URBASON - PACKAGE LEAFLET - LEAFLETS

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Urbason - Package Leaflet

Indications Contraindications Precautions for use Interactions Warnings Dosage and method of use Overdose Undesirable Effects Shelf life and Storage Composition and pharmaceutical form

Active ingredients: Methylprednisolone

URBASON 4 mg tablets

Urbason package inserts are available for pack sizes:

URBASON 4 mg tablets
URBASON 8 mg prolonged-release tablets, URBASON 4 mg prolonged-release tablets

Why is Urbason used? What is it for?

PHARMACOTHERAPEUTIC CATEGORY

Systemic corticosteroids, glucocorticoids.

THERAPEUTIC INDICATIONS

The most important fields of application are: rheumatic disease, bronchial asthma, hay fever, serum sickness, hypersensitivity to drugs and other allergic reactions. Urticaria, generalized eczema, dermatitis, disseminated erythematodes, dermatomyositis, pemphigus, exfoliative dermatitis. Agranulocytosis, thrombopenia, acquired haemolytic anemia, myeloblastosis, lymphadenosis, lymphogranulomatosis. Hepatitis, ulcerative colitis, adrenogenital syndrome, nephrotic syndrome (also in combination with the saluretic Lasix).

Contraindications When Urbason should not be used

It must not be used in patients with hypersensitivity to methylprednisolone or to other glucocorticoids or to any of the excipients (see "Composition").

Except in replacement or emergency therapy, Urbason should not be administered in:

patients with gastric or duodenal ulcers;
patients with bone demineralization (osteoporosis);
patients with mental disorders;
patients with open and closed angle glaucoma;
patients with herpetic keratitis;
patients with some viral diseases such as: chicken pox, herpes simplex, and during the viral phase of herpes zoster;
patients with latent or manifest tuberculosis and even if only suspected (risk of onset of the disease until then latent or worsening of the disease already in progress);
patients with lymphadenopathy following BCG vaccinations;
patients suffering from amoebiasis;
patients with systemic mycosis;
patients with poliomyelitis (with the exception of the encephalitic bulbar form);
for approximately 8 weeks before and 2 weeks after vaccinations.

It is recommended that patients treated with therapeutic doses of glucocorticoids (other than replacement therapy) are not vaccinated because the antibody response may be inadequate or they may develop neurological complications. In the case of severe infections Urbason can only be used in combination with specific therapy.

Due to the risk of stunted growth Urbason should only be given to children when clearly needed.

Precautions for use What you need to know before taking Urbason

Due to the risk of intestinal perforation with peritonitis, Urbason should only be used when clearly needed and with adequate monitoring of patients with:

severe ulcerative colitis with risk of perforation, abscess or purulent inflammation;
diverticulitis;
recent intestinal anastomoses.

Unless they have already had chickenpox, children and adults should avoid having contact with people with chickenpox or shingles.

If they are exposed to such infections while taking Urbason they should contact a doctor immediately even in the absence of symptoms.

Patients with tuberculin reactivity should be monitored due to the risk of reactivation.

In these patients, chemoprophylaxis is recommended during long-term glucocorticoid therapy. In patients with myasthenia gravis, particularly if they are receiving high doses of glucocorticoids, there is a risk of the disease getting worse, usually within the first two weeks of starting glucocorticoid therapy. It is therefore recommended that Urbason doses are low at the start of therapy and gradually increased.

The metabolic conditions of diabetic patients should be monitored and antidiabetic therapy adjusted if necessary.

In particular, after prolonged therapies with high doses of the drug, a possible water and sodium retention should be considered. In this case it is necessary to ensure an adequate supply of potassium, the level of which must be monitored in the blood and a decreased intake of sodium.

Possible worsening of hypertension and heart disease should be taken into consideration, therefore appropriate monitoring of patients is required.

In long-term treatment with glucocorticoids, medical checks include ophthalmological ones.

In hypothyroid patients or patients with liver cirrhosis, the response to corticosteroids may be increased and therefore dose reduction and patient monitoring are required.

Interactions Which drugs or foods can change the effect of Urbason

Digitalis glucosides: the action of glucosides could be enhanced by hypokalaemia.
Diuretics: increased potassium excretion.
Antidiabetics: the hypoglycaemic effect may be diminished.
Coumarin derivatives: anticoagulant effects may be reduced.
Rifampicin, phenytoin and barbiturates: the corticosteroid effect may be decreased (see "Undesirable effects").
Non-depolarizing muscle relaxants: Muscle relaxation could be prolonged.
Estrogen (contraceptive products): Concomitant use of estrogen may reduce the metabolism of corticosteroids including methylprednisolone.
Non-steroidal anti-inflammatories increase the risk of gastrointestinal bleeding.
Ciclosporin: inhibition of metabolism; increased risk of seizures.
Allergy tests: Skin reactions to allergy tests may be suppressed.
Diltiazem: inhibition of methylprednisolone (CYP3A4) metabolism and inhibition of P-glycoprotein. The patient should be monitored when starting methylprednisolone therapy. Methylprednisolone dosage adjustment may be needed.

