In men: DuracanTM - SFDA...atrophic oral candidiasis. DOSAGE AND ADMINISTRATION: Most patients of...

COMPOSITION: DuracanTM 150 mg: Each capsule contains 150 mg fluconazole. Excipients: lactose anhydrous, crospovidone NF, magnesium stearate, aerosil 200 (colloidal silicon dioxide).

PROPERTIES: Fluconazole is a systemic antimycotic compound belonging to the triazole class, is a powerful specific inhibitor of the synthesis of fungal steroids. It is active against a wide range of fungi, its activity has been proved against opportunistic mycotic infections such as those caused by Candida spp., including systemic candidiasis, and by Cryptococcus neoformans (including intracranial infections), by Microsporum spp. And by Trichophyton spp and others. When fluconazole is administrated orally, it is well absorbed, showing a systemic bioavailability higher than 90% with respect to the levels reached after intravenous administration.Oral administration is not modified by the concomitant intake of food. Peaks in plasma concentration under fasted conditions are reached after a period between 30 and 90 minutes. fluconazole shows a good penetration throughout all organic fluids investigated. Its levels in saliva and in excreta are similar to the plasma levels. In patients affected by mycotic meningitis the fluconazole levels in cerebrospinal fluids are about 80% of corresponding levels in the plasma. The principal way of excretion is the renal way: about 80% of the dose administrated is found unchanged in urine. Fluconazole clearance is proportional to that of creatinine. There is no evidence of metabolites in circulation.The prolonged half-life time in the plasma is the rational of the therapy with a single dose in the treatment of vaginal candidiasis and with a single daily administration in the treatments of all other fungal infections.

INDICATIONS:Fluconazole is indicated for: - Acute or recurrent vaginal candidiasis. - Mucosal Candidiasis - Treatment of tinea cruris, tinea corporis and pityriasis versicolor and for the treatment of skin candidiasis- Treatment of oropharyngeal candidiasis (thrush), including those cases in which such disease affects patients having compromised immune function due to malignancies or to acquired immunodeficiency syndrome (AIDS), as well as atrophic oral candidiasis.

DOSAGE AND ADMINISTRATION: Most patients of vaginal candidiasis respond to a single dose of DuracanTM 150mg capsule, therapy for infections that needs multiple doses should be continued until the clinical parameters and laboratory tests show that mycotic infection has been resolved.

RENAL IMPAIRMENT: No adjustments are necessary when a single dose therapy is realized (Vaginal candidiasis). When a repeated-dose therapy is realized in patients affected with renal impairment, the dosage schedule should be adjusted according to the following table:

CHILDREN:Dosage has been not established for children under the age of 16 years. However a dose of 3-6 mg/kg/day can be used in systemic candidiasis.

CONTRAINDICATIONS: Fluconazole is contraindicated in patients with known hypersensitivity to triazole compounds or any of its excipients.It is contraindicated in acute or chronic hepatopathies or in hepatic insufficiency patients. It is contraindicated in pregnancy and lactation.

WARNING:In some patients particularly with serious underlying diseases such as AIDS and cancer, abnormalities of hepatic, renal, hematological function tests have been observed during the treatment with fluconazole. But the clinical significance and relationship to treatment is uncertain. Hepatic function (transaminase etc) must be carefully and frequently checked. The fluconazole therapy should be discontinued if bullous lesions or erythema multiform develop or with AIDS patient who develop an exfoliative cutaneous reactions.

Some azoles, including fluconazole, have been associated with prolongation of the QT interval on the electrocardiogram. During postmarketing surveillance, there have been very rare cases of QT prolongation and torsade de pointes in patients taking fluconazole.These reports included seriously ill patients with multiple confounding risk factors, such as structural heart disease, electrolyte abnormalities and concomitant medications that may have been contributory. Fluconazole should be administered with caution to patients with these potentially proarryhthmic conditions.

