Nizoral - instructions for use, dose, side effects, contraindications

K90 6.6 mg, microcrystalline cellulose 3 mg, silicon dioxide colloid 0.7 mg, magnesium stearate 0.7 mg, purified water (removed during manufacturing).

Description:

Round flat tablets of white color with bevelled edge. On one side of the tablets there is engraving "JANSSEN", and on the other - the risk and engraving "K 200".

Pharmacotherapeutic group:antifungal agent

ATX: & nbsp

J.02.A.B.02 Ketoconazole

D.01.A.C.08 Ketoconazole

Pharmacodynamics:

Ketoconazole is a synthetic imidazole dioxolane derivative, which has a fungiacidic or mycostatic action against dermatophytes, yeast (Candida, Malassezia, Torulopsis, Cryptococcus), dimorphic fungi and higher fungi (eumycetes). Less sensitive to the action of ketoconazole: Aspergillus spp., Sporothrix schenckii, some Dermatiaceae, Mucor spp. and other fikomitsety, except for Enomophthorales.

Ketoconazole inhibits the biosynthesis of ergosterol in fungi and changes the composition of other lipid components in membranes. Data from clinical studies and the study of drug interactions showed that when taking the drug at a dose of 200 mg twice a day for 3-7 days, there may be a slight increase in the interval QT: mean maximum interval increase QT up to 6-12 msec was observed 1-4 hours after the administration of the drug Nizoral®, when the concentration of ketoconazole in the blood plasma reached its maximum values. However, such an increase in the interval QT is considered clinically insignificant.

At a therapeutic dose of 200 mg once a day, there may be a transient decrease in testosterone concentration in the plasma. The testosterone concentration returns to the initial value within 24 hours after the administration of ketoconazole. During prolonged therapy with this dosage, the testosterone concentration usually differs slightly from the control.

Ketoconazole in a daily dose of 400 mg and above caused a decrease in the "cortisol response" to ACTH stimulation in volunteers.

Pharmacokinetics:

Absorption

Ketoconazole is a weak dibasic compound that dissolves and is absorbed in an acidic medium. The maximum average concentration of ketoconazole in the plasma of about 3.5 μg / ml is achieved 1-2 hours after a single oral intake of 200 mg of the drug during meals. Bioavailability of ketoconazole is maximal when taken with food.

Absorption of ketoconazole is reduced in patients with decreased gastric acidity, for example, antacid drugs such as aluminum hydroxide, and antisecretory drugs such as H2 receptor antagonists and proton pump inhibitors, as well as in patients with achlorhydria caused by a particular disease. sections "Special instructions" and "Interaction with other medicinal products and other forms of interaction"). Absorption of ketoconazole in these patients with fasting is increased when taking the drug with drinks containing acid (such as non-diet cola).

Preliminary administration of the proton pump inhibitor omeprazole reduced the bioavailability of a single 200 mg dose of ketoconazole to 17% of its bioavailability when administered on an empty stomach.With the intake of ketoconazole with acid-containing beverages (nondietic cola) and preliminary administration of omeprazole, the bioavailability of ketoconazole was 65% of its bioavailability when taken on an empty stomach without concomitant medications.

Distribution

In vitro binding to plasma proteins, mainly with the albumin fraction, is 99%. Ketoconazole widely distributed in tissues, but only a small part of the drug penetrates into the cerebrospinal fluid.

Metabolism

After absorption from the gastrointestinal tract ketoconazole metabolized in the liver with the formation of a large number of inactive metabolites. In vitro studies have shown that the isoenzyme CYP3A4 is involved in the metabolism of ketoconazole. The main ways of metabolism are oxidation and cleavage of imidazole and piperazine rings, oxidative O-dealkylation and aromatic hydroxylation. Ketoconazole It is not an inductor of its own metabolism.

Excretion

Excretion from the plasma is biphasic: during the first 10 hours, the elimination half-life is 2 hours, and in the subsequent - 8 hours. About 13% of the dose is excreted in the urine, of which 2 to 4% is unchanged drug substance.The drug is excreted mainly with bile in the gastrointestinal tract and about 57% is excreted with feces.

Special patient groups

Hepatic and renal insufficiency

The pharmacokinetic characteristics of ketoconazole generally differ slightly in healthy individuals and in patients with hepatic or renal insufficiency.

