Package leaflet: Information for the patient

FLUCONAZIN
5 mg/ml, syrup
Fluconazolum
Please read this leaflet carefully before using the medicine, as it contains
important information for the patient.

Keep this leaflet, so that you can read it again if necessary.
If you have any questions, please consult your doctor, pharmacist, or nurse.
This medicine has been prescribed for a specific individual. Do not pass it on to others. The medicine may harm another person, even if their symptoms are the same.
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor, pharmacist, or nurse. See section 4.

Table of contents

What Fluconazin is and what it is used for
Important information before taking Fluconazin
How to take Fluconazin
Possible side effects
How to store Fluconazin
Contents of the pack and other information

1. What Fluconazin is and what it is used for

Fluconazin contains fluconazole, an antifungal agent which inhibits the synthesis of a key component of the fungal cell wall, thereby disrupting its normal function.
Fluconazole is used to treat infections caused by yeast-like fungi: vaginal candidiasis, oral and oesophageal candidiasis, systemic candidiasis (including candidaemia, disseminated candidiasis, and other forms of invasive candidiasis such as pulmonary candidiasis, peritoneal candidiasis, urinary tract candidiasis), cryptococcal meningitis, cryptococcal meningitis in patients with AIDS, and fungal skin infections.
Additionally, Fluconazin is used for prevention of candidiasis in patients at increased risk (patients with malignant tumors, organ transplant recipients, and patients undergoing chemotherapy and/or radiotherapy), in accordance with current guidelines on the management of fungal infections.

2. Important information before using Fluconazin

When not to use Fluconazin:

if the patient is allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6);
if the patient is allergic to other so-called azole derivatives;
during treatment with terfenadine, pimozide, astemizole, or cisapride.

Warnings and precautions
Before starting treatment with Fluconazin, discuss the following with your doctor:
If the patient has ever experienced severe skin rash or
skin peeling, blisters, and/or oral mucosal ulcers after taking Fluconazin.
Severe skin reactions, including drug reaction with eosinophilia
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and systemic symptoms (DRESS), have been reported in patients treated with Fluconazin. If the patient develops any of the symptoms of severe skin reactions
described in section 4, treatment with Fluconazin must be discontinued immediately and medical help should be sought without delay.
In some patients, especially those suffering from serious diseases such as AIDS or malignancies, and in patients with liver function abnormalities, regular monitoring of liver function is necessary to reduce the risk of liver disorders. If symptoms of liver failure occur, the doctor will decide whether to discontinue fluconazole administration.
Rarely, skin reactions (such as Stevens-Johnson syndrome—variants of erythema multiforme and toxic epidermal necrolysis—Lyell’s syndrome) have been observed during fluconazole treatment.
Patients with AIDS are more susceptible to skin reactions during therapy with various drugs.
If a rash appears in patients being treated for superficial fungal infections, the doctor will decide whether to discontinue fluconazole.
If a rash appears in patients being treated for systemic or invasive candidiasis, fluconazole treatment may be continued, provided the patient is monitored regularly.
If bullous lesions or erythema multiforme occur, the doctor will decide to discontinue fluconazole.
If the fungal infection does not resolve, alternative antifungal therapy may be necessary.
Rare cases of anaphylaxis have also been reported (see section 4. "Possible side effects").
Fluconazole treatment may rarely lead to changes in the ECG (so-called QT interval prolongation) or even to the development of very serious cardiac arrhythmias (so-called polymorphic ventricular tachycardia—“Torsade de pointes”). Administration of fluconazole may predispose to arrhythmias in the following cases:

congenital or documented QT interval prolongation on ECG;
cardiomyopathy (especially in patients with heart failure);
sinus bradycardia;
other cardiac rhythm disorders;
concomitant use of other drugs that prolong the QT interval on ECG;
electrolyte imbalances (low blood levels of potassium, magnesium, calcium).

