Fluconazole Noridem

Patient Information Leaflet: Information for the User

Fluconazole Noridem 2 mg/mL infusion solution

Fluconazole
Generic medicine
Please read this leaflet carefully before receiving this medicine as it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any questions, ask your doctor, pharmacist, or nurse.
• This medicine has been prescribed for you only. Do not give it to others, even if their symptoms are the same as yours, as it could be harmful.
• If you experience any side effects, including those not listed in this leaflet, tell your doctor, pharmacist, or nurse. See section 4.

The name of the medicine is Fluconazole Noridem infusion solution.
In the remainder of this patient information leaflet, Fluconazole Noridem infusion solution will be referred to as

Fluconazole Noridem.

Contents of this leaflet

1. What Fluconazole Noridem is and what it is used for
2. What you need to know before receiving Fluconazole Noridem
3. How Fluconazole Noridem is administered
4. Possible side effects
5. How to store Fluconazole Noridem
6. Contents of the pack and other information

1. What Fluconazole Noridem is and what it is used for

Fluconazole Noridem belongs to a group of medicines called "antifungals". The active substance is
fluconazole.
Fluconazole Noridem is used to treat fungal infections and may also be used to prevent Candida infections. The most common cause of fungal infections is a yeast called Candida.
Adults
Your doctor may prescribe this medicine to treat the following fungal infections:

• Cryptococcal meningitis – a fungal infection of the brain
• Coccidioidomycosis – a disease affecting the bronchopulmonary system
• Infections caused by Candida found in the bloodstream, organs (e.g. heart, lungs) or urinary tract
• Oral candidiasis – infection of the oral mucosa, throat, and denture-related stomatitis.

Fluconazole Noridem may also be prescribed to:

• prevent recurrence of cryptococcal meningitis
• prevent recurrence of oral candidiasis
• prevent Candida infections (if your immune system is weakened or not functioning properly).

Children and adolescents (0 to 17 years of age)
Your doctor may prescribe this medicine to treat the following fungal infections:

• Oral candidiasis – infection of the oral mucosa, throat
• Infections caused by Candida found in the bloodstream, organs (e.g. heart, lungs) or urinary tract
• Cryptococcal meningitis – a fungal infection of the brain

Fluconazole Noridem may also be prescribed to:

• prevent Candida infections (if the immune system is weakened or not functioning properly)
• prevent recurrence of cryptococcal meningitis.

2. What you should know before receiving Fluconazole Noridem

Do not take Fluconazole Noridem:

• if you are allergic to fluconazole, to other antifungal medicines, or to any of the other ingredients of this medicine (listed in section 6). Symptoms may include itching, skin redness, or difficulty breathing
• if you are taking astemizole or terfenadine (antihistamines used to treat allergies)
• if you are taking cisapride (used to treat stomach disorders)
• if you are taking pimozide (used to treat mental disorders)
• if you are taking quinidine (used to treat heart arrhythmias)
• if you are taking erythromycin (an antibiotic used to treat infections).

Warnings and precautions
Talk to your doctor or nurse before taking Fluconazole Noridem

• if you have liver or kidney problems
• if you have heart disease, including heart rhythm problems
• if you have abnormal levels of potassium, calcium, or magnesium in your blood
• if you develop severe skin reactions (itching, skin redness, or difficulty breathing)
• if you develop symptoms of "adrenal insufficiency", in which the adrenal glands do not produce enough steroid hormones such as cortisol (chronic or long-lasting fatigue, muscle weakness, loss of appetite, weight loss, abdominal pain)
• if you have ever developed a severe rash, skin peeling, blistering, and/or skin ulcers after taking fluconazole.

Severe skin reactions, including drug reaction with eosinophilia and systemic symptoms (DRESS), have been reported with fluconazole treatment. Stop using Fluconazole Noridem and contact a doctor immediately if you notice any of the symptoms related to these severe skin reactions described in section 4.
Talk to your doctor or pharmacist if your fungal infection does not improve, as alternative treatment may be needed.

Other medicines and Fluconazole Noridem
Tell your doctor or pharmacist if you are taking, have recently taken, or might take any other medicines. Inform your doctor immediately if you are taking astemizole, terfenadine (antihistamines used to treat allergies), cisapride (used to treat stomach disorders), pimozide (used to treat mental disorders), quinidine (used to treat heart arrhythmias), or erythromycin (an antibiotic used to treat infections), as these must not be taken together with Fluconazole Noridem (see section: "Do not take Fluconazole Noridem").

