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 or

pharmacist.

* 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 or pharmacist.

This includes any possible side effects not listed in this leaflet.

See section 4.

1-DESCRIPTION:

FUNGOZOL-UBSA 150 mg hard capsules have a transparent cap and blue body.

They have “UBSA” with black ink printed on them.

2-COMPOSITION:

Each hard capsule contains 150 mg of fluconazole.

Excipients: Sugar spheres (20#24), Povidone k-30, Sucrose, Sodium Lauryl

sulphate, croscarmellose sodium, Hydroxy propyl methyl cellulose E5, FD&C Blue

FCF.

3-THERAPEUTIC INDICATIONS:

FUNGOZOL-UBSA is indicated for the treatment of:

1. Oropharyngeal and esophageal candidiasis. FUNGOZOL-UBSA is also effective

for the treatment of serious systemic candidal infections, including urinary tract

infection, peritonitis, and pneumonia.

2. Cryptococcal meningitis.

3. Prevention of the recurrence of cryptococcal meningitis in patients with

acquired immunodeficiency syndrome (AIDS).

Prophylaxis:

FUNGOZOL-UBSA is also indicated to decrease the incidence of candidiasis in

patients undergoing bone marrow transplantation who receive cytotoxic

chemotherapy and/or radiation therapy.

4-PHARMACOLOGICAL PROPERTIES: ANTIFUNGALS

Mechanism of action:

Fluconazole is a polar bis-triazole antifungal drug. Studies have shown that

fluconazole exhibits specificity as an inhibitor of the fungal as opposed to

mammalian cytochrome P-450 mediated reactions, including those involved in

steroid biosynthesis and drug metabolism. Many of the clinical advantages of

FUNGOZOL-UBSA (fluconazole) are a result of its unique pharmacokinetic

properties.

5-PHARMACOKINETICS

Absorption

The pharmacokinetic properties of fluconazole are similar following

administration by the intravenous or oral routes and do not appear to be

affected by gastric pH.

In normal volunteers, the bioavailability of orally administered fluconazole is

over 90% compared with intravenous administration. Essentially all of the

administered drug reaches systemic circulation; thus, there is no evidence of

first-pass metabolism of the drug. In addition, no adjustment in dosage is

necessary when changing from p.o. to i.v. or vice versa. Peak plasma

concentrations (Cmax) in fasted normal volunteers occur rapidly following oral

administration, usually between 1 and 2 hours of dosing with a terminal plasma

elimination half-life of approximately 30 hours (range 20-50 hours) after oral

administration.

The long plasma elimination half-life provides the basis for once daily dosing

with FUNGOZOL-UBSA in the treatment of fungal infections. In fasted normal

volunteers, administration of a single oral 400 mg dose of FUNGOZOL-UBSA

leads to a mean Cmax of 6.72 µg/mL (range: 4.12 to 8.08 µg/mL) and after single

oral doses of 50- 400 mg, fluconazole plasma concentrations and AUC (area

under the plasma concentration-time curve) are dose proportional. In normal

volunteers, oral bioavailability as measured by Cmax and AUC was not affected

by food when FUNGOZOL-UBSA was administered as a single 50 mg capsule;

however Tmax was doubled. Steady-state concentrations are reached within

5-10 days following oral doses of 50-400 mg given once daily. Administration of a

loading dose on the first day of treatment of twice the usual daily dose results in

plasma concentrations close to steady state by the second day.

Distribution

The apparent volume of distribution of fluconazole approximates that of total

body water. Plasma protein binding is low (11%-12%) and is constant over the

concentration range tested (0.1 mg/L to 10 mg/L). This degree of protein binding

is not clinically meaningful. Following either single- or multiple-oral doses for up

to 14 days, fluconazole penetrates into all body tissues and fluids studied (see

Table III). 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 CSF (cerebrospinal fluid) are

approximately 80% of the corresponding plasma concentrations. Whole blood

concentrations of fluconazole indicated that the drug freely enters erythrocytes

and maintains a concentration equivalent to that of plasma.

