SUBA-i Capsule

SUBA-i Capsule is used for: Candidiasis, Fungal infections, Tinea pedis, Tinea cruris, Tinea corporis, Onychomycosis, Pityriasis versicolor, Blastomycosis, Histoplasmosis, Aspergillosis

Oral Adult Conventional 100 mg or 200 mg preparations Oropharyngeal candidiasis As cap: 100 mg/day for 15 days. Vulvovaginal candidiasis As cap: 200 mg twice daily for 1 day. Pityriasis versicolor As cap: 200 mg/day for 7 days. Tinea corporis; Tinea cruris As cap: 100 mg/day for 15 days. Fungal nail infections As cap: 200 mg/day for 3 mth. Systemic fungal infections As cap: 100-200 mg once daily, up to 200 mg twice daily for invasive or disseminated infections. Prophylaxis of infections in neutropenic or AIDS patients As cap: 200 mg/day, up to 200 mg twice daily if needed. Tinea pedis; Tinea manuum As cap: 100 mg/day for 30 days or 200 mg bid for 7 days. SUBA (Super Bio-available) technology SUBA 65 mg & 130 mg preparations: For non-systemic fungal disease- Vulvovaginal candidiasis: 130 (65 mg 2 capsules) mg twice daily for 1 day Pityriasis versicolor: 65 mg twice daily for 7 days Tinea corporis and tinea cruris: 65 mg daily for 15 days OR 65 mg twice daily for 7 days Tinea pedis and tinea manuum: 65 mg once daily for 30 days Oropharyngeal Candidiasis: 65 mg once daily for 15 days, increase dose to 65 mg twice daily for 15 days in AIDS or neutropenic patients because of impaired absorption in these groups. Onychomycosis (toenails with or without fingernail involvement): Either 65 mg twice daily for 3 months or a course (pulse) of 130 mg (65 mg 2 capsules) twice daily for 7 days, subsequent courses repeated after 21 days interval. Fingernails two courses, toenails three courses. For systemic fungal disease- Aspergillosis: 65 mg twice daily for 2-5 months. Increase dose to 130 mg (65 mg 2 capsules) twice daily in case of invasive or disseminated disease Candidiasis: 65-130 mg once daily for 3 weeks - 7 months. Increase dose to 65 mg twice daily in case of invasive or disseminated disease Non-meningeal Cryptococcosis: 65 mg twice daily for 10 weeks Cryptococcal meningitis: 130 mg (65 mg 2 capsules) twice daily for 2-6 months Histoplasmosis: 130 mg (65 mg 2 capsules) once daily-twice daily for 8 months Blastomycosis: 130 mg (65 mg 2 capsules) once daily Maintenance in AIDS: 65 mg twice daily until immune recovery Prophylaxis in neutropenia: 65 mg twice daily until immune recovery The dose and duration of treatment for systemic anti-fungal disease should be adjusted depending on the clinical response.

Child: Oral Conventional strength dosing 5 mg/kg once daily (maximum per dose 200 mg), Increased to 5 mg/kg twice daily (maximum per dose 200 mg); increased dose used in invasive or disseminated infection For endemic mycoses, 2–5 mg/kg/dose three times a day for 3 days, then 2–5 mg/kg/dose twice daily (maximum of 200 mg) <3 years: Safety and efficacy not established SUBA (Super Bio-available) technology Treatment: 5 mg/kg twice daily (up to 400 mg/day). Median prescribed dose: 8.5 mg/kg/day for 6 weeks Prophylaxis: 2.5 mg/kg/day.

Renal impairment Limited data are available on use of oral itraconazole in patients with renal impairment Exercise caution when administering in this patient population

Should be taken with food. Take immediately after a full meal.

Hypersensitivity Contraindicated with certain CYP3A4 substrate drugs (see Black Box Warnings) Coadministration with colchicine, fesoterodine, and solifenacin in patients with varying degrees of renal or hepatic impairment Coadministration with eliglustat in patients who are poor or intermediate CYP2D6 metabolizers, or if coadministered with strong or moderate CYP2D6 inhibitors Increased plasma concentrations resulting from coadministration with itraconazole of some of the aforementioned drugs can lead to QT prolongation and ventricular tachyarrhythmias Treatment of onychomycosis in women who are pregnant or plan to become pregnant Coadministration with venetoclax in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) during dthe ose initiation and ramp-up phase of venetoclax

