SPORANOX

Sporanox is for oral administration and must be taken immediately after a meal for maximal absorption. The capsules must be swallowed whole.

Treatment schedules in adults for each indication are as follows:

Indication Dose Remarks Vulvovaginal candidosis 200 mg twice daily for 1 day Pityriasis versicolor 200 mg once daily for 7 days Tinea corporis, tinea cruris 100 mg once daily for 15 days or 200 mg once daily for 7 days Tinea pedis, tinea manuum 100 mg once daily for 30 days Oropharyngeal candidosis 100 mg once daily for 15 days Increase dose to 200 mg once daily for 15 days in AIDS or neutropenic patients because of impaired absorption in these groups.

Onychomycosis (toenails with or without fingernail involvement) 200 mg once daily for 3 months For skin, vulvovaginal and oropharyngeal infections, optimal clinical and mycological effects are reached 1 - 4 weeks after cessation of treatment and for nail infections, 6 - 9 months after the cessation of treatment.

This is because elimination of itraconazole from skin, nails and mucous membranes is slower than from plasma. The length of treatment for systemic fungal infections should be dictated by the mycological and clinical response to therapy: Indication Dose1 Remarks Aspergillosis Candidosis Non-meningeal Cryptococcosis 200 mg once daily 100-200 mg once daily 200 mg once daily Increase dose to 200 mg twice daily in case of invasive or disseminated disease Increase dose to 200 mg twice daily in case of invasive or disseminated disease Cryptococcal meningitis Histoplasmosis Maintenance therapy for Talaromycosis (formerly penicilliosis) and histoplasmosis only in AIDS patients Maintenance therapy of cryptococcal meningitis only in AIDS patients Prophylaxis of fungal infections in immunocompromised patients with severe neutropenia 200 mg twice daily 200 mg once daily - 200 mg twice daily 200 mg once or 200 mg twice daily until immune recovery 200 mg twice daily until immune recovery 200 mg twice daily until immune recovery The duration of treatment should be based upon the status of the immune recovery.

Summary of the safety profile The most frequently reported adverse drug reactions (ADRs) with Sporanox Capsules treatment identified from clinical trials and/or from spontaneous reporting were headache, abdominal pain, and nausea. The most serious ADRs were serious allergic reactions, cardiac failure/congestive heart failure/pulmonary oedema, pancreatitis, serious hepatotoxicity (including some cases of fatal acute liver failure), and serious skin reactions.

Refer to subsection Tabulated list of adverse reactions for the frequencies and for other observed ADRs. 4 Special warnings and precautions for use for additional information on other serious effects. Tabulated list of adverse reactions The ADRs in the table below were derived from open-label and double-blind clinical trials with Sporanox Capsules involving 8499 patients in the treatment of dermatomycoses or onychomycosis, and from spontaneous reporting.

The table below presents ADRs by System Organ Class. Within each System Organ Class, the ADRs are presented by incidence, using the following convention: Very common (≥ 1/10); Common (≥ 1/100 to < 1/10); Uncommon (≥ 1/1,000 to < 1/100); Rare (≥ 1/10,000 to < 1/1,000); Very rare (< 1/10,000).

, excluding the ADR term “Injection site inflammation”, which is specific to the injection route of administration.

Blood and lymphatic system disorders:

Granulocytopenia, Thrombocytopenia Immune system disorders: Anaphylactoid reaction Metabolism and nutrition disorders: Hyperglycaemia, Hyperkalaemia, Hypokalaemia, Hypomagnesaemia Psychiatric disorders: Confusional state Nervous system disorders: Peripheral neuropathy*, Dizziness, Somnolence Cardiac disorders: Cardiac failure, Left ventricular failure, Tachycardia Vascular disorders: Hypertension, Hypotension Respiratory, thoracic and mediastinal disorders: Pulmonary oedema, Dysphonia, Cough Gastrointestinal disorders: Gastrointestinal disorder Hepatobiliary disorders: Hepatic failure*, Hepatitis, Jaundice Skin and subcutaneous tissue disorders: Rash erythematous, Hyperhidrosis Musculoskeletal and connective tissue disorders: Myalgia, Arthralgia Renal and urinary disorders: Renal impairment, Urinary incontinence General disorders and administration site conditions: Generalised oedema, Face oedema, Chest pain, Pyrexia, Pain, Fatigue, Chills Investigations: Alanine aminotransferase increased, Aspartate aminotransferase increased, Blood alkaline phosphatase increased, Blood lactate dehydrogenase increased, Blood urea increased, Gamma- glutamyltransferase increased, Hepatic enzyme increased, Urine analysis abnormal Paediatric population The safety of Sporanox Capsules was evaluated in 165 paediatric patients aged 1 to 17 years who participated in 14 clinical trials (4 double-blind, placebo controlled trials; 9 open-label trials; and 1 trial had an open-label phase followed by a double-blind phase).

Elderly Clinical data on the use of Sporanox Capsules in elderly patients are limited. It is advised to use Sporanox Capsules in these patients only if it is determined that the potential benefit outweighs the potential risks. In general, it is recommended that the dose selection for an elderly patient should be taken into consideration, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

4 Special warnings and precautions for use. Renal impairment Limited data are available on the use of oral itraconazole in patients with renal impairment. The exposure of itraconazole may be lower in some patients with renal insufficiency.

Caution should be exercised when this drug is administered in this patient population and adjusting the dose may be considered. Hepatic impairment Limited data are available on the use of oral itraconazole in patients with hepatic impairment.

Caution should be exercised when this drug is administered in this patient population. 3 Contraindications • Sporanox Capsules are contra-indicated in patients with known hypersensitivity to itraconazole or to any of the excipients.

5). g. dihydroergotamine, ergometrine, ergotamine, methylergometrine) Anti-bacterials for Systemic Use; Anti-mycobacterials; Antimycotics for Systemic Use Isavuconazole Anthelmintics; Antiprotozoals Halofantrine Antihistamines for Systemic Use Astemizole Mizolastine Terfenadine Antineoplastic Agents Irinotecan Venetoclax (in patients with chronic lymphocytic leukaemia during dose initiation/titration/ramp-up phase of venetoclax) Antithrombotic Agents Dabigatran Ticagrelor Antivirals for Systemic Use Ombitasvir/Paritaprevir/Ritonavir (with or without Dasabuvir) Cardiovascular System (Agents Acting on the Renin-Angiotensin System; Antihypertensives; Beta Blocking Agents; Calcium Channel Blockers; Cardiac Therapy; Diuretics) Aliskiren Dronedarone Nisoldipine Bepridil Eplerenone Quinidine Disopyramide Ivabradine Ranolazine Dofetilide Lercanidipine Sildenafil (pulmonary hypertension) Gastrointestinal Drugs, including Antidiarrheals, Intestinal Anti-inflammatory/Anti-infective Agents; Antiemetics and Antinauseants; Drugs for Constipation; Drugs for Functional Gastrointestinal Disorders Cisapride Domperidone Naloxegol Lipid Modifying Agents Lovastatin Lomitapide Simvastatin Psychoanaleptics; Psycholeptics (eg, antipsychotics, anxiolytics, and hypnotics) Lurasidone Pimozide Sertindole Midazolam (oral) Quetiapine Triazolam Urologicals Avanafil Darifenacin Solifenacin (in patients with severe renal impairment or moderate to severe hepatic impairment) Dapoxetine Fesoterodine (in patients with moderate or severe renal or hepatic impairment).

• Sporanox Capsules are contra-indicated in patients with known hypersensitivity to itraconazole or to any of the excipients. 5). g. dihydroergotamine, ergometrine, ergotamine, methylergometrine) Anti-bacterials for Systemic Use; Anti-mycobacterials; Antimycotics for Systemic Use Isavuconazole Anthelmintics; Antiprotozoals Halofantrine Antihistamines for Systemic Use Astemizole Mizolastine Terfenadine Antineoplastic Agents Irinotecan Venetoclax (in patients with chronic lymphocytic leukaemia during dose initiation/titration/ramp-up phase of venetoclax) Antithrombotic Agents Dabigatran Ticagrelor Antivirals for Systemic Use Ombitasvir/Paritaprevir/Ritonavir (with or without Dasabuvir) Cardiovascular System (Agents Acting on the Renin-Angiotensin System; Antihypertensives; Beta Blocking Agents; Calcium Channel Blockers; Cardiac Therapy; Diuretics) Aliskiren Dronedarone Nisoldipine Bepridil Eplerenone Quinidine Disopyramide Ivabradine Ranolazine Dofetilide Lercanidipine Sildenafil (pulmonary hypertension) Gastrointestinal Drugs, including Antidiarrheals, Intestinal Anti-inflammatory/Anti-infective Agents; Antiemetics and Antinauseants; Drugs for Constipation; Drugs for Functional Gastrointestinal Disorders Cisapride Domperidone Naloxegol Lipid Modifying Agents Lovastatin Lomitapide Simvastatin Psychoanaleptics; Psycholeptics (eg, antipsychotics, anxiolytics, and hypnotics) Lurasidone Pimozide Sertindole Midazolam (oral) Quetiapine Triazolam Urologicals Avanafil Darifenacin Solifenacin (in patients with severe renal impairment or moderate to severe hepatic impairment) Dapoxetine Fesoterodine (in patients with moderate or severe renal or hepatic impairment).

Vardenafil (in patients older than 75 years). Miscellaneous Drugs and Other Substances Colchicine (in patients with renal or hepatic impairment) Eliglustat (in patients that are CYP2D6 poor metabolisers (PM), CYP2D6 intermediate metabolisers (IMs) or extensive metabolisers (EMs) that are taking a strong or moderate CYP2D6 inhibitor).