FLUDIS Capsule

COMPOSITION :

Fludis^® Capsule 150 mg, each capsule contains : Fluconazole 150 mg.

 

DESCRIPTIONS :

Fludis^® contains Fluconazole as active ingredient is available in capsule 150 mg.

 

INDICATIONS :

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.

• Cryptococcosis, including cryptococcal meningitis and infections of other sites (e.g., pulmonary and cutaneous). Normal hosts and patients with AIDS, organ transplants or other causes of immunosuppression may be treated. Fluconazole can be used as maintenance therapy to prevent relapse of cryptococcal disease in patients with AIDS.
• Systemic candidiasis, including candidemia, disseminated candidiasis and other forms of invasive candidal infection including infections of the peritoneum, endocardium and pulmonary and urinary tracts. Patients with malignancy, in intensive care units, receiving cytotoxic or immunosuppressive therapy or with other factors predisposing to candidal infection may be treated.
• Mucosal candidiasis. These include oropharyngeal, esophageal, non-invasive bronchopulmonary infections, candiduria, mucocutaneous and chronic oral atropic candidiasis (denture sore mouth). Normal hosts and patients with compromised immune function may be treated. Prevention of relapse of oropharyngeal candidiasis in patients with AIDS.
• Genital candidasis, vaginal candidiasis, acute or recurrent; Candida balanitis.
• Prevention of fungal infections in patients with malignancy who are predisposed to such infections as a result of cytotoxic chemotherapy or radiotherapy.
• Dermatomycosis including tinea pedis, tinea corporis, tinea cruris, tinea versicolor and dermal candida infections.

 

DOSAGE AND ADMINISTRATIONS :

The daily dose of Fludis^® should be based on the nature and severity of the fungal infection. Most cases of the vaginal candidiasis respond to single dose therapy.

Therapy for those types of infections requiring multiple dose treatment 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. Patients with AIDS and cryptococcal meningitis or recurrent oropharyngeal candidiasis usually require maintenance therapy to prevent relapse.

Adults :

• Cryptococcal meningitis and cryptococcal infections at other sites : The usual dose is 400 mg on the first day followed by 200 mg – 400 mg once daily. Duration of treatment for cryptococcal infections will depend on the clinical and mycological response, but is usually at least 6 – 8 weeks for cryptococcal meningitis.
  For the prevention of relapse of cryptococcal meningitis in patients with AIDS, after the patient receives a full course of primary therapy, Fludis^® may be administered indefinitely at a daily dose of 200 mg.
• Candidemia, disseminated candidiasis and other invasive candidal infections : The usual dose is 400 mg on the first day followed by 200 mg daily. Depending on the clinical response, the dose may be increased to 400 mg daily. Duration of treatment is based upon the clinical response.
• Oropharyngeal candidiasis : The usual dose is 50 mg – 100 mg once daily for 7 – 14 days. If necessary, treatment can be continued for longer periods in patients with severely compromised immune function.
  For atropic oral candidiasis associated with dentures, the usual dose is 50 mg once daily for 14 days administered concurrently with local antiseptic measures to the denture.
  For other candidal infections of mucosa (except genital candidiasis) e.g., esophagitis, non-invasive bronchopulmonary infections, candiduria, mucocutaneous candidiasis, etc., the usual effective dose is 50 – 100 mg daily, given for 14 – 30 days. For the prevention of relapse of oropharyngeal candidiasis in patient with AIDS, after the patient receives a full course of primary therapy, Fludis^® may be administered at a 150 mg once weekly dose.
• Candida balanitis : Fluconazole 150 mg should be administered as a single oral dose.
• Prevention of candidiasis : 50 – 400 mg once daily, based on the patients risk for developing fungal infection. For patients at high risk of systemic infection, e.g., patients who are anticipated to have profound or prolonged neutropenia, the recommended daily dose is 400 mg once daily. Fludis^® administration should start several days before the anticipated onset of neutropenia and continue for 7 days after the neutrophil count rises above 1000 cells/mm³.
  A higher dose of 100 mg once daily may be used in patients at risk of severe recurrent infections.
• Dermal infections including tinea pedis, corporis, cruris and candida infections : The recommended dosage is 150 mg once weekly or 50 mg once daily. Duration of treatment is normally 2 – 4 weeks but tinea pedis may require treatment for up to 6 weeks. For tinea versicolor the recommended dose is 50 mg once daily for 2 – 4 weeks. Duration of treatment should not exceed 6 weeks.
• For the treatment of vaginal candidiasis : Fluconazole 150 mg should be administered as a single dose.

Children :

Use in children below the age of 16 years is not recommended. However, when the treating physician considers Fludis^® therapy imperative, the following daily doses for children aged 1 year and older with normal renal function are recommended :

1. Superficial candidal infections : 1 – 2 mg/kg.
2. Systemic candidal/cryptococcal infections : 3 – 6 mg/kg.

These recommendations approximate the doses used in adults on a mg/kg basis.

However, preliminary data in children aged 5 – 13, indicate Fludis^® elimination may be faster than in adults. Therefore, for serious or life-threatening infections, higher daily doses may be required. Daily doses up to 12 mg/kg have been used in a small number of children. The maximum approved adult daily dose of 400 mg should not be exceeded.

