Fluconazole Tablets IP 50mg (FANTIZOLE) Taj Pharma

Overview

Introduction

Fantizole 50mg Tablet belongs to a group of medicines called antifungals. It works by stopping the growth of fungus and is used to treat infections of the mouth, throat, vagina and other parts of the body including fingernails and toenails. It kills fungi by destroying the fungal cell membrane.

Fantizole 50mg Tablet should be taken in the dose and duration as prescribed by your doctor. It should be swallowed whole and can be taken with or without food. The dosage and length of treatment will depend on the condition you are being treated for. Sometimes this will be in cycles of use and non-use. To get the most benefit, take this medicine at evenly spaced times and continue using it until your prescription is finished, even if your symptoms disappear after a few days. If you stop treatment too early, the infection may return and if you miss doses you can increase your risk of infections that are resistant to further treatment. Tell your doctor if the infection does not get better or if it gets worse. Avoid taking antacid treatments within one hour before or two hours after you take it.

The most common side effects of this medicine include stomach pain, headache and feeling sick (nausea). You could ask your doctor about ways of preventing or reducing these effects. You should stop taking it straight away if you have any signs of an allergic reaction or of congestive heart failure. Signs of this include rash, swelling of the lips, throat or face, swallowing or breathing problems, feeling dizzy or faint and nausea.

Do not take it if you are pregnant or could become pregnant unless your doctor has told you to. Talk to your doctor before taking it if you have ever had heart failure, a weak immune system (including HIV/AIDS), kidney problems or liver problems such as yellow skin (jaundice). This medicine may not be suitable for you. If your course of treatment is for more than a month, your doctor may want to check your liver by testing your blood. This medicine may make you dizzy or have blurred vision so do not drive or operate machines until it is safe.

Uses of Fantizole Tablet

• Fungal infections

How to use Fantizole Tablet

Take this medicine in the dose and duration as advised by your doctor. Swallow it as a whole. Do not chew, crush or break it. Fantizole 50mg Tablet may be taken with or without food, but it is better to take it at a fixed time.

How Fantizole Tablet works

Fantizole 50mg Tablet is an antifungal medication. It kills fungi by destroying the fungal cell membrane. This treats your infection.

Safety Advice

Alcohol

CAUTION

Caution is advised when consuming alcohol with Fantizole 50mg Tablet. Please consult your doctor.

Pregnancy

CONSULT YOUR DOCTOR

Fantizole 50mg Tablet is unsafe to use during pregnancy as there is definite evidence of risk to the developing baby. However, the doctor may rarely prescribe it in some life-threatening situations if the benefits are more than the potential risks. Please consult your doctor.

Breastfeeding

SAFE IF PRESCRIBED

Fantizole 50mg Tablet is safe to use during breastfeeding. Human studies suggest that the drug does not pass into the breastmilk in a significant amount and is not harmful to the baby.

Driving

UNSAFE

Fantizole 50mg Tablet may cause side effects which could affect your ability to drive.
Fantizole 50mg Tablet may cause dizziness or seizures. This may affect your ability to drive.

Kidney

UNSAFE

Fantizole 50mg Tablet is probably unsafe to use in patients with kidney disease and should be avoided. Please consult your doctor.
Caution to be advised in patients with impaired renal function.

Liver

There is no data available. Please consult doctor before consuming the drug.

What if you forget to take Fantizole Tablet?

If you miss a dose of Fantizole 50mg Tablet, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular schedule. Do not double the dose.

Fluconazole Tablets IP 50mg (FANTIZOLE) Taj Pharma

1.Name of the medicinal product
a) Fluconazole Tablets IP 50mg Taj Pharma (Fantizole)
b) Fluconazole Tablets IP 150mg Taj Pharma (Fantizole)
c) Fluconazole Tablets IP 200mg Taj Pharma (Fantizole)
d) Fluconazole Tablets IP 400mg Taj Pharma (Fantizole)

2. Qualitative and quantitative composition
a) Each tablet Contains:
Fluconazole 50mg
Excipients q.s.
b) Each tablet contains:
Fluconazole 150mg
Excipients q.s.
c) Each tablet contains:
Fluconazole 200mg
Excipients q.s.
d) Each tablet contains:
Fluconazole 400mg
Excipients q.s.

3.PHARMACEUTICAL FORM:

Tablets

4.CLINICAL PARTICULARS:

4.1. Therapeutic indications:

Fluconazole is indicated for the treatment of: Vaginal candidiasis (vaginal yeast infections due to Candida).

2. Oropharyngeal and esophageal candidiasis. In open noncomparative studies of relatively small numbers of patients, 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 to amphotericin B in non-HIV infected patients have not been conducted.

Prophylaxis:  is also indicated to decrease the incidence of candidiasis in patients undergoing bone marrow transplantation who receive cytotoxic chemotherapy and/or radiation therapy.

Specimens for fungal culture and other relevant laboratory studies (serology, histopathology) should be obtained prior to therapy to isolate and identify causative organisms. 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.