Metabolism and Excretion

Fluconazole is cleared primarily by renal excretion, with approximately 80% of the

administered dose appearing in the urine as unchanged drug. Following

administration of radiolabeled fluconazole, greater than 90% of the radioactivity

is excreted in the urine. Approximately 11% of the radioactivity in urine is due to

metabolites. An additional 2% of the total radioactivity is excreted in feces.

The pharmacokinetics of fluconazole do not appear to be affected by age alone

but are markedly affected by reduction in renal function. There is an inverse

relationship between the elimination half-life and creatinine clearance.

The dose of FUNGOZOL-UBSA may need to be reduced in patients with impaired

renal function . A 3-hour hemodialysis session decreases plasma concentrations

by approximately 50%.

6-CONTRAINDICATIONS

FUNGOZOL-UBSA (fluconazole) is contraindicated in patients who have shown

hypersensitivity to fluconazole, to any of its excipients or to related azole

compounds.

Co-administration of drugs known to prolong the QT interval and which are

metabolized via the enzyme CYP3A4 such as erythromycin, pimozide and

quinidine are contraindicated in patients receiving fluconazole (see

Precautions-Drug Interactions).

7-POSOLOGY AND METHOD OF ADMINISTRATION

For Adults:

To treat Cryptococcal Meningitis: Give 400mg on the first day than 200mg to

400mg once daily for 6 to 8 weeks or longer if needed. Sometime doses are

increased up to 800mg.

To stop Cryptococcal meningitis from coming back: Give 200mg once daily until

you are told to stop.

To treat Coccidioidomycosis: Give 200mg to 400mg once daily from 11months for

up to 24months or longer if needed. Sometimes doses are increased up to

800mg.

To treat internal fungal infections caused by Candida: Give 800mg on the first

day than 400mg once daily until your told to stop.

To teat Mucosal infection affecting the lining of mouth, throat and denture sore

mouth: Give 200 to 400mg on the first day than 100mg to 200mg until you are told

to stop.

To treat mucosal Thrush-dose depends on where the infection is located:

50mg to 400mg once daily for 7 to 30days until you are told to stop.

To stop mucosal infection affecting the lining of mouth,throat from coming

back: 100mg to 200mg once daily , or 200mg 3 times a week, while you are at risk

of getting an infection.

To treat genital thrush: give 150mg as a single dose.

To reduce reccurence of vaginal thrush: 150mg every third day for a total of

3doses ( day 1, day 4 and 7) and than once a week for 6months, while u are at risk

of getting an infection.

To treat fungal skin and nail infection: Depending on the site of the infection

50mg once daily. 150mg once weekly, 300 to 400mg once weekly for 1 to 4weeks

for nail infection treatment, until infected nail is replaced.

To stop you from getting an infection caused by Candida ( if ur immune

system is weak and not working properly): 200 to 400mg once daily while you

are at risk of getting an infection.

8-WARNINGS AND PRECAUTIONS

Fluconazole should be administered with caution to patients with liver

dysfunction.

Hepatic injury: FUNGOZOL-UBSA (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-associ-

ated hepatotoxicity, no obvious relationship to total daily dose, duration of

therapy, sex or age of the patient has been observed. Fluconazole

hepatotoxicity has usually, but not always been reversible on discontinua-

tion of therapy. Patients who develop abnormal liver function tests during

FUNGOZOL-UBSA therapy should be monitored for the development of more

severe hepatic injury. FUNGOZOL-UBSA should be discontinued if clinical

signs and symptoms consistent with liver disease develop that may be

attributable to fluconazole.

Fluconazole should be administered with caution to patients with renal

dysfunction (see DOSAGE and ADMINISTRATION- Impaired Renal Function).

Adrenal insufficiency has been reported in patients receiving other azoles (e.g.,

ketoconazole). Reversible cases of adrenal insufficiency were reported in

patients while receiving fluconazole or when fluconazole was discontinued (see

Drug Interactions).

Anaphylaxis: In rare cases, anaphylaxis has been reported.

