Sporanox Oral Solution

/ J-C Health Care Ltd

For optimal absorption, SPORANOX oral solution should be taken without food (patients are advised to refrain from eating or drinking for at least 1 hour after intake).
For the treatment of oral and/or esophageal candidosis, the oral solution should be swished around the oral cavity (approx. 20 seconds) and swallowed. There should be no rinsing after swallowing.
Treatment of oral and/or esophageal candidosis: 200 mg (2 measuring cups) per day in two intakes, or alternatively in one intake, for 1 week. If there is no response after 1 week, treatment should be continued for another week. Treatment of fluconazole resistant oral and/or esophageal candidosis 100 to 200 mg (1-2 measuring cups) twice daily for 2 weeks. If there is no response after 2 weeks, treatment should be continued for another 2 weeks. The 400 mg daily dose should not be used for longer than 14 days if there are no signs of improvement.
Prophylaxis of fungal infections: 5 mg/kg per day administered in two intakes. In clinical trials, prophylaxis treatment was started immediately prior to the cytostatic treatment and generally one week before transplant procedure. Treatment was continued until recovery of neutrophils (i.e. > 1000 cells/µl). Empiric therapy of febrile neutropenic patients with suspected systemic mycoses Treatment should be started with SPORANOX IV. The recommended dose of SPORANOX IV is 200 mg b.i.d. for four doses, followed by 200 mg once daily for up to 14 days. Each intravenous dose should be infused over 1 hour. Treatment should be continued with SPORANOX oral solution 200 mg (20 ml) b.i.d. until resolution of clinically significant neutropenia. The safety and efficacy of SPORANOX use exceeding 28 days in empiric therapy of febrile patients with suspected systemic mycoses is not known.
Use in pediatric patients: Clinical data on the use of SPORANOX oral solution in pediatric patients are limited. The use of SPORANOX oral solution in pediatric patients is not recommended unless it is determined that the potential benefit outweighs the potential risks.
Prophylaxis of fungal infections: there are no efficacy data available in neutropenic children. Limited safety experience is available with a dose of 5 mg/kg per day administered in two intakes. The incidence of adverse events such as diarrhea, abdominal pain, vomiting, fever, rash and mucositis was higher than in adults. However, it is not clear to what extent this is attributable to SPORANOX oral solution or the chemotherapy.
Use in elderly: Clinical data on the use of SPORANOX oral solution in elderly patients are limited, it is advised to use SPORANOX oral solution in these patients only if it is determined that the potential benefits 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.
For full details see prescribing information.

Treatment of oropharyngeal and esophageal candidiasis, prevention of fungal infection during neutropenia in immunodeficient patients.

-SPORANOX oral solution is contraindicated in patients with known hypersensitivity to itraconazole or to any of the excipients.
-Co-administration of the following drugs is contraindicated with Sporanox Oral Solution.
– CYP3A4 metabolised substrates that can prolong the QT-interval e.g., astemizole, bepridil, cisapride, dofetilide, levacetylmethadol (levomethadyl), mizolastine, pimozide, quinidine, sertindole and terfenadine are contraindicated with Sporanox oral solution. Co-administration may result in increased plasma concentrations of these substrates, which can lead to QT prolongation and rare
occurrences of torsade de pointes.
– CYP3A4 metabolized HMG-CoA reductase inhibitors such as atorvastatin, lovastatin and simvastatin- Triazolam and oral midazolam
– Ergot alkaloids such as dihydroergotamine, ergometrine (ergonovine), ergotamine and methylergometrine (methylergonovine).
– Eletriptan
– Nisoldipine
-Sporanox oral solution should not be administered to patients with evidence of ventricular dysfunction such as congestive heart failure (CHF) or a history of CHF except for the treatment of life-threatening or other serious infections.
-SPORANOX oral solution must not be used during pregnancy (except for life-threatening cases).
– Women of childbearing potential taking SPORANOX oral solution should use contraceptive precautions. Effective contraception should be continued until the menstrual period following the end of SPORANOX oral solution therapy.
For full details see prescribing information.

Cardiac effects: In a healthy volunteer study with SPORANOX IV, a transient asymptomatic decrease of the left ventricular ejection fraction was observed; this resolved before the next infusion. The clinical relevance of these findings to the oral formulations is unknown. Itraconazole has been shown to have a negative inotropic effect and SPORANOX has been associated with reports of congestive heart failure. Heart failure was more frequently reported among spontaneous reports of 400 mg total daily dose than among those of lower total daily doses, suggesting that the risk of heart failure might increase with the total daily dose of itraconazole. SPORANOX should not be used in patients with congestive heart failure or with a history of congestive heart failure unless the benefit clearly outweighs the risk. This individual benefit/risk assessment should take into consideration factors such as the severity of the indication, the dosing regimen, (e.g., total daily dose), and individual risk factors for congestive heart failure. These risk factors include cardiac disease, such as ischemic and valvular disease; significant pulmonary disease, such as chronic obstructive pulmonary disease; and renal failure and other edematous disorders. Such patients should be informed of the signs and symptoms of congestive heart failure, should be treated with caution, and should be monitored for signs and symptoms of congestive heart failure during treatment; if such signs or symptoms do occur during treatment, SPORANOX should be discontinued. Calcium channel blockers can have negative inotropic effects which may be additive to those of itraconazole. In addition itraconazole can inhibit the metabolism of calcium channel blockers. Therefore, caution should be used when co-administering itraconazole and calcium channel blockers due to an increased risk of CHFInteraction potential Coadministration of specific drugs with itraconazole may result in changes in efficacy of itraconazole and/or the coadministered drug, life-threatening effects and/or sudden death. Drugs that are contraindicated, not recommended or recommended for use with caution in combination with itraconazole are listed in.
Cystic fibrosis: In cystic fibrosis patients, variability in therapeutic levels of itraconazole was observed with steady state dosing of oral solution using 2.5 mg/kg bid. Steady state concentrations of > 250 ng/mL were achieved in approximately 50% of subjects greater than 16 years of age, but in none of the patients less than 16 years of age. If a patient does not respond to SPORANOX oral solution, consideration should be given to switching to SPORANOX IV or to alternative therapy.
Use in pediatric patients: Clinical data on the use of SPORANOX oral solution in pediatric patients are limited. The use of SPORANOX oral solution in pediatric patients is not recommended unless it is determined that the potential benefit outweighs the potential risks.
Use in elderly: Clinical data on the use of SPORANOX oral solution in elderly patients are limited. It is advised to use SPORANOX oral solution 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.
Hepatic effects: Very rare cases of serious hepatotoxicity, including some cases of fatal acute liver failure, have occurred with the use of SPORANOX. Most of these cases involved patients who, had preexisting liver disease, were treated for systemic indications, had significant other medical conditions and/or were taking other hepatotoxic drugs. Some patients had no obvious risk factors for liver disease. Some of these cases were observed within the first month of treatment,including some within the first week. Liver function monitoring should be considered in patients receiving SPORANOX treatment. Patients should be instructed to promptly report to their physician signs and symptoms suggestive of hepatitis such as anorexia, nausea, vomiting, fatigue, abdominal pain or dark urine. In these patients treatment should be stopped immediately and liver function testing should be conducted. Limited data are available on the use of oral itraconazole in patients with hepatic impairment. Caution should be exercised when the drug is administered in this patient population. It is recommended that patients with impaired hepatic function be carefully monitored when taking itraconazole. It is recommended that the prolonged elimination half-life of itraconazole observed in the single oral dose clinical trial with itraconazole capsules in cirrhotic patients be considered when deciding to initiate therapy with other medications metabolized bCYP3A4. In patients with elevated or abnormal liver enzymes or active liver disease, or who have experienced liver toxicity with other drugs, treatment with SPORANOX oral solution is strongly discouraged unless there is a serious or life threatening situation where the expected benefit exceeds the risk. It is recommended that liver function monitoring should be done in patients with pre-existing hepatic function abnormalities or those who have experienced liver toxicity with other medications.
For full details see prescribing information.

Throughout this section, adverse reactions are presented. Adverse reactions are adverse events that were considered to be reasonably associated with the use of itraconazole based on the comprehensive assessment of the available adverse event information. A causal relationship with itraconazole cannot be reliably established in individual cases. Further, because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
Clinical Trial Data: The safety of SPORANOX oral solution was evaluated in 889 patients who participated in six double-blind and four open-label clinical trials. Of the 889 patients treated with SPORANOX oral solution, 624 patients were treated with SPORANOX oral solution during the double-blind trials. All 889 patients received at least one dose of SPORANOX oral solution for the treatment of oropharyngeal and esophageal candidiasis and provided safety data.
For full details see prescribing information.

Itraconazole is mainly metabolized through CYP3A4. Other substances that either share this metabolic pathway or modify CYP3A4 activity may influence the pharmacokinetics of itraconazole. Similarly, itraconazole may modify the pharmacokinetics of other substances that share this metabolic pathway. Itraconazole is a potent CYP3A4 inhibitor and a Pglycoprotein inhibitor. When using concomitant medication, it is recommended that thecorresponding label be consulted for information on the route of metabolism and the possible need to adjust dosages.
Drugs that may decrease itraconazole plasma concentrations Coadministration of itraconaozle with potent enzyme inducers of CYP3A4 may decrease the bioavailability of itraconazole and hydroxy-itraconazole to such an extent that efficacy may be largely reduced. Examples include: Antibacterials: isoniazid, rifabutin, rifampicin. Anticonvulsants: carbamazepine, (see also under Drugs that may have their plasma concentrations increased by itraconazole), phenobarbital, phenytoin.
Antivirals: efavirenz, nevirapine.
Hypericum perforatum (St. John’s wort). Therefore, administration of potent enzyme inducers of CYP3A4 with itraconazole is not recommended. It is recommended that the use of these drugs be avoided from 2 weeks before and during treatment with itraconazole, unless the benefits outweigh the risk of potentially reduced itraconazole efficacy. Upon coadministration, it is recommended that the antifungal activity be monitored and the itraconazole dose increased as deemed necessary.
Drugs that may increase itraconazole plasma concentrations
Potent inhibitors of CYP3A4 may increase the bioavailability of itraconazole. Examples include: Antibacterials:ciprofloxacin, clarithromycin, erythromycin; Antivirals: ritonavir-boosted darunavir, ritonavir-boosted fosamprenavir, indinavir (see also under Drugs that may have their plasma concentrations increased by itraconazole), ritonavir, It is recommended that these drugs be used with caution when coadministered with itraconazole oral solution. It is recommended that patients who must take itraconazoleconcomitantly with potent inhibitors of CYP3A4 be monitored closely for signs or symptoms of increased or prolonged pharmacologic effects of itraconazole, and the itraconazole dose be decreased as deemed necessary. When appropriate, it is recommended that itraconazole plasma concentrations be measured. Drugs that may have their plasma concentrations increased by itraconazole Itraconazole and its major metabolite, hydroxy-itraconazole, can inhibit the metabolism of drugs metabolized by CYP3A4 and can inhibit the drug transport by P-glycoprotein, which may result in increased plasma concentrations of these drugs and/or their active metabolite(s) when they are administered with itraconazole. These elevated plasma concentrations may increase or prolong both therapeutic and adverse effects of these drugs. CYP3A4-metabolized drugs known to prolong the QT interval may be contraindicated with itraconazole, since the combination may lead to ventricular tachyarrhythmias including occurrences of torsade de pointes, a potentially fatal arrhythmia. Once treatment is stopped, itraconazole plasma concentrations decrease to an almost undetectable concentration within 7 to 14 days, depending on the dose and duration of treatment. In patients with hepatic cirrhosis or in subjects receiving CYP3A4 inhibitors, the decline in plasma concentrations may be even more gradual. This is particularly important when initiating therapy with drugs whose metabolism is affected by itraconazole.
For full details see prescribing information.

Pregnancy: SPORANOX must not be used during pregnancy except for life-threatening cases where the potential benefit to the mother outweighs the potential harm to the fetus (See Contraindications). In animal studies itraconazole has shown reproduction toxicity. There is limited information on the use of SPORANOX during pregnancy. During postmarketing experience, cases of congenital abnormalities have been reported. These cases included skeletal, genitourinary tract, cardiovascular and ophthalmic malformations as well as chromosomal and multiple malformations. A causal relationship with SPORANOX has not been established. Epidemiological data on exposure to SPORANOX during the first trimester of pregnancy – mostly in patients receiving short-term treatment for vulvovaginal candidosis – did not show an increased risk for malformations as compared to control subjects not exposed to any known teratogens.
Women of childbearing potential: Women of childbearing potential taking SPORANOX oral solution should use contraceptive precautions. Effective contraception should be continued until the menstrual period following the end of SPORANOX therapy.A very small amount of itraconazole is excreted in human milk. The expected benefits of treatment with SPORANOX oral solution should therefore be weighed against the potential risk of breast-feeding. In case of doubt, the patient should not breast-feed.
Fertility: Refer to Non-Clinical Information for in animal fertility information relevant to itraconazole and hydroxypropyl-β-cyclodextrin.

Symptoms and signs: In general, adverse events reported with overdose have been consistent with those reported for itraconazole use.
Treatment: In the event of an overdose, supportive measures should be employed. Activated charcoal may  be given if considered appropriate. Itraconazole cannot be removed by hemodialysis. No specific antidote is available.