Congestive heart failure Can cause or exacerbate congestive heart failure (CHF) When itraconazole IV was administered to healthy human volunteers and dogs, negative inotropic effects were seen Do not use for the treatment of onychomycosis in patients with ventricular dysfunction (eg, history of CHF) If signs or symptoms of CHF occur during administration, continued use of this drug should be reassessed Contraindicated drug interactions Itraconazole is potent CYP4503A4 inhibitor Coadministration of the following drugs are contraindicated with itraconazole: methadone, disopyramide, dofetilide, dronedarone, quinidine, isavuconazole, ergot alkaloids (eg, dihydroergotamine, ergonovine, ergotamine, methylergonovine), irinotecan, ivabradine, lurasidone, oral midazolam, pimozide, triazolam, felodipine, nisoldipine, ranolazine, eplerenone, cisapride, naloxegol, lomitapide, lovastatin, simvastatin, avanafil, ticagrelor, finerenone, voclosporin In patients with varying degrees of renal or hepatic impairment, coadministration of itraconazole with colchicine, fesoterodine, and solifenacin are contraindicated Coadministration with eliglustat is contraindicated in subjects that are poor or intermediate metabolizers of CYP2D6 and in subjects taking strong or moderate CYP2D6 inhibitors Elevated plasma concentrations of some of these drugs and may increase or prolong both the pharmacologic effects and/or adverse reactions to these drugs (eg, increased plasma concentrations of some of these drugs can lead to QT prolongation and ventricular tachyarrhythmias including occurrences of torsades de pointes) Coadministration with venetoclax is contraindicated in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) during the dose initiation and ramp-up phase of venetoclax Hepatotoxicity: Serious hepatotoxicity, including liver failure and death were reported with the use of itraconazole. Discontinue treatment if signs of liver dysfunction occur Cardiac Dysrhythmias: Life-threatening cardiac dysrhythmias and/or sudden death have occurred in patients using certain drugs that are metabolized by human CYP450 enzymes concomitantly with oral itraconazole and/or other CYP3A4 inhibitors. Peripheral Neuropathy: This has been reported in patients on long-term therapy with itraconazole. Monitor and promptly evaluate neurologic symptoms. Hearing Loss: Reversible or permanent has been reported in patients. Discontinue treatment if hearing loss occurs. MONITORING PARAMETERS Absorption is reduced in AIDS and neutropenia (monitor plasma-itraconazole concentration and increase dose if necessary). Monitor liver function if treatment continues for longer than one month, if receiving other hepatotoxic drugs, or if history of hepatotoxicity with other drugs. Monitor blood pressure and potassium levels in Pseudoaldosteronism.

Pregnancy There are no data on exposure to itraconazole during pregnancy Published epidemiologic studies of women exposed to short courses of treatment with itraconazole in the first trimester of pregnancy have reported no risk of major birth defects overall and inconclusive findings on the risk of miscarriage Drug should be used for treatment of systemic fungal infections in pregnancy only if benefit outweighs potential risk; therapy should not be administered for treatment of onychomycosis to pregnant patients or to women contemplating pregnancy; drug should not be administered to women of childbearing potential for treatment of onychomycosis unless they are using effective measures to prevent pregnancy and they begin therapy on the second or third day following the onset of menses; highly effective contraception should be continued throughout therapy and for 2 months following the end of treatment Animal In animal reproduction studies, itraconazole was found to cause a dose-related increase in maternal toxicity, embryotoxicity, and teratogenicity in rats at dosage levels of approximately (6-25 times the maximum recommended human dose [MRHD] of 390 mg/day based on mg/kg comparisons), and in mice at dosage levels of ~80 mg/kg/day (12 times the MRHD). Lactation Itraconazole is excreted in human milk No data on the amount of itraconazole in human milk, the effects on the breastfed child, or the effects on milk production Developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for itraconazole and any potential adverse effects on the breastfed child from itraconazole or from underlying maternal condition

