Flucess Bss

Flucess®   Each capsule, hard contains 150 mg/200 mg Excipient(s) with known effect: Lactose monohydrate.T

Indications: adults for the treatment of Cryptococcal meningitis ,Coccidioidomycosis ,Invasive candidiasis,Mucosal candidiasis including oropharyngeal, oesophageal candidiasis, candiduria and chronic mucocutaneous candidiasis,Chronic oral atrophic candidiasis (denture sore mouth) if dental hygiene or topical treatment are insufficient,Vaginal candidiasis, acute or recurrent; when local therapy is not appropriate,Candidal balanitis when local therapy is not appropriate,Dermatomycosis including tinea pedis, tinea corporis, tinea cruris, tinea versicolor and dermal candida infections when systemic therapy is indicated,Tinea unguinium (onychomycosis) when other agents are not considered appropriate.Fluconazole is indicated in adults for the prophylaxis of :Relapse of cryptococcal meningitis in patients with high risk of recurrence,Relapse of oropharyngeal or oesophageal candidiasis in patients infected with HIV who are at high risk of experiencing relapse,To reduce the incidence of recurrent vaginal candidiasis (4 or more episodes a year),Prophylaxis of candidal infections in patients with prolonged neutropenia (such as patients with haematological malignancies receiving chemotherapy or patients receiving Haematopoietic Stem Cell Transplantation Fluconazole is indicated in term newborn infants, infants, toddlers, children, and adolescents aged from 0 to 17 years old:Fluconazole is used for the treatment of mucosal candidiasis (oropharyngeal, oesophageal), invasive candidiasis, cryptococcal meningitis and the prophylaxis of candidal infections in immunocompromised patients. Fluconazole can be used as maintenance therapy to prevent relapse of cryptococcal meningitis in children with high risk of reoccurrence Therapy may be instituted before the results of the cultures and other laboratory studies are known; however, once these results become available, anti-infective therapy should be adjusted accordingly.Consideration should be given to official guidance on the appropriate use of antifungals.Posology:The dose should be based on the type and severity of the fungal infection. Treatment of infections requiring multiple dosing should be continued until clinical parameters or laboratory tests indicate that active fungal infection has subsided. An inadequate period of treatment may lead to recurrence of active infection.Cryptococcosis:Treatment of cryptococcal meningitis:Loading dose: 400 mg on Day 1,Subsequent dose: 200-400 mg daily.Duration:Usually at least 6 to 8 weeks.In life threatening infections the daily dose can be increased to 800 mg- Maintenance therapy to prevent relapse of cryptococcal meningitis in patients with high risk of recurrence:200 mg daily.Duration:Indefinitely at a daily dose of 200 mg.Coccidioido-mycosis:200-400 mg.Duration:11 months up to 24 months or longer depending on the patient. 800 mg daily may be considered for some infections and especially for meningeal disease. Invasive candidiasis:Loading dose: 800 mg on Day 1Subsequent dose: 400 mg daily.In general, the recommended duration of therapy for candidaemia is for 2 weeks after first negative blood culture result and resolution of signs and symptoms attributable to candidaemia. Treatment of mucosal candidiasis- Oropharyngeal candidiasis:Loading dose: 200-400 mg on Day 1.Subsequent dose: 100-200 mg daily.Duration7 to 21 days (until oropharyngeal candidiasis is in remission).Longer periods may be used in patients with severely compromised immune function- Oesophageal candidiasis.Loading dose: 200-400 mg on Day 1Subsequent dose: 100-200 mg daily,14 to 30 days (until oesophageal candidiasis is in remission).Longer periods may be used in patients with severely compromised immune function- Candiduria:200-400 mg daily            7 to 21 days. Longer periods may be used in patients with severely compromised immune function.- Chronic atrophic candidiasis :50 mg daily for 14 days.- Chronic mucocutaneous candidiasis:50-100 mg daily,Up to 28 days. Longer periods depending on both the severity of infection or underlying immune compromisation and infection.Prevention of relapse of mucosal candidiasis in patients infected with HIV who are at high risk of experiencing relapse:- Oropharyngeal candidiasis:100-200 mg daily or 200 mg 3 times per week.An indefinite period for patients with chronic immune suppression.- Oesophageal candidiasis:100-200 mg daily or 200 mg 3 times per week.An indefinite period for patients with chronic immune suppression. Genital candidiasis.- Acute vaginal candidiasis.- Candidal balanitis:150 mg ,Single dose.- Treatment and prophylaxis of recurrent vaginal candidiasis (4 or more episodes a year):150 mg every third day for a total of 3 doses (Day 1, 4, and 7) followed by 150 mg once weekly maintenance dose.Maintenance dose: 6 months . Dermatomycosis: - Tinea pedis,Tinea corporis,Tinea cruris,Candida infections:150 mg once weekly or 50 mg once daily,2 to 4 weeks, Tinea pedis may require treatment for up to 6 weeks.Tinea versicolor:300-400 mg once weekly,1 to 3 weeks or 50 mg once daily,2 to 4 weeks.Tinea unguium (onychomycosis ):150 mg once weekly.Treatment should be continued until infected nail is replaced (uninfected nail grows in). Regrowth of fingernails and toenails normally requires 3 to 6 months and 6 to 12 months, respectively. However, growth rates may vary widely in individuals, and by age. After successful treatment of long-term chronic infections, nails occasionally remain disfigured. Prophylaxis of candidal infections in patients with prolonged neutropenia:200-400 mg.Treatment should start several days before the anticipated onset of neutropenia and continue for 7 days after recovery from neutropenia after the neutrophil count rises above 1,000 cells per mm3.

