Fluconazole (Fluconazole) - Indications and Dosage

INDICATIONS AND USAGE

Fluconazole is indicated for the treatment of:

1. Vaginal candidiasis (vaginal yeast infections due to Candida).
2. Oropharyngeal and esophageal candidiasis. In open noncomparative studies of relatively small numbers of patients, fluconazole was also effective for the treatment of Candida urinary tract infections, peritonitis, and systemic Candida infections including candidemia, disseminated candidiasis, and pneumonia.
3. Cryptococcal meningitis. Before prescribing fluconazole for AIDS patients with cryptococcal meningitis, please see CLINICAL STUDIES section. Studies comparing fluconazole to amphotericin B in non-HIV infected patients have not been conducted.

DOSAGE AND ADMINISTRATION

Dosage and Administration in Adults:

Single Dose

Vaginal candidiasis

The recommended dosage of fluconazole for vaginal candidiasis is 150 mg as a single oral dose.

Multiple Dose

SINCE ORAL ABSORPTION IS RAPID AND ALMOST COMPLETE, THE DAILY DOSE OF FLUCONAZOLE IS THE SAME FOR ORAL (TABLETS AND SUSPENSION) AND INTRAVENOUS ADMINISTRATION. In general, a loading dose of twice the daily dose is recommended on the first day of therapy to result in plasma concentrations close to steady-state by the second day of therapy.

The daily dose of fluconazole for the treatment of infections other than vaginal candidiasis should be based on the infecting organism and the patient's response to therapy. 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.

Oropharyngeal candidiasis

The recommended dosage of fluconazole for oropharyngeal candidiasis is 200 mg on the first day, followed by 100 mg once daily. Clinical evidence of oropharyngeal candidiasis generally resolves within several days, but treatment should be continued for at least 2 weeks to decrease the likelihood of relapse.

Esophageal candidiasis

The recommended dosage of fluconazole for esophageal candidiasis is 200 mg on the first day, followed by 100 mg once daily. Doses up to 400 mg/day may be used, based on medical judgment of the patient's response to therapy. Patients with esophageal candidiasis should be treated for a minimum of three weeks and for at least two weeks following resolution of symptoms.

Systemic Candida infections

For systemic Candida infections including candidemia, disseminated candidiasis, and pneumonia, optimal therapeutic dosage and duration of therapy have not been established. In open, noncomparative studies of small numbers of patients, doses of up to 400 mg daily have been used.

Urinary tract infections and peritonitis

For the treatment of Candida urinary tract infections and peritonitis, daily doses of 50 to 200 mg have been used in open, noncomparative studies of small numbers of patients.

Cryptococcal meningitis

The recommended dosage for treatment of acute cryptococcal meningitis is 400 mg on the first day, followed by 200 mg once daily. A dosage of 400 mg once daily may be used, based on medical judgment of the patient's response to therapy. The recommended duration of treatment for initial therapy of cryptococcal meningitis is 10 to 12 weeks after the cerebrospinal fluid becomes culture negative. The recommended dosage of fluconazole for suppression of relapse of cryptococcal meningitis in patients with AIDS is 200 mg once daily.

Prophylaxis in patients undergoing bone marrow transplantation

The recommended fluconazole daily dosage for the prevention of candidiasis of patients undergoing bone marrow transplantation is 400 mg, once daily. Patients who are anticipated to have severe granulocytopenia (less than 500 neutrophils per cu mm) should start fluconazole prophylaxis several days before the anticipated onset of neutropenia, and continue for 7 days after the neutrophil count rises above 1000 cells per cu mm.

Dosage and Administration in Children

The following dose equivalency scheme should generally provide equivalent exposure in pediatric and adult patients:

Pediatric Patients	Adults
* Some older children may have clearances similar to that of adults. Absolute doses exceeding 600 mg/day are not recommended.
3 mg/kg	100 mg
6 mg/kg	200 mg
12* mg/kg	400 mg

Experience with fluconazole in neonates is limited to pharmacokinetic studies in premature newborns. (See CLINICAL PHARMACOLOGY.) Based on the prolonged half-life seen in premature newborns (gestational age 26 to 29 weeks), these children, in the first two weeks of life, should receive the same dosage (mg/kg) as in older children, but administered every 72 hours. After the first two weeks, these children should be dosed once daily. No information regarding fluconazole pharmacokinetics in full-term newborns is available.

Oropharyngeal candidiasis

The recommended dosage of fluconazole for oropharyngeal candidiasis in children is 6 mg/kg on the first day, followed by 3 mg/kg once daily. Treatment should be administered for at least 2 weeks to decrease the likelihood of relapse.