Children

Clinical data on the pharmacokinetics of ketoconazole, taken in the form of tablets, are limited in children.

Indications:

Infections of the skin, scalp and mucous membranes caused by dermatophytes and / or yeast fungi in cases where local treatment is not applicable due to the large size of the affected areas, significant lesion depth or in the absence of the effect of previous local treatment, as well as for the treatment of patients with persistent or with intolerance to therapy with other antifungal drugs for systemic use:

- dermatophytosis;

- colored lichen;

- folliculitis caused by fungi of the genus Malassezia;

- chronic candidiasis of the mucous membranes and candidiasis of the skin;

Candidiasis of the mouth and pharynx;

- chronic recurrent candidiasis of the vagina.

Systemic fungal infections:

- Paracoccidioidosis;

- Histoplasmosis;

- coccidioidosis;

- blastomycosis.

The use of ketoconazole in fungal meningitis is inappropriate, since the drug does not penetrate the blood-brain barrier well.

Because of the risk of serious hepatotoxicity, Niazoral ® tablets should be taken only if the benefit of the treatment exceeds the potential risk, taking into account the availability of alternative antifungal therapy options.

Contraindications:

- Hypersensitivity to ketoconazole or any of the components of the drug;

- acute or chronic liver disease;

- children's age till 3 years;

- deficiency of lactase;

lactose intolerance;

- glucose-galactose malabsorption;

- simultaneous reception with some substrates of the isoenzyme CYP3A4.

An increase in the concentration of these drugs in plasma, caused by a joint intake with ketoconazole, may lead to an increase or prolongation of both the therapeutic and side effects and the development of a potentially dangerous condition. For example, an increase in the concentration of some of these drugs in the plasma may lead to an extension of the QT interval and the development of ventricular tachyarrhythmias (incl.arrhythmias of the "torsades de pointes" type, representing a potential threat to life):

- analgesics: levacetylmetadol (levometadil), methadone;

- antiarrhythmics: disopyramide, dofetilide, dronedaron, quinidine;

- anthelmintic and antiprotozoal drugs: halofantrine;

- antihistamines preparations: astemizole, misolastine, terfenadine;

- preparations for the treatment of migraine: ergot alkaloids, for example, dihydroergotamine, ergometrine (ergonovine), ergotamine, methylergomethrin (methylergonovine);

- antitumor drugs: irinotecan;

- antipsychotic drugs: anxiolytics and hypnotics: lourazidone, midazolam orally, pimozide, sertindole, triazolam;

- blockers of calcium channels: beprideal, felodipine, lercanidipine, nisoldipine;

- cardiovascular drugs of different groups: ivabradine, ranolazine;

- diuretics: eplerenone;

- immunosuppressants: everolimus;

- gastrointestinal drugs: cisapride, domperidone;

- lipid-lowering drugs: lovastine, simvastin;

- other: colchicine in the treatment of patients with impaired liver and kidney function.

(See section "Interaction with other drugs and other forms of interaction")

Carefully:

The drug Nizoral® is used with caution in patients with low gastric acidity, at this state, the absorption of the drug worsens. Patients taking antacid preparations (eg, aluminum hydroxide) should be taken no earlier than 2 hours after taking Nizoral®.

Patients with achlorhydria or patients taking medications suppressing the secretion of hydrochloric acid in the stomach (eg, H2-histamine receptor blockers or "proton pump" inhibitors), it is desirable to take Nizoral® with beverages containing cola.

In patients with adrenal insufficiency or with borderline conditions, as well as in patients undergoing significant stress (extensive surgical interventions, etc.), when administering the drug, adrenal function should be monitored, when using the drug Nizoral® at a dose of 400 mg or more, a decrease in the "cortisol response" was observed when stimulating the adrenals with adrenocorticotropic hormone (ACTH).

Nisoral® is prescribed with caution to alcohol abusers.while taking the drug with alcohol may occur disulfiramopodobnyh reactions, characterized by redness, rash, edema, nausea and headache.

Because of the risk of hepatotoxicity, patients with hepatic impairment, as well as patients taking potentially hepatotoxic drugs, should be cautioned with Nizoral® Tablets and only if the potential benefit outweighs the potential risk, given the availability of other effective antifungal agents .

Pregnancy and lactation:

At the moment, there is limited information on the use of tablets Nizoral® during pregnancy. In animal studies, reproductive toxicity of ketoconazole was found. The degree of potential risk to a person is unknown. Therefore, Nizoral® tablets should not be given to pregnant women unless the potential benefit to the mother is greater than the potential risk to the fetus.