CLINICAL STUDIES

Cryptococcal meningitis

In a multicenter study comparing  (200 mg/day) to amphotericin B (0.3 mg/kg/day) for treatment of cryptococcal meningitis in patients with AIDS, a multivariate analysis revealed three pretreatment factors that predicted death during the course of therapy: abnormal mental status, cerebrospinal fluid cryptococcal antigen titer greater than 1:1024, and cerebrospinal fluid white blood cell count of less than 20 cells/mm3. Mortality among high risk patients was 33% and 40% for amphotericin B and patients, respectively (p=0.58), with overall deaths 14% (9 of 63 subjects) and 18% (24 of 131 subjects) for the 2 arms of the study (p=0.48). Optimal doses and regimens for patients with acute cryptococcal meningitis and at high risk for treatment failure remain to be determined. (Saag, et al. N Engl J Med 1992; 326:83-9.)

Vaginal candidiasis

Two adequate and well-controlled studies were conducted in the U.S. using the 150 mg tablet. In both, the results of the fluconazole regimen were comparable to the control regimen (clotrimazole or miconazoleintravaginally for 7 days) both clinically and statistically at the one month post-treatment evaluation.

The therapeutic cure rate, defined as a complete resolution of signs and symptoms of vaginal candidiasis (clinical cure), along with a negative KOH examination and negative culture for Candida (microbiologic eradication), was 55% in both the fluconazole group and the vaginal products group.

Approximately three-fourths of the enrolled patients had acute vaginitis (<4 episodes/12 months) and achieved 80% clinical cure, 67% mycologic eradication, and 59% therapeutic cure when treated with a 150 mg  tablet administered orally. These rates were comparable to control products. The remaining one-fourth of enrolled patients had recurrent vaginitis (≥4 episodes/12 months) and achieved 57% clinical cure, 47% mycologic eradication, and 40% therapeutic cure. The numbers are too small to make meaningful clinical or statistical comparisons with vaginal products in the treatment of patients with recurrent vaginitis.

Substantially more gastrointestinal events were reported in the fluconazole group compared to the vaginal product group. Most of the events were mild to moderate. Because fluconazole was given as a single dose, no discontinuations occurred.

Pediatric Studies

Oropharyngeal candidiasis

An open-label, comparative study of the efficacy and safety of (2 to 3 mg/kg/day) and oral nystatin (400,000 I.U. 4 times daily) in immunocompromised children with oropharyngeal candidiasis was conducted. Clinical and mycological response rates were higher in the children treated with fluconazole.

Clinical cure at the end of treatment was reported for 86% of fluconazole-treated patients compared to 46% of nystatin treated patients. Mycologically, 76% of fluconazole treated patients had the infecting organism eradicated compared to 11% for nystatin treated patients.

The proportion of patients with clinical relapse 2 weeks after the end of treatment was 14% for subjects receiving and 16% for subjects receiving nystatin. At 4 weeks after the end of treatment, the percentages of patients with clinical relapse were 22% for and 23% for nystatin.

4.2.  Dosage and Administration in Children

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

Experience with 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  pharmacokinetics in full-term newborns is available.

Oropharyngeal candidiasis

The recommended dosage of fororopharyngeal 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 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 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 an initial loading dose of 50 mg to 400 mg should be given. After the loading dose, the daily dose (according to indication) should be based on the following table:

Patients on hemodialysis should receive 100% of the recommended dose after each hemodialysis; on non-dialysis days, patients should receive a reduced dose according to their creatinine clearance.

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:

Females: 0.85 × 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:

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

Administration

is administered orally.  can be taken with or without food.

Note: Shake oral suspension well before using. Store reconstituted suspension between 86°F (30°C) and 41°F (5°C) and discard unused portion after 2 weeks. Protect from freezing.

4.3. Contraindications

Fluconazole is contraindicated in patients who have shown hypersensitivity to fluconazole or to any of its excipients. There is no information regarding cross-hypersensitivity between fluconazole and other azole antifungal agents. Caution should be used in prescribing to patients with hypersensitivity to other azoles. Coadministration of terfenadine is contraindicated in patients receiving  fluconazole at multiple doses of 400 mg/day or higher based upon results of a multiple dose interaction study. Coadministration of other drugs known to prolong the QT interval and which are metabolized via the enzyme CYP3A4 such as cisapride, astemizole, erythromycin, pimozide, and quinidine are contraindicated in patients receiving fluconazole. (see clinical pharmacology: drug interaction studies and precautions.)

4.4 Warnings and Precautions

(1) Hepatic injury:  should be administered with caution to patients with liver dysfunction.  has been associated with rare cases of serious hepatic toxicity, including fatalities primarily in patients with serious underlying medical conditions. In cases of -associated hepatotoxicity, no obvious relationship to total daily dose, duration of therapy, sex, or age of the patient has been observed.  hepatotoxicity has usually, but not always, been reversible on discontinuation of therapy. Patients who develop abnormal liver function tests during therapy should be monitored for the development of more severe hepatic injury.  should be discontinued if clinical signs and symptoms consistent with liver disease develop that may be attributable to.

(2) Anaphylaxis: In rare cases, anaphylaxis has been reported.

