Orungal capsules 100 mg No. 15

Instructions for Orungal capsules 100 mg No. 15

Composition

active ingredient: itraconazole;

1 capsule contains 100 mg of itraconazole;

excipients: sucrose, hypromellose and macrogol 20,000;

capsule shell: titanium dioxide (E 171), indigo carmine (E 132), erythrosine (E 127), gelatin.

Dosage form

Capsules.

Main physicochemical properties: hard gelatin capsules consisting of a transparent pink body and an opaque blue cap. The contents of the capsules are cream or almost white granules.

Pharmacotherapeutic group

Antifungal drugs for systemic use. Triazole derivatives. Itraconazole. ATX code J02A C02.

Pharmacological properties

Pharmacodynamics.

Itraconazole is a triazole derivative with a broad spectrum of activity. In vitro studies have shown that itraconazole inhibits the synthesis of ergosterol in fungal cells. Ergosterol is an important component of the fungal cell membrane, and inhibition of its synthesis provides an antifungal effect.

For itraconazole, breakpoints have only been established for Candida spp. In the case of superficial mycotic infections (CLSI M27-A2, breakpoints have not been established according to EUCAST methodology). CLSI breakpoints: susceptible ≤0.125; susceptible dose-dependent 0.25–0.5 and resistant ≥1 μg/ml. Breakpoints have not been established for mycelial fungi.

In vitro studies have shown that itraconazole inhibits the growth of a wide range of fungi pathogenic to humans at concentrations usually ≤1 μg/ml. These include: dermatophytes (Trichophyton spp., Microsporum spp., Epidermophyton floccosum); yeasts (Candida spp., including C. albicans, C. tropicalis, C. parapsilosis and C. krusei, Cryptococcus neoformans, Malassezia spp., Trichosporon spp., Geotrichum spp.), Aspergillus spp.; Histoplasma spp., including H. capsulatum; Paracoccidioides brasiliensis; Sporothrix schenckii; Fonsecaea spp.; Cladosporium spp.; Blastomyces dermatitidis; Coccidiodes immitis; Pseudallescheria boydii; Penicillium marneffei and other species of yeasts and fungi.

Candida krusei, Candida glabrata, and Candida tropicalis are generally the least susceptible Candida species, and some isolates demonstrate resistance to itraconazole in vitro.

The main types of fungi that are not inhibited by itraconazole are zygomycetes (Rhizopus spp., Rhizomucor spp., Mucor spp. and Absidia spp.), Fusarium spp., Scedosporium proliferans and Scopulariopsis spp.

Resistance to azoles develops slowly and is usually the result of multiple genetic mutations. Mechanisms described include overexpression of ERG11, which encodes 14α-demethylase (the target enzyme), point mutations in ERG11 that result in reduced affinity of 14α-demethylase for itraconazole, and/or overexpression of a transporter that results in increased efflux of itraconazole from fungal cells (i.e., removal of itraconazole from its target). Cross-resistance among azoles has been observed within Candida species, but resistance to one member of the class does not necessarily imply resistance to other azoles. Itraconazole-resistant strains of Aspergillus fumigatus have been reported.

Pharmacokinetics.

General pharmacokinetic characteristics.

Peak plasma concentrations of itraconazole are reached within 2 to 5 hours after oral administration. Due to nonlinear pharmacokinetics, itraconazole accumulates in plasma after multiple administration. Steady-state concentrations are generally reached within 15 days with Cmax values of 0.5 μg/ml, 1.1 μg/ml and 2.0 μg/ml after 100 mg once daily, 200 mg once daily and 200 mg twice daily, respectively. The terminal half-life of itraconazole varies from 16 to 28 hours after a single dose and increases to 34–42 hours after multiple doses. After discontinuation of treatment, itraconazole concentrations decline to levels that are almost undetectable in plasma within 7–14 days, depending on the dose and duration of treatment. The mean plasma clearance of itraconazole after intravenous administration is 278 ml/min. Due to saturable hepatic metabolism, clearance of itraconazole decreases at higher doses.

Absorption.

Itraconazole is rapidly absorbed after oral administration. Peak plasma concentrations of unchanged drug are reached within 2–5 hours after oral administration of capsules. Absolute bioavailability of itraconazole is 55%. Maximum oral bioavailability is observed when the drug is taken immediately after a high-calorie meal.