For children with impaired renal function the daily dose should be reduced in accordance with the guidelines given for adults, depend on degree of renal impairment.

Elderly :

Where there is no evidence of renal impairment, normal dosage recommendations should be adopted. For patients with renal impairment (creatinine clearance < 50 ml/minute) the dosage schedule should be adjusted as described below.

Patients with renal impairment :

Fluconazole is predominantly excreted in the urine as unchanged drug. No adjustments in single dose therapy are necessary. In patients with impaired renal function who will receive multiple doses of Fludis^®, an initial loading dose of 50 – 400 mg should be given. After the loading dose, the daily dose (according to indication) should be based on the following table :

Creatinine clearance (ml/minute)	Percent of recommended dose
> 50	100%
≤ 50 (no dialysis)	50%
Regular dialysis	100% after every dialysis

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.

When serum creatinine is the only measure of renal function available, the following formula (based on sex, weight and age of the patient) should be based on the following :

Male     :	Weight (kg) x (140 – Age)
	72 x Serum creatinine (mg/100 ml)
Female  :	0.85 x above value

Administration :

Fluconazole may be administered either orally or by intravenous infusion at a rate not exceeding 200 mg/hour given as a continuous 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 dosage. Capsules should be swallowed whole.

 

OVERDOSAGE :

There have been reports of overdosage with Fluconazole by hallucination and paranoid behavior. In the event of overdosage, symptomatic treatment (with supportive measures and gastric lavage if necessary) may be adequate. Fluconazole is largely excreted in urine; forced volume diuresis would probably increases the elimination rate. A three-hours hemodialysis session decreases plasma levels by approximately 50%.

 

CONTRAINDICATIONS :

• Fluconazole should not be used in patients with known sensitivity to the drug or to related Azole compounds.
• Coadministration of Terfenadine is contraindicated in patients receiving Fluconazole at multiple doses of 400 mg per day or higher based upon result of a multiple dose interaction study. Coadministration of other drugs known to prolong QT interval and which are metabolised via the enzyme CYP3A4 such as Cisapride, Astemizole, Pimozide and Quinidine are contraindicated in patients receiving Fluconazole. (see WARNINGS AND PRECAUTIONS and DRUG INTERACTIONS).
• Coadministration of Cisapride is contraindicated in patients receiving Fluconazole (see DRUG INTERACTIONS).

 

WARNINGS AND PRECAUTIONS :

• Fluconazole should be administered with caution to patients with liver dysfunction.
• Fluconazole has been associated with rare cases of serious hepatic toxicity, including fatalities, primarily in patients with serious underlying medical conditions. In cases of Fluconazole-associated hepatotoxicity, no obvious relationship to total daily dose, duration of therapy, sex or age of the patient has been observed. Fluconazole hepatotoxicity has usually been reversible on discontinuation of therapy.
• Patients who develop abnormal liver function tests during Fluconazole therapy should be monitored for the development of more serious hepatic injury. Fluconazole should be discontinued if clinical signs or symptoms consistent with liver disease develop that may be attributable to Fluconazole.
• Patients have rarely developed exfoliative cutaneous reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, during treatment with Fluconazole. AIDS patients are more prone to the development of severe cutaneous reactions to many drugs. If a rash, which is considered attributable to Fluconazole, develops in patients treated for a superficial fungal infection further therapy with this agent should be discontinued.
• If patients with invasive/systemic fungal infections develop rashes, they should be monitored closely and Fluconazole discontinued if bullous lesions or erythema multiforme develop.
• The coadministration of Fluconazole at doses lower than 400 mg per day with Terfenadine should be carefully monitored (see DRUG INTERACTIONS).
• In rare cases, as with other Azoles, anaphylaxis has been reported.
• 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 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.
• Fluconazole should be administered with caution to patients with renal dysfunction (see also DOSAGE AND ADMINISTRATIONS).
• Fluconazole is a potent CYP2C9 inhibitor and a moderate CYP3A4 inhibitor. Fluconazole treated patients who are concomitantly treated with drugs with a narrow therapeutic window metabolised through CYP2C9 and CYP3A4 should be monitored (see DRUG INTERACTIONS).
• Use during pregnancy :
  Use in pregnancy should be avoided except in patients with severe or potentially life-threatening fungal infections in whom Fluconazole may be used if the anticipated benefit outweighs the possible risk to the fetus.
  There’s a distinctive and a rare pattern of birth defects among infants whose mother 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.
• Use during lactation :
  Fluconazole is found in human breast milk at concentrations similar to plasma, therefore use in nursing mothers is not recommended.
• Effects on ability to drive and use machines :
  Experience with Fluconazole indicates that therapy is unlikely to impair a patient ability to drive or use machinery.

 

PRESENTATION :

Fludis^® Capsule 150 mg              Box, 1 bottle @ 1 capsule              Reg. No. DKL9602323201B2

 

STORAGE :

STORE BELOW 30°C, PROTECT FROM LIGHT

 

ON MEDICAL PRESCRIPTION ONLY

 

Manufactured by :

PT. BERNOFARM

Sidoarjo – Indonesia