Triflucan IV

/ Pfizer

The dose should be based on the nature and severity of the fungal infection. Treatment of infections requiring multiple dosing 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.
Cryptococcosis: 1) Treatment of cryptococcal meningitis: Loading dose: 400 mg on Day 1 Subsequent dose: 200 mg to 400 mg once daily.
Duration of treatment: Usually at least 6 to 8 weeks. In life threatening infections the daily dose can be increased to 800 mg.
2) Maintenance therapy to prevent relapse of cryptococcal meningitis in patients with high risk of recurrence: 200 mg once daily.
Duration of treatment: Indefinitely at a daily dose of 200 mg.
Coccidioidomycosis: 200 mg to 400 mg once daily. Duration of treatment: 11 months up to 24 months or longer depending on the patient. 800 mg daily may be considered for some infections and especially for meningeal disease.
Invasive candidiasis: Loading dose: 800 mg on Day 1, Subsequent dose: 400 mg once daily. Duration of treatment: In general, the recommended duration of therapy for candidemia is for 2 weeks after first negative blood culture result and resolution of signs and symptoms attributable to candidemia.
Treatment of mucosal candidiasis: 1) Oropharyngeal candidiasis: Loading dose: 200 mg to 400 mg on Day 1. Subsequent dose: 100 mg to 200 mg once daily. Duration of treatment: 7 to 21 days (until oropharyngeal candidiasis is in remission). Longer periods may be used in patients with severely compromised immune function.
2) Oesophageal candidiasis: Loading dose: 200 mg to 400 mg on Day 1. Subsequent dose: 100 mg to 200 mg once daily. Duration of treatment:
14 to 30 days (until oesophageal candidiasis is in remission). Longer periods may be used in patients with severely compromised immune function.
3) Candiduria: 200 mg to 400 mg once daily. Duration of treatment: 7 to 21 days. Longer periods may be used in patients with severely compromised immune function.
4) Chronic atrophic candidiasis: 50 mg once daily. Duration of treatment: 14 days.
5) Chronic mucocutaneous candidiasis: 50 mg to 100 mg once daily. Duration of treatment: Up to 28 days. Longer periods depending on both the severity of infection or underlying immune compromisation and infection.
Prevention of relapse of mucosal candidiasis in patients infected with HIV who are at high risk of experiencing relapse: 1) Oropharyngeal candidiasis: 100 mg to 200 mg once daily or 200 mg 3 times per week. Duration of treatment: An indefinite period for patients with chronic immune suppression.
2) Oesophageal candidiasis: 100 mg to 200 mg once daily or 200 mg 3 times per week. Duration of treatment: An indefinite period for patients with chronic immune suppression.
Prophylaxis of candidal infections: 200 mg to 400 mg once daily. Duration of treatment: Treatment should start several days before the anticipated onset of neutropenia and continue for 7 days after recovery from neutropenia after the neutrophil count rises above 1000 cells per mm³.
Special populations
Elderly: Dosage should be adjusted based on the renal function.
Renal impairment: Fluconazole is predominantly excreted in the urine as unchanged active substance. No adjustments in single dose therapy are necessary. In patients (including paediatric population) with impaired renal function who will receive multiple doses of fluconazole, an initial dose of 50 mg to 400 mg should be given, based on the recommended daily dose for the indication. After this initial loading dose, the daily dose (according to indication) should be based on the following:
Creatinine clearance (ml/min) >50: 100% Percent of recommended dose
Creatinine clearance (ml/min) ≤50 (no haemodialysis): 50% Percent of recommended dose
Haemodialysis: 100%  Percent of recommended dose after each haemodialysis
Patients on haemodialysis should receive 100% of the recommended dose after each haemodialysis; on non-dialysis days, patients should receive a reduced dose according to their creatinine clearance.
Hepatic impairment: Limited data are available in patients with hepatic impairment, therefore fluconazole should be administered with caution to patients with liver dysfunction.
Paediatric population: A maximum dose of 400 mg daily should not be exceeded in paediatric population. As with similar infections in adults, the duration of treatment is based on the clinical and mycological response. Fluconazole is administered as a single daily dose.
For paediatric patients with impaired renal function, see dosing in “Renal impairment”. The pharmacokinetics of fluconazole has not been studied in paediatric population with renal insufficiency.
Infants, toddlers and children (from 28 days to 11 years old):
Mucosal candidiasis: Initial dose: 6 mg/kg. Subsequent dose: 3 mg/kg once daily. Initial dose may be used on the first day to achieve steady state levels more rapidly.
Invasive candidiasis and Cryptococcal meningitis: Dose: 6 to 12 mg/kg once daily, depending on the severity of the disease.
Maintenance therapy to prevent relapse of cryptococcal meningitis in children with high risk of recurrence: Dose: 6 mg/kg once ,daily depending on the severity of the disease.
Prophylaxis of Candida in immunocompromised patients: Dose: 3 to 12 mg/kg once daily, depending on the extent and duration of the induced neutropenia (see Adults posology).
Adolescents (from 12 to 17 years old): Depending on the weight and pubertal development, the prescriber would need to assess which posology (adults or children) is the most appropriate. Clinical data indicate that children have a higher fluconazole clearance than observed for adults. A dose of 100, 200 and 400 mg in adults corresponds to a 3, 6 and 12 mg/kg dose in children to obtain a comparable systemic exposure.
Term newborn infants (0 to 27 days): Neonates excrete fluconazole slowly. There are few pharmacokinetic data to support this posology in term newborn infants.
Term newborn infants (0 to 14 days): The same mg/kg dose as for infants, toddlers and children should be given every 72 hours. A maximum dose of 12 mg/kg every 72 hours should not be exceeded.
Term newborn infants (from 15 to 27 days): The same mg/kg dose as for infants, toddlers and children should be given every 48 hours. A maximum dose of 12 mg/kg every 48 hours.
Method of administration: Fluconazole may be administered either orally or by intravenous infusion (Solution for Infusion), the route being dependent on the clinical state of the patient. On transferring from the intravenous to the oral route, or vice versa, there is no need to change the daily dose.
The physician should prescribe the most appropriate pharmaceutical form and strength according to age, weight and dose. The capsule formulation is not adapted for use in infants and small children. Oral liquid formulations of fluconazole are available that are more suitable in this population.
Intravenous infusion should be administrated at a rate not exceeding 10 ml/minute. Triflucan I.V. is formulated in sodium chloride 9 mg/ml (0.9%) solution for infusion, each 200 mg (100 ml bottle) containing 15 mmol each of Na+ and C1-. Because Triflucan I.V. is available as a dilute sodium chloride solution, in patients requiring sodium or fluid restriction, consideration should be given to the rate of fluid administration.

