CANDITRAL is a new orally active triazole antifungal drug with a broad spectrum of activity and a favourable pharmacokinetic profile. It is a potent inhibitor of most human fungal pathogens and is extremely effective in a wide range of superficial and serious deep sealed fungal infections when administered once or twice daily.
CANDITRAL is a promising drug for prophylaxis of opportunistic fungal infections in women with chronic recurrent vaginal candidiasis, immunodeficient patients with chronic mucocutaneous candidiasis, AIDS patients and patients receiving immunosuppressant drugs.
Pharmacology: Pharmacodynamics: Mechanism of Action: CANDITRAL acts by inhibition of Cytochrome-P450 dependent fungal enzyme systems which synthesize ergosterol, the primary cellular sterol in fungi. This leads to disruption of intracellular membranes with inhibition of lanosterol demthylase leading to accumulation of membrane precursor lipids such as lanosterol.
CANDITRAL has less affinity for mammalian cytochromes as compared to Ketoconazole and thus causes a lower incidence of adverse effects than Ketoconazole.
Pharmacokinetics: Absorption of CANDITRAL after oral administration is maximal immediately after a main meal. Peak plasma concentrations are achieved after 14 days of administration and the concentrations attained with 100 mg daily are effective against most common fungal pathogens.
CANDITRAL is highly keratophilic and lipophilic and is widely distributed in the body, achieving concentrations in fatty tissues, omentum, liver, kidney, nails and skin tissues that are 2-20 times higher than corresponding plasma concentrations. Fluids equivalent to body water such as CSF, eye fluid and saliva contain low to negligible amounts of CANDITRAL whereas exudates like pus have up to 3.5 times the simultaneous plasma concentration. Most tissues which are prone to fungal invasion such as skin and female genital tract issues have several times the plasma concentration of CANDITRAL.
The major route of CANDITRAL delivery to the skin appears to be via sebum. Sebum levels of CANDITRAL are 5 to 10 times higher than corresponding plasma levels within 4 days of starting the drug and detectable amounts persist for up to 14 days after the drug is stopped. CANDITRAL can be detected in stratum corneum up to 4 weeks after discontinuing therapy, which reflects the drug's affinity for sebum and keratinocytes. CANDITRAL is 99.8% bound, 94.9% to plasma proteins (primarily albumin) and 4.9% to blood cells leaving only 0.2% as free drug.
CANDITRAL undergoes extensive hepatic metabolism prior to being excreted in inactive form in urine and bile. The major metabolite of CANDITRAL is Hydroxyitraconazole. Elimination half life is about 20 hours after a single oral dose of 100 mg and approximately 30 hours following 2 to 4 weeks treatment with CANDITRAL 100 mg once daily.
Dermatophytoses, Onychomycoses, Tinea versicolor, Cutaneous Candidiasis, Oropharyngeal Candidiasis, Vulvovaginal Candidiasis Recurrent Vaginal Candidiasis.
Chronic Mucocutaneous Candidiasis (CMC), Oculomycoses.
Subcutaneous Mycoses: Sporotrichosis, Chromomycosis.
Dimorphic Mycoses: Coccidiodomycosis, Paracoccidiodomycosis, Histoplasmosis, Blastomycosis.
Systemic Mycoses: Candidiasis, Cryptococcosis, Aspergillosis.
Prophylaxis against Opportunistic Mycoses in: AIDS Patients and Patients on Immunosuppressant Therapy.
CANDITRAL should be taken with or after a principal meal to ensure maximum absorption. Treatment schedules are as follows: Dermatophytoses: 1 Capsule daily for 15-30 days.
Onychomycoses: 1 Capsule daily for 3-6 months.
Tinea versicolor: 1-2 Capsules daily for 5-7 days.
Cutaneous candidiasis: 1 Capsule daily for 15-30 days.
Oropharyngeal candidiasis: 1 Capsule daily for 15 days.
Vulvovaginal candidiasis: 2 Capsules twice daily for 1 day or 2 Capsules once daily for 3 days.
Recurrent Vaginal Candidiasis: 2 Capsules once daily for 3 days followed by 2 Capsules (single dose) on the first day of menses of 6 consecutive cycles.
Chronic Mucocutaneous: 1-2 Capsules daily for 1-2 months.
Candidiasis (CMC), Oculomycoses: 2 Capsules once daily for 3-4 weeks.