"Use in Pregnancy":"There are no adequate and well-controlled studies of fluconazole in pregnant women. Available human data do not suggest an increased risk of congenital anomalies following a single maternal dose of 150 mg. A few published case reports describe a rare pattern of distinct congenital anomalies in infants exposed in-utero to high dose maternal fluconazole (400-800 mg/day) during most or all of the first trimester. These reported anomalies are similar to those seen in animal studies. If this drug is used during pregnancy, or if the patient becomes pregnant while taking the drug, the patient should be informed of the potential hazard to the fetus. (See PRECAUTIONS, Pregnancy)”.

PRECAUTIONS:Fluconazole does not alter the ability of the patient to drive cars or to use machines. The concomitant use of fluconazole with other agents like Warfarin, tolbutamide, hydrochlorothiazide, sulphonylureas may increase the plasma concentration of these agents and it is sufficient to adapt the doses to the therapeutic requirements to the mentioned drugs. Fluconazole does not affect the endogenous steroid levels.The capsules contain lactose and should not be given to patients with rare hereditary problems of galactose intolerance, LAPP lactase deficiency or glucose-galactose malabsorption.

Not to be use without consulting a doctor if:

In women: -If you have any abnormal or irregular vaginal bleeding or a blood stained discharge. -If you have vulval or vaginal sores, ulcers or blisters.-If you are experiencing lower abdominal pain or burning on passing urine. -If you have fever or chills. -If you are feeling sick and vomiting-If you are experiencing Diarrhea. -If you are experiencing foul smelling discharge from the vagina.

DuracanTMfluconazole

DuracanTM

- Rev. 01/

Capsule

• Medicament is a product that affects your health, and its consumption contrary to instructions is dangerous for you.• Follow strictly the doctor's prescription, the method of use and the instructions of the pharmacist who sold the medicament.• The doctor and the pharmacist are experts in medicine, its benefits and risks.• Do not by yourself interrupt the period of treatment prescribed.• Do not repeat the same prescription without consulting your doctor.

Keep medicament out of the reach of children.

THIS IS A MEDICAMENT

Council of Arab Health Ministers & Union of Arab Pharmacists

Creatinine clearance (ml /min)> 4021 - 4010 - 20Patients receiving regularhaemodialysis

Dosage interval / daily dose24 hours (normal regimen)48 hours or half normal daily dose72 hours or one third normal daily doseOne recommended dose afterreach dialysis

150 mm 150 mm

In men: -If you have penile sores, ulcers or blisters. -If you have an abnormal penile discharge (leakage). -If your penis has started to smell. -If you have pain on passing urine. -The product should never be used again if the patient experiences a rash or anaphylaxis follows the use of the drug.- Your sexual partner does not have thrush.

Precautions/Pregnancy :

Teratogenic effects."Pregnancy Category C""Single 150 mg tablet use for Vaginal Candidiasis""There are no adequate and well-controlled studies of fluconazole in pregnant women. Available human data do not suggest an increased risk of congenital anomalies following a single maternal dose of 150 mg".

"Pregnancy Category D""All other indications""A few published case reports describe a rare pattern of distinct congenital anomalies in infants exposed in-utero to high dose maternal fluconazole (400-800 mg/day) during most or all of the first trimester. These reported anomalies are similar to those seen in animal studies. lf this drug is used during pregnancy, or if the patient becomes pregnant while taking the drug, the patient should be informed of the potential hazard to the fetus. (See WARNINGS, Use in Pregnancy)"

“Human Data”"Several published epidemiologic studies do not suggest an increased risk of congenital anomalies associated with low dose exposure to fluconazole in pregnancy (most subjects received a single oral dose of 150 mg). A few published case reports describe a distinctive and rare pattern of birth defects among infants whose mothers received high-dose(400-800 mg/day) fluconazole during most or all of the first trimester of pregnancy. The features seen in these infants include: brachycephaly, abnormal facies, abnormal calvarial development, cleft palate, femoral bowing, thin ribs and long bones, arthrogryposis, and congenital heart disease. These effects are similar to those seen in animal studies".