Special populations:Elderly:Dose should be adjusted based on the renal function.

Renal impairment:No adjustments in single dose therapy are necessary. In patients (including paediatric population) with impaired renal function who will receive multiple doses of fluconazole, an initial dose of 50 mg to 400 mg should be given, based on the recommended daily dose for the indication. After this initial loading dose, the daily dose (according to indication) should be based on the following : Creatinine clearance (ml/min)

Patients on regular dialysis should receive 100% of the recommended dose after each dialysis; on non-dialysis days, patients should receive a reduced dose according to their creatinine clearance.Hepatic impairment:Limited data are available in patients with hepatic impairment, therefore fluconazole should be administered with caution to patients with liver dysfunction .Paediatric population:maximum dose of 400 mg daily should not be exceeded in paediatric population.As with similar infections in adults, the duration of treatment is based on the clinical and mycological response. Fluconazole is administered as a single daily dose.For paediatric patients with impaired renal function, see dosing in “Renal impairment”. The pharmacokinetics of fluconazole has not been studied in paediatric population with renal insufficiency (for “Term newborn infants” who often exhibit primarily renal immaturity please see below).Infants, toddlers and children (from 28 days to 11 years old) - Mucosal candidiasis :Initial dose: 6 mg/kg,Subsequent dose: 3 mg/kg daily.Initial dose may be used on the first day to achieve steady state levels more rapidly.Invasive candidiasis: Cryptococcal meningitis:Dose: 6-12 mg/kg daily,Depending on the severity of the disease. Maintenance therapy to prevent relapse of cryptococcal meningitis in children with high risk of recurrence.Dose: 6 mg/kg daily     Depending on the severity of the disease. Prophylaxis of Candida in immuno-compromised patients:Dose: 3-12 mg/kg daily:Depending on the extent and duration of the induced neutropenia (see Adults posology).Adolescents (from 12 to 17 years old)Depending on the weight and pubertal development, the prescriber would need to assess which posology (adults or children) is the most appropriate. Clinical data indicate that children have a higher fluconazole clearance than observed for adults. A dose of 100, 200 and 400 mg in adults corresponds to a 3, 6 and 12 mg/kg dose in children to obtain a comparable systemic exposure.Safety and efficacy for genital candidiasis indication in paediatric population has not been established. Current available safety data for other paediatric indications are described in section 4.8. If treatment for genital candidiasis is imperative in adolescents (from 12 to 17 years old), the posology should be the same as adults posology.Term newborn infants (0 to 27 days).Neonates excrete fluconazole slowly. There are few pharmacokinetic data to support this posology in term newborn infants. Term newborn infants (0 to 14 days):the same mg/kg dose as for infants, toddlers and children should be given every 72 hours.A maximum dose of 12 mg/kg every 72 hours should not be exceeded.Term newborn infants (from 15 to 27 days):the same mg/kg dose as for infants, toddlers and children should be given every 48 hours.A maximum dose of 12 mg/kg every 48 hours should not be exceeded.Method of administration:Fluconazole may be administered either orally or by intravenous infusion, the route being dependent on the clinical state of the patient. On transferring from the intravenous to the oral route, or vice versa, there is no need to change the daily dose.The capsules should be swallowed whole