Dermatologic: Patients have rarely developed exfoliative skin disorders during

treatment with FUNGOZOL-UBSA. In patients with serious underlying diseases

(predominantly AIDS and malignancy), those have rarely resulted in a fatal

outcome. Patients who develop rashes during treatment with FUNGOZOL-UBSA

should be monitored closely and the drug discontinued if lesions progress.

Use in Pregnancy

FUNGOZOL-UBSA (fluconazole) should not be used in pregnant women except

in patients with severe or potentially life-threatening fungal infections in whom

FUNGOZOL-UBSA (fluconazole) may be used if the anticipated benefit

outweighs the possible risk to the fetus. If this drug is used during pregnancy, or

if the patient becomes pregnant while taking the drug, the patient should be

informed of the potential hazard to the fetus. There have been reports as well

as observational studies that have suggested an increased risk of spontaneous

abortion and congenital abnormalities in infants whose mothers were treated

with doses as low as 150 mg of fluconazole as a single or repeated dose during

the first trimester. There have been reports of multiple congenital abnormalities

in infants whose mothers were treated with high-dose (400 mg/day to 800

mg/day) fluconazole therapy for coccidioidomycosis (an unapproved

indication). Exposure to fluconazole began during the first trimester in all cases

and continued for three months or longer. Case reports describe a distinctive

and rare pattern of birth defects among infants whose mothers received

high-dose (400-800 mg/day) fluconazole during most or all of the first

trimester of pregnancy. The features seen in these infants include brachyceph-

aly, abnormal facies, abnormal calvarial development, cleft palate, femoral

bowing, thin ribs and long bones, arthrogryposis, and congenital heart disease.

These reported anomalies are similar to those seen in animal studies (see

TOXICOLOGY, Reproduction and Teratology).

Use in Women of Child-bearing Potential

Effective contraceptive measures should be considered in women of

child-bearing potential and should continue throughout the treatment period

with FUNGOZOL-UBSA(fluconazole) and for approximately 1 week (5 to 6

half-lives) after the final dose.

Precautions

QT Prolongation

Some azoles, including fluconazole, have been associated with prolongation of

the QT interval on an electrocardiogram.

During postmarketing surveillance, there have been very rare cases of QT

prolongation and torsade de pointes in patients taking fluconazole.

The potential for proarrhythmic events increases with coadministration of other

drugs that prolong the QT interval such as some antiarrhythmics,

antihistamines, psychotropic agents and antibacterials. Caution and careful

monitoring should be 5 used with concomitant administration of such drugs

(see PRECAUTIONS - Drug Interactions – Amiodarone and Drugs prolonging the

QTc interval as well as PHARMACOLOGY - QT

Prolongation).

Fluconazole should be administered with caution

to patients with proarrhythmic conditions (see

PRECAUTIONS - Drug Interactions - Drugs

prolonging the QTc interval and ADVERSE

REACTIONS).

CYP2C9, CYP2C19 and CYP3A4 metabolized drugs

Fluconazole is a moderate CYP2C9 inhibitor and a

moderate CYP3A4 inhibitor. Fluconazole is also a

strong inhibitor of the isoenzyme CYP2C19.

Fluconazole treated patients who are

concomitantly treated with drugs with a narrow

therapeutic window metabolised through CYP2C9,

CYP2C19 and CYP 3A4 should be monitored (see

CONTRAINDICATIONS).

Use in Nursing Mothers Fluconazole is secreted in

human breast milk at concentrations similar to

plasma, hence its use in nursing mothers is not

recommended.

Use in Elderly

FUNGOZOL-UBSA was well tolerated by patients

aged 65 years and over.

Fluconazole is primarily cleared by renal excretion

as unchanged drug. Because elderly patients are

more likely to have decreased renal function,

caution should be exercised and dose adjusted

based on creatinine clearance. It may be useful to

monitor renal function.

In a small number of elderly patients with bone

marrow transplant (BMT) in which FUNGOZOL-UBSA

was administered prophylactically there was a

greater incidence of drug discontinuation due to

adverse reactions (4.3%) than in younger patients

(1.7%).

Lactose Intolerance

FUNGOZOL-UBSA Capsules contain lactose and

should not be given to patients with rare hereditary

problems of galactose intolerance, Lapp lactase

deficiency or glucose-galactose malabsorption.