Esophageal candidiasis

For the treatment of esophageal candidiasis, the recommended dosage of fluconazole in children is 6 mg/kg on the first day, followed by 3 mg/kg once daily. Doses up to 12 mg/kg/day may be used based on medical judgment of the patient's response to therapy. Patients with esophageal candidiasis should be treated for a minimum of three weeks and for at least 2 weeks following the resolution of symptoms.

Systemic Candida infections

For the treatment of candidemia and disseminated Candida infections, daily doses of 6 to 12 mg/kg/day have been used in an open, noncomparative study of a small number of children.

Cryptococcal meningitis

For the treatment of acute cryptococcal meningitis, the recommended dosage is 12 mg/kg on the first day, followed by 6 mg/kg once daily. A dosage of 12 mg/kg once daily may be used, based on medical judgment of the patient's response to therapy. The recommended duration of treatment for initial therapy of cryptococcal meningitis is 10 to 12 weeks after the cerebrospinal fluid becomes culture negative. For suppression of relapse of cryptococcal meningitis in children with AIDS, the recommended dose of fluconazole is 6 mg/kg once daily.

Dosage In Patients With Impaired Renal Function

Fluconazole is cleared primarily by renal excretion as unchanged drug. There is no need to adjust single dose therapy for vaginal candidiasis because of impaired renal function. In patients with impaired renal function who will receive multiple doses of fluconazole, an initial loading dose of 50 to 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/min)	Percent of Recommended Dose
> 50	100%
≤ 50 (no dialysis)	50%
Regular dialysis	100% after each dialysis

These are suggested dose adjustments based on pharmacokinetics following administration of multiple doses. Further adjustment may be needed depending upon clinical condition.

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 used to estimate the creatinine clearance in adults:

Males:	Weight (kg) x (140-age)
	72 x serum creatinine (mg/100 mL)

Females: 0.85 x above value

Although the pharmacokinetics of fluconazole has not been studied in children with renal insufficiency, dosage reduction in children with renal insufficiency should parallel that recommended for adults. The following formula may be used to estimate creatinine clearance in children:

K x	linear length or height (cm
	Serum creatinine (mg/100 mL)

(Where K = 0.55 for children older than 1 year and 0.45 for infants.)

HOW SUPPLIED

Fluconazole tablets, 50 mg are pink, circular, debossed with “RX803” on one side and plain on the other. They are supplied as follows

NDC 63304-803-30 bottles of 30

NDC 63304-803-05 bottles of 500

Fluconazole tablets, 100 mg are pink, circular, debossed with “RX804” on one side and plain on the other. They are supplied as follows:

NDC 63304-804-30 bottles of 30

NDC 63304-804-01 bottles of 100

NDC 63304-804-05 bottles of 500

Fluconazole tablets, 150 mg are pink, circular, debossed with “RX805” on one side and plain on the other. They are supplied as follows:

NDC 63304-805-01 1 Blister card of 1 unit-dose tablet

Fluconazole tablets, 200 mg are pink, circular, debossed with “RX806” on one side and plain on the other. They are supplied as follows:

NDC 63304-806-30 bottles of 30

NDC 63304-806-01 bottles of 100

NDC 63304-806-05 bottles of 500

Store tablets at 20 - 25° C (68 - 77° F). (See USP Controlled Room Temperature)

* Maalox is a registered trademark of Aventis Pharmaceuticals.

Manufactured for:

Ranbaxy Pharmaceuticals Inc.

Jacksonville, FL 32216 USA

by: Ranbaxy Laboratories Limited

New Delhi – 110 019, India

October 2006

PATIENT INFORMATION

FLUCONAZOLE TABLETS

This leaflet contains important information about fluconazole (floo-kon' -zol). It is not meant to take the place of your doctor's instructions. Read this information carefully before you take fluconazole. Ask your doctor or pharmacist if you do not understand any of this information or if you want to know more about fluconazole.

What is Fluconazole?

Fluconazole is a tablet you swallow to treat vaginal yeast infections caused by a yeast called Candida. Fluconazole helps stop too much yeast from growing in the vagina so the yeast infection goes away.

Fluconazole is different from other treatments for vaginal yeast infections because it is a tablet taken by mouth. Fluconazole is also used for other conditions. However, this leaflet is only about using fluconazole for vaginal yeast infections. For information about using fluconazole for other reasons, ask your doctor or pharmacist. See the section of this leaflet for information about vaginal yeast infections.

What Is A Vaginal Yeast Infection?

It is normal for a certain amount of yeast to be found in the vagina. Sometimes too much yeast starts to grow in the vagina and this can cause a yeast infection. Vaginal yeast infections are common. About three out of every four adult women will have at least one vaginal yeast infection during their life.