(3) Dermatologic: Exfoliative skin disorders during treatment with have been reported. Fatal outcomes have been reported in patients with serious underlying diseases. Patients with deep seated fungal infections who develop rashes during treatment with should be monitored ly and the drug discontinued if lesions progress. fluconazole should be discontinued in patients treated for superficial fungal infection who develop a rash that may be attributed to fluconazole.

(4) potential for fetal harm: there are no adequate and well-controlled clinical trials of  inpregnant women. case reports describe a pattern of distinct congenital anomalies in infants exposed in utero to high dose maternal fluconazole (400 to 800 mg/day) during most or all of the first trimester. these reported anomalies are similar to those seen in animal studies. if 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. effective contraceptive measures should be considered in women of child-bearing potential who are being treated with 400 to 800 mg/day and should continue throughout the treatment period and for approximately 1 week (5 to 6 half-lives) after the final dose. epidemiological studies suggest a potential risk of spontaneous abortion and congenital abnormalities in infants whose mothers were treated with 150 mg of fluconazole as a single or repeated dose in the first trimester, but these epidemiological studies have limitations and these findings have not been confirmed in controlled clinical trials. (see precautions: pregnancy.)

precautions

general

some azoles, including fluconazole, have been associated with prolongation of the qt interval on the electrocardiogram. fluconazole causes qt prolongation via the inhibition of rectifier potassium channel current (ikr). the qt prolongation caused by other medicinal products (such as amiodarone) may be amplified via the inhibition of cytochrome p450 (cyp) 3a4. (see precautions: drug interactions.) During post-marketing surveillance, there have been rare cases of QT prolongation and torsade de pointes in patients taking fluconazole. Most of these reports involved seriously ill patients with multiple confounding risk factors, such as structural heart disease, electrolyte abnormalities, and concomitant medications that may have been contributory. Patients with hypokalemia and advanced cardiac failure are at an increased risk for the occurrence of life-threatening ventricular arrhythmias and torsade de pointes.

Fluconazole should be administered with caution to patients with these potentially proarrhythmic conditions.

Concomitant use of fluconazole and erythromycin has the potential to increase the risk of cardiotoxicity (prolonged QT interval, torsade de pointes) and consequently sudden heart death. This combination should be avoided.

Fluconazole should be administered with caution to patients with renal dysfunction.

Adrenal insufficiency has been reported in patients receiving azoles, including fluconazole. Reversible cases of adrenal insufficiency have been reported in patients receiving fluconazole.

Powder for Oral Suspension contains sucrose and should not be used in patients with hereditary fructose, glucose/galactosemalabsorption, and sucrase-isomaltase deficiency.

When driving vehicles or operating machines, it should be taken into account that occasionally dizziness or seizures may occur.

Single Dose

The convenience and efficacy of the single dose oral tablet of fluconazole regimen for the treatment of vaginal yeast infections should be weighed against the acceptability of a higher incidence of drug related adverse events with  (26%) versus intravaginal agents (16%) in u.s. comparative clinical studies. (see adverse reactions and clinical studies.)

4.5. Drug Interactions: (see contraindications.) Fluconazole is a moderate CYP2C9 and CYP3A4 inhibitor. Fluconazole is also a strong inhibitor of CYP2C19. Patients treated with, who are also concomitantly treated with drugs with a narrow therapeutic window metabolized through CYP2C9 and CYP3A4, should be monitored for adverse reactions associated with the concomitantly administered drugs. In addition to the observed /documented interactions mentioned below, there is a risk of increased plasma concentration of other compounds metabolized by CYP2C9, CYP2C19, and CYP3A4 coadministered with fluconazole. Therefore, caution should be exercised when using these combinations and the patients should be carefully monitored. The enzyme inhibiting effect of fluconazole persists 4 to 5 days after discontinuation of fluconazole treatment due to the long half-life of fluconazole. Clinically or potentially significant drug interactions between and the following agents/classes have been observed and are described in greater detail below:

Alfentanil

Amiodarone

Amitriptyline, nortriptyline

Amphotericin B

Astemizole

Azithromycin

Calcium channel blockers

Carbamazepine

Celecoxib

Coumarin-type anticoagulants

Cyclophosphamide

Cyclosporine

Fentanyl

Halofantrine

HMG-CoA reductase inhibitors

Hydrochlorothiazide

Losartan

Methadone

Non-steroidal anti-inflammatory drugs

Olaparib

Oral contraceptives

Oral hypoglycemics

Phenytoin

Pimozide

Prednisone

Quinidine

Rifabutin

Rifampin

Saquinavir

Short-acting benzodiazepines

Sirolimus

Tacrolimus

Terfenadine

Theophylline

Tofacitinib

Triazolam

Vinca alkaloids

Vitamin A

Voriconazole

Zidovudine

Carcinogenesis, Mutagenesis, and Impairment of Fertility

Fluconazole showed no evidence of carcinogenic potential in mice and rats treated orally for 24 months at doses of 2.5 mg/kg/day, 5 mg/kg/day, or 10 mg/kg/day (approximately 2 to 7 times the recommended human dose). Male rats treated with 5 mg/kg/day and 10 mg/kg/day had an increased incidence of hepatocellular adenomas.