Effects on Ability to Drive and Use Machines When

driving vehicles or operating machines it should be

taken into account that occasionally dizziness or

seizures may occur.

9-DRUG INTERACTIONS

Fluconazole is a moderate inhibitor of cytochrome

P450 (CYP) isoenzymes 2C9 and 3A4. Fluconazole is

also a strong inhibitor of the isoenzyme CYP2C19. In

addition to the observed 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 4-5 days after discontinuation

of fluconazole treatment due to the long half-life of

fluconazole.

Clinically or potentially significant drug interactions

between fluconazole and the following

agents/classes have been observed: Alfentanil,

Amiodarone, Amitriptyline,Nortriptyline,

Amphotericin B, Azithromycin, Benzodiazepines

(Short Acting), Carbamazepine, Calcium Channel

Blockers, Celecoxib, Cimetidine, Coumarin-Type, or

Indanedione Anticoagulants, Cyclosporine,

Cyclophosphamide, Drugs prolonging QTc interval:

(Pimozide, Quinidine, Erythromycin), Fentanyl

Halofantrine, HMG-CoA reductase inhibitors, Hydrochlorothiazide, Losartan,

Methadone, Non-steroidal anti-inflammatory drugs, Olaparib, Oral

Contraceptives, Oral Hypoglycemics, Phenytoin, Prednisone, Rifabutin, Rifampin,

Saquinavir, Sirolimus, Sulfonylureas, Tacrolimus, Theophylline, Tofacitinib,

Triazolam, Vinca Alkaloids, Vitamin A, Zidovudine, Voriconazole.

Amiodarone Concomitant administration of fluconazole with amiodarone may

increase QT prolongation. Caution must be exercised if the concomitant use of

fluconazole and amiodarone is necessary, notably with high-dose fluconazole

(800 mg).

Amitriptyline, nortriptyline Fluconazole increases the effect of amitriptyline and

nortriptyline. 5- nortriptyline and/or Samitriptyline may be measured at initiation

of the combination therapy and after 1 week. Dosage of amitriptyline/nortriptyline

should be adjusted, if necessary.

Amphotericin B Concurrent administration of fluconazole and amphotericin B in

infected normal and immunosuppressed mice showed the following results: a

small additive antifungal effect in systemic infection with Candida albicans, no

interaction in intracranial infection with Cryptococcus neoformans, and

antagonism of the two drugs in systemic infection with Aspergillus fumigatus. The

clinical significance of results obtained in these studies is unknown.

Benzodiazepines (short acting) Following oral or intravenous administration of

midazolam, fluconazole resulted in substantial increases in midazolam

concentrations and psychomotor effects. This effect on midazolam appears to

be more pronounced following oral administration of fluconazole than with

fluconazole administered intravenously. If short-acting benzodiazepines, which

are metabolized by the cytochrome P450 system, are concomitantly

administered with fluconazole, consideration should be given to decreasing the

benzodiazepine dosage, and the patients should be appropriately monitored.

Carbamazepine Fluconazole inhibits the metabolism of carbamazepine and an

increase in serum carbamazepine of 30% has been observed. There is a risk of

developing carbamazepine toxicity. Dosage adjustment of carbamazepine may

be necessary depending on concentration measurements/effect.

Calcium channel blockers Certain calcium channel antagonists (nifedipine,

isradipine, amlodipine, verapamil and felodipine) are metabolized by CYP3A4.

Fluconazole has the potential to increase the systemic exposure of the calcium

channel antagonists. Frequent monitoring for adverse events is recommended.

Coumarin-Type or Indanedione Anticoagulants Prothrombin time may be

increased in patients receiving concomitant fluconazole and coumarin type or

indanedione anticoagulants. In post-marketing experience, as with some azole

antifungals, bleeding events (bruising, epistaxis, gastrointestinal bleeding,

hematuria, and melena) have been reported in association with increases in

prothrombin time in patients receiving fluconazole concurrently with warfarin.