May increase the plasma concentrations of oral anticoagulants, digoxin, cilostazol, alprazolam, midazolam (IV), repaglinide, corticosteroids (e.g. budesonide, dexamethasone, fluticasone, methylprednisolone). May increase plasma concentration w/ HIV protease inhibitors (e.g. ritonavir, indinavir, saquinavir), erythromycin, clarithromycin. May reduce plasma concentration w/ isoniazid, carbamazepine, nevirapine, phenytoin, Phenobarbital, rifampicin, rifabutin. May reduce absorption w/ PPIs, antacids, antimuscarinics, histamine H2 receptor antagonists. Concomitant use w/ dihydropyridines may cause oedema. May increase negative inotropic effects of verapamil. May increase risk of potentially fatal resp depression w/ fentanyl. Potentially Fatal: May increase risk of QT prolongation or torsades de pointes w/ astemizole, bepridil, cisapride, dofetilide, levacetylmethadol (levomethadyl), mizolastine, pimozide, quinidine, sertindole, terfenadine, methadone, ranolazine, dronedarone, halofantrine. May increase risk of myopathy including rhabdomyolysis w/ HMG-CoA reductase inhibitors (e.g. atorvastatin, lovastatin, simvastatin). May increase risk of ergotism w/ ergot alkaloids (e.g. ergotamine, dihydroergotamine, ergometrine, methylergometrine). May potentiate hypnotic and sedative effect of triazolam and oral midazolam. May increase plasma concentration of eletriptan, nisoldipine, felodipine, disopyramide, irinotecan, lurasidone; colchicine (patient w/ renal or hepatic failure). May increase risk of hypotension and hyperkalaemia w/ eplerenone. Contraindicated (46) alfuzosin avanafil conivaptan dihydroergotamine dihydroergotamine intranasal disopyramide dofetilide dronedarone eliglustat eplerenone ergoloid mesylates ergotamine estazolam felodipine fesoterodine finerenone flibanserin gepirone indapamide irinotecan irinotecan liposomal isavuconazonium sulfate ivabradine lomitapide lonafarnib lovastatin lurasidone methadone methylergonovine midazolam naloxegol nisoldipine pacritinib pimozide quinidine ranolazine silodosin simvastatin solifenacin suzetrigine ticagrelor tolvaptan triazolam ubrogepant venetoclax voclosporin

Side effects of Itraconazole : >10% Systemic fungal infections Nausea (11%) 1-10% (Systemic fungal infections) Rash (9%) Vomiting (5%) Edema (4%) Headache (4%) Abnormal liver function test results (3%) Diarrhea (3%) Fever (3%) Fatigue (3%) Hypertension (3%) Pruritus (3%) Abdominal pain (2%) Dizziness (2%) Hypertriglyceridemia (2%) Hypokalemia (2%) Albuminuria (1%) Anorexia (1%) Decreased libido (1%) Somnolence (1%) Anorexia (1%) Impotence (1%) 1-10% (Toenail infections) Headache (10%) Rhinitis (9%) Upper respiratory tract infection (8%) Sinusitis, injury (7%) Diarrhea (4%) Dyspepsia (4%) Flatulence (4%) Abdominal pain (4%) Dizziness (4%) Rash (4%) Elevated liver enzymes (4%) Gastrointestinal disorders (4%) Rash (3%) Cystitis (3%) Urinary tract infection (3%) Liver function abnormality (3%) Myalgia (3%) Nausea (3%) Hypertension (2%) Appetite increased (2%) Constipation (2%) Gastritis, gastroenteritis (2%) Pharyngitis (2%) Abnormal dreaming (2%) Orthostatic hypertension (1%) Headache (1%) Malaise (1%) Myalgia (1%) Vasculitis (1%) Vertigo (1%) Frequency Not Defined Hepatobiliary disorders: Hyperbilirubinemia Cardiac disorders: Cardiac failure, left ventricular failure, tachycardia General disorders and administration site conditions: Face edema, chest pain, chills Hepatobiliary disorders: Hepatic failure, jaundice Investigations: ALT increased, AST increased, blood alkaline phosphatase increased, blood lactate dehydrogenase increased, blood urea increased, gamma glutamyltransferase increased, urine analysis abnormal Metabolism and nutrition disorders: Hyperglycemia, hyperkalemia, hypomagnesemia Psychiatric disorders: Confusional state Renal and urinary disorders: Renal impairment Respiratory, thoracic and mediastinal disorders: Dysphonia, cough Skin and subcutaneous tissue disorders: Hyperhidrosis Vascular disorders: Hypotension Potentially Fatal: Liver failure; heart failure; pulmonary oedema; CV disease.

Itraconazole decreases ergosterol synthesis by interfering w/ cytochrome P450 activity. This inhibits cell membrane function of susceptible fungi including Microsporum spp., Trichophyton spp., Candida spp., Aspergillus spp., Epidermophyton spp., Cryptococcus neoformans, Histoplasma capsulatum, Blastomyces dermatitidis, sporothrix schenckii, Malassezia furfur, Coccidioides immitis and Paracoccidiodes brasiliensis. It also has antiprotozoal activity against Leishmania spp. SUBA (Super Bio-available) technology is a novel technology for enhancing the bioavailability of poorly soluble drugs. This technology utilizes a solid dispersion of drug in a polymer that improves the dissolution of poorly soluble drugs compared to their normal crystalline form. SUBA technology Itraconazole is an orally active triazole antifungal drug that has demonstrated a broad spectrum of activity and a favorable pharmacokinetic profile.

SUBA-i 65 mg Capsule manufactured by Beximco Pharmaceuticals Ltd.. Its generic name is Itraconazole. SUBA-i is availble in Bangladesh. Farmaco BD drug index information on SUBA-i Capsule is not intended for diagnosis, medical advice or treatment; neither intended to be a substitute for the exercise of professional judgment.