Patients with renal impairment
In patients with renal impairment, appropriate dose adjustment of fluconazole is necessary (see section 3. "How to use Fluconazin").
Children
See section 3. "How to use Fluconazin".
Fluconazin and other medicines
Inform your doctor or pharmacist about all medicines currently or recently taken, as well as those the patient plans to take.
In patients receiving fluconazole concomitantly with other drugs, appropriate dose adjustments or changes in the current treatment regimen may be necessary, and sometimes even discontinuation of one of the drugs. The decision on appropriate therapy modification is made solely by the physician after a thorough assessment of the patient's condition.
It is known that increasing the dose of fluconazole may sometimes be necessary in patients treated with rifampicin.
Dose reduction of fluconazole may sometimes be necessary in patients treated with hydrochlorothiazide.
Fluconazole enhances the effect of certain sedatives—so-called short-acting benzodiazepines (e.g. midazolam); therefore, appropriate dose adjustment and patient monitoring are necessary.
Fluconazole enhances the effect of anticoagulant drugs, which may lead to bleeding (bruising, nosebleeds, gastrointestinal bleeding, haematuria, and tarry stools). Therefore, in patients receiving coumarin derivatives and fluconazole, the doctor should recommend close monitoring of blood coagulation parameters (so-called Prothrombin Time).
Patients with diabetes may be given fluconazole together with oral glucose-lowering agents (sulfonylureas: chlorpropamide, glyburide, glipizide, tolbutamide), but the possibility of hypoglycemic episodes should be considered.
If concomitant administration of phenytoin and fluconazole is necessary, its blood concentration should be monitored and the dose adjusted to achieve the required therapeutic effect.
Concomitant use of fluconazole probably does not affect the efficacy of oral contraceptives.
Administration of fluconazole does not affect steroid hormone activity in women, and only slightly alters their activity in men.
In kidney transplant patients receiving cyclosporine and fluconazole, monitoring of cyclosporine blood levels is recommended. However, fluconazole did not affect cyclosporine blood levels in bone marrow transplant patients.
Patients receiving fluconazole and high doses of theophylline (or those at risk of theophylline toxicity) should be closely monitored, and the doctor should recommend appropriate treatment modifications if necessary.
Due to the risk of serious cardiac contractile dysfunction (prolongation of the QT interval on ECG, palpitations, tachycardia, dizziness, and chest pain) resulting from enhanced terfenadine effects in patients taking fluconazole, concomitant use of terfenadine and fluconazole is not recommended.
Similarly, due to the risk of serious cardiac arrhythmias, including “Torsade de pointes”, concomitant use of cisapride and fluconazole should be avoided.
Since fluconazole increases zidovudine blood levels, increasing the risk of its adverse effects, the doctor should monitor patients undergoing such treatment.
Fluconazole increases rifabutin blood levels; therefore, patients treated with rifabutin and fluconazole should be monitored.
Similarly, since fluconazole increases tacrolimus blood levels, potentially causing kidney damage, patients undergoing such treatment should be monitored.
Some drugs are metabolized in the body using the same enzyme systems responsible for fluconazole metabolism. Therefore, in certain cases, concomitant administration of fluconazole and certain drugs may reduce treatment safety or reveal adverse effects of the administered drugs, particularly when using drugs affecting heart rhythm (e.g. those prolonging the QT interval on ECG) or altering the efficacy of fluconazole treatment.
During fluconazole treatment in patients receiving astemizole or other drugs metabolized via the cytochrome P-450 system, close monitoring of the patient is necessary.
Administration of fluconazole with food, cimetidine, antacids, or during irradiation prior to bone marrow transplantation has practically no effect on fluconazole absorption.
Taking Fluconazin with food and drink
Concomitant food intake does not affect fluconazole absorption.
Pregnancy and breastfeeding
If the patient is pregnant or breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should not take Fluconazin unless otherwise directed by a doctor.
If the patient plans to become pregnant, it is recommended to wait one week after taking a single dose of fluconazole before attempting conception.
For longer treatment courses with fluconazole, discuss with your doctor the need for appropriate contraception during treatment and for one week after the last dose.
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Fluconazole taken during the first or second trimester of pregnancy may increase the risk of miscarriage.
Fluconazole taken during the first trimester of pregnancy may increase the risk of congenital heart, bone, and/or muscle defects in the newborn.
Cases of infants with congenital skull, ear, femur, and ulna defects have been reported in mothers treated for coccidioidomycosis with high-dose fluconazole (400–800 mg daily) for at least three months. The relationship between fluconazole use and these cases is unclear.
Fluconazole should not be administered to pregnant women or women of childbearing potential who are not using effective contraception.
The drug passes into breast milk at concentrations lower than those in plasma. Breastfeeding may be continued after a single dose of 40 ml syrup (i.e. 200 mg fluconazole) per day or less (see section 3. "How to use Fluconazin"). Breastfeeding is not recommended after multiple doses or high doses of fluconazole.
Driving and operating machinery
The medicine has no effect or a negligible effect on the ability to drive and operate machinery.
Fluconazin contains maltitol
If the patient has previously been diagnosed with intolerance to certain sugars, the patient should consult a doctor before taking the medicine. The medicine may have a mild laxative effect.
Calorific value: 2.3 kcal/g of maltitol.
Fluconazin contains sodium benzoate (E 211)
The medicine contains 1.808 mg sodium benzoate per 1 ml of syrup.
Fluconazin contains propylene glycol (E 1520)
The medicine contains 60.797 mg propylene glycol per 1 ml of syrup.
Before administering the medicine to a child under 5 years of age, consult a doctor or pharmacist, especially if the child is taking other medicines containing propylene glycol or alcohol.
Women who are pregnant or breastfeeding should not take this medicine without medical advice.
The doctor may decide to perform additional tests in such patients.
Patients with impaired liver or kidney function should not take this medicine without medical advice. The doctor may decide to perform additional tests in such patients.
Fluconazin contains ethanol
This medicine contains 0.361 mg ethanol per each ml of syrup. The amount of alcohol in 5 ml of syrup is equivalent to less than 1 ml of beer or 1 ml of wine. The small amount of alcohol in this medicine will not cause noticeable effects.
Fluconazin contains sodium
The medicine contains less than 1 mmol (23 mg) of sodium in 5 ml of syrup, meaning the medicine is considered "sodium-free".

3. How to use Fluconazin

This medicine should always be used exactly as prescribed by your doctor. If in doubt, consult your
doctor or pharmacist.
Fluconazin is taken orally.
This medicine does not contain sugar.
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General instructions
Treatment should be continued until clinical symptoms have resolved and mycological test results
confirm the absence of yeast activity in the collected specimen.
Inadequate dosing or too short a duration of treatment may expose the patient to recurrence of infection.
In patients with AIDS and cryptococcal meningitis, maintenance therapy is usually required to prevent
recurrence of infection.
Dosage for adults
Therapeutic use :

Vaginal candidiasis : single dose of 150 mg fluconazole (i.e. 30 ml of syrup);
Oropharyngeal candidiasis : the usual dose is 50 mg fluconazole (i.e. 10 ml of syrup) once daily for 7 to 14 days. Treatment typically lasts no longer than 14 days, except in immunocompromised patients. In severe cases, the doctor may increase the dose to 100 mg fluconazole (i.e. 20 ml of syrup) once daily;
Oesophageal candidiasis : the usual dose is 50 mg fluconazole (i.e. 10 ml of syrup) daily; in severe cases, the doctor may increase the dose to 100 mg fluconazole (i.e. 20 ml of syrup) daily. Treatment usually lasts 14 to 30 days;
Systemic candidiasis, including candidaemia, disseminated candidiasis and other forms of invasive candidiasis (e.g. pulmonary candidiasis, peritoneal candidiasis, urinary tract candidiasis) : 400 mg fluconazole (i.e. 80 ml of syrup) on the first day, followed by 200 mg fluconazole (i.e. 40 ml of syrup) daily. Depending on clinical response, the doctor may increase the dose to 400 mg fluconazole (i.e. 80 ml of syrup) daily. Duration of treatment depends on clinical response;
Cryptococcal meningitis : 400 mg fluconazole (i.e. 80 ml of syrup) on the first day, followed by 200 to 400 mg fluconazole (i.e. 40 to 80 ml of syrup) once daily. Duration of treatment depends on clinical response and obtaining negative mycological results in cerebrospinal fluid, usually lasting at least 6 to 8 weeks;
Prevention of recurrence of cryptococcal meningitis : in patients with AIDS, following initial treatment, a daily dose of 100 to 200 mg fluconazole (i.e. 20 to 40 ml of syrup) is recommended;
Dermatophytoses (fungal skin infections) : the recommended dose is 50 mg fluconazole (i.e. 10 ml of syrup) once daily for 2 to 4 weeks, and up to 6 weeks in the case of tinea pedis (athlete’s foot). Treatment duration should not exceed 6 weeks.

Prophylactic use:
Prevention of candidiasis in patients at high risk of infection (immunocompromised patients due to neutropenia resulting from cytotoxic chemotherapy or radiotherapy) : a daily dose of 50 to 400 mg fluconazole (i.e. 10 to 80 ml of syrup) is recommended, depending on the level of infection risk. In cases of anticipated prolonged neutropenia (e.g. bone marrow transplantation), 400 mg fluconazole (i.e. 80 ml of syrup) once daily is recommended. Treatment should begin several days before the expected onset of neutropenia and continue for 7 days after achieving a peripheral neutrophil count above 1000/mm³.
Dosage for children
Fluconazin syrup may be used in children over 1 year of age.
Children over 1 year of age:

Oropharyngeal candidiasis, oesophageal candidiasis : 6 mg fluconazole/kg body weight (i.e. 1.2 ml syrup/kg body weight) on the first day, followed by 3 mg fluconazole/kg body weight (i.e. 0.6 ml syrup/kg body weight) daily;
Systemic candidiasis and cryptococcal meningitis : 6 to 12 mg/kg body weight daily (i.e. 1.2 to 2.4 ml syrup/kg body weight daily), depending on severity of infection;
Prevention of candidiasis in children at high risk of infection (immunocompromised due to neutropenia resulting from cytotoxic chemotherapy or radiotherapy) : daily doses of 3 to 12 mg/kg body weight (i.e. 0.6 to 2.4 ml syrup/kg body weight) are recommended, depending on the severity and duration of neutropenia. See: adults, prophylactic use.
Do not exceed a daily dose of 400 mg fluconazole (i.e. 80 ml syrup) in children.
Due to limited data on the use of fluconazole in the treatment of vaginal candidiasis in children under 16 years of age, its use is not recommended in these cases unless no alternative treatment is available.
Dosage in elderly patients
If renal function is not impaired (creatinine clearance value above 50 ml/min), no dosage adjustment of fluconazole is necessary in elderly patients.
Dosage in patients with renal impairment
A single dose of fluconazole does not require dosage adjustment in patients with renal impairment.
In repeated dosing (including in children), patients receive the initial dose according to the indications and age groups specified above. Subsequent daily doses should be adjusted by the doctor according to the following scheme:
Creatinine clearance (ml/min) Percentage of recommended daily dose for
patients with renal impairment

50 100% (no change)
≤ 50 (without dialysis) 50% (reduce by half)
Patients undergoing regular haemodialysis 100% (no change) after each dialysis session
If only serum creatinine concentration is known, creatinine clearance can be calculated using the following formula to facilitate appropriate fluconazole dosage adjustment:
For adult males:
(140 - patient's age in years) x patient's body weight in kg
72 x serum creatinine concentration (in mg/100 ml)
For adult females: multiply the value calculated above by a factor of 0.85.
Use of a higher than recommended dose of Fluconazin
In case of fluconazole overdose, the doctor will administer symptomatic treatment (if necessary, supported by gastric lavage) and forced diuresis. Three-hour haemodialysis reduces plasma drug concentration by 50%.
Missed dose of Fluconazin
Do not take a double dose to make up for a missed dose.
If you have any further questions about the use of this medicine, consult your doctor, pharmacist, or nurse.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone experiences them.
Fluconazole is generally well tolerated.
If any of the following symptoms occur in a patient, treatment with Fluconazin must be discontinued and immediate medical help must be sought:

widespread rash, high fever, and swollen lymph nodes (DRESS syndrome or drug hypersensitivity syndrome),
sudden difficulty breathing, speaking, or swallowing,
itching of the lips, tongue, face, and neck,
severe dizziness or fainting,
itchy rash or blisters on the skin, accompanied by pain in the mouth or genital organs.

Other adverse reactions:

headache, dizziness, seizures, taste disturbances,
hepatotoxic effects, rarely fatal cases, and changes in blood laboratory tests (increased activity of alkaline phosphatase, aspartate dehydrogenase, alanine dehydrogenase, and elevated bilirubin levels), cases of liver failure, hepatitis, hepatic necrosis, jaundice,
rash, hair loss, excessive skin desquamation including Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome),
dyspepsia, vomiting, abdominal pain, diarrhea, flatulence, nausea. In some patients, especially those suffering from serious conditions such as AIDS or cancer, changes in parameters reflecting liver and kidney function, as well as hematological and biochemical test results have been reported,
changes in white blood cell and platelet counts (leukopenia with neutropenia and agranulocytosis, thrombocytopenia),
anaphylactic reactions (including angioedema, facial swelling, itching), urticaria,
increased cholesterol and triglyceride levels, and decreased blood potassium concentration,
cardiac arrhythmias (prolongation of the so-called QT interval, polymorphic ventricular tachycardia known as Torsade de pointes).

Reporting of adverse reactions
If any adverse reactions occur, including any possible adverse reactions not listed in this leaflet, inform a doctor, pharmacist, or nurse.
Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the Office for Registration of Medicinal Products, Medical Devices and Biocidal Products:
Aleje Jerozolimskie 181C, 02-222 Warsaw
Tel: +48 22 49 21 301, Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder.
Reporting adverse reactions helps to gather more information on the safety of the medicine.

5. How to store Fluconazin

Store in the original packaging at a temperature below 25°C.
Keep the medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the packaging. The expiry date refers to the last day of the stated month.
Medicines must not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. Such measures help protect the environment.

6. Contents of the packaging and other information

What Fluconazin contains
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The active substance is fluconazole. 1 ml of syrup contains 5 mg of fluconazole.
The other ingredients (excipients) are: liquid maltitol, propylene glycol (E 1520), monohydrate citric acid, sodium benzoate (E 211), strawberry flavour AR0012/F (containing ethanol and propylene glycol (E 1520)), sodium saccharin dihydrate, purified water.

What Fluconazin looks like and contents of the pack
The medicine is a syrup. One pack contains 150 ml of syrup.
Marketing Authorisation Holder and Manufacturer
„PRZEDSIĘBIORSTWO PRODUKCJI FARMACEUTYCZNEJ HASCO-LEK” S.A.
51-131 Wrocław, ul. Żmigrodzka 242 E
Medicine Information
tel.: 22 742 00 22
e-mail: [email protected]
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