Dose adjustments of these anticoagulants maybe necessary. Careful monitoring

of prothrombin time in patients receiving FUNGOZOL-UBSA and coumarin-type or

indanedione anticoagulants is recommended.

Cyclosporine Fluconazole may significantly increase the concentration and AUC

of cyclosporine levels in renal transplant patients with or without renal

impairment. Careful monitoring of cyclosporine concentrations and serum

creatinine is recommended in patients receiving FUNGOZOL-UBSA and

cyclosporine. This combination may be used by reducing the dosage of

cyclosporine depending on cyclosporine concentration.

Cyclophosphamide Combination therapy with cyclophosphamide and

fluconazole results in an increase in serum bilirubin and serum creatinine. The

combination may be used while taking into consideration the risk of increased

serum bilirubin and serum creatinine. Caution should be exercised and patients

should be monitored for increased toxicity of cyclophosphamide.

Drugs prolonging the QTc interval: The use of fluconazole in patients

concurrently taking drugs metabolized by the Cytochrome P450 system may be

associated with elevations in the serum levels of these drugs. In the absence of

definitive information caution should be used when coadministering

FUNGOZOL-UBSA and such agents (Erythromycin, Pimozide, Quinidine) . Patients

should be carefully monitored.

HMG-CoA reductase inhibitors The risk of myopathy and rhabdomyolysis

increases when fluconazole is coadministered with HMG-CoA reductase

inhibitors metabolized through CYP3A4, such as atorvastatin and simvastatin, or

through CYP2C9, such as fluvastatin. If concomitant therapy is necessary, the

patient should be observed for symptoms of myopathy and rhabdomyolysis and

creatine kinase should be monitored. HMG-CoA reductase inhibitors should be

discontinued if a marked increase in creatine kinase is observed or

myopathy/rhabdomyolysis is diagnosed or suspected.



Fluconazole 150mg

concomitantly administered oral sulfonylureas

(e.g., chlorpropamide, glibenclamide, glipizide,

tolbutamide) in healthy volunteers. Frequent monitoring of blood glucose and

appropriate reduction of sulfonylurea dosage are recommended during co

administration.

Tacrolimus Fluconazole significantly increases the serum concentrations of

orally administered tacrolimus up to 5 times due to inhibition of tacrolimus

metabolism through CYP3A4. Increased levels of tacrolimus have been

associated with nephrotoxicity. Dosage adjustment of tacrolimus should be

made depending on tacrolimus concentration. Patients receiving tacrolimus and

FUNGOZOL-UBSA concomitantly should be carefully monitored for tacrolimus

associated adverse effects, especially nephrotoxicity.

Theophylline Patients who are receiving high-dose theophylline or who are

otherwise at increased risk for theophylline toxicity should be observed for signs

of theophylline toxicity while receiving FUNGOZOL-UBSA, and therapy modified

appropriately if signs of toxicity develop. FUNGOZOL-UBSA increases the serum

concentrations of theophylline. Careful monitoring of serum theophylline

concentrations in patients receiving FUNGOZOL-UBSA and theophylline is

recommended.

Triazolam Fluconazole increases the AUC of triazolam (single dose) by

approximately 50%, Cmax by 20-32% and increases t½ by 25-50 % due to the

inhibition of metabolism of triazolam. Dosage adjustments of triazolam may be

necessary. Caution should be exercised and patients should be monitored for

increased toxicity of triazolam.

Vinca alkaloids Although not studied, fluconazole may increase the plasma

levels of the vinca alkaloids (e.g., vincristine and vinblastine) and lead to

neurotoxicity, which is possibly due to an inhibitory effect on CYP3A4. Caution

should be exercised and patients should be monitored for increased toxicity of

vinca alkaloids (e.g. vincristine and vinblastine).

Vitamin A Based on a case-report in one patient receiving combination therapy

with all-trans-retinoid acid (an acid form of vitamin A) and fluconazole, central

nervous system (CNS) related undesirable effects have developed in the form of

pseudotumor cerebri, which disappeared after discontinuation of fluconazole

treatment. This combination may be used but the incidence of CNS related

undesirable effects should be borne in mind.