Fluconazole, with or without metabolic activation, was negative in tests for mutagenicity in four strains of S. typhimurium, and in the mouse lymphoma L5178Y system. Cytogenetic studies in vivo (murine bone marrow cells, following oral administration of fluconazole) and in vitro (human lymphocytes exposed to fluconazole at 1000 mcg/mL) showed no evidence of chromosomal mutations.

Fluconazole did not affect the fertility of male or female rats treated orally with daily doses of 5 mg/kg, 10 mg/kg, or 20 mg/kg or with parenteral doses of 5 mg/kg, 25 mg/kg, or 75 mg/kg, although the onset of parturition was slightly delayed at 20 mg/kg PO. In an intravenous perinatal study in rats at 5 mg/kg, 20 mg/kg, and 40 mg/kg, dystocia and prolongation of parturition were observed in a few dams at 20 mg/kg (approximately 5 to 15 times the recommended human dose) and 40 mg/kg, but not at 5 mg/kg. The disturbances in parturition were reflected by a slight increase in the number of still born pups and decrease of neonatal survival at these dose levels. The effects on parturition in rats are consistent with the species specific estrogen-lowering property produced by high doses of fluconazole. Such a hormone change has not been observed in women treated with fluconazole. (see clinical pharmacology.)

Pregnancy

Teratogenic Effects

Potential for Fetal Harm

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. A few published case reports describe a pattern of distinct congenital anomalies in infants exposed in utero to high dose maternal fluconazole (400 to 800 mg/day) during most or all of the first trimester. These reported anomalies are similar to those seen in animal studies. Effective contraceptive measures should be considered in women of child-bearing potential who are being treated with 400 to 800 mg/day and should continue throughout the treatment period and for approximately 1 week (5 to 6 half-lives) after the final dose. If isused during pregnancy, or if the patient becomes pregnant while taking the drug, the patient should be informed of the potential hazard to the fetus. Spontaneous abortions and congenital abnormalities have been suggested as potential risks associated with 150 mg of fluconazole as a single or repeated dose in the first trimester of pregnancy based on retrospective epidemiological studies. There are no adequate and well-controlled studies of in pregnant women. (see warnings: potential for fetal harm.)

Human Data

Case reports describe a distinctive and rare pattern of birth defects among infants whose mothers received high-dose (400 to 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.

Epidemiological studies suggest a potential risk of spontaneous abortion and congenital abnormalities in infants whose mothers were treated with 150 mg of fluconazole as a single or repeated dose in the first trimester, but these epidemiological studies have limitations and these findings have not been confirmed in controlled clinical trials.

Animal Data

Fluconazole was administered orally to pregnant rabbits during organogenesis in two studies at doses of 5 mg/kg, 10 mg/kg, and 20 mg/kg and at 5 mg/kg, 25 mg/kg, 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 body surface area [BSA] comparison), and abortions occurred at 75 mg/kg (approximately 4 times the 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 mg/kg or 10 mg/kg; increases in fetal anatomical variants (supernumerary ribs, renal pelvis dilation) and delays in ossification were observed at 25 mg/kg 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 craniofacial 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.

Nursing Mothers

Fluconazole was present in low levels in breast milk following administration of a single 150 mg dose, based on data from a study in 10 breastfeeding women who temporarily or permanently discontinued breastfeeding 5 days to 19 months postpartum. The estimated daily infant dose of fluconazole from breast milk (assuming mean milk consumption of 150 mL/kg/day) based on the mean peak milk concentration (2.61 mcg/mL [range: 1.57 to 3.65 mcg/mL] at 5.2 hours post-dose) was 0.39 mg/kg/day, which is approximately 13% of the recommended pediatric dose for oropharyngeal candidiasis. (Labeled pediatric dose is 6 mg/kg/day on the first day followed by 3 mg/kg/day; estimated infant dose is 13% of 3 mg/kg/day maintenance dose). There are no data on fluconazole levels in milk after repeated use or after high-dose fluconazole. A published survey of 96 breastfeeding women who were treated with fluconazole 150 mg every other day (average of 7.3 capsules [range 1 to 29 capsules]) for lactation-associated candida of the breasts reported no serious adverse reactions in infants. Caution should be exercised when is administered to a nursing woman.

Pediatric Use

An open-label, randomized, controlled trial has shown to be effective in the treatment of oropharyngeal candidiasis in children 6 months to 13 years of age. (see clinical studies.)

The use of in children with cryptococcal meningitis, Candida esophagitis, or systemic Candida infections is supported by the efficacy shown for these indications in adults and by the results from several small noncomparative pediatric clinical studies. In addition, pharmacokinetic studies in children (see clinical pharmacology) have established a dose proportionality between children and adults. (see dosage and administration.)

In a noncomparative study of children with serious systemic fungal infections, most of which were candidemia, the effectiveness of  was similar to that reported for the treatment of candidemia in adults. Of 17 subjects with culture-confirmed candidemia, 11 of 14 (79%) with baseline symptoms (3 were asymptomatic) had a clinical cure; 13/15 (87%) of evaluable patients had a mycologic cure at the end of treatment but two of these patients relapsed at 10 and 18 days, respectively, following cessation of therapy.