Because Nizoral® penetrates into breast milk, breastfeeding is not recommended when taking the drug.

Dosing and Administration:

The drug Nizoral® is taken orally, during meals to improve absorption.

With infections of the skin, scalp and mucous membranes caused by dermatophytes and / or yeast fungi and systemic infections

Adults

One tablet (200 mg) once a day with meals. If, upon admission, the indicated dose does not improve, the dose should be doubled (400 mg once a day).

Vaginal candidiasis: two tablets (400 mg) once a day with meals.

Children over 3 years old

- with a body weight of 15 to 30 kg: 1/2 tablet (100 mg) once a day (since the experience of using the drug by children with a body weight of less than 15 kg is limited, it is not recommended to prescribe the drug to children weighing less than 15 kg);

- with a body weight of more than 30 kg: the doses indicated for adults.

Average duration of treatment:

- vaginal candidiasis - 7 days;

- skin mycoses caused by dermatophytes - about 4 weeks;

- multi-colored lichen-10 days;

- Candidiasis of the skin and oral cavity - 2-3 weeks;

- fungal lesions of the scalp - 1-2 months;

- paracoccidioidomycosis, histoplasmosis, coccidiodomycosis - usually the duration of treatment is 6 months.

For all indications, treatment should be continuous,until the clinical parameters and laboratory indicators will not indicate eradication of the pathogen. Inadequate duration of treatment can lead to a relapse of infection. However, if signs and symptoms of hepatitis such as anorexia, nausea, vomiting, fatigue, jaundice, abdominal pain and dark urine occur, the treatment should be immediately discontinued and the liver function evaluated.

Side effects:

Listed below are the side effects noted with frequency ≥ 1.0% in patients with superficial and deep mycoses who received ketoconazole (data from a multicentre open clinical trial):

Impaired nervous system: headache.

Disturbances from the gastrointestinal tract: nausea, abdominal pain, diarrhea, impaired liver function.

The following side effects were noted with a frequency of <1.0% in patients with superficial and deep mycoses who received ketoconazole (data of a multicenter open clinical research):

Disorders from the endocrine system: gynecomastia.

Disorders from organs feelings: photophobia.

Disorders from the gastrointestinal tract: vomiting, indigestion, constipation, dry mouth, dysgeusia, bloating, discoloration of the tongue, toxic hepatitis (increased activity of "liver" transaminases or alkaline phosphatases, hypercreatininaemia), jaundice.

Immune system disorders: pseudo-anaphylactic shock.

Impaired nervous system: dizziness, paresthesia, drowsiness, increased excitability, insomnia, anxiety, fatigue, general weakness.

Disorders from the metabolism and nutrition: alcohol intolerance, anorexia, hyperlipidemia, increased appetite.

Disturbances from the musculoskeletal system: myalgia.

Disorders from the reproductive system: violation of the menstrual cycle.

Disturbances from the respiratory system: nose bleed.

Disturbances from the skin and subcutaneous fat: alopecia, dermatitis, erythema, erythema multiforme, pruritus, rash, allergic rash, xeroderma, "hot flushes" of blood, acute generalized exentematous pustulosis.

Disorders from the cardiovascular system: orthostatic depression blood pressure.

Violations from laboratory indicators: decrease in the number of platelets.

Violations from general indicators: fever, peripheral edema, chills.

Data on side effects in the post-marketing period

Side effects of the drug are systematized relative to each of the organ systems, using the following classification of frequency: very often (≥ 1/10); often (≥ 1/100, <1/10); infrequently (≥ 1/1000, <1/100); rarely (≥ 1/10 000, <1/1000); very rarely (<1/10 000), including isolated cases.

Infringements from laboratory indicators

Very rarely: thrombocytopenia.

Immune system disorders

Very rare: allergic conditions, including hives, anaphylactic shock, anaphylactic reactions, angioedema.

Disorders from the endocrine system

Very rarely: insufficiency of adrenal function.

Disorders from the central nervous system

Very rarely: a reversible increase in intracranial pressure (eg, edema of the optic discs, swelling of the fontanelle in young children).

Disorders from the gastrointestinal tract

Very rarely: severe hepatotoxicity, including cholestatic hepatitis, hepatonecrosis (biopsy), liver cirrhosis,hepatic insufficiency (including cases of transplantation and death).