The absorption of itraconazole capsules is reduced in patients with reduced gastric acidity, patients taking drugs that suppress gastric acid secretion (H2-receptor antagonists, proton pump inhibitors), or in patients with achlorhydria caused by certain diseases (see sections "Special instructions for use" and "Interaction with other medicinal products and other types of interaction"). Absorption of itraconazole on an empty stomach in such patients increases if Orungal® capsules are taken with drinks with increased acidity (e.g. non-diet cola). When a single dose of 200 mg of Orungal® on an empty stomach with non-diet cola was taken after taking ranitidine, an H2-receptor antagonist, the absorption of itraconazole was comparable to that after taking Orungal® capsules alone.

The concentration of itraconazole after administration in the capsule dosage form is lower than after administration of the oral solution at the same dose (see section "Special instructions for use").

Itraconazole is largely bound to plasma proteins (99.8%), albumin being the main binding component (99.6% for the hydroxymetabolite). It also has a high affinity for lipids. Only 0.2% of itraconazole in the blood remains unbound. The apparent volume of distribution of itraconazole is quite large (> 700 l), suggesting its wide distribution in tissues: concentrations in the lungs, kidneys, liver, bones, stomach, spleen and muscles were 2–3 times higher than those in plasma. The accumulation of itraconazole in keratinous tissues, especially in the skin, was 4 times higher than that in plasma. The concentration in cerebrospinal fluid is much lower than in plasma, but efficacy against infections localized in the cerebrospinal fluid has been demonstrated.

Biotransformation.

Itraconazole is extensively metabolized in the liver to a large number of metabolites. In vitro studies indicate that CYP3A4 is the major enzyme involved in the metabolism of itraconazole. The major metabolite is hydroxyitraconazole, which has comparable antifungal activity to itraconazole in vitro. Plasma concentrations of hydroxyitraconazole are approximately 2-fold higher than those of itraconazole.

Breeding.

Approximately 35% of itraconazole is excreted as inactive metabolites in the urine and approximately 54% in the feces within 1 week of a dose of oral solution. Renal excretion of itraconazole and the active metabolite hydroxyitraconazole after intravenous administration is less than 1% of the dose. Fecal excretion of unchanged drug varies from 3 to 18%.

Special categories of patients.

Liver failure.

Itraconazole is primarily metabolized in the liver. A pharmacokinetic study using a single dose of 100 mg itraconazole (1 capsule of 100 mg) was conducted in 6 healthy subjects and 12 cirrhotic subjects. A statistically significant decrease in mean Cmax (47%) and a 2-fold increase in the half-life of itraconazole (37±17 vs. 16±5 hours) were found in cirrhotic subjects compared to healthy subjects. Although total itraconazole concentrations, based on AUC, were comparable in both groups.

There are no data available on the long-term use of itraconazole in patients with cirrhosis.

Kidney failure.

Data on the use of oral itraconazole in patients with renal impairment are limited. A pharmacokinetic study using a single dose of 200 mg itraconazole (4 capsules of 50 mg) was conducted in 3 groups of patients with renal impairment (uremia: n=7, hemodialysis: n=7, chronic ambulatory peritoneal dialysis: n=5). In uremic patients with a mean creatinine clearance of 13 ml/min × 1.73 m2, the AUC-based concentration was slightly lower compared to healthy volunteers. This study did not demonstrate any significant effect of hemodialysis or chronic ambulatory peritoneal dialysis on the pharmacokinetics of itraconazole (Tmax, Cmax, AUC0-8h). Plasma concentration-time profiles showed significant intersubject variability in all 3 groups.

After a single intravenous dose, the mean terminal half-life values in patients with mild (CrCl 50–79 mL/min), moderate (CrCl 20–49 mL/min), and severe (CrCl <20 mL/min) renal impairment were similar to those in healthy volunteers (range 42–49 hours vs. 48 hours in renally impaired patients and healthy volunteers, respectively). Total itraconazole concentrations based on AUC were reduced in patients with moderate and severe renal impairment (by 30% and 40%, respectively) compared to healthy volunteers.

There are no data available on the long-term use of itraconazole in patients with renal impairment. Dialysis has no effect on the half-life or clearance of itraconazole or hydroxyitraconazole.

Children.