Fluconazole is indicated in the following fungal infections.
Fluconazole is indicated in adults for the treatment of: Cryptococcal meningitis, Coccidioidomycosis, Invasive candidiasis, Mucosal candidiasis (including oropharyngeal candidiasis, oesophageal candidiasis, candiduria and chronic mucocutaneous candidiasis), Chronic oral atrophic candidiasis (denture sore mouth) if dental hygiene or topical treatment are insufficient.
Fluconazole is indicated in adults for the prophylaxis of: Relapse of cryptococcal meningitis in patients with high risk of recurrence. Relapse of oropharyngeal or oesophageal candidiasis in patients infected with HIV who are at high risk of experiencing relapse. Prophylaxis of candidal infections in patients with prolonged neutropenia (such as patients with haematological malignancies receiving chemotherapy or patients receiving Haematopoetic Stem Cell Transplantation).
Fluconazole is indicated in term newborn infants, infants, toddlers, children and adolescents aged from 0 to 17 years old:
Fluconazole is used for the treatment of mucosal candidiasis (oropharyngeal, oesophageal), invasive candidiasis, cryptococcal meningitis and the prophylaxis of candidal infections in immunocompromised patients. Fluconazole can be used as maintenance therapy to prevent relapse of cryptococcal meningitis in children with high risk of reoccurrence. 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. Consideration should be given to official guidance on the appropriate use of antifungals.

