Orungal capsules 100 mg of 14 pcs

Orungal – antifungal broad-spectrum triazole derivative. Itraconazole violates the synthesis of ergosterol, the cell membrane of fungi, which leads to the antifungal effect of the drug.

Itraconazole is active against infections caused by dermatophytes (Trichophyton spp, Microsporum spp, Epidermophyton floccosum..); yeast and yeast-like fungi (Candida spp, including Candida albicans, Candida glabrata and Candida krusei, Cryptococcus neoformans, Pityrosporum spp, Trichosporon spp, Geotrichum spp….); Aspergillus spp .; Histoplasma spp .; Paracoccidioides brasiliensis; Sporothrix schenckii; Fonsecaea spp .; Cladosporium spp .; Blastomyces dermatitidis; Pseudoallescheria boydii; Penicillium marneffei and others.

Candida glabrata and Candida tropicalis are the least sensitive to the action of itraconazole Candida species.

The main types of fungi, the development of which is not inhibited by itraconazole are Zygomycetes (Rhizopus spp., Rhizomucor spp., Mucor spp., Absidia spp.), Fusarium spp., Scedosporium spp., Scopulariopsis spp.

Active substance:
Itraconazole

Manufacturer

Janssen Pharmaceutica NV, Belgium

Prescribing

Pregnant by a doctor, children prescribed by a doctor, prescribed by a doctor Adults

Composition

The active ingredient is:

100 mg itraconazole.

Excipients:

Sucrose – 192 mg;

Hypromellose – 150 mg;

macrogol 20000 – 18 mg.

The shell capsules :

 Gelatin – 93.2 mg; colorant titanium dioxide (E171) – 2.8 mg; dye indigo carmine (E132) – q.s; azorubin dye (E122) – q.s.

Indications

from yeast

Treatment of fungal infections caused by pathogens susceptible to the drug, including .:

• ringworm;
• fungal keratitis;
• onychomycosis caused by dermatophytes and / or yeasts and molds;
• systemic mycoses: systemic aspergillosis and candidiasis, cryptococcosis (including cryptococcal meningitis in immunocompromised patients and in all patients with kriptokkozom CNS Orungal should only be used in cases where the first-line drugs treatment is not applicable in this case or not effective), histoplasmosis , sporotrichosis, paracoccidioidomycosis, blastomycosis and other systemic mycoses and tropical;
• kandidomikoz with skin lesions, and mucosal membranes (including vulvovaginal candidiasis);
• deep visceral candidiasis;
• chromophytosis.

Contraindications

• simultaneous reception of drugs metabolized by CYP3A4 enzyme can increase the QT-interval, including terfenadine, astemizole, mizolastine, cisapride, dofetilide, quinidine, pimozide, sertindole, Levo;
• simultaneous reception of midazolam and oral triazolam;
• simultaneous reception metabolized by the enzyme CYP3A4 inhibitors of HMG-CoA reductase inhibitors such as simvastatin and lovastatin;
• simultaneous reception of ergot alkaloids such as dihydroergotamine, ergometrine, ergotamine and metilergometrin;
• Hypersensitivity to itraconazole and other ingredients.

Precautions: should be prescribed to liver cirrhosis, chronic renal failure, chronic heart failure, hypersensitivity to other drugs of the group of azoles, as well as children and elderly patients.

Side effects

Immune system: very rarely – anaphylactic, anaphylactoid and allergic reactions.

Metabolic: very rarely – hypokalemia.

From the nervous system: very rarely – peripheral neuropathy, headache, dizziness.

With the cardiovascular system: very rarely – congestive heart failure.

The respiratory system: very rarely – swelling of the lungs;

On the part of the digestive tract: very rare – abdominal pain, vomiting, dyspepsia, nausea, decreased appetite, diarrhea, constipation.

On the part of the hepatobiliary system: very rarely – severe hepatotoxicity (including some cases of acute liver failure with fatal outcome), hepatitis, reversible elevation of liver enzymes.

For the skin and subcutaneous fat: very rarely – Stevens-Johnson syndrome, angioedema, rash, alopecia, photosensitivity, rash, itching.

Reproductive system: very rarely – a violation of the menstrual cycle.

General disorders: very rarely – edema syndrome.

How to accept, acceptance rate and dosage

The capsules should be taken immediately after a meal, without chewing, swallowing whole and washed down with a little water.

Itraconazole bioavailability when given orally can be reduced in some patients with compromised immune systems, such as in patients with neutropenia, AIDS patients or transplant organs. Therefore, it may require a doubling of the dose.

