Sporal is the first orally active broad-spectrum triazole antifungal.
Pharmacology: In vitro studies have demonstrated that Sporal interferes with the heme-iron and apoprotein-binding activity of the fungal cytochrome P-450. This blocks the normal action of the enzymes and prevents the demethylation reaction which is necessary for the biosynthesis of ergosterol. Activity of membrane-bound enzymes decrease and uncoordinate synthesis of chitin. These abnormalities are toxic to fungal cell.
Pharmacokinetics: The oral bioavailability of Sporal is maximal when the capsules are given immediately after a full meal. Peak plasma levels are reached 3-4 hrs following an oral dose. Elimination from plasma is biphasic with a terminal half-life of 1-1.5 days. During chronic administration, steady state is reached after 1-2 weeks. Steady-state plasma concentrations of Sporal 3-4 hrs after drug intake are 0.4 mcg/mL (100 mg once daily), 1.1 mcg/mL (200 mg once daily) and 2 mcg/mL (200 mg twice daily).
The plasma protein-binding of Sporal is 99.8%. Concentrations of Sporal in whole blood are 60% of those in plasma. Uptake in keratinous tissues, especially the skin, is up to 4 times higher than in plasma and elimination of Sporal is related to epidermal regeneration. Therefore, therapeutic levels in the skin persist for 2-4 weeks after discontinuation of a 4-week treatment.
Sporal is also present in sebum and to a lesser extent in sweat. Sporal is also extensively distributed into tissues which are prone to fungal invasion. Concentrations in lung, kidney, liver, bone, stomach, spleen and muscle were found to be 2-3 times higher than the corresponding plasma concentration.
Therapeutic levels in vaginal tissue are maintained for another 2 days after discontinuation of a 3-day course with 200 mg daily and for another 3 days after discontinuation of a 1-day course with 200 mg twice daily.
Sporal is extensively metabolized by the liver into a large number of metabolites. One of the metabolites is hydroxy-itraconazole, which has in vitro a comparable antifungal activity to Sporal. Antifungal drug levels measured by bioassay were about 3 times those of Sporal assayed by high-performance liquid chromatography. Faecal excretion of the parent drug varies between 3-18% of the dose. Renal excretion of the parent drug is <0.03% of the dose.
About 35% of a dose is excreted as metabolites in the urine within 1 week.
Microbiology: Sporal is active against infections with dermatophytes (Trichophyton and Microsporum sp, Epidermophyton floccosum), yeasts (Candida and Pityrosporum sp), Aspergillus sp and various other yeasts and fungi.
Short-Term Therapy: Treatment of vulvovaginal candidosis, pityriasis versicolor, dermatophytoses, fungal keratitis and oral candidosis.
Long-Term Therapy: Treatment of systemic aspergillosis and candidosis, cryptococcosis (including cryptococcal meningitis), histoplasmosis, sporotrichosis, paracoccidioidomycosis, blastomycosis and other rarely occurring systemic or topical mycoses.
For maximal absorption, it is essential to administer Sporal immediately after a full meal.
The capsules must be swallowed whole.
Short-term treatment schedules are shown in Table 1.
Click on icon to see table/diagram/image
Elimination of Sporal from skin tissue is slower than from plasma. Optimal clinical and mycological effects are thus reached 2-4 weeks after the cessation of these treatment courses.
Long-term treatment schedules are as follows:
Dosage recommendations vary according to the infection treated (see Table 2):
Click on icon to see table/diagram/image
No data are available. In the event of accidental overdosage, supportive measures, including gastric lavage, should be employed.
Itraconazole cannot be removed by haemodialysis.
Patients who have shown hypersensitivity to Sporal or its excipients.
Sporal is predominantly metabolised in the liver. The oral bioavailability in cirrhotic patient is somewhat increased. It is advised to monitor the Sporal plasma concentrations and to adapt the dose when necessary.
Although with short courses, Sporal has not been associated with hepatic dysfunction, it is advisable not to give this drug to patients with a known history of liver disease or to patients who have experienced liver toxicity with other drugs. For therapy >30 days, liver function tests should be carried out monthly.
Renal Impairment: The oral bioavailability of Sporal was lower in patients with renal insufficiency. Monitoring of the Sporal plasma concentrations and a dose adaption is advisable.
Use in children: Since clinical data of the use of Sporal in paediatric patients is limited, it is advised that Sporal should not be used in these patients unless the potential benefit outweighs the potential risks.
When administered at high doses to pregnant rats (≥40 mg/kg/day) and mice (≥80 mg/kg/day), Sporal was shown to increase the incidence of foetal abnormalities and did produce adverse effects on the embryo. No studies are available on the use of Sporal in pregnant women. Therefore, Sporal should only be given in life-threatening cases of systemic mycosis and when in these cases the potential benefit outweighs the risk.
It is recommended not to breastfeed whilst taking itraconazole.
Adverse experiences during short-term Sporal therapy occurred in about 7% of the patients. The most frequently reported adverse experiences were nausea (1.3%), abdominal pain (1.2%), headache (1%) and dyspepsia (0.7%).
During long-term therapy in patients, most of whom had major underlying pathology and multiple concomitant treatments, the incidence of adverse experiences was higher (16.2%). The most frequently reported adverse experiences were of gastrointestinal origin (6.1%), where nausea (2%) and epigastralgia (0.9%) were most commonly reported. A few cases of hypokalaemia have been observed during long-term therapy.
Enzyme-inducing drugs eg, rifampicin and phenytoin significantly reduce the oral bioavailability of itraconazole. Consequently, monitoring of the Sporal plasma concentrations is advised when enzyme-inducing agents are co-administered.
In vitro studies have shown that there are no interactions on the plasma protein-binding between Sporal and imipramine, propranolol, diazepam, cimetidine, indomethacin, tolbutamide and sulfamethazine.
An interaction with cyclosporin A has been documented. Consequently, the dosage of cyclosporin A, if co-administered with itraconazole, should be reduced if necessary.
An interaction with warfarin and digoxin has been reported. Therefore, the dosage of these drugs, if co-administered with itraconazole, should be reduced if necessary.
An interaction has also been observed with terfenadine and astemizole. Therefore terfenadine and astemizole should not be used by patients treated with Sporal.
No interaction of Sporal with AZT (zidovudine) has been observed.
No inducing effects of Sporal on the metabolism of ethinyloestradiol and norethisterone were observed.
J02AC02 - itraconazole ; Belongs to the class of triazole and tetrazole derivatives. Used in the systemic treatment of mycotic infections.
Cap 100 mg x 1 x 4's, 10 x 4's.