Zidovudine Fluconazole increases the Cmax and AUC of zidovudine by 84% and

74%, respectively, due to an approximately 45% decrease in oral zidovudine

clearance. The half-life of zidovudine was likewise prolonged by approximately

128% following combination therapy with fluconazole. Patients receiving this

combination should be monitored for the development of zidovudine- 14 related

adverse reactions. Dosage reduction of zidovudine may be considered.

Voriconazole (CYP2C9, CYP2C19 and CYP3A4 inhibitors) Avoid concomitant

administration of voriconazole and fluconazole at any dose. Monitor for adverse

events and toxicity related to voriconazole; especially, if voriconazole is started

within 24 h after the last dose of fluconazole.

10-ADVERSE REACTIONS

Like all medicines, this medicine can cause side effects, although not everybody

gets them. Stop taking FUNGOZOL-UBSA and seek medical attention immediately

if you notice any of the following symptoms:

-Widespread rash, high body temperature and enlarged lymph nodes (DRESS

syndrome) A few people develop allergic reactions although serious allergic

reactions are rare.

-Sudden wheezing, difficulty in breathing or tightness in the chest; swelling of

eyelids,face or lips; itching all over the body,reddening of the skin or itchy red

pots; skin rash; severe skin reactions such as a rash that causes blistering (this

can affect mouth and toungue).

FUNGOZOL-UBSA may affect your liver. The signs of liver problems include:

-Tiredness; loss of appetite; vomiting; yellowing of your skin or the white of your

eyes (jaundice).

If any of these happen, stop taking FUNGOZOL-UBSA and tell your doctor

immediately.

Common side effects (may affect up to 1 in 10 people) are:

-Headache; stomach discomfort, diarrhea,feeling sick, vomiting ;increase in

blood test of liver function; rash.

Uncommon side effects (may affect up to 1 in 100 people) are:

-Reduction in red blood cells wich can make skin pale and cause weakness or

breathlessness; decreased appetite; inability to sleep, feeling drowsy; fit,

Hydrochlorothiazide In a pharmacokinetic interaction study, coadministration of

multiple-dose hydrochlorothiazide to healthy volunteers

receiving fluconazole increased plasma concentration of fluconazole by 40%. An

effect of this magnitude should not necessitate a change in the fluconazole dose

regimen in subjects received concomitant diuretics.

Losartan Fluconazole inhibits the metabolism of losartan to its active metabolite

(E-31 74) which is responsible for most of the angiotensin II-receptor antagonism

which occurs during treatment with losartan. Patients should have their blood

pressure monitored continuously.

Methadone Fluconazole may enhance the serum concentration of methadone.

Dosage adjustment of methadone may be necessary.

Non-steroidal anti-inflammatory drugs The Cmax and AUC of flurbiprofen were

increased by 23% and 81%, respectively, when coadministered with fluconazole

compared to administration of flurbiprofen alone. Similarly, the Cmax and AUC of

the pharmacologically active isomer [S-(+)-ibuprofen] were increased by 15%

and 82%, respectively, when fluconazole was coadministered with racemic

ibuprofen (400 mg) compared to administration of racemic ibuprofen alone.

Although not specifically studied, fluconazole has the potential to increase the

systemic exposure of other non-steroidal anti-inflammatory drugs (NSAIDs) that

are metabolized by CYP2C9 (e.g., naproxen, lornoxicam, meloxicam, diclofenac).

Frequent monitoring for adverse events and toxicity related to NSAIDs is

recommended. Adjustment of dosage of NSAIDs may be needed.

Olaparib Moderate inhibitors of CYP3A4 such as fluconazole increase olaparib

plasma concentrations; concomitant use is not recommended. If the

combination cannot be avoided, the dose of olaparib should be adjusted.

Oral contraceptives Two pharmacokinetic studies with a combined oral

contraceptive have been performed using multiple doses of fluconazole. There

were no relevant effects on hormone level in the 50 mg fluconazole study, while

at 200 mg daily, the AUCs of ethinyl estradiol and levonorgestrel were increased

40% to 24%, respectively. Thus, multiple dose use of fluconazole at these doses is

unlikely to have an effect on efficacy of the combined oral contraceptive.