The efficacy of for the suppression of cryptococcal meningitis was successful in 4 of 5 children treated in a compassionate-use study of fluconazole for the treatment of life-threatening or serious mycosis. There is no information regarding the efficacy of fluconazole for primary treatment of cryptococcal meningitis in children.

The safety profile of  in children has been studied in 577 children ages 1 day to 17 years who received doses ranging from 1 to 15 mg/kg/day for 1 to 1,616 days. (see adverse reactions.)

Efficacy of has not been established in infants less than 6 months of age. (see clinical pharmacology.) A small number of patients (29) ranging in age from 1 day to 6 months have been treated safely with.

Geriatric Use

In non-AIDS patients, side effects possibly related to fluconazole treatment were reported in fewer patients aged 65 and older (9%, n =339) than for younger patients (14%, n=2240). However, there was no consistent difference between the older and younger patients with respect to individual side effects. Of the most frequently reported (>1%) side effects, rash, vomiting, and diarrhea occurred in greater proportions of older patients. Similar proportions of older patients (2.4%) and younger patients (1.5%) discontinued fluconazole therapy because of side effects. In post-marketing experience, spontaneous reports of anemia and acute renal failure were more frequent among patients 65 years of age or older than in those between 12 and 65 years of age. Because of the voluntary nature of the reports and the natural increase in the incidence of anemia and renal failure in the elderly, it is however not possible to establish a causal relationship to drug exposure.

Controlled clinical trials of fluconazole did not include sufficient numbers of patients aged 65 and older to evaluate whether they respond differently from younger patients in each indication. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

Fluconazole is primarily cleared by renal excretion as unchanged drug. Because elderly patients are more likely to have decreased renal function, care should be taken to adjust dose based on creatinine clearance. it may be useful to monitor renal function. (see clinical pharmacology and dosage and administration.)

4.7. Undesirable Effects

is generally well tolerated.

In some patients, particularly those with serious underlying diseases such as AIDS and cancer, changes in renal and hematological function test results and hepatic abnormalities have been observed during treatment with fluconazole and comparative agents, but the clinical significance and relationship to treatment is uncertain.

In Patients Receiving a Single Dose for Vaginal Candidiasis

During comparative clinical studies conducted in the United States, 448 patients with vaginal candidiasis were treated with, 150 mg single dose. The overall incidence of side effects possibly related to was 26%. In 422 patients receiving active comparative agents, the incidence was 16%. The most common treatment-related adverse events reported in the patients who received 150 mg single dose fluconazole for vaginitis were headache (13%), nausea (7%), and abdominal pain (6%). Other side effects reported with an incidence equal to or greater than 1% included diarrhea (3%), dyspepsia (1%), dizziness (1%), and taste perversion (1%). Most of the reported side effects were mild to moderate in severity. Rarely, angioedema and anaphylactic reaction have been reported in marketing experience.

In Patients Receiving Multiple Doses for Other Infections

Sixteen percent of over 4000 patients treated with fluconazole in clinical trials of 7 days or more experienced adverse events. Treatment was discontinued in 1.5% of patients due to adverse clinical events and in 1.3% of patients due to laboratory test abnormalities.

Clinical adverse events were reported more frequently in HIV infected patients (21%) than in non-HIV infected patients (13%); however, the patterns in HIV infected and non-HIV infected patients were similar. The proportions of patients discontinuing therapy due to clinical adverse events were similar in the two groups (1.5%).

The following treatment-related clinical adverse events occurred at an incidence of 1% or greater in 4048 patients receiving for 7 or more days in clinical trials: nausea 3.7%, headache 1.9%, skin rash 1.8%, vomiting 1.7%, abdominal pain 1.7%, and diarrhea 1.5%.

Hepato-biliary

In combined clinical trials and marketing experience, there have been rare cases of serious hepatic reactions during treatment with. (see warnings.) The spectrum of these hepatic reactions has ranged from mild transient elevations in transaminases to clinical hepatitis, cholestasis and fulminant hepatic failure, including fatalities. Instances of fatal hepatic reactions were noted to occur primarily in patients with serious underlying medical conditions (predominantly AIDS or malignancy) and often while taking multiple concomitant medications. Transient hepatic reactions, including hepatitis and jaundice, have occurred among patients with no other identifiable risk factors. In each of these cases, liver function returned to baseline on discontinuation of .

In two comparative trials evaluating the efficacy of  for the suppression of relapse of cryptococcal meningitis, a statistically significant increase was observed in median AST (SGOT) levels from a baseline value of 30 IU/L to 41 IU/L in one trial and 34 IU/L to 66 IU/L in the other. The overall rate of serum transaminase elevations of more than 8 times the upper limit of normal was approximately 1% in fluconazole-treated patients in clinical trials. These elevations occurred in patients with severe underlying disease, predominantly AIDS or malignancies, most of whom were receiving multiple concomitant medications, including many known to be hepatotoxic. The incidence of abnormally elevated serum transaminases was greater in patients taking concomitantly with one or more of the following medications: rifampin, phenytoin, isoniazid, valproic acid, or oral sulfonylurea hypoglycemic agents.