One course of pulse therapy is daily administration of 2 capsules Orungal 2 times a day (200 mg, 2 times a day) for 1 week.

For the treatment of fungal infections of the nail plate brushes recommended 2 courses. For the treatment of fungal infections of the nail plate is recommended to stop the 3 rd year. The gap between courses, during which it is not necessary to take the drug, up to 3 weeks. Clinical results become apparent after treatment, as the nail regrowth.

In addition to pulse therapy may conduct a continuous course. The drug is administered at 2 capsules per day (1 200 mg once a day) for 3 months.

Orungal excretion from skin and nail tissue is slower than from plasma. Thus, the optimal clinical and mycological effects are achieved within 2-4 weeks after the treatment of skin infections and 6-9 months after completion of treatment of nail infections.

Storage conditions

At a temperature of 15-30 ° C.

Keep out of the reach of children.

Active substance

Itraconazole

Interaction

1. Drugs affecting the absorption of itraconazole.
Drugs that reduce stomach acidity, reduce the absorption of itraconazole, which is related to the solubility of the capsule shell.

2. Drugs affecting the metabolism of itraconazole.
Itraconazole is mainly cleaved by the enzyme CYP3A4. It was studied the interaction of itraconazole with rifampicin, rifabutin and phenytoin, which are potent inducers of CYP3A4 enzyme. The study found that, in these cases, the bioavailability of itraconazole and hydroxy-itraconazole significantly reduced, which leads to a substantial reduction in efficacy. Concomitant use of itraconazole with these drugs, which are potential inducers of hepatic enzymes, it is not recommended. Studies of interaction with other hepatic enzyme inducers, such as carbamazepine, phenobarbital and isoniazid not performed, however, similar results can be expected.
Strong inhibitors of the enzyme CYP3A4, such as ritonavir, indinavir, clarithromycin and erythromycin may increase the bioavailability of itraconazole.

3. The effect of itraconazole on the metabolism of other drugs.
Itraconazole can inhibit the metabolism of drugs, cleavable by the enzyme CYP3A4. This may result in gain or prolongation of their actions, including side effects. Before taking concomitant medications should consult with a physician on the metabolic pathways of the drug, specified in the instructions for medical use. After the cessation of treatment in a plasma concentration of itraconazole is gradually reduced depending on the dose and duration of treatment (see. “Pharmacokinetics” section). It must be taken into account when discussing the inhibitory effect of itraconazole on concomitant medications.
Examples of such drugs are:
Drugs that should not be administered concurrently with itraconazole:

• Terfenadine, astemizole, mizolastine, cisapride, dofetilide, quinidine, pimozide, levomethadone, sertindole – joint use of these drugs with itraconazole can cause increased levels of these substances in the plasma and increase the risk of lengthening the interval QT and in rare cases – the occurrence of atrial fibrillation ventricles (torsade de pointes);
• cleavable enzyme CYP3A4 inhibitors of HMG-CoA reductase inhibitors such as simvastatin and lovastatin;
• midazolam and oral triazolam;
• ergot alkaloids such as dihydroergotamine, ergometrine, ergotamine and metilergometrin;
• calcium channel blockers – in addition to a possible pharmacokinetic interaction associated with the common pathway involving metabolic enzyme CYP3A4, calcium channel blockers can have a negative inotropic effect, which is enhanced by simultaneous administration with itraconazole

.

Preparations in the appointment which is necessary to monitor their plasma concentrations, effects, side effects. In the case of co-administration with itraconazole dose of these preparations, if necessary, should be reduced.

• Oral anticoagulants;
• HIV protease inhibitors such as ritonavir, indinavir, saquinavir;
• Some anticancer drugs such as vinca alkaloids, busulfan, docetaxel, trimetrexate;
• Cleavable enzyme CYP3A4 calcium channel blockers such as verapamil and derivatives dihydropyridine;
• Certain immunosuppressive agents: cyclosporine, tacrolimus, sirolimus (also known as rapamycin);
• Some cleavable enzyme CYP3A4 inhibitors of HMG-CoA reductase inhibitors such as atorvastatin;
• Certain glucocorticosteroids such as budesonide, dexamethasone and methylprednisolone
• Other drugs: digoxin, carbamazepine, buspirone, alfentanil, alprazolam, brotizolam, midazolam intravenous, rifabutin, ebastine, reboxetine, cilostazol, disopyramide, eletriptan, halofantrine, repaglinide;

Interactions between itraconazole and zidovudine and fluvastatin is not revealed.
There was no effect of itraconazole on the metabolism of ethinyl estradiol and norethisterone.

