Product Information: Fluconazole - (Diflucan / Loitin)

Product Information
The Number 1 drug to treat yeast infections.

This famous anti-fungal drug is the world's most commonly used drug to treat yeast infections, which are far more common than many people believe.

Fluconazole is available under the trade name Loitin®.

Chemical: Fluconazole

Excipients:
Lactose, cornstarch, precipitate silica, magnesium stearate, sodium laurel sulphate capsules also contain: gelatin, indigotin, and titanium dioxide. Each 100-phial for intravenous injection- Sodium chloride, sterile water.

Classification:
Antimycotic drug

Diflucan is recommended for:
The treatment of acute and recurrent vaginal candidosis, cases of dermatomycosis such as tinea pedis (athlete's foot), tinea cruris (dhobie itch) tinea corporis and tinea versicolor, and skin candidosis.

It is also recommended for the treatment of candidosis of the oropharnynx (parasitic stomatitis), even in the case of patients with immunity problems caused by malignant mycotic pathologies or by acquired immune deficiency syndrome (AIDS) or atrophic oral candidosis.

Fluconazole is recommended in the treatment of serious mycotic infections arising from Candida albicans and Cryptococcus neoformans, including those which reveal problems in the immune system arising from malignant pathologies, acquired immune deficiency syndrome or mycoses caused by antineoplastic chemotherapy. This medicine can also be used in the treatment of cryptococcic meningitis, in anti-relapse maintenance treatment and in the treatment of skin and pulmonary cryptococcosis.

This treatment of candida infections includes oesophagitis, peritonitis, pulmonary and genito-urinary infections as well as extended candidemia and candidosis. It is also recommended for the prevention of those fungal infections, which respond to DIFLUCAN (fluconazole), in patients with neoplastic affections and who are undergoing cytotoxic chemotherapy. In the treatment of skin or mucous infections, this product should be limited only to those cases which are particularly extended or serious and which have not been cured by traditional local treatment.

Contraindications:
Fluconazole should not be used by patients with hypersensitivity to any of the ingredients contained in this product or to triazolic compounds.

It should also not be used by patients with either acute and chronic hepatic problems or renal insufficiency.

Pregnant Women and Nursing Mothers:
This product should not be administered during pregnancy. Before taking it, any woman in the childbearing age should ensure by means of the proper test that she is not expecting a baby. Moreover, during treatment she should take the necessary contraceptives to avoid conception-taking place. Similarly, this product should not be taken by nursing mothers.

Children:
Since the information available concerning the use of DIFLUCAN by children under the age of 16 is limited, this product is not recommended for these patients.

Special Precautions:
Before beginning and during the course of DIFLUCAN treatment, the hepatic functions should be observed regularly (transaminase, etc.).

Interactions:
The interaction of DIFLUCAN (fluconazole) has been studied with warfarin (extension of prothrombin time), with tolbutamide and sulphonylurea drugs (prolongation of serum half-life), with hydrochlorothiazide (40% increase in the plasmatic concentrations of DIFLUCAN), with fenitoin (increased haematic levels), Rifampicin* (25% decrease of AUC and 20% decrease in the half-life of DIFLUCAN), with theophylline (18% lowering in plasmatic clearance). If these products must be taken together with DIFLUCAN, it will be sufficient to monitor the haematic levels with the respective medicines and adapt the dosages to therapeutic needs.

It should be specially noted that in the simultaneous use of DIFLUCAN (fluconazole) and tolbutamide, both sugar levels and the dosage of medicine for hypoglycemia should be controlled.

Patients who have had kidney transplants and are undergoing simultaneous treatment of DIFLUCAN and cyclosporin A are advised to monitor the plasmatic concentration of cyclosporin.

No clinically significant interactions have been seen with DIFLUCAN, cimetidine or antacids.

There are no known negative effects due to the simultaneous use of DIFLUCAN and oral contraceptives.

Special Warning:
Very rare cases have been seen of patients who have died as a result of their serious base pathologies, have also been treated with multiple doses of DIFLUCAN, and whose autopsy reports have revealed hepatic necrosis. These patients had simultaneously taken numerous other pharmaceutical products, some of which were known for their hepatotoxic effects and/or were patients whose base illnesses could have caused hepatic alterations. Even though no causal relation has been established between these events and DIFLUCAN, patients who experience a significant increase in hepatic enzymes should seriously consider whether it is worthwhile to continue DIFLUCAN treatment.
For DIFLUCAN's effect on Children, see CONTRAINDICATIONS.

DRIVING AND OPERATING MACHINERY: Tests have shown that DIFLUCAN does not affect the patient's capacity for driving or operating machinery.

Dosage:
The daily dosage of DIFLUCAN must be based on the nature and degree of the mycotic infection.

The majority of cases of vaginal candidosis respond to a single dose. Treatment for infections requiring multiple doses should be continued until clinical parameters and laboratory tests show that the active infection has been cured. An insufficient period of treatment may lead to a relapse of the active infection.

Patients suffering from AIDS and cryptococcic meningitis or from recurrent candidosis of the oropharnynx require maintenance treatment to avoid a relapse.

ADULTS:
For vaginal candidosis, 150 mg in a single dose on a single day. For dermatomycosis, the usual dosage is 50-100 mg per day in one single dose for a period of 14-28 days.