Adverse Reactions in Children

The pattern and incidence of adverse events and laboratory abnormalities recorded during pediatric clinical trials are comparable to those seen in adults.

In Phase II/III clinical trials conducted in the United States and in Europe, 577 pediatric patients, ages 1 day to 17 years were treated with at doses up to 15 mg/kg/day for up to 1,616 days. Thirteen percent of children experienced treatment-related adverse events. The most commonly reported events were vomiting (5%), abdominal pain (3%), nausea (2%), and diarrhea (2%). Treatment was discontinued in 2.3% of patients due to adverse clinical events and in 1.4% of patients due to laboratory test abnormalities. The majority of treatment-related laboratory abnormalities were elevations of transaminases or alkaline phosphatase.

4.8. Overdosage

There have been reports of overdose with fluconazole accompanied by hallucination and paranoid behavior.

In the event of overdose, symptomatic treatment (with supportive measures and gastric lavage if clinically indicated) should be instituted.

Fluconazole is largely excreted in urine. A 3-hour hemodialysis session decreases plasma levels by approximately 50%.

In mice and rats receiving very high doses of fluconazole, clinical effects in both species included decreased motility and respiration, ptosis, lacrimation, salivation, urinary incontinence, loss of righting reflex, and cyanosis; death was sometimes preceded by clonic convulsions.

Dosage and administration

 In Adults

Single Dose

Vaginal candidiasis

The recommended dosage of 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   to steady-state by the second day of therapy.

The daily dose of 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 fororopharyngeal 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 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 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 daily dosage for the prevention of candidiasis in patients undergoing bone marrow transplantation is 400 mg, once daily. Patients who are anticipated to have severe granulocytopenia (less than 500 neutrophils cells/mm3) should start prophylaxis several days before the anticipated onset of neutropenia, and continue for 7 days after the neutrophil count rises above 1000 cells/mm3.

5. Pharmacological properties

Pharmacokinetics and Metabolism

The pharmacokinetic properties of fluconazole are similar following administration by the intravenous or oral routes. In normal volunteers, the bioavailability of orally administered fluconazole is over 90% compared with intravenous administration. Bioequivalence was established between the 100 mg tablet and both suspension strengths when administered as a single 200 mg dose.

Peak plasma concentrations (Cmax) in fasted normal volunteers occur between 1 and 2 hours with a terminal plasma elimination half-life of approximately 30 hours (range: 20 to 50 hours) after oral administration.

In fasted normal volunteers, administration of a single oral 400 mg dose of  fluconazole leads to a mean Cmax of 6.72 mcg/mL (range: 4.12 to 8.08 mcg/mL) and after single oral doses of 50 to 400 mg, fluconazole plasma concentrations and area under the plasma concentration-time curve (AUC) are dose proportional.

The Cmax and AUC data from a food-effect study involving administration of  Fluconazole Tablets (FANTIZOLE) to healthy volunteers under fasting conditions and with a high-fat meal indicated that exposure to the drug is not affected by food. Therefore, may be taken without regard to meals. (see dosage and administration.)

Steady-state concentrations are reached within 5 to 10 days following oral doses of 50 to 400 mg given once daily. Administration of a loading dose (on Day 1) of twice the usual daily dose results in plasma concentrations   to steady-state by the second day. The apparent volume of distribution of fluconazole approximates that of total body water. Plasma protein binding is low (11 to 12%). Following either single- or multiple oral doses for up to 14 days, fluconazole penetrates into all body fluids studied (see table below). In normal volunteers, saliva concentrations of fluconazole were equal to or slightly greater than plasma concentrations regardless of dose, route, or duration of dosing. In patients with bronchiectasis, sputum concentrations of fluconazole following a single 150 mg oral dose were equal to plasma concentrations at both 4 and 24 hours post dose. In patients with fungal meningitis, fluconazole concentrations in the cerebrospinal fluid (CSF) are approximately 80% of the corresponding plasma concentrations.

A single oral 150 mg dose of fluconazole administered to 27 patients penetrated into vaginal tissue, resulting in tissue: plasma ratios ranging from 0.94 to 1.14 over the first 48 hours following dosing.

A single oral 150 mg dose of fluconazole administered to 14 patients penetrated into vaginal fluid, resulting in fluid: plasma ratios ranging from 0.36 to 0.71 over the first 72 hours following dosing.

In normal volunteers, fluconazole is cleared primarily by renal excretion, with approximately 80% of the administered dose appearing in the urine as unchanged drug. About 11% of the dose is excreted in the urine as metabolites.

The pharmacokinetics of fluconazole are markedly affected by reduction in renal function. There is an inverse relationship between the elimination half-life and creatinine clearance. The dose of may need to be reduced in patients with impaired renal function. (see dosage and administration.) A 3-hour hemodialysis session decreases plasma concentrations by approximately 50%.

In normal volunteers,  administration (doses ranging from 200 mg to 400 mg once daily for up to 14 days) was associated with small and inconsistent effects on testosterone concentrations, endogenous corticosteroid concentrations, and the adrenocorticotropic hormone (ACTH)-stimulated cortisol response.