4. Effects on the binding of proteins.
Studies in vitro have demonstrated no interaction between itraconazole and drugs such as imipramine, propranolol, diazepam, cimetidine, indomethacin, tolbutamide and sulfamethazine in the binding to plasma proteins.

Special conditions

Women of childbearing age receiving Orungal ^® , adequate methods of contraception throughout the course of treatment should be used until the onset of the first menstrual period after its completion.

When the dosage form study drug Orungal ^® for / in the conducted in healthy volunteers observed a decrease transient asymptomatic left ventricular ejection fraction, normalized to the next infusion.

The clinical relevance of the data to oral dosage forms is unknown.

It is found that itraconazole has a negative inotropic effect. At the same time taking itraconazole and BPC, which may have the same effect, you must be careful. It reported cases of congestive heart failure associated with taking Orungal ^® . Orungal ^® should not be taken in patients with chronic heart failure or the presence of disease history except when the potential benefit greatly outweighs the potential risk. When an individual assessment of benefit-risk ratio should be taken into account such factors as the severity of indications, dosing regimen and individual risk factors for congestive heart failure.

Risk factors include the presence of diseases such as coronary heart disease or valvular heart disease; obstructive lung disease; renal failure or other diseases, accompanied by edema. Such patients should be informed about the signs and symptoms of congestive heart failure. Must be treated with caution, and the patient should be monitored for the onset of symptoms of congestive heart failure. When they appear reception Orungal ^® should be discontinued.

At low acidity of the stomach: in this condition the absorption of itraconazole capsules Orungal ^® is violated. Patients taking antacids (e.g. aluminum hydroxide), it is recommended to use them no sooner than 2 hours after taking the capsules Orungal ^® .

In patients with achlorhydria or applying blockers H ₂ histamine receptors or proton pump inhibitors, are advised to take capsules Orungal ^® Coke.

In very rare cases, the application of Orungal ^® develop severe hepatotoxicity, including cases of acute liver failure with fatal consequences. In most cases it was observed in patients who already had liver disease, patients with other serious illnesses treated by systemic itraconazole therapy indications, as well as patients treated with other drugs, have hepatotoxic effects. Some patients were not found obvious risk factors for liver disease. Several such cases have arisen in the first month of therapy, and some – in the first week of treatment. In this connection, it is recommended to regularly monitor liver function in patients receiving treatment with itraconazole.

Patients should be warned of the need to immediately contact your doctor in case of symptoms suggestive of hepatitis, such as: anorexia, nausea, vomiting, weakness, abdominal pain, and dark urine. In the event of such symptoms should immediately discontinue therapy and a study of liver function.

Patients with elevated levels of liver enzymes, or liver disease in its active phase, or migrated toxic liver injury when taking other medications should not be given treatment Orungalom ^® except where the expected benefits justify the risk of liver damage. In these cases it is necessary during treatment to monitor the level of liver enzymes.

Human liver: itraconazole is metabolized primarily in the liver. As in patients with impaired hepatic function a complete T _1/2 itraconazole increased slightly, it is recommended to monitor the itraconazole concentration in plasma and adjust the dose if necessary.

Impaired renal function: As patients with renal insufficiency, a complete T _1/2 itraconazole increased slightly, it is recommended to monitor the itraconazole concentration in plasma and adjust the dose if necessary.

Patients with immunodeficiency: itraconazole bioavailability when given orally can be reduced in some patients with compromised immune systems, such as in neutropenic patients with AIDS or undergoing organ transplants.

Patients with systemic fungal infections that threaten life due to pharmacokinetic characteristics Orungal ^® in capsule form is not recommended to start the treatment of systemic mycoses, threatening the patients life.

AIDS: the physician must evaluate the need for the appointment of maintenance therapy to AIDS patients who have received prior treatment for systemic fungal infections such as sporotrichosis, blastomycosis, histoplasmosis or cryptococcosis (meningeal how and nemeningealnogo), in which there is a risk of recurrence.

Clinical data on the use of capsules Orungal ^® limited in pediatric patients. Capsules Orungal ^® should not be administered to children, except in cases when the expected benefits exceed the risks.

The treatment should be discontinued when a peripheral neuropathy, which may be associated with the reception of capsules Orungal ^® .

No data on the cross-hypersensitivity to itraconazole and other azole antifungal agents.

Overdose

No cases of overdose were reported Orungal.

Treatment: the accidental overdose during the first hour after ingestion should conduct gastric lavage and, if necessary, appoint activated carbon.

Itraconazole not appear in hemodialysis. There is no specific antidote.