Disturbances from the skin and subcutaneous fat

Very rarely: acute generalized exentematous pustulosis, photosensitivity.

Disturbances from the musculoskeletal system

Very rarely: arthralgia.

Disorders from the genitourinary system

Very rarely: erectile dysfunction, azoospermia at doses exceeding therapeutic - 200 or 400 mg per day.

Other

Probably a temporary decrease in the concentration of testosterone in the blood plasma (normalized after 24 h after administration).

Overdose:

Symptoms

The most common symptoms of overdose were: nausea (27.2%), fatigue, including drowsiness and confusion (14.2%), vomiting (12.6%), abdominal pain (12.0%), anorexia, including weight loss , loss of appetite (7.4%), hyperemia including increased sweating (6.3%), edema (5.7%), gynecomastia (4.8%), rash, including eczema, purpura, dermatitis (3.3 %), diarrhea (2.2%), headache (2.0%), dysgeusia (1.3%), alopecia (1.1%).

Treatment

The specific antidote of ketoconazole is not known.

In case of an overdose within the first hour after taking the drug, it is necessary to take Activated carbon. In case of overdose, careful monitoring of the patient's condition and symptomatic treatment are necessary. If necessary, you can wash the stomach.

Interaction:

In the metabolism of ketoconazole, isozyme CYP3A4. The pharmacokinetics of ketoconazole can be influenced by other substances with the same pathway of metabolism or affecting activity of cytochrome P450. Ketoconazole can also affect the pharmacokinetics of other substances with the same pathway of metabolism. Ketoconazole is a potent inhibitor of cytochrome P450 CYP3A4 and P-glycoprotein. When performing concomitant therapy, it is necessary to familiarize yourself with the relevant instructions for use to obtain information on the pathway of their metabolism and the possible need for dose adjustment. The study of interaction between drugs was carried out only in adults. The significance of the results of these studies for children is unknown.

Drugs capable of reducing ketoconazole in the plasma

Absorption of ketoconazole is reduced by simultaneous administration with antacid preparations such as aluminum hydroxide and antisecretory drugs, such as H2 receptor antagonists and proton pump inhibitors.When using these drugs together with ketoconazole, care must be taken:

- in the case of joint application with drugs that reduce the acidity of the stomach, ketoconazole should be washed down with a sour drink (for example, non-dietary cola);

- Neutralizing drugs (eg aluminum hydroxide) should be taken at least 1 hour before or 2 hours after taking Nizoral®;

- in case of combination therapy, it is necessary to monitor antifungal activity with ketoconazole dose adjustment, if required;

- in the case of combined use of ketoconazole with powerful inducers of cytochrome P450 CYP3A4 it is possible to reduce the bioavailability of ketoconazole to a degree sufficient to significantly decrease the efficacy. Examples of such drugs include: antibacterial drugs: isoniazid, rifabutin, rifampicin; anticonvulsants: carbamazepine (see also in the section "Preparations, the concentration in the blood plasma of which can increase with simultaneous administration with ketoconazole"), phenytoin; antiviral drugs: efavirenz, nevirapine.

Thus, the combined use of powerful cytochrome P450 inducers CYP3A4 with ketoconazole is not recommended. The use of these drugs should avoid 2 weeks prior to initiation of ketoconazole therapy and throughout the use of the drug, unless the benefits of treatment outweigh the risk of a potential decrease in ketoconazole. In case of joint application, it is necessary to monitor the antifungal activity and increase the dose of ketoconazole, if necessary.

Drugs that can increase the concentration of ketoconazole in plasma

Powerful inhibitors of cytochrome P450 CYP3A4 (for example, antiviral drugs, including ritonavir, ritonavir-boosted darunavir and ritonavir-boosted fosamprenavir) can increase the bioavailability of ketoconazole. These drugs should be used with caution in the case of combined use with ketoconazole in tablets.

In patients receiving ketoconazole in combination with powerful inhibitors of cytochrome P450 CYP3A4 careful monitoring is needed to determine the appearance of symptoms or complaints of an increase in the intensity or duration of pharmacological effects of ketoconazole, and, if necessary, reduce the dose of ketoconazole.If necessary, the concentration of ketoconazole in the plasma should be measured.