* Hypersensitivity to fluconazole or to any of its excipients.
* Co-administration of other drugs known to prolong the QT interval and which are metabolized via the enzyme CYP3A4 such as erythromycin, pimozide, and quinidine.

Hepatic injury
Has been associated with rare cases of serious hepatic toxicity, including fatalities primarily in patients with serious underlying medical conditions.
Should be administered with caution to patients with liver dysfunction.
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 the medical product.
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 closely 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.
Potential for fetal harm
There are no adequate and well-controlled clinical trials. 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 this medical product 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 fluconazole 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.
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. 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.
See prescribing information for full details.

Common: Nausea, Headache, Skin rash, Vomiting, Abdominal pain and Diarrhea.
See prescribing information for full details.

There is a risk of increased plasma concentration of other compounds metabolized by CYP2C9, CYP2C19, and CYP3A4 co-administered with fluconazole. Therefore, caution should be exercised when using these combinations and the patients should be carefully monitored. In some cases dose redaction is needed.
Drugs with potential for interaction: Amiodarone, Amitriptyline, nortriptyline, Calcium channel blockers, Carbamazepine, Celecoxib, Coumarin type anticoagulants, Cyclophosphamide, Cyclosporine, HMG-CoA reductase inhibitors, Ibrutinib, Ivacaftor, Lemborexant, Losartan, Lurasidone, Methadone, Non-steroidal anti-inflammatory drugs, Olaparib, Phenytoin, Rifabutin, Saquinavir, Short-acting benzodiazepines, Sirolimus, Tacrolimus, Tofacitinib, Triazolam.
Fentanyl: In a randomized crossover study with 12 healthy volunteers, it was shown that fluconazole delayed the elimination of fentanyl significantly. Elevated fentanyl concentration may lead to respiratory depression.
Oral hypoglycemics: Clinically significant hypoglycemia may be precipitated by the use of this medical product with oral hypoglycemic agents. When used concomitantly with sulfonylurea oral hypoglycemic agents, blood glucose concentrations should be carefully monitored and the dose of the sulfonylurea should be adjusted as necessary.
Pimozide: Although not studied in vitro or in vivo, concomitant administration of fluconazole with pimozide may result in inhibition of pimozide metabolism. Increased pimozide plasma concentrations can lead to QT prolongation and rare occurrences of torsade de pointes. Coadministration of fluconazole and pimozide is contraindicated.
Prednisone: Patients on long-term treatment with fluconazole and prednisone should be carefully monitored for adrenal cortex insufficiency when fluconazole is discontinued.
Quinidine: Although not studied in vitro or in vivo, concomitant administration of fluconazole with quinidine may result in inhibition of quinidine metabolism. Use of quinidine has been associated with QT prolongation and rare occurrences of torsade de pointes. Co-administration of fluconazole and quinidine is contraindicated.
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-related adverse reactions. Dosage reduction of zidovudine may be considered.
See prescribing information for full details.

Pregnancy:
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.
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.
Lactation:
Fluconazole was present in low levels in breast milk following administration of a single 150 mg dose. There are no data on fluconazole levels in milk after repeated use or after high-dose fluconazole.Caution should be exercised when this medical product is administered to a nursing woman.          
See prescribing information for full details

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%.

Storage: Store below 30°C.
Compatibility: This medicinal product must not be mixed with other medicinal products except those mentioned below. Fluconazole intravenous infusion is compatible with the following administration fluids:
a) Dextrose 5% and 20% b) Ringer’s solution c) Hartmann’s solution d) Potassium chloride in dextrose e) Sodium bicarbonate 4.2% and 5% f) Aminosyn 3.5% g) Sodium chloride 9 mg/ml (0.9%)
h) Dialaflex (interperitoneal dialysis Soln 6.36%).
Fluconazole may be infused through an existing line with one of the above- listed fluids. Although no specific incompatibilities have been noted, mixing with any other medicinal products prior to infusion is not recommended. The solution for infusion is for single use only. The dilution is to be made under aseptic conditions. The solution is to be inspected visually for particulate matter and discoloration prior to administration. The solution should only be used if the solution is clear and free from particles. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.