Some medicines may interact with Fluconazole Noridem. Make sure your doctor knows if you are taking any of the following medicines, as dose adjustments or monitoring may be needed to ensure these medicines remain effective:

• rifampicin or rifabutin (antibiotics used to treat infections)
• abrocitinib (used to treat atopic dermatitis, also known as atopic eczema)
• alfentanil, fentanyl (used as anesthetics)
• amitriptyline, nortriptyline (used as antidepressants)
• amphotericin B, voriconazole (antifungals)
• medicines that thin the blood to prevent blood clots (warfarin or similar medicines)
• benzodiazepines (midazolam, triazolam or similar medicines) used to help sleep or for anxiety
• carbamazepine, phenytoin (used to treat seizures)
• nifedipine, isradipine, amlodipine, verapamil, felodipine, and losartan (used to treat high blood pressure)
• olaparib (used to treat ovarian cancer)
• ciclosporin, everolimus, sirolimus, or tacrolimus (used to prevent transplant rejection)
• cyclophosphamide, vinca alkaloids (vincristine, vinblastine or similar medicines) used to treat cancer
• halofantrine (used to treat malaria)
• statins (atorvastatin, simvastatin, fluvastatin and similar medicines) used to reduce high cholesterol levels
• methadone (used to treat pain)
• celecoxib, flurbiprofen, naproxen, ibuprofen, lornoxicam, meloxicam, diclofenac (non-steroidal anti-inflammatory drugs - NSAIDs)
• oral contraceptives
• prednisone (a steroid)
• zidovudine, also known as AZT; saquinavir (used in patients with HIV)
• diabetes medicines such as chlorpropamide, glibenclamide, glipizide, or tolbutamide
• theophylline (used to control asthma)
• tofacitinib (used to treat rheumatoid arthritis)
• tolvaptan, used to treat hyponatremia (low sodium levels in the blood) or to slow the decline in kidney function
• vitamin A (nutritional supplement)
• ivacaftor (alone or in combination with other medicines, used to treat cystic fibrosis)
• amiodarone (used to treat irregular heartbeats, or arrhythmias)
• hydrochlorothiazide (a diuretic)
• ibrutinib (used to treat blood cancers)
• lurasidone (used to treat schizophrenia)

Pregnancy, breastfeeding, and fertility
If you are pregnant, think you may be pregnant, planning to become pregnant, or breastfeeding, ask your doctor or pharmacist for advice before taking this medicine.
If you are planning a pregnancy, it is advisable to wait one week after a single dose of fluconazole before trying to conceive.
For longer treatment cycles with fluconazole, consult your doctor about the need for adequate contraception during treatment and for one week after the last dose.
Do not take Fluconazole Noridem if you are pregnant, suspect you are pregnant, trying to become pregnant, or breastfeeding, unless your doctor has specifically instructed you to do so. If you become pregnant while taking this medicine or within one week of your most recent dose, contact your doctor.
Fluconazole Noridem administered during the first or second trimester of pregnancy may increase the risk of spontaneous abortion.
Fluconazole Noridem administered during the first trimester may increase the risk of congenital malformations in the baby affecting the heart, bones, and/or muscles.
Cases of babies born with congenital malformations of the skull, ears, and thigh and elbow bones have been reported in women treated for three months or more with high doses (400–800 mg daily) of fluconazole for coccidioidomycosis. The link between fluconazole and these cases is not fully established.
You may continue breastfeeding if you have received a single 150 mg dose of fluconazole. You must not breastfeed if you are receiving repeated doses of Fluconazole Noridem.

Driving and using machines
Bear in mind that dizziness or seizures may occasionally occur when driving or operating machinery.

Fluconazole Noridem contains sodium (salt)
Fluconazole Noridem contains salt (3.54 mg of sodium chloride per mL).
This medicine contains 708 mg of sodium (the main component of table salt) per 200 mL vial. This corresponds to 35.4% of the recommended maximum daily dietary intake for an adult.
Talk to your doctor or pharmacist if you need 400 mg or more vials/bags per day over a prolonged period, especially if you have been advised to follow a low-salt diet.