Drugs, the concentration in the blood plasma of which may increase with simultaneous admission with ketoconazole

Ketoconazole is able to inhibit the metabolism of drugs, metabolized by cytochrome P450 CYP3A4, as well as transport of drugs under the action of P-glycoprotein, which can lead to an increase in the concentration of these drugs and / or their active metabolites in plasma in the case of combined use with ketoconazole. An increase in plasma concentration can lead to an increase in the intensity or duration of the therapeutic and / or adverse effects of these drugs. When ketoconazole is used, cytochrome P450 metabolized can be contraindicated CYP3A4 drugs able to lengthen the interval QT, since their simultaneous administration with ketoconazole may lead to the development of ventricular tachyarrhythmias (including arrhythmias of the "torsades de pointes", representing a potential threat to life).

Entering agents can be classified as follows:

1. "Contraindicated": under no circumstances should this drug be used simultaneously with ketoconazole and within one week after its withdrawal;

2."Not recommended": during the treatment with ketoconazole and within one week after it is withdrawn, the use of this drug should be avoided, unless the benefits of treatment exceed the possible risk of side effects. If joint use is not possible, clinical monitoring of complaints or symptoms of increased intensity or duration of therapeutic or side effects is recommended, in addition, if necessary, reduce the dosage of the drug taken concomitantly with ketoconazole, or suspend its use. In appropriate cases, the concentration of the drug in the blood plasma should be measured;

3. "Use with caution": when combined with ketoconazole, careful monitoring of the patient's clinical condition is recommended. In case of simultaneous administration, patients should be carefully monitored to identify symptoms or complaints of increased intensity or duration of therapeutic or side effects, and, if necessary, dosage should be reduced.If necessary, the concentration of the drug in the blood plasma should be measured.

Below are examples of drugs whose plasma concentration may be increased by ketoconazole (the drugs are listed by class and recommended for joint use with ketoconazole):

Class preparation	Contraindicated	Not recommended	Use with caution
α-adrenoblockers		tamsulosin
Analgesics	levacetylmethadol (levometadil), methadone	fentanyl	alfentanil, buprenorphine intravenously and sublingually, oxycodone
Antiarrhythmics	disopyramide, dofetilide, dronedaron, quinidine		digoxin
Antibacterial drugs		rifabutin
Anticoagulant and antiplatelet drugs		rivierok saban	coumarins, cilostazol
Anticonvulsant drugs		carbamazepine
Antidiabetic drugs			repaglinide, saxagliptin
Anthelmintic and antiprotozoal drugs	halofantrine		praziquantel
Antihistamines drugs	astemizole, misolastine, terfenadine		ebastine
Migraine medications	alkaloids ergot, eg dihydroergotamine, ergometrine (ergonovine), ergotamine, methylergomethrin (methylergonovine)		eletriptan
Antineoplastic drugs	irinotecan	dasatinib, nilotinib, trabetedin	bortezomib, busulfan, docetaxel, erlotinib, imatinib, Ixabep, ylon, lapatinib, trimetrexate, vinca alkaloids
Antipsychotic drugs, anxiolytics and sleeping pills drugs	lurasidone, midazolam orally, pimozide, sertindole, triazolam		alprazolam,aripiprazole, brotisolam, buspirone, haloperidol, midazolam intravenously, perosporone, quetiapine, ramelteon, risperidone
Antiviral drugs drugs			maraviroc, indinavir, saquinavir,
β-blockers			nad
Blockers calcium channels	beprideil, felodipine, lercanidipine, nisoldipine		other dihydropyridines, including verapamil
Cardiovascular drugs of different groups	ivabradine, ranolazine		aliskiren
Diuretics	eplerenone
Gastrointestinal drugs	cisapride, domperidone		aprepitant
Immunosuppressive drugs	everolimus		budesonide,ciclesonide, cyclosporine, dexamethasone, fluticasone, methylprednisolone, rapamycin (other name sirolimus), tacrolimus, tessirolimus
Lipid-lowering drugs	lovastatin, simvastatin		atorvastatin
Drugs for treatment diseases of organs respiratory system		salmeterol
Selective inhibitors re-acquisition serotonin, tricyclic and related to them antidepressants			reboxetine
Urological drugs		vardenafil	fesoterodine, imidafenacin, sildenafil, solifenacin, tadalafil, tolterodine
Other	Colchicine for treatment of patients with violations functions liver and kidney	colchicine	* Alcohol, Alitretinoin, (oral medication the form), zincalcet, mozavaptan, tolvoptan

* Single cases of a disulfiram-like reaction to alcohol, characterized by the appearance of "hot flashes", rashes, peripheral edema, have been documented. nausea and headache. All symptoms were completely resolved within a few hours.