Pharmacokinetics in Children

In children, the following pharmacokinetic data {Mean (%cv)} have been reported:

Clearance corrected for body weight was not affected by age in these studies. Mean body clearance in adults is reported to be 0.23 (17%) mL/min/kg.

In premature newborns (gestational age 26 to 29 weeks), the mean (%cv) clearance within 36 hours of birth was 0.180 (35%, N=7) mL/min/kg, which increased with time to a mean of 0.218 (31%, N=9) mL/min/kg six days later and 0.333 (56%, N=4) mL/min/kg 12 days later. Similarly, the half-life was 73.6 hours, which decreased with time to a mean of 53.2 hours six days later and 46.6 hours 12 days later.

Pharmacokinetics in Elderly

A pharmacokinetic study was conducted in 22 subjects, 65 years of age or older receiving a single 50 mg oral dose of fluconazole. Ten of these patients were concomitantly receiving diuretics. The Cmax was 1.54 mcg/mL and occurred at 1.3 hours post dose. The mean AUC was 76.4 ± 20.3 mcg∙h/mL, and the mean terminal half-life was 46.2 hours. These pharmacokinetic parameter values are higher than analogous values reported for normal young male volunteers. Coadministration of diuretics did not significantly alter the AUC or Cmax. In addition, creatinine clearance (74 mL/min), the percent of drug recovered unchanged in urine (0 to 24 hours, 22%), and the fluconazole renal clearance estimates (0.124 mL/min/kg) for the elderly were generally lower than those of younger volunteers. Thus, the alteration of fluconazole disposition in the elderly appears to be related to reduced renal function characteristic of this group. A plot of each subject’s terminal elimination half-life versus creatinine clearance compared to the predicted half-life – creatinine clearance curve derived from normal subjects and subjects with varying degrees of renal insufficiency indicated that 21 of 22 subjects fell within the 95% confidence limit of the predicted half-life-creatinine clearance curves. These results are consistent with the hypothesis that higher values for the pharmacokinetic parameters observed in the elderly subjects compared to normal young male volunteers are due to the decreased kidney function that is expected in the elderly.

Drug Interaction

(see precautions, drug interactions)

Oral contraceptives, Cimetidine, Antacid, Hydrochlorothiazide, Rifampin, Warfarin, Phenytoin, Cyclosporine, Zidovudine, Theophylline, Terfenadine, Quinidine, Oral hypoglycemic, Tolbutamide, Glipizide, Glyburide, Rifabutin, Tacrolimus, Cisapride, Midazolam, Azithromycin, Voriconazole

Mechanism of Action

Fluconazole is a highly selective inhibitor of fungal cytochrome P450 dependent enzyme lanosterol 14-α-demethylase. This enzyme functions to convert lanosterol to ergosterol. The subsequent loss of normal sterols correlates with the accumulation of 14-α-methyl sterols in fungi and may be responsible for the fungistatic activity of fluconazole. Mammalian cell demethylation is much less sensitive to fluconazole inhibition.

Resistance

A potential for development of resistance to fluconazole is well known. Fungal isolates exhibiting reduced susceptibility to other azoles may also show reduced susceptibility to fluconazole. The frequency of drug resistance development for the various fungi for which this drug is indicated is not known.

Fluconazole resistance may arise from a modification in the quality or quantity of the target enzyme (lanosterol 14-α-demethylase), reduced access to the drug target, or some combination of these mechanisms.

Point mutations in the gene (ERG11) encoding for the target enzyme lead to an altered target with decreased affinity for azoles. Overexpression of ERG11 results in the production of high concentrations of the target enzyme, creating the need for higher intracellular drug concentrations to inhibit all of the enzyme molecules in the cell.

The second major mechanism of drug resistance involves active efflux of fluconazole out of the cell through the activation of two types of multidrug efflux transporters; the major facilitators (encoded by MDR genes) and those of the ATP-binding cassette superfamily (encoded by CDR genes). Upregulation of the MDR gene leads to fluconazole resistance, whereas, upregulation of CDR genes may lead to resistance to multiple azoles.

Resistance in Candida glabrata usually includes upregulation of CDR genes resulting in resistance to multiple azoles. For an isolate where the minimum inhibitory concentration (MIC) is categorized as Intermediate (16 to 32 mcg/mL), the highest fluconazole dose is recommended.

Candida krusei should be considered to be resistant to fluconazole. Resistance in C. krusei appears to be mediated by reduced sensitivity of the target enzyme to inhibition by the agent.

There have been reports of cases of superinfection with Candida species other than C. albicans, which are often inherently not susceptible to (e.g., Candida krusei). Such cases may require alternative antifungal therapy.

Antimicrobial Activity

Fluconazole has been shown to be active against most isolates of the following microorganisms both in vitro and in clinical infections.

Susceptibility Testing

For specific information regarding susceptibility test interpretive criteria and associated test methods and quality control standards recognized by FDA for this drug, please see: https://www.fda.gov/STIC.

6. PHARMACEUTICAL PARTICULARS:

6.1 Incomaptibilities:

None stated.