Some medicines and medical conditions can increase your chance of getting a yeast infection. If you are pregnant, have diabetes, use birth control pills, or take antibiotics you may get yeast infections more often than other women. Personal hygiene and certain types of clothing may increase your chances of getting a yeast infection. Ask your doctor for tips on what you can do to help prevent vaginal yeast infections.

If you get a vaginal yeast infection, you may have any of the following symptoms:

• itching
• a burning feeling when you urinate
• redness
• soreness
• a thick white vaginal discharge that looks like cottage cheese

What To Tell Your Doctor Before You Start Fluconazole?

Do not take fluconazole if you take certain medicines. They can cause serious problems. Therefore, tell your doctor about all the medicines you take including:

• diabetes medicines you take by mouth such as glyburide, tolbutamide, glipizide
• blood thinners such as warfarin
• cyclosporine (used to prevent rejection of organ transplants)
• rifampin or rifabutin (used for tuberculosis)
• astemizole (used for allergies)
• tacrolimus (used to prevent rejection of organ transplants)
• phenytoin (used for seizures)
• theophylline (used for asthma)
• cisapride (Propulsid^®†; used for stomach acid problems)

Since there are many brand names for these medicines, check with your doctor or pharmacist if you have any questions.

• are taking any over-the-counter medicines you can buy without a prescription, including natural or herbal remedies.
• have any liver problems.
• have any other medical conditions
• are pregnant, plan to become pregnant, or think you might be pregnant. Your doctor will discuss whether fluconazole is right for you.
• are breast-feeding. Fluconazole can pass through breast milk to the baby.
• are allergic to any other medicines including those used to treat yeast and other fungal infections.
• are allergic to any of the ingredients in fluconazole tablets. The main ingredient is fluconazole. If you need to know the inactive ingredients, ask your doctor or pharmacist.

Who Should Not Take Fluconazole?

To avoid a possible serious reaction, do NOT take fluconazole if you are taking cisapride (Propulsid^®) since it can cause changes in heartbeat in some people if taken with fluconazole.

How Should I Take Fluconazole?

Take fluconazole by mouth with or without food. You can take fluconazole at any time of the day. Fluconazole keeps working for several days to treat the infection. Generally the symptoms start to go away after 24 hours. However, it may take several days for your symptoms to go away completely. If there is no change in your symptoms after a few days, call your doctor.

Just swallow 1 fluconazole tablet to treat your vaginal yeast infection.

What Should I Avoid While Taking Fluconazole?

Some medicines can affect how well fluconazole works. Check with your doctor before starting any new medicines within seven days of taking fluconazole.

What Are The Possible Side Effects of Fluconazole?

Like all medicines, fluconazole may cause some side effects that are usually mild to moderate. The most common side effects of fluconazole are:

• headache
• diarrhea
• nausea or upset stomach
• dizziness
• stomach pain
• changes in the way food tastes

Allergic reactions to fluconazole are rare, but they can be very serious if not treated right away by a doctor. If you cannot reach your doctor, go to the nearest hospital emergency room. Signs of an allergic reaction can include shortness of breath; coughing; wheezing; fever; chills; throbbing of the heart or ears; swelling of the eyelids, face, mouth, neck, or any other part of the body; or skin rash, hives, blisters or skin peeling.

Fluconazole has been linked to rare cases of serious liver damage, including deaths, mostly in patients with serious medical problems. Call your doctor if your skin or eyes become yellow, your urine turns a darker color, your stools (bowel movements) are light-colored, or if you vomit or feel like vomiting or if you have severe skin itching.

In patients with serious conditions such as AIDS or cancer, rare cases of severe rashes with skin peeling have been reported. Tell your doctor right away if you get a rash while taking fluconazole.

Fluconazole may cause other less common side effects besides those listed here. If you develop any side effects that concern you, call your doctor. For a list of all side effects, ask your doctor or pharmacist.

What To Do For An Overdose

In case of an accidental overdose, call your doctor right away or go to the nearest emergency room.

How To Store Fluconazole

Keep fluconazole and all medicines out of the reach of children.

General Advice About Prescription Medicines

Medicines are sometimes prescribed for conditions that are mentioned in patient information leaflets. Do not use fluconazole for a condition for which it was not prescribed. Do not give fluconazole to other people, even if they have the same symptoms you have. It may harm them.

This leaflet summarizes the most important information about fluconazole. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about fluconazole that is written for health professionals.

^†Propulsid (cisapride) is a registered trademark of Janssen Pharmaceutica.