Oral Hypoglycemic Clinically significant hypoglycemia may be precipitated by

the use of fluconazole with oral hypoglycemic agents; one fatality has been

reported from hypoglycemia in association with combined fluconazole and

glyburide use. Fluconazole reduces the metabolism of tolbutamide, glyburide,

and glipizide and increases the plasma concentration of these agents. When

FUNGOZOL-UBSA is used concomitantly with these or other sulfonylurea oral

hypoglycemic agents, blood glucose concentrations should be carefully

monitored and the dose of the sulfonylurea should be adjusted as necessary.

Phenytoin Fluconazole increases the plasma concentrations of phenytoin.

Careful monitoring of phenytoin concentrations in patients receiving

FUNGOZOL-UBSA and phenytoin is recommended.

Prednisone There was a case report that a liver-transplanted patient treated

with prednisone developed acute adrenal cortex insufficiency when a 3-month

therapy with fluconazole was discontinued. The discontinuation of fluconazole

presumably caused an enhanced CYP3A4 activity which led to increased

metabolism of prednisone. Patients on long-term treatment with fluconazole and

prednisone should be carefully monitored for adrenal cortex insufficiency when

fluconazole is discontinued.

Rifabutin There have been reports that an interaction exists when fluconazole is

administered concomitantly with rifabutin, leading to increased serum levels of

rifabutin up to 80%. There have been reports of uveitis in patients to whom

fluconazole and rifabutin were coadministered. Patients receiving rifabutin and

FUNGOZOL-UBSA concomitantly should be carefully monitored.

Rifampin enhances the metabolism of concurrently administered fluconazole.

Depending on clinical circumstances, consideration should be given to

increasing the dose of FUNGOZOL-UBSA when it is administered with rifampin.

Saquinavir Fluconazole increases the AUC of saquinavir by approximately 50%,

Cmax by approximately 55% and decreases the clearance of saquinavir by

approximately 50% due to inhibition of saquinavir’s hepatic metabolism by

CYP3A4 and inhibition of P-glycoprotein. Dosage adjustment of saquinavir may

be necessary. Caution should be exercised and patients should be monitored for

increased toxicity of saquinavir.

Sirolimus Fluconazole increases plasma concentrations of sirolimus presumably

by inhibiting the metabolism of sirolimus via CYP3A4 and P-glycoprotein. This

combination may be used with a dosage adjustment of sirolimus depending on

the effect/concentration measurements.Caution should be exercised and

patients should be monitored for increased toxicity of sirolimus.

Sulfonylureas Fluconazole has been shown to prolong the serum half-life of

dizziness, sensation of spinning, tingling, pricking or

numbness, changes in sense of taste;

constipation,difficult digestion, wind, dry mouth;

muscle pain; liver damage and yellowing of the

skin and eyes (jaundice);wheals, blistering,itching,

increased sweating, tiredness, general feeling of

being unwell, fever.

Rare side effects (may affect up to 1 in 1000

people) are:

-Lower than normal White blood cells that help

defend against infections and blood cells that help

to stop bleeding; red or purple discoloration of the

skin which may be caused by low platelet count,

other blood cell changes; blood chemistry

changes (high blood levels of cholesterol,fats); low

blood potassium; shaking; abnormal ECG, change

in heart rate or rhythm; liver failure; allergic

reactions (sometimes severe),including

widespread blistering rash and skin peeling, severe

skin reactions, swelling of the lips or face; hair loss.

Frequency not known, but may occur (cannot be

estimated from the available data):

-Hypersensitivity reaction with skin rash, fever,

swollen glands, increase in an type of white blood

cell (eosinophilia) and inflammation of internal

organs (liver,lungs, heart,kidney, and large

intestine) (Drug Reaction or rash with Eosinophilia

and Systemic Symptoms. (DRESS).

11-STORAGE CONDITIONS:

Keep all medicine out of reach of children.

Store below 30°C. Protect from the light

Marketing Authorization Holder and

Manufacturer: