ORUNGAL 100 mg. 15 capsules
Vulvar and vaginal candidiasis.
Dermatological / ophthalmic indications
ORUNGAL 100 mg. 15 capsules
QUALITATIVE AND QUANTITATIVE COMPOSITION
Each capsule contains 100 mg itraconazole in the form of pellets.
3 . PHARMACEUTICAL FORM
Capsules for oral administration.
4 . CLINICAL FEATURES
ORUNGAL capsule for oral administration is indicated for the treatment of :
• Gynecological indications:
- Vulva - vaginal candidiasis .
• Dermatological / ophthalmic indications
- Tinea versicolor
- Oral candidiasis
- Fungal keratitis
• onychomycosis caused by dermatophyte and / or yeasts.
• Systemic mycoses
- Systemic aspergillosis and candidiasis
- Cryptococcosis ( including cryptococcal meningitis ): in immunocompromised patients with cryptococcosis and in all patients with cryptococcosis of the central nervous system , Sporanox is indicated only when the first-line therapy is considered to be unsuitable or has proven ineffective
- Other less common systemic or tropical mycoses
4.2 . Dosage and method of administration
For optimal resorption is essential Sporanox capsule be administered immediately after a meal .
The capsules should be swallowed whole.
Elimination of itraconazole from skin tissue and nails is slower than its elimination from plasma . Optimal clinical and mycological effects in skin infections are obtained 2 to 4 weeks after treatment , and in infections of the nails 6 to 9 months after treatment .
Use in children :
Data on the use of Sporanox capsules in children are limited, therefore it is not recommended unless the potential benefit outweighs the potential risks. ( See Section 4.4 . " Special warnings and precautions for use")
Use in patients with renal impairment
The bioavailability upon oral administration of itraconazole may be lower in patients with renal failure. It is appropriate dose adjustment ( See section 4.4 . " Special warnings and precautions for use").
Use in patients with hepatic impairment:
Itraconazole is metabolized primarily in the liver. The plasma half-life of itraconazole in patients with hepatic cirrhosis is slightly extended. In patients with cirrhosis, a decrease in oral bioavailability . It is appropriate dose adjustment ( See section 4.4 . Special warnings and precautions for use).
4.3 . Contraindications
? Sporanox capsules are contraindicated in patients with known hypersensitivity to itraconazole or any of the excipients .
? Concomitant administration of Sporanox capsules with these medicinal products (see section " Interactions with other medicaments and other forms of interaction " ):
-CYP3A4 metabolised substrates that can prolong the QT-interval such as astemizole , cisapride, dofetilide levatsetilmetadol ( levomethadyl ) , mizolastine , pimozide , quinidine , sertindole and terfenadine must be administered concomitantly with Sporanox capsule . As a result of co- administration may increase plasma concentrations of these substrates , leading to a prolongation of QT- interval prolongation and rare occurrences of torsade de pointes;
-CYP3A4 metabolized HMG-CoA reductase inhibitors such as atorvastatin , lovastatin , and simvastatin ;
- Triazolam and oral midazolam ;
- Ergotilovi alkaloids such as dihydroergotamine, ergometrine ( ergonovine ) , ergotamine and methylergometrine ( methylergonovine ) .
? ORUNGAL capsules should not be used during pregnancy ( except in life-threatening situations. Look. Chapter 4.6 . "Pregnancy and lactation " ) .
4.4 . Special warnings and precautions for use
Effects on heart :
In a clinical study conducted with Sporanox for intravenous administration in healthy volunteers transient asymptomatic decrease in left ventricular ejection. This effect goes before the next infusion . The clinical relevance of these observations on oral administration is unknown.
Itraconazole has been shown to have a negative inotropic effect and there are reports of congestive heart failure with the use of Sporanox capsules. Sporanox capsules should not be used in patients with congestive heart failure or a previous history of such disease unless the benefits of its application clearly outweighs the risk. In the individual benefit / risk assessment should take into account factors such as the severity of the indication, dosing regimen and duration , and individual risk factors for congestive heart failure. These risk factors include heart disease, such as coronary artery disease and valvular disease, significant pulmonary diseases such as chronic obstructive pulmonary disease , and renal failure and other edematous states. Such patients must be informed of the signs and symptoms of congestive heart failure , it must be treated with caution and should be monitored for signs and symptoms of congestive heart failure during the treatment , if such a sign or symptom occurs during treatment , administration of Sporanox capsules should be discontinued.
Calcium channel blockers can have a negative effect inotoropen which may be added to that of itraconazole , the itraconazole can inhibit the metabolism of calcium channel blockers . So we need to caution should be exercised when co-administering itraconazole and calcium channel blockers (see section 4.5 . " Interactions with other medicaments and other forms of interaction " ) .
Potential interactions :
Sporanox capsules can cause clinically significant drug-drug interactions (see Section 4.5 . " Interactions with other medicaments and other forms of interaction " ) .
Decreased gastric acidity:
Absorption of itraconazole from Sporanox capsules is impaired by reduced gastric acidity. In patients who are also taking antacids (eg, aluminum hydroxide) , the latter must be taken at least two hours after taking Sporanox capsules. In patients with achlorhydria , some AIDS patients and patients taking preparations for suppression of acid secretion (eg, H2 blockers, proton pump inhibitors ) , it is advisable Sporanox capsules should be taken with a drink like Coke.
Use in children
Data on the use of Sporanox capsules in children are limited. Administration of Sporanox capsules in children is not recommended unless the potential benefit outweighs the potential risks .
Hepatic effects :
Very rare cases of serious hepatotoxicity , including some cases of fatal acute liver failure occurred with the use of Sporanox capsules. Some of these cases include patients with pre-existing liver disease. Some of the nurse observed during the first month of treatment , including the first week. In patients taking Sporanox capsules should be performed monitoring of liver function. Patients should be instructed to promptly report to their physician any signs or symptoms that may be manifestations of hepatitis such as anorexia, nausea , vomiting , weakness, abdominal pain, or dark urine . In these patients, therapy should be discontinued immediately and continued monitoring of liver function . Most cases of serious hepatotoxicity include patients with pre-existing liver disease in systemic indications, had other significant medical conditions and / or are taking other hepatotoxic medications. Patients with elevated liver enzymes or active liver disease , and in patients with a history of liver toxicity with other drugs should not be initiated Sporanox capsules, unless the expected benefit outweighs the risk of liver damage. In these cases, liver enzymes .
Itraconazole is metabolized primarily in the liver. Slightly decreased the oral bioavailability in patients with cirrhosis, which may require dose adjustment . Terminal half-life , however, was slightly increased . If necessary, the dose should be adjusted .
The oral bioavailability of itraconazole in patients with renal failure is less . You may need a dose adjustment .
In certain immunocompromised individuals (e.g., with neutropenia, AIDS or organ transplant patients ) , the bioavailability of Sporanox capsule can be reduced .
Patients with life-threatening emergency systemic fungal infections:
Due to the pharmacokinetic properties ( see Section 5.2) , Sporanox capsules are not recommended for initiating therapy in patients with immediately life-threatening systemic fungal iinfektsii .
AIDS patients receiving treatment for systemic fungal infections such as sporotrichosis , histoplasmosis and cryptococcosis ( meningeal and non- meningeal ), where it is considered that the risk of recurrence, the physician should evaluate the need for maintenance treatment .
If there is a neuropathy which is may be due to treatment with Sporanox capsule , it should be stopped .
Cross sensitivity :
No data regarding cross-hypersensitivity between itraconazole and other azole antifungals . Sporanox capsules should be prescribed with caution in patients with hypersensitivity to other azole derivatives.
Systemic candidiasis :
In systemic candidiasis , assuming that the strains of Candida are resistant to fluconazole , it can not be alleged that they are sensitive to itraconazole, from which it follows that the sensitivity must be checked prior to initiation of treatment with Sporanox capsule .
4.5 . Interactions with other medicaments and other forms of interaction
Drugs affecting Absorption of itraconazole :
Drugs reduce stomach atsiditet impair the absorption of itraconazole from Sporanox capsules ( see section 4.4 . " Special warnings and precautions for use").
Drugs affecting the metabolism of itraconazole :
Itraconazole is mainly metabolised by the cytochrome CYP3A4.Itrakonazol is mainly metabolized by CYP3A4. Interaction studies have been performed with rifampicin , rifabutin and phenytoin, which are potent inducers of CYP3A4. Since the bioavailability of itraconazole and Hydroxyitraconazole was decreased in these studies and thus the extent of its effectiveness , the combination of itraconazole with these potent enzyme inducers is not recommended. No data is available from studies concerning other enzyme inducers such as carbamazepine, phenobarbital and isoniazid, but can expect similar effects.
Potent inhibitors of this enzyme such as ritonavir , indinavir , clarithromycin and erythromycin may increase the bioavailability of itraconazole.
3 . Effect of itraconazole on the metabolism of other drugs :
3.1. Itraconazole can inhibit the transformation of drugs which are metabolized by enzymes of the cytochrome ON . This may result in an increase and / or prolong their effects , including side effects . When concomitant medication should be taken into account information about the way of the metabolism of other drugs . After cessation of treatment, the plasma levels of itraconazole gradually, depending on dose and duration of treatment (see section 5.2 . " Pharmacokinetics " ) . This should be borne in mind when the inhibitory effect of itraconazole on medicine.
> Drugs are to be used together with itraconazole :
, Astemizole, cisapride, dofetilide levatsetilmetadol ( levomethadyl ) , mizolastine , pimozide , triazolam , quinidine , sertindole and terfenadine are contraindicated for administration simultaneously with Sporanox capsule , as this can lead to elevated plasma concentrations of these drugs , which in turn country may cause prolongation of the QT- interval prolongation and rare occurrences of torsade de pointes.
-CYP3A4 metabolized HMG-CoA reductase inhibitors such as atorvastatin , lovastatin and simvastatin.
- Triazolam and oral midazolam .
- Ergotilovi alkaloids such as dihydroergotamine, ergometrine ( ergonovine ) , ergotamine and methylergometrine ( methylergonovine ) .
When co-administering itraconazole and calcium channel blockers should be approached with caution . In addition to pharmacokinetic interactions involving enzyme CYP3A4, metabolized drugs , calcium channel blockers can have negative inotropic effects , which may be additive to those of itraconazole .
> Drugs should be used with caution and their plasma concentrations, effects or adverse reakiii should be monitored . With concomitant use with itraconazole their dose should be reduced , if necessary :
- oral anticoagulants ;
- H1V protease inhibitors such as ritonavir , indinavir , saquinavir ;
, certain antineoplastic agents, such as busulfan , docetaxel, trimetrexate and vinca alkaloids ;
-CYP3A4 metabolised calcium channel blockers such as dihydropyridine and verapamil ;
- Certain immunosuppressive agents : ciclosporin , tacrolimus , rapamycin (also known as sirolimus ) ;
-CYP3A4 metabolized HMG-CoA reductase inhibitors such as atorvastatin .
- Some as butezonid glucocorticoids , dexamethasone and methylprednisolone
- other : digoxin, carbamazepine, cilostazol , buspirone , alfentanil, alprazolam, brotizolam , midazolam IV, disopiramid , eletriptan , halofantrine , rifabutin, repaglinide , ebastine , reboxetine . The importance of increasing the concentration and clinical relevance of these changes in both application must be established .
3.2 . No interaction of itraconazole with AZT ( zidovudine ) and fluvastatin .
No induction was observed in the metabolism of ethinyl estradiol and norethisterone of itraconazole .
4 . Effect on protein binding :
In vitro studies indicate that no interaction occurs at the level of protein binding between itraconazole and imipramine , propranolol , diazepam , cimetidine, indomethacin, tolbutamide and sulfamethazine .
pregnancy and lactation
ORUNGAL capsules should not be used during pregnancy except in life-threatening situations when the potential benefit outweighs the potential risk to the fetus ( see section 4.3. "Contraindications" ) .
In animal studies, itraconazole showed toxicity to reproduction ( see Section 5.3. " Preclinical safety data ').
There is limited information on the use of Sporanox capsules during pregnancy . In post-marketing experience , cases of congenital abnormalities. These cases include musculoskeletal , urogenital, cardiovascular and ophthalmic and chromosomal and the multiple malformations. There is no causal connection with Sporanox kapsuli.Nyama epidemiological data showing an increased risk of malformations in the application of Sporanox capsules in the first trimester of pregnancy - especially in patients on short-term treatment of vulvar and vaginal candidiasis - compared with a control group of patients which is not exposed to other known teratogens .
Women of childbearing age :
Women of childbearing potential taking Sporanox capsules should use contraceptive precautions. Effective contraception should be continued until the first menstruation after stopping treatment with Sporanox capsules.
Very small amount of itraconazole is excreted in human milk. The expected benefit of treatment with Sporanox capsules should not exceed the potential risk for breastfeeding. In case of doubt , breastfeeding should be discontinued.
Effects on ability to drive and use machines
No known .
The table below lists adverse reactions reported by patients in clinical trials (pooled data) performed with Sporanox capsules for the treatment of tinea and onychomycoses . Included are all adverse reactions ( incidence of 1% or more ) reported in patients treated with Sporanox . About 28 % of patients treated with Sporanox capsules and approximately 23% of patients receiving placebo reported at least one adverse reaction. Reported adverse reactions are summarized without regard to the assessment of the case by the researchers. The most common adverse events in clinical trials were related to the gastrointestinal tract.
Table : Adverse reactions reported in patients treated with Sporanox capsules with a frequency> 1%. Sporanox capsules N = 929 (% ) Placebo N = 661 ( %)
Body as a whole 5.8 5.9
Damage 2.9 3.0
Disorders of the central and peripheral nervous system 5,7 6,4
Headache 4.0 5.0
Gastrointestinal disturbances 9.0 6.5
Nausea 2.4 2.6
Diarrhea 2.3 2.0
Abdominal pain 1.8 1.4
Dyspepsia 1.7 0.9
Flatulence 1.3 0.5
Hepatobiliary disorders 2.2 1.1
Hepatic impairment 1.0 0.3
Respiratory system disorders 6.0 5.7
Rhinitis 2.0 2.1
Infection of the upper respiratory tract 1.8 1.1
Sinusitis 1.7 1.2
Skin and subcutaneous tissue 5.1 2.1
Rash 2.5 0.6
For all organs and systems , adverse reactions are ranked under headings of frequency using the following convention:
- Very common (> 1/10)
- Common ( > 1/100 , <1 /10)