Tinea pedis (athlete's foot) may require treatment for up to 42 days.
For candidosis of the oropharnynx, even in patients with immunity problems, the usual dosage is 50 mg once daily for 7-14 days. If necessary, this treatment may be prolonged for a longer period, especially in the case of serious immunodepressive problems. For atrophic oral candidosis in denture wearers, the normal dosage is 50 mg daily for 14 days. During this time an antiseptic treatment of the oral cavity and dentures should be carried out.

For serious, potentially life-threatening pathologies, including cryptococcic meningitis and extended candidosis, the usual dosage is 400 mg, to be taken in a single dose on one day. Following this, the dosage should be 200 mg, once daily. Depending on the patient's reaction, these successive doses can also be maintained at 400 mg/daily. In general, the duration of this treatment for cryptococcic meningitis is 6-8 weeks. Duration of treatment for extended candidosis depends on the clinical reaction of the patient.

To prevent a relapse of cryptococcic meningitis in AIDS patients, 200 mg of DIFLUCAN can be administered daily on an indefinite basis, once the patient has finished the first cycle of treatment and the culture examination has proved negative.

For other local candida infections, such as oesophagitis, infections of the urinary apparatus, etc., the usual effective dosage is 50 mg daily for 14-30 days.

This dosage may be increased to 100 mg daily in cases, which are especially difficult to treat.

For preventive treatment in high-risk patients who may develop mycotic infections as a consequence of neutropenia caused by cytotoxic chemotherapy or radiotherapy, the dosage is 50 mg per day.

ELDERLY PATIENTS:
If there is no evidence of renal insufficiency, the patient is to follow the normal recommended dosage. For patients with renal insufficiency (creatine clearance < 40 ml/min), the dosage should be regulated as follows.

PATIENTS WITH RENAL INSUFFICIENCY: DIFLUCAN is eliminated in large part with urine. No measures should be taken if a single dosage is applied (vaginal candidosis). However, when treatment for patients with renal problems consists of two doses, the normal dose can be administered on the first and second day of therapy. After this, the interval between one dose and the next is modified based on the creatine clearance:

Creatine clearance (ml/min) Interval between doses (hours)
> 40 24 (normal dose)
21 - 40 48 (or half-dose)
10-20 72 (or 1/3 dose)

Dialysis patients 1 administration following each session of dialysis

Directions for Use:
DIFLUCAN can be taken either by mouth or by intravenous injection (introducing not more than 10 ml/minute), with the choice of the administration route depending on the clinical conditions of the patient. In changing from intravenous injection to taking the pharmaceutical product by mouth and vice versa, it is not necessary to modify the daily dosage. DIFLUCAN is formulated in a solution of 9% sodium chloride; every 200 mg.

Because DIFLUCAN is available diluted in saline solution, the percentage of liquid administered is well tolerated by patients who require sodium and liquid restrictions. DIFLUCAN by intravenous injection is compatible with the administration of the following liquids:

1. 20% dextrose
2. Ringer's solution
3. Hartmann's solution
4. Potassium chloride in dextrose
5. 4.2% sodium bicarbonate
6. Aminofusina
7. Solution for peritoneal dialysis

DIFLUCAN can be administered using a pre-established intravenous route with one of the aforementioned solutions. Although specific incompatibilities have not been observed, mixing other pharmaceutical products before administering this medicine is not recommended.

In Case Of Overdose (Symptoms, Assistence, and Antidotes)
Should overdose take place, a symptomatic treatment will be necessary with adequate support therapy and possible gastric lavage. DIFLUCAN is largely excreted by means of urine; forced diuresis probably increases the percentage of the elimination.

A 3-hour haemodialysis session lowers plasmatic levels by approximately 50%.

Unpleasant Side Effects:
DIFLUCAN (fluconazole) is generally well tolerated.
The most common unpleasant side effects caused by this product are related with the gastrointestinal apparatus, including nausea, abdominal pain, diarrhea, flatulence, vomiting.

In addition to gastrointestinal symptoms, the side effect most frequently seen is skin rash; also possible are headaches, lack of appetite and dizziness. Alterations involving the hepatic enzymes are also occasionally seen.

In some patients, particularly those suffering serious illnesses such as AIDS or cancer, alternations in the liver, kidney and blood functions have been observed during treatment with DIFLUCAN and similar products. The clinical significance and relation with the treatment, however, have not been established. A small number of patients suffering from AIDS have shown this type of reaction when taking DIFLUCAN together with other agents known for causing exfoliate skin rashes. Should it be seen that DIFLUCAN is the cause of skin rash, treatment with this pharmaceutical product should be interrupted.

In patients with systematic fungal infections causing rash, careful monitoring should be carried out and treatment with DIFLUCAN should be interrupted if blistered lesions or multiform erythema develop. In rare cases, such as other azoles, it is possible to verify anaphylactic phenomena.

The patient should inform his doctor or pharmacist of any unpleasant side effects not described in this leaflet.

Expity Date:
Be careful not to use this medicine following the expiry date on the box.

Storage:
No special care is required for storage.

KEEP THIS AND ALL OTHER MEDICINE OUT OF THE REACH OF CHILDREN