug USE FOR Unknown Indication

Furosemide

Fragmin
    Indication: Drug USE FOR Unknown Indication

Fluconazole
    Indication: Drug USE FOR Unknown Indication

Dobutamine HCL
    Indication: Drug USE FOR Unknown Indication

Clexane
    Indication: Drug USE FOR Unknown Indication

Calcium Gluconate
    Indication: Drug USE FOR Unknown Indication

Calcium Chloride
    Indication: Drug USE FOR Unknown Indication

Bactroban
    Indication: Drug USE FOR Unknown Indication

Aquasept
    Indication: Drug USE FOR Unknown Indication

Amoxicillin
    Indication: Drug USE FOR Unknown Indication

Alfentanil
    Indication: Drug USE FOR Unknown Indication

Other drugs received by patient: Amoxicillin; Aspirin; Atrovent; Ciprofloxacin; Amoxicillin + Clavulanate Potassium; Erythromycin; Metoclopramide; Midodrine; Pantoprazole Sodium; Tazocin; Vancomycin; Zopiclone

Possible Fluconazole side effects / adverse reactions in 54 year old male

Reported by a health professional (non-physician/pharmacist) from United Kingdom on 2007-01-10

Patient: 54 year old male

Reactions: Toxic Epidermal Necrolysis

Suspect drug(s):
Acetaminophen

Amoxicillin

Furosemide

Furosemide
    Administration route: Oral

Hydrocortisone

Potassium Chloride

Ventolin

Silver Sulfadiazine
    Administration route: Topical

Actrapid

Alfentanil

Aquasept

Bactroban

Calcium Chloride

Calcium Gluconate

Ceftriaxone

Clexane

Dobutamine HCL

Fluconazole

Fragmin

Lactulose

Lansoprazole

Lorazepam

Magnesium Sulfate

Noradrenaline

Omeprazole

Piriton

Potassium Phosphates

Propofol

Sando-K

Simvastatin

Sodium Bicarbonate

Sodium Chloride

Thiamin
    Administration route: Oral

Tinzaparin

Vitamin K

Other drugs received by patient: Aspirin; Atrovent; Ciprofloxacin; Amoxicillin + Clavulanate Potassium; Erythromycin; Metoclopramide; Midodrine HCL; Pantoprazole Sodium; Tazocin; Vancomycin; Zopiclone; Amoxicillin