Data on the use of oral itraconazole in children are limited. Clinical pharmacokinetic studies in children and adolescents aged 5 months to 17 years were conducted with itraconazole capsules, oral solution, and intravenous solution. Individual doses with the capsules and oral solution ranged from 1.5 to 12.5 mg/kg/day, administered once or twice daily. A single intravenous dose of 2.5 mg/kg was administered as an infusion or 2.5 mg/kg as infusions once or twice daily. There was no significant age-related relationship between itraconazole AUC and total clearance, but there was a weak relationship between patient age, volume of distribution, Cmax, and terminal elimination of itraconazole. Apparent clearance and volume of distribution were dependent on patient weight.

Indication

Vulvovaginal candidiasis;

lichen planus;

dermatophytosis caused by itraconazole-sensitive pathogens (Trichophyton spp., Microsporum spp., Epidermophyton floccosum), e.g. tinea pedis, inguinal tinea, tinea corporis, tinea corporis of the hands;

oropharyngeal candidiasis;

onychomycoses caused by dermatophytes and/or yeasts;

histoplasmosis;

systemic mycoses (in cases where first-line antifungal therapy cannot be used or in case of ineffectiveness of treatment with other antifungal drugs, which may be due to the existing pathology, insensitivity of the pathogen or toxicity of the drug):

Cryptococcosis (including cryptococcal meningitis): treatment of immunocompromised patients with cryptococcosis and all patients with cryptococcosis of the central nervous system;

maintenance therapy in patients with AIDS to prevent recurrence of an existing fungal infection.

Orungal® is also prescribed for the prevention of fungal infections in patients with prolonged neutropenia in cases where standard therapy is insufficient.

Contraindication

Orungal® capsules are contraindicated in patients with known hypersensitivity to the active substance or any of the excipients.

Concomitant use of Orungal® and CYP3A4 substrates is contraindicated. Concomitant use may result in increased plasma concentrations of these medicinal products, which may lead to increased or prolonged therapeutic and adverse reactions and potentially life-threatening conditions. For example, increased concentrations of these medicinal products may lead to QT prolongation and ventricular tachyarrhythmias, including ventricular fibrillation, a potentially fatal arrhythmia. These medicinal products are listed in the section “Interaction with other medicinal products and other forms of interaction”.

The use of Orungal® capsules is contraindicated in patients with ventricular dysfunction, such as congestive heart failure, or a history of congestive heart failure, except for the treatment of life-threatening infections (see section "Special warnings and precautions for use").

Orungal® capsules should not be used during pregnancy, except for the treatment of life-threatening conditions (see section “Use during pregnancy or breastfeeding”).

Women of reproductive age should use effective methods of contraception during treatment with Orungal® capsules, as well as until the end of the menstrual cycle after the end of treatment.

Interaction with other medicinal products and other types of interactions

Itraconazole is primarily metabolized by cytochrome CYP3A4. Other drugs that are metabolized by this pathway or modify CYP3A4 activity may affect the pharmacokinetics of itraconazole. Itraconazole, in turn, may also affect the pharmacokinetics of other substances. Itraconazole is a potent inhibitor of CYP3A4 and P-glycoprotein. When used concomitantly with other drugs, the Summary of Product Characteristics of these drugs should also be consulted for information on the metabolic pathways and the possible need for dose adjustment.

Drugs that may reduce itraconazole plasma concentrations

Medicines that reduce stomach acidity (acid-neutralizing medicines such as aluminium hydroxide or acid-suppressing medicines such as H2-receptor antagonists and proton pump inhibitors) affect the absorption of itraconazole from the capsules. Caution should be exercised when using the following medicines and itraconazole capsules at the same time:

When using itraconazole and antacids, Orungal® capsules should be taken with acidic beverages, such as non-diet cola;

Acid-neutralizing drugs (e.g. aluminum hydroxide) should be taken at least 1 hour before or 2 hours after taking Orungal® capsules;

The level of antifungal activity should be monitored and the dose of itraconazole increased if necessary.

Concomitant use of itraconazole with potent CYP3A4 enzyme inducers results in a decrease in the bioavailability of itraconazole and hydroxyitraconazole, resulting in a significant reduction in the effectiveness of treatment. These drugs include:

antibacterials: isoniazid, rifabutin (also see the subsection "Drugs whose plasma concentration is increased by itraconazole"), rifampicin;

anticonvulsants: carbamazepine (also in the subsection "Medicines whose plasma concentration is increased by itraconazole"), phenobarbital, phenytoin;

antivirals: efavirenz, nevirapine.

