APR FRUZOX 150

AZ-07:

INFORMATION FOR THE USER

Fluconazole 150mgCapsules

Read all of this information carefully before you start taking this medicine because it contains important information for you.
• Keep this information. You may need to read it again.
• If you have any further questions, ask your doctor, pharmacist or nurse.
• This medicine is 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 information.

1. COMPOSITION:
Eachcapsule contains:
Fluconazole- 150mg

For oral use only.

2. DESCRIPTION:
Fluconazole is an azole anti-fungal medication. It inhibitsfungal ergosterol synthesis leading to cell death.

3. PHARMACOLOGICAL ACTION:
Fluconazole is a triazole class of antifungal agents. Its mode of action is the inhibition of fungal ergosterol biosynthesis. The accumulation of 14 alpha-methyl sterols correlates with the subsequent loss of ergosterol in the fungal cell membrane & may be responsible for the antifungal activity. It has been shown to be more selective for fungal cytochrome P-450 enzymes than for various mammalian cytochrome P-450 enzyme systems. Given daily up to 28 days has been shown not to effect testosterone plasma conc. in males or steroid conc. in females of child-bearing age. It has no clinically significant effect on endogenous steroid levels or on ACTH stimulated response. Interaction studies with antipyrine indicate that single or multiple doses do not affect its metabolism.
4. CLINICAL PHARMACOKINETICS:
After oral administration it is well absorbed& plasma levels are over 90% of the levels achieved after IV administration. Oral absorption is not affected by concomitant food intake. Peak plasma conc. in the fasting state occur0.5-1.5 hrs with a plasma elimination half-life of approx. 30 hrs. Plasma conc. are proportional to dose. 90% steady state levels are reached by day 4-5 with multiple once daily dosing. Administration of a loading dose of twice the usual daily dose enables plasma levels to approx. to 90% steady state level by day 2. The volume of distribution approx. to total body water. Plasma protein binding is low (11-12%). It achieves good penetration in all body fluids. The levels in saliva & sputum are similar to plasma levels. In patients with fungal meningitis levels in the CSF are approx. 80% of the corresponding plasma levels. High skin conc. above serum conc. are achieved in the stratum corneum, epidermis-dermis & eccrine sweat. It accumulates in the stratum corneum. It is metabolised only to a minor extent. Only 11% is excreted in a changed form in the urine. It is a selective inhibitor of the isozymes CYP2C9 & CYP3A4. It is also an inhibitor of the isozyme CYP2C19.Plasma elimination half-life f is approx. 30 hrs. The major route of excretion is renal with approx. 80% of the administered dose appearing in the urine as unchanged drug. Clearance is proportional to creatinine clearance. There is no evidence of circulating metabolites. The long plasma elimination half-life provides the basis for single dose therapy for vaginal candidiasis, once daily & once weekly dosing for other indications.
5. INDICATIONS:
Fluconazole 150mg capsules are indicated for the treatment of:
– Vaginal candidiasis, acute or recurrent
– Candidal balanitis associated with vaginal candidiasis.

6. CONTRAINDICATIONS:
Should not be used in patients with known hypersensitivity to fluconazole, to related azole compounds or to any of the excipients.
Co-administration of terfenadine is contraindicated in patients receiving fluconazole.
Coadministration of other medicinal products known to prolong the QT interval & which are metabolised via the cytochrome P450 (CYP) 3A4 such as cisapride, astemizole, pimozide, quinidine & erythromycin are contraindicated in patients receiving fluconazole.

7. WARNINGS AND PRECAUTIONS:
Hepatobiliary system: Should be administered with caution to patients with liver dysfunction.
Has been associated with rare cases of serious hepatic toxicity, primarily in patients with serious underlying medical conditions. Hepatotoxicity has usually been reversible on discontinuation of therapy.
Dermatological reactions: Patients have rarely developed exfoliative cutaneous reactions. AIDS patients are more prone to the development of severe cutaneous reactions to many drugs.
Terfenadine: The coadministration with terfenadine should be carefully monitored.
Hypersensitivity: In rare cases anaphylaxis has been reported.
Cardiovascular system: Has been associated with prolongation of the QT interval on the ECG. Should be administered with caution to patients with these potentially proarryhthmic conditions.
Renal System: Use with caution in patients with renal dysfunction.

8. ADVERSE EFFECTS:
• Common: rash, headache, dizziness, nausea, vomiting, abdominal pain, diarrhea, &/or elevated liver enzymes
• Infrequent: anorexia, fatigue, constipation
• Rare: oliguria, hypokalaemia, paraesthesia, seizures, alopecia, Stevens–Johnson syndrome, thrombocytopenia, other blood dyscrasias, serious hepatotoxicity including liver failure, anaphylactic/anaphylactoid reactions
• Very rare: prolonged QT interval, torsades de pointes

9. DRUG INTERACTIONS:
Hydrochlorothiazide: Increases plasma conc. of fluconazole
Rifampicin: Decreases the AUC & shortens half-life of fluconazole.
Alfentanil: AUC 10 increased 2-fold, probably through inhibition of CYP3A4. Dosage adjustment of alfentanil may be necessary.
Amitriptyline, nortriptyline: Increases the effect of amitriptyline & nortriptyline.
Amphotericine B: A small additive antifungal effect in systemic infection with C. albicans, no interaction in intracranial infection with Cryptococcus neoformans& antagonism of the 2 drugs in systemic infection with Aspergillus fumigatus.
Anticoagulants: Bleeding events (bruising, epistaxis, gastrointestinal bleeding) have been reported, in association with increases in prothrombin time in patients receiving fluconazole concurrently with warfarin.
Benzodiazepines (Short acting). i.e. midazolam, triazolam: Substantial increases in midazolam conc.& psychomotor effects. Increase in the triazolam AUC & half-life.
Carbamazepine: Inhibits metabolism of carbamazepine & an increase in serum carbamazepine has been observed.
Calcium Channel Blockers: Has the potential to increase the systemic exposure of the calcium channel antagonists.
Celecoxib: Cmax& AUC increase.
Cyclophosphamide: Increase in serum bilirubin & serum creatinine.
HMG-CoA reductase inhibitors: The risk of myopathy & rhabdomyolysis increases when coadministered with HMG-CoA reductase inhibitors metabolised through CYP3A4, such as atorvastatin & simvastatin.
Ciclosporin: Significantly increases the conc. & AUC of ciclosporin.
Sirolimus: Increases plasma conc. of sirolimus presumably by inhibiting the metabolism of sirolimus via CYP3A4 & P-glycoprotein.
Tacrolimus: May increase the serum conc. of orally administered tacrolimus.
Losartan: Inhibits the metabolism of losartan to its active metabolite which is responsible for most of the angiotensin II-receptor antagonism which occurs during treatment with losartan.
Methadone: May enhance the serum conc. of methadone.
Phenytoin: Inhibits the hepatic metabolism of phenytoin.
Rifabutin: Increases serum conc. of rifabutin.
Saquinavir: Increases the AUC of saquinavir.
Sulphonylureas: Shown to prolong the serum half-life of concomitantly administered oral sulphonylureas (e.g., chlorpropamide, glibenclamide).
Theophylline: Decreases the mean plasma clearance of theophylline.
Zidovudine: Increases Cmax & AUC of zidovudine.
10. DOSAGE:
Adults: 1 tablet daily.

11. ADMINISTRATION:
For oral administration only.

12. STORAGE:
Do not store above 25°C. Store in the original package. Keep away from children. Do not expose to direct sunlight.

13. MANUFACTURED BY:

14. MARKETED BY:

Last revised on October 2020.