3. How Fluconazolo Noridem is administered

This medicine will be administered to you by a doctor or nurse as a slow injection (infusion) into a vein. Fluconazolo Noridem is available as a solution that should not be further diluted.
Further instructions for healthcare professionals are included in a section at the end of this leaflet.
The recommended doses of this medicine, depending on the type of infection, are listed below. If you have any doubts about why you are receiving Fluconazolo Noridem, consult your doctor or pharmacist.
Adults

Adolescents aged 12 to 17 years
Follow the dose prescribed by the doctor (adult or pediatric dosage)
Children up to 11 years
The maximum dose for children is 400 mg per day.
The dose will be based on the child's weight in kilograms.

Use in children from 0 to 4 weeks of age
Use in children aged 3 or 4 weeks:

• The same dosage described above, but administered once every 2 days. The maximum dose is 12 mg per kg of body weight every 48 hours.
  Use in children under 2 weeks of age:
• The same dosage described above, but administered once every 3 days. The maximum dose is 12 mg per kg of body weight every 72 hours.

Elderly
The same dose as recommended for adults should be used, except in cases of renal impairment.
Patients with renal impairment
The doctor may adjust the dosage according to renal function.
If you receive more Fluconazolo Noridem than you should
If you are concerned that you may have received more Fluconazolo Noridem than you should have, inform your doctor or nurse immediately. Symptoms of a possible overdose may include sensing, seeing, feeling, or thinking things that are not real (hallucinations and paranoid behaviour).
If you forget to take Fluconazolo Noridem
Since this medicine will be administered under close medical supervision, it is unlikely that a dose will be missed. However, inform your doctor or pharmacist if you think a dose has been missed.
If you have any doubts about how to use this medicine, consult your doctor, pharmacist, or nurse.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everyone gets them.
Stop taking Fluconazole Noridem and contact a doctor immediately if you notice any of the following symptoms:

• widespread skin rash, high body temperature and swollen lymph nodes (DRESS syndrome or drug hypersensitivity syndrome)

Some people may experience allergic reactions, although severe allergic reactions are rare. If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. If you experience any of the following symptoms, contact your doctor immediately:

• sudden breathlessness, difficulty breathing or tightness in the chest
• swelling of the eyelids, face or lips
• itching all over the body, redness of the skin or itchy red patches
• skin rash
• severe skin reactions such as rash with blistering (which may affect the mouth and tongue)

Fluconazole Noridem may affect the liver. Signs of liver problems include:

• fatigue
• loss of appetite
• vomiting
• yellowing of the skin and whites of the eyes (jaundice)

If you experience any of these symptoms, stop taking Fluconazole Noridem and contact your doctor immediately.
Other side effects:
Additionally, if any of the following side effects become severe, or if you notice any side effects not listed in this leaflet, inform your doctor or pharmacist.
Common side effects (may affect up to 1 in 10 people) are:

• headache
• stomach discomfort, diarrhoea, nausea, vomiting
• increased liver function test values in blood tests
• skin rash

Uncommon side effects (may affect up to 1 in 100 people) are:

• reduced red blood cells, which may cause paleness, weakness or shortness of breath
• reduced appetite
• insomnia, drowsiness
• seizures, dizziness, vertigo, tingling, pricking or numbness, altered sense of taste
• constipation, indigestion, flatulence, dry mouth
• muscle pain
• liver damage and yellowing of the skin and eyes (jaundice)
• swelling, blisters (urticaria), itching, increased sweating
• fatigue, general feeling of being unwell, fever

Rare side effects (may affect up to 1 in 1,000 people) are:

• lower than normal numbers of white blood cells that help fight infections and of blood cells that help stop bleeding
• red or purple skin discolouration, which may be caused by low platelet count, other changes in blood cells
• changes in blood chemistry (high levels of cholesterol, fats)
• low levels of potassium in the blood
• abnormal electrocardiogram (ECG), changes in heart rhythm and rate
• liver failure
• allergic reactions (sometimes severe), including widespread rash with blistering and skin peeling, severe skin reactions, swelling of lips or face
• hair loss

Frequency not known (cannot be estimated from the available data):

• hypersensitivity reaction with skin rash, fever, swollen glands, increase in a type of white blood cells (eosinophilia) and inflammation of internal organs (liver, lungs, heart, kidneys and large intestine) (drug reaction with eosinophilia and systemic symptoms (DRESS))

Reporting of side effects
If you experience any side effect, including those not listed in this leaflet, talk to your doctor, pharmacist or nurse. You can also report side effects directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse . By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store Fluconazole Noridem

The doctor, nurse, or pharmacist will usually store the medicine for you.
Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the label of the plastic container after "Exp". The expiry date refers to the last day of that month.
Do not use if the solution is cloudy, has changed colour, or contains particles.
Do not store above 25 °C. Do not freeze or refrigerate.
Keep the bag and bottle in the outer packaging to protect the medicine from light.
For single use only. Use immediately after first opening of the vial.
Chemical and physical in-use stability has been demonstrated for 24 hours at 25 °C. From a microbiological standpoint, the product should be used immediately. If not used immediately, the storage times and conditions prior to use are the responsibility of the user and are normally no longer than 24 hours at 2–8 °C, unless dilution has been carried out under controlled and validated aseptic conditions.
This medicine may be mixed with certain other medicines that may also be administered by infusion. If you require further information on this, please consult your doctor, nurse, or pharmacist.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This will help protect the environment.

6. Package contents and other information

What Fluconazolo Noridem contains

• The active substance is fluconazole. 1 mL of solution contains 2 mg of fluconazole. Each 50 mL (millilitre) bag contains 100 mg (milligrams) of fluconazole. Each 100 mL (millilitre) bag/bottle contains 200 mg (milligrams) of fluconazole. Each 200 mL (millilitre) bottle contains 400 mg (milligrams) of fluconazole.
• The other components are sodium chloride (see section 2), hydrochloric acid and water for injections.

Description of the appearance of Fluconazolo Noridem and package contents
Fluconazolo Noridem 2 mg/mL solution for infusion is a clear, colourless aqueous infusion solution.
It is a ready-to-use plastic bag with rubber closures and aluminium caps.
It is a ready-to-use plastic bottle with a rubber stopper, plastic caps and a tear-off ring or with plastic caps and twin ports.
Pack sizes: 50 mL bags (100 mg fluconazole) in packs of 10
100 mL bags (200 mg fluconazole) in packs of 10
100 mL bottles (200 mg fluconazole) in packs of 10 or 20
200 mL bottles (400 mg fluconazole) in packs of 10 or 20
Not all pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer
Marketing Authorisation Holder:
Noridem Enterprises Limited
Evagorou & Makariou
Mitsi Building 3, Office 115
1065 Nicosia, Cyprus

Manufacturer:
DEMO S.A. INDUSTRIA FARMACEUTICA
21st Km National Road Athens–Lamia,
14568 Krioneri, Attiki, Greece
T: +30 210 8161802, F: +30 2108161587

This medicinal product is authorised in the European Economic Area and the United Kingdom (Northern Ireland) under the following names:

The following information is intended exclusively for physicians or healthcare professionals:
The infusion rate must not exceed 10 mL per minute. Fluconazole Noridem is formulated in
sodium chloride 9 mg/mL (0.9%) solution for infusion; 200 mg (100 mL vial) contain 15 mmol
each of Na and Cl. Since Fluconazole Noridem is supplied diluted in sodium chloride solution, care must be taken with the rate of fluid administration in patients requiring restriction of sodium or fluids.
Intravenous infusion of fluconazole is compatible with the following infusion fluids:
Diluent Resulting fluconazole
concentration
Sodium chloride 0.9% for injection 1.0 mg/mL
20% Dextrose for injection 1.0 mg/mL
Ringer's lactate for injection 1.0 mg/mL
Ringer's solution for injection 1.0 mg/mL
0.3% Potassium chloride in 5% dextrose 1.0 mg/mL
for injection
Sodium bicarbonate 4.2% for injection 1.0 mg/mL
Fluconazole Noridem may be administered using an existing infusion line containing one of the fluids listed above. Although no specific incompatibilities have been observed, mixing with other medicinal products prior to infusion is not recommended.
The infusion solution is for single use only.
From a microbiological standpoint, diluted solutions should be used immediately. If not used immediately, storage times and conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at 2–8 °C, unless dilution has been carried out under controlled and validated aseptic conditions.
Dilution must be performed under aseptic conditions. The solution should be inspected visually for the presence of particulate matter or discoloration prior to administration. The solution should only be used if it is clear and free of particles.
Any unused medicinal product and waste material derived from this medicinal product must be disposed of in accordance with current local regulations.