Concomitant use of potent CYP3A4 inducers with itraconazole is not recommended. The above-mentioned drugs should not be initiated 2 weeks before, during, or 2 weeks after treatment with itraconazole, unless the potential benefit clearly outweighs the potential risk. The level of antifungal activity should be carefully monitored and the dose of itraconazole increased if necessary.

Drugs that increase itraconazole plasma concentrations

Potent inhibitors of the CYP3A4 enzyme may increase the bioavailability of itraconazole. For example:

antibacterial: ciprofloxacin, clarithromycin, erythromycin;

antivirals: darunavir, ritonavir-boosted, fosamprenavir, ritonavir-boosted, indinavir, ritonavir (also in the subsection "Medicines whose plasma concentration is increased by itraconazole").

These drugs should be used with caution when used concomitantly with itraconazole. Such patients should be carefully monitored for symptoms of increased or prolonged pharmacological effects of itraconazole and, if necessary, the dose of itraconazole should be reduced. It is recommended to monitor the concentration of itraconazole in the blood plasma.

Itraconazole and its major metabolite hydroxyitraconazole may inhibit the metabolism of drugs metabolized by CYP3A4 and the transport of drugs by P-glycoprotein, which may lead to an increase in the concentration of these drugs and/or their metabolites in the blood plasma. Such an increase in plasma concentrations may lead to an increase or prolongation of the therapeutic effect and the occurrence of adverse reactions. The simultaneous administration of itraconazole and drugs metabolized by CYP3A4 and prolonging the QT interval is contraindicated, as this may lead to the occurrence of ventricular tachyarrhythmias, including cases of ventricular fibrillation with a fatal outcome. After discontinuation of treatment, the concentration of itraconazole decreases to a level that is almost undetectable in the blood plasma within 7 to 14 days, depending on the dose and duration of treatment. In patients with cirrhosis of the liver or in patients who are simultaneously using inhibitors of the CYP3A4 enzyme, the drug should be discontinued gradually. This is especially true for drugs whose metabolism is affected by itraconazole.

Concomitant medications are grouped into the following categories:

Contraindicated: under no circumstances should it be used simultaneously with or within 2 weeks of the end of treatment with itraconazole.

Not recommended: The use of these drugs concomitantly and within 2 weeks after discontinuation of itraconazole treatment should be avoided unless the benefit of treatment outweighs the potential risk of adverse reactions. If concomitant use cannot be avoided, such patients should be carefully monitored for signs or symptoms of increased or prolonged pharmacological effects of itraconazole and the dose of itraconazole should be reduced if necessary. It is recommended to monitor the level of itraconazole plasma concentrations.

Use with caution: Close monitoring is recommended in case of concomitant use with itraconazole. Such patients should be carefully observed for symptoms of increased or prolonged pharmacological effect of itraconazole and, if necessary, the dose of itraconazole should be reduced. It is recommended to monitor the concentration of itraconazole in the blood plasma.

Table 1

Examples of drugs whose concentrations increase when used concomitantly with itraconazole and recommendations for use

a See also “Drugs that decrease itraconazole plasma concentrations.”

b See also “Drugs that increase itraconazole plasma concentrations.”

Drugs whose concentration is reduced by itraconazole.

Concomitant use of itraconazole with meloxicam reduces the concentration of the latter. Meloxicam should be prescribed with caution when used concomitantly with itraconazole and therapeutic and side effects should be monitored. It is recommended to adjust the dose of meloxicam.

Children.

Drug interaction studies have only been conducted in adults.

Application features

Cross-hypersensitivity.

There is no data on cross-sensitivity between itraconazole and other azole antifungals. Caution should be exercised when prescribing Orungal® capsules to patients with hypersensitivity to other azoles.

Effect on the heart.

In studies of the drug Orungal® for intravenous administration in healthy volunteers, a transient asymptomatic decrease in left ventricular ejection fraction was observed; it was restored before the next infusion. The clinical significance of these data for oral forms has not been established.

Itraconazole is known to have a negative inotropic effect, and cases of congestive heart failure have been reported in association with the use of Orungal®. Among spontaneous reports, the incidence of congestive heart failure was higher at a total daily dose of 400 mg per day than at lower daily doses. Therefore, the risk of heart failure may increase with the total daily dose of itraconazole.

The drug should not be taken by patients with congestive heart failure or a history of it, except in cases where the expected benefit significantly outweighs the potential risk. When assessing the individual benefit/risk ratio, factors such as the severity of the diagnosis, dosage regimen and duration of treatment (total daily dose), as well as individual risk factors for the development of congestive heart failure should be taken into account. These risk factors include the presence of heart disease, such as ischemic heart disease or valvular disease; severe lung disease, in particular chronic obstructive pulmonary disease; renal failure or other diseases accompanied by edema. Such patients should be informed about the symptoms of congestive heart failure, treatment should be carried out with caution and symptoms of congestive heart failure should be monitored. If these symptoms appear during the course of treatment, the use of Orungal® should be discontinued.

Calcium channel blockers may have a negative inotropic effect, which may potentiate the same effect of itraconazole. Itraconazole may also inhibit the metabolism of calcium channel blockers. Therefore, caution should be exercised when itraconazole and calcium channel blockers are used simultaneously due to an increased risk of congestive heart failure (see section "Interaction with other medicinal products and other forms of interaction").

Effect on the liver

Severe hepatotoxicity, including fatal acute liver failure, has been reported very rarely with Orungal® capsules. Most of these cases occurred in patients with a history of liver disease who were being treated for systemic indications, had other serious illnesses and/or were taking other hepatotoxic drugs. Some patients had no obvious risk factors for liver disease. Some of these cases occurred during the first month of treatment, including the first week. Therefore, it is advisable to monitor liver function in patients taking Orungal®. Patients should be advised to seek immediate medical attention if symptoms of hepatitis occur, such as anorexia, nausea, vomiting, fatigue, abdominal pain or dark urine. If these symptoms occur, treatment should be discontinued immediately and liver function tests should be performed.

Data on the use of oral forms of itraconazole in patients with hepatic impairment are limited. This drug should be used with caution in this category of patients. Close monitoring of patients with impaired hepatic function who are taking itraconazole is recommended. When deciding on treatment with other drugs that are metabolized by CYP3A4, it is recommended to take into account the prolonged half-life of itraconazole, which was observed in clinical studies in patients with cirrhosis who were given single doses of itraconazole capsules.

In patients with elevated liver enzymes, active liver disease, or hepatotoxicity from other medications, treatment should only be initiated if the expected benefit outweighs the risk of liver damage. In such cases, liver function should be monitored.

With reduced gastric acidity, the absorption of itraconazole from Orungal® capsules is impaired. Patients with reduced gastric acidity caused by disease (e.g. achlorhydria) or concomitant use of other drugs (e.g. to reduce acidity) are recommended to take Orungal® capsules with drinks with increased acidity (e.g. non-diet cola) (see section "Interaction with other medicinal products and other types of interactions"). Antifungal activity should be monitored and the dose of itraconazole should be increased if necessary (see section "Interaction with other medicinal products and other types of interactions").

Elderly patients.

Clinical data on the use of Orungal® capsules in elderly patients are limited. Orungal® capsules should not be used in elderly patients unless the benefits outweigh the potential risks.

Liver dysfunction.

Limited data are available on the use of oral itraconazole in patients with hepatic impairment. Caution should be exercised when administering the drug to these patients.

Kidney dysfunction.

Data on the use of oral itraconazole in patients with renal impairment are limited. The bioavailability of oral itraconazole may be reduced in patients with renal insufficiency. Caution should be exercised when using the drug in this category of patients and dose adjustment should be considered.

Hearing loss.

Cases of temporary or permanent hearing loss have been reported in patients taking itraconazole. In some cases, hearing loss occurred in the context of concomitant use with quinidine, which is contraindicated (see section "Interaction with other medicinal products and other forms of interaction"). Hearing usually recovers after discontinuation of Orungal® therapy, however, in some patients, hearing loss is irreversible.

Patients with immunodeficiency.

In some patients with immunodeficiency (e.g., patients with neutropenia, AIDS, or organ transplants), the oral bioavailability of itraconazole from Orungal® capsules may be reduced.

Patients with systemic fungal infections that are immediately life-threatening.

Due to its pharmacokinetic properties (see section "Pharmacokinetics"), Orungal® capsules are not recommended for primary treatment of emergency conditions caused by systemic fungal infections.

Patients with AIDS.

For patients with AIDS who have been treated for a systemic fungal infection such as sporotrichosis, blastomycosis, histoplasmosis, or cryptococcosis (meningeal or non-meningeal) and who are at risk of relapse, the physician should assess the need for maintenance treatment.

Neuropathy.

If neuropathy occurs associated with the use of Orungal® capsules, the drug should be discontinued.

Disorders of carbohydrate metabolism.

Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

Cross-resistance.

If, in the case of systemic candidiasis, it is suspected that the Candida species causing the disease are resistant to fluconazole, it cannot be assumed that they will be sensitive to itraconazole. Therefore, a sensitivity test should be performed before starting treatment with Orungal® capsules.

Interchangeability.

It is not recommended to interchange the medicines Orungal®, capsules, and Orungal®, oral solution, since when the same doses are taken orally, the bioavailability of the oral solution is higher.

Interaction potential.

Concomitant use of itraconazole and certain medicinal products may result in altered efficacy of itraconazole and/or the concomitant medicinal product, potentially life-threatening adverse reactions and/or sudden death. Medicinal products that are contraindicated, not recommended or recommended for use with caution in combination with itraconazole are listed in the section “Interaction with other medicinal products and other forms of interaction”.

Use during pregnancy or breastfeeding

Pregnancy.

Orungal® should not be prescribed to pregnant women, except in life-threatening conditions when the potential benefit to the pregnant woman outweighs the risk of adverse effects on the fetus (see section "Contraindications").

In animal studies, itraconazole has shown reproductive toxicity.

Data on the use of Orungal® during pregnancy are limited. In the post-marketing period, cases of developmental anomalies, such as skeletal, genitourinary, cardiovascular and visual malformations, as well as chromosomal abnormalities and multiple malformations, have been reported. A causal relationship with Orungal® capsules has not been established.

Epidemiological data on the effects of Orungal® on women in the first trimester of pregnancy (the drug was used mainly for short-term treatment of vulvovaginal candidiasis) did not reveal an increased risk of malformations compared to women who did not use drugs with a teratogenic effect.

Women of reproductive age.

Breastfeeding period.

Very small amounts of itraconazole are excreted in breast milk. Therefore, during breastfeeding, the possible risk to the child should be weighed against the expected benefit of treatment with Orungal® for the mother. In doubtful cases, the woman should stop breastfeeding.

Ability to influence reaction speed when driving vehicles or other mechanisms

No studies have been conducted on the effect on the reaction rate when driving vehicles or operating other mechanisms. It should be borne in mind that side effects such as dizziness, visual disturbances and hearing loss may occur (see section "Adverse reactions"), which may lead to negative consequences when driving vehicles or operating other mechanisms.

Method of administration and doses

Orungal® capsules should be taken orally immediately after a meal to ensure maximum absorption of the drug. The capsules should be swallowed whole.

Table 2

Adult treatment regimens for each indication:

The duration of treatment for systemic fungal infections should be adjusted depending on the mycological and clinical response to therapy.

Table 3

Systemic mycoses
Indications for use	Dosage1	Notes
Aspergillosis	200 mg once daily	Increase dose to 200 mg twice daily in case of invasive or disseminated disease
Candidiasis	100–200 mg once daily	Increase dose to 200 mg twice daily in case of invasive or disseminated disease
Cryptococcosis (without signs of meningitis)	200 mg once daily
Cryptococcal meningitis	200 mg 2 times a day	Support Specifications Characteristics Active ingredient Itraconazole Adults Can ATC code J ANTIMIBRICANTS FOR SYSTEMIC USE; J02 ANTIFUNGALS FOR SYSTEMIC USE; J02A ANTIFUNGALS FOR SYSTEMIC USE; J02A C Triazole derivatives; J02A C02 Itraconazole Country of manufacture Italy Diabetics With caution Dosage 100 мг Drivers With caution For allergies With caution For children It is impossible. Form Capsules Method of application Inside, solid Nursing Considering the benefit/risk ratio Pregnant By vital signs Primary packaging blister Producer Johnson & Johnson Quantity per package 15 pcs Trade name Orungal Vacation conditions By prescription Reviews There are no reviews for this product. + Add review Write a review Orungal capsules 100 mg No. 15 My mark: Continue There are no reviews for this product, be the first to leave your review. Answers & questions Add your question and we will answer as soon as possible. + Ask a question Ask a question Add your question and we will answer as soon as possible. * Your question Continue No questions about this product, be the first and ask your question. You are watched new Hit Ofloxacin-Darnitsa tablets 200 mg No. 10 In stock 0 152.54 грн. Add to Cart new Hit Turusol solution irrigation container 3000 ml In stock 0 1 046.36 грн. Add to Cart