6.2 Shelf life:

• 3 years

6.3 Storage

Store tablets below 86°F (30°C).

7. Manufactured in India By:
TAJ PHARMACEUTICALS LTD.
29, Xcelon Industrial Park-1,
Behind Intas Pharmaceuticals,
At & Po Vasna – Chacharwadi,
Tal- Sanand, Dist- Ahmedabad-382213,
Gujarat, India

Fluconazole Tablets IP 50mg (FANTIZOLE) Taj Pharma

Package leaflet: Information for the patient

(fluconazole)

Read all of this leaflet carefully before you start taking this medicine because it contains important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

What is in this leaflet

1. What Taj Pharma Fluconazole Tablets are and what they are used for
   2. What you need to know before you take Taj Pharma Fluconazole Tablets
   3.How to take Taj Pharma Fluconazole Tablets
   4. Possible side effects
   5.How to store Taj Pharma Fluconazole Tablets
   6. Contents of the pack and other information

FANTIZOLE  (fluconazole Tablets)

This leaflet contains important information about FANTIZOLE (dye-FLEW-kan). It is not meant to take the place of your doctor’s instructions. Read this information carefully before you take FANTIZOLE. Ask your doctor or pharmacist if you do not understand any of this information or if you want to know more about FANTIZOLE.

1. What Is FANTIZOLE?

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

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

2. 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

3. What To Tell Your Doctor

 Before You Start FANTIZOLE?

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

• diabetes medicines such as glyburide, tolbutamide, glipizide
• blood pressure medicines like hydrochlorothiazide, losartan, amlodipine, nifedipine or felodipine
• blood thinners such as warfarin
• cyclosporine, tacrolimus or sirolimus (used to prevent rejection of organ transplants)
• rifampin or rifabutin for tuberculosis
• astemizole for allergies
• phenytoin or carbamazepine to control seizures
• theophylline to control asthma
• cisapride for heartburn
• quinidine (used to correct disturbances in heart rhythm)
• amiodarone (used for treating uneven heartbeats ‘arrhythmias’)
• amitriptyline or nortriptyline for depression
• pimozide for psychiatric illness
• amphotericin B or voriconazole for fungal infections
• erythromycin for bacterial infections
• olaparib, cyclophosphamide or vinca alkaloids such as vincristine or vinblastine for treatment of cancer
• fentanyl, afentanil or methadone for chronic pain
• halofantrine for malaria
• lipid lowering drugs such as atorvastatin, simvastatin, and fluvastatin
• non-steroidal anti-inflammatory drugs including celecoxib, ibuprofen, and naproxen
• prednisone, a steroid used to treat skin, gastrointestinal, hematological or respiratory disorders
• antiviral medications used to treat HIV like saquinavir or zidovudine
• tofacitinib for rheumatoid arthritis
• vitamin A nutritional supplement

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 FANTIZOLE is right for you. Women who can become pregnant should think about using effective birth control while taking FANTIZOLE.
• are breastfeeding. FANTIZOLE 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 FANTIZOLE. The main ingredient of FANTIZOLE is fluconazole. If you need to know the inactive ingredients, ask your doctor or pharmacist.

4. Who Should Not Take FANTIZOLE?

To avoid a possible serious reaction, do NOT take FANTIZOLE if you are taking erythromycin, astemizole, pimozide, quinidine, and cisapride (Propulsid®) since it can cause changes in heartbeat in some people if taken with FANTIZOLE.

5. How Should I Take FANTIZOLE

Take FANTIZOLE by mouth with or without food. You can take FANTIZOLE at any time of the day.

FANTIZOLE 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 FANTIZOLE tablet to treat your vaginal yeast infection.

6. What Should I Avoid while Taking FANTIZOLE?

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

What Are the Possible Side Effects of FANTIZOLE?

Like all medicines, FANTIZOLE may cause some side effects that are usually mild to moderate.

The most common side effects of FANTIZOLE are:

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

Allergic reactions to FANTIZOLE 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.

Tell your doctor or pharmacist if you experience skin rash, fever, swollen glands, increase in a type of white blood cell (eosinophilia), and inflammation of internal organs (liver, lungs, heart, kidneys, and large intestine) as they may be signs of a hypersensitivity reaction (Drug Reaction or rash with Eosinophilia and Systemic Symptoms (DRESS)).

FANTIZOLE 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 FANTIZOLE.

FANTIZOLE 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.

Cases of reversible adrenal insufficiency have been reported with FANTIZOLE. Tell your doctor is you experience chronic, or long lasting fatigue, muscle weakness, loss of appetite, weight loss or abdominal pain.

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 FANTIZOLE

Keep FANTIZOLE 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 FANTIZOLE for a condition for which it was not prescribed. Do not give FANTIZOLE to other people, even if they have the same symptoms you have. It may harm them.

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

7. Manufactured in India By:
TAJ PHARMACEUTICALS LTD.
29, Xcelon Industrial Park-1,
Behind Intas Pharmaceuticals,
At & Po Vasna – Chacharwadi,
Tal- Sanand, Dist- Ahmedabad-382213,
Gujarat, India