Special instructions:

Hepatotoxicity. Because of the risk of hepatotoxicity, Nizoral® tablets should only be used when the potential benefit outweighs the potential risk, taking into account the availability of other effective antifungal agents.

Before the beginning of treatment it is necessary to evaluate the function of the liver in order to avoid acute or chronic diseases.During treatment, it is necessary to regularly monitor the picture of peripheral blood, the functional state of the liver and kidneys in patients in order to not miss the first signs of hepatotoxicity.

Against the background of taking oral forms of ketoconazole, very rare cases of hepatotoxicity were reported, including cases with fatal outcome or cases requiring liver transplantation. In some patients, there were no obvious risk factors for liver damage. Several such cases occurred in the first month of therapy, and some in the first week of treatment. The total dose of ketoconazole is a risk factor for severe hepatotoxicity. In this regard, it is recommended to regularly monitor liver function in patients receiving ketoconazole therapy.

Patients should be warned about the need to contact their doctor immediately if there are any symptoms suggesting hepatitis, namely: anorexia, nausea, vomiting, weakness, jaundice, abdominal pain and darkening of the urine. In the case of such symptoms it is necessary to immediately stop therapy and conduct a study of liver function.

It is necessary to monitor liver function in all patients treated with Nizoral®. Control of liver function should be performed before starting therapy with Nizoral®, (to exclude acute or chronic liver disease, see the section "Contraindications"), regularly during therapy and when the first signs or symptoms of liver dysfunction occur. When receiving test results indicating a violation of liver function, treatment with Nizoral® should be stopped immediately.

Patients with increased hepatic enzyme activity or with transferred toxic liver damage due to taking other medications should not be treated with Nizoral®, unless the expected benefit justifies the risk of liver damage. In these cases, it is necessary to control the level of hepatic enzymes during treatment.

Since the volunteers ketoconazole in a daily dose of 400 mg and higher caused a decrease in the "cortisol response" to the stimulation of drenocorticotropic hormone (ACTH), adrenal function in patients with adrenal insufficiency or borderlinestates in patients undergoing significant stress (extensive

surgical interventions, intensive care conditions, etc.), in patients with long-term course of therapy with suspected adrenocortical insufficiency.

Reduced acidity of the stomach. The absorption of the drug taken in the form of tablets deteriorates when the acidity of the gastric juice decreases. Patients with a low acidity of the stomach caused by the disease (for example, with achlorhydria) or taking medications that reduce the acidity of the gastric juice, it is desirable to take Nizoral® with acidic drinks.

It is recommended to monitor antifungal activity with an increase in the dose of ketoconazole, if necessary (see the section "Interaction with other medicinal products and other forms of interaction (Preparations capable of reducing the concentration of ketoconazole in plasma)" and the section "Pharmacokinetics (Absorption)").

If treatment of skin lesions was carried out glucocorticosteroids, then ketoconazole appoint not earlier than two weeks after their cancellation.

Use acid drinks increases the absorption of ketoconazole.

Joint application some drugs with ketoconazole may lead to changes in the effectiveness of ketoconazole and / or other medicines, the emergence of life-threatening conditions and / or sudden death. Medications that are contraindicated, not recommended, or should be used with caution in combination with ketoconazole are listed in the section "Interaction with other drugs and other forms of interaction.

Effect on the ability to drive transp. cf. and fur:

Has no influence.

Form release / dosage:

Tablets 200 mg.

Packaging:

10 tablets in a blister pack.

For 1 or 3 blisters together with instructions for use in a cardboard box.

Storage conditions:

In a dry place at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:П N011192

Date of registration:15.08.2011

Date of cancellation:2016-11-17

The owner of the registration certificate:Johnson & Johnson, LLC Johnson & Johnson, LLC Russia

Manufacturer: & nbsp

JANSSEN-CILAG, S.p.A. Italy

Representation: & nbspJohnson & Johnson LLC Johnson & Johnson LLC Russia

Information update date: & nbsp17.11.2016

Illustrated instructions

Instructions

Nizoral® (Nizoral®)