Subcutaneous Mycoses: Sporotrichosis, Chromomycosis: In all these conditions, the dose and duration of Therapy will need to be idividualised depending on the response.
Dimorphic Mycoses: Coccidioidomycosis, Paracoccidioidomycosis: The dose range will vary from 1-4 capsules daily and the duration will vary from 1 month to 6 months or as long as required.
Histoplasmosis, Blastomycosis.
Systemic Mycoses: Candidiasis, Prophylaxis against Opportunistic Mycoses in: AIDS Patients and Patients on Immunosuppressant Therapy.
Itraconazole is not removed by dialysis in the event of accidental overdosage, supportive measures, including gastric lavage with Sodium bicarbonate should be employed.
No significant lethality was observed when Itraconazole was administered orally to mice and rats at dosage levels of 320 mg/kg or to dogs at 200 mg/kg.
Coadministration of Terfenadine or Astemizole with CANDITRAL is also contraindicated in patients with known hypersensitivity to the drug. Caution should be used in prescribing CANDITRAL to patients with hypersensitivity to other azoles.
CANDITRAL is contraindicated in pregnancy and appropriate means of contraception should be employed in women of childbearing potential. CANDITRAL is excreted in human milk and should no be administered to nursing mothers.
The efficacy and safety of CANDITRAL have not been established in children. A small number of patients between 3-16 years of age have been treated with 100 mg/day of CANDITRAL for systemic fungal infections and no serious adverse effects have been reported.
CANDITRAL should not be used in patients taking Rifampicin which appears to initially inhibit and then enhance metabolism of Itraconazole.
Use of CANDITRAL in patients with non-life threatening conditions who have known hepatic disease is not advised.
If clinical signs and symptoms consistent with liver disease develop that may be attributable to Itraconazole, CANDITRAL should be discontinued.
Coadministration of terfenadine with Itraconazole is contraindicated. Rare cases of serious cardiovascular adverse effects including death, ventricular tachycardia and torsades de pointes have been observed in patients taking Itraconazole concomitantly with terfenadine due to increased terfenadine concentrations induced by Itraconazole.
Pharmacokinetic data indicate that another oral antifungal. Ketoconazole inhibits the metabolism of astemizole, resulting in elevated plasma levels of astemizole and its active metabolite desmethylastemizole which may prolong QT intervals. In vitro data suggest that Itraconazole, when compared to Ketoconazole, has a less pronounced effect on the biotransformation system responsible for the metabolism of astemizole. Based on the chemical resemblance of Itraconazole and Ketoconazole, Coadministration of astemizole with itraconazole is contraindicated.
Hepatic enzyme test values should be monitored in patients with pre-existing hepatic function abnormalities.
CANDITRAL is well tolerated. Most of the adverse reactions are transient and of mild to moderate severity. Dyspepsia, abdominal pain, nausea, diarrhoea, pruritus, dizziness and headache have been reported.
Coadministration of Terfenadine with CANDITRAL has led to elevated plasma concentrations of terfenadine, resulting in rare instances of life threatening cardiac dysrythmias. CANDITRAL when compared to Ketoconazole has a less pronounced effect on the biotransformation system responsible for the metabolism of Astemizole. Based on the chemical resemblance of Itraconazole and Ketoconazole, Coadministration of Astemizole with CANDITRAL is contraindicated.
Co-administration of CANDITRAL and cyclosporine or digoxin increases plasma concentration of latter two drugs and the concentrations of cyclosporine and digoxin should be monitored frequently and dose adjustment as necessary.
When CANDITRAL is coadministered with phenytoin, rifampicin or H2 antagoists, plasma concentrationsof CANDITRAL are reduced.
CANDITRAL enhances the anticoagulant effect of coumarin drugs.
Plasma concentrations of CANDITRAL are reduced when it is coadministered with isoniazid. Itraconazole plasma concentrations should be monitored when CANDITRAL and isoniazid is coadministered.
Severe hypoglycemia has been reported in patients concomitantly receiving azole antifungal agents and oral hypoglycemic agents. Blood glucose concentrations should be carefully monitored when CANDITRAL and oral hypoglycemic agents are coadministered.
J02AC02 - itraconazole ; Belongs to the class of triazole and tetrazole derivatives. Used in the systemic treatment of mycotic infections.
Sign Out