"Preclinical safety data""Animal Data""Fluconazole was administered orally to pregnant rabbits during organogenesis in two studies at doses of 5, 10, and 20 mg/kg and at 5, 25, and 75 mg/kg, respectively. Maternal weight gain was impaired at all dose levels (approximately 0.25 to 4 times the 400 mg clinical dose based on BSA) , and abortions occurred at 75 mg/kg (approximately 4 timesthe 400 mg clinical dose based on BSA); no adverse fetal effects were observed"."In several studies in which pregnant rats received fluconazole orally during organogenesis, maternal weight gain was impaired and placental weights were increased at 25 mg/kg. There were no fetal effects at 5 or 10 mg/kg; increases in fetal anatomical variants (supernumerary ribs, renal pelvis dilation) and delays in ossification were observed at 25 and 50 mg/kg and higher doses. At doses ranging from 80 to 320 mg/kg (approximately 2 to 8 times the 400 mg clinical dose based on BSA). embryolethality in rats was increased and fetal abnormalities included wavy ribs, cleft palate, and abnormal cranio-facial ossification. These effects are consistent with the inhibition of estrogen synthesis in rats and may be a result of known effects of lowered estrogen on pregnancy, organogenesis, and parturition".

SIDE EFFECTS: Fluconazole is generally well tolerated, and most reported side effects are correlated to the gastrointestinal tract and they include nausia, abdominal pain, diarrhoea and flatulence. Occasional abnormalities of liver enzymes have been observed. An allergic reaction may include: Rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue, weakness; feeling dizzy or faint.The following side effects have also been reported:Feeling sick or being sick, Stomach discomfort, change in sense of taste, headaches, liver disorders with symptoms such as yellowing of skin or eyes. Dark urine or pale stools, change in heart rhythm or rate, abnormal ECG (Electrocardiogram) heart tracing, high blood levels of cholesterol or fat. Reduction in number of blood cells and platelets, low levels of potassium. severe condition with blistering of the skin, mouth, eyes or genitals. Rash, itching, hair loss, seizure, recurrent Infections (e.g. cold and flu). If you experience any of the above effect or react badly to the capsule in any not listed in this leaflet, tell your doctor or pharmacist immediately.

DRUG INTERACTIONS: Concomitant use of rifampicin or theophylline with fluconazole results in reduced fluconazole serum levels. In case of concomitant administration of fluconazole and cyclosporin, monitoring of plasma concentrations of cyclosporin is advised. No negative effects were observed in the case of simultaneous intake of fluconazole and oral contraceptives. Do not use this medicine if you are taking the antihistamine terfenadine, the medicine cisapride or an ergot-derivatives e.g. (ergotamine used for migraine). Inform your doctor if you are taking: anticoagulants (to prevent blood clots) ,sulphonylureas (to control diabetes), hydrochlorothiazide (used to treat fluid retention and high blood pressure), benzodiazepines (used as tranquilisers), phenytoin, carbamazepine or phenobarbital (used to control epilepsy), rifabutin or rifapentine (antibiotics), cyclosporin, sirolimus or tacrolimus (used to reduce the immune response), zidovudine (used to treat HIV infections ), astemizole (antihistamine), anti - arrhythmics (to control irregular heartbeats), losartan (to reduce blood pressure), fentanyl or methadone (to treat pain).

OVER DOSAGE: In case of accidental over dosage, supportive measure and symptomatic treatment with gastric lavage (if necessary) may be adequate, a forced diuresis is likely to increase the excretion percentage, hemodialysis decreases plasma level by 50%.

PRESENTATION: DuracanTM 150 mg: Box containing 1 capsule.

STORAGE: Do not store above 30 OC. Keep out of the reach of children.

This leaflet was last revised on December 2012.