and independent of food intake.Contraindications:Hypersensitivity to the active substance, to related azole substances, or to any of the excipients.Co-administration of terfenadine is contraindicated in patients receiving fluconazole at multiple doses of 400 mg per day or higher based upon results of a multiple dose interaction study. Co-administration of other medicinal products known to prolong the QT interval and which are metabolised via the cytochrome P450 (CYP) 3A4 such as cisapride, astemizole, pimozide, quinidine, and erythromycin are contraindicated in patients receiving fluconazole .Special warnings and precautions for use:Tinea capitis,Cryptococcosis,Deep endemic mycoses:The evidence for efficacy of fluconazole in the treatment of other forms of endemic mycoses such as paracoccidioidomycosis, lymphocutaneous sporotrichosis and histoplasmosis is limited, which prevents specific dosing recommendations.Renal system:administer with caution to patients with renal dysfunction.Adrenal insufficiency :Ketoconazole is known to cause adrenal insufficiency, and this could also, although rarely seen, be applicable to fluconazole. Hepatobiliary system:Fluconazole should be administered with caution to patients with liver dysfunction. Rare cases of serious hepatic toxicity including fatalities, primarily in patients with serious underlying medical conditions.. Fluconazole hepatotoxicity has usually been reversible on discontinuation of therapy.Patients who develop abnormal liver function tests during fluconazole therapy must be monitored closely for the development of more serious hepatic injury.Cardiovascular system:Some azoles, including fluconazole, have been associated with prolongation of the QT interval on the electrocardiogram. During post-marketing surveillance, there have been very rare cases of QT prolongation and torsades de pointes in patients taking fluconazole..Co-administration of other medicinal products known to prolong the QT interval and which are metabolised via the cytochrome P450 (CYP) 3A4 are contraindicated.Halofantrine.Halofantrine has been shown to prolong QTc interval at the recommended therapeutic dose and is a substrate of CYP3A4. The concomitant use of fluconazole and halofantrine is therefore not recommended.Dermatological reactions:Patients have rarely developed Stevens-Johnson syndrome and toxic epidermal necrolysis. If a rash develops in a patient treated for a superficial fungal infection, further therapy with this medicinal product should be discontinued.Hypersensitivity:In rare cases anaphylaxis has been reported .Cytochrome P450:Fluconazole is a moderate CYP2C9 and CYP3A4 inhibitor.

Concomitantcontraindications:Cisapride,Terfenadine,Astemizole,Pimozide,Quinidine,

Erythromycin.Concomitant use of the following other medicinal products cannot be recommended:Halofantrin.

Pregnancy: increased risk of spontaneous abortion in women in the first trimester.Breast-feeding:Fluconazole passes into breast milk to reach concentrations similar to those in plasma .Breast-feeding may be maintained after a single dose of 150 mg fluconazole.Breast-feeding is not recommended after repeated use or after high dose fluconazole.Effects on ability to drive and use machines:No studies have been performed .Patients should be warned about the potential for dizziness or seizures ,while taking fluconazole and should be advised not to drive or operate machines if any of these symptoms occur.Undesirable effects:The most frequently (>1/10) reported adverse reactions are headache, abdominal pain, diarrhoea, nausea, vomiting, alanine aminotransferase increased, aspartate aminotransferase increased, blood alkaline phosphatase increased and rash.  CDS June 2018.