Inform your doctor or pharmacist if you have recently taken any other medicines, even without a prescription.

Warnings It is important to know that:

The use of glucocorticoids can weaken the immune system causing the onset of infections, some microorganisms can be activated with consequent manifestation of latent infections.

Glucocorticoids can hide the signs of an infection making the diagnosis of its existence or development more difficult.

In patients receiving systemic glucocorticoids, certain viral diseases such as chicken pox, herpes simplex, and during the viral phase of herpes zoster can also become severe in replacement therapies.

Systemic glucocorticoid treatment can cause chorioretinopathy which can lead to visual disturbances including vision loss. Prolonged use of systemic treatment with glucocorticoids even at low doses can cause chorioretinopathy (see section "Undesirable effects").

Pregnancy and breastfeeding

Ask your doctor or pharmacist for advice before taking any medicine.

Methylprednisolone crosses the placenta and passes into breast milk.

Since there is very limited experience with the use of methylprednisolone in pregnancy, Urbason should only be administered when clearly needed, under direct medical supervision. If high doses of the drug are administered, for clinical reasons, breastfeeding should be stopped to prevent the infant from ingesting methylprednisolone with breast milk.

Effects on ability to drive and use machines

Some undesirable effects (decreased visual capacity, onset of an opacification of the lens, increased intraocular pressure, dizziness and migraine) can decrease the ability to concentrate and react of patients, constituting a risk in all those situations in which these skills are of particular importance. (driving a car or using machines).

Important information about some of the ingredients of URBASON

URBASON contains lactose.

If your doctor has diagnosed an intolerance to some sugars, contact him before taking this medicine.

For those who play sports:

The use of the drug without therapeutic necessity constitutes doping and can in any case determine positive anti-doping tests.

Dose, Method and Time of Administration How to use Urbason: Posology

In general, treatment begins with relatively high doses which are reduced over the course of treatment. After successful initial treatment the daily dose is gradually reduced (at intervals of one to several days) to the minimum dose required to achieve a satisfactory result (maintenance dose).

In bronchial asthma and allergic diseases, starting doses between 16-40 mg per day are recommended, while the maintenance dose is mostly 4-16 mg per day. In mild cases of chronic polyarthritis, 8-16 mg may suffice for starting therapy, however, in severe cases, 16-40 mg are required, and a daily dose of 4-16 mg is usually sufficient to maintain therapeutic success.

According to the most recent experience, high doses of steroids are required in acute rheumatic fever. For this reason the daily dose of 40-80-120 mg (in children under 14 years, 1.2-1.6 mg / kg body weight) should be administered until the erythrocyte sedimentation rate has remained normal at least one week; then the dosage is gradually decreased.

A considerably higher dosage, up to daily doses of 100 mg and more, is sometimes necessary in acute Erythematodes, pemphigus vulgaris, and in various hemopathies.

In patients treated with prednisone or prednisolone, when switching to Urbason, the maintenance dose is usually 80% of the previously administered dose, i.e. the 4 mg Urbason tablet corresponds to one prednisone or prednisolone tablet. from 5 mg.

The tablets should not be ingested on an empty stomach; the distribution of the dose during the day and the duration of the therapy are left to the judgment of the doctor who will decide, as in any therapy with glucocorticoids, based on the severity of the disease and the different response of patients to treatment.

Overdose What to do if you have taken too much Urbason

There are no known cases of acute intoxication. However, if necessary, gastric lavage should be performed and any symptoms checked.

In case of accidental ingestion / intake of an excessive dose of URBASON, notify your doctor immediately or go to the nearest hospital.

If you have any questions about the use of URBASON, ask your doctor or pharmacist.

Side Effects What are the side effects of Urbason

Like all medicines, URBASON can cause side effects, although not everybody gets them.

During corticosteroid therapy, especially for intense and prolonged treatments, some of the following effects may occur:

abnormal distribution of body fat as in the case of lunar facies, obesity and very rarely also a distribution of fat in the vertebral canal (epidural) or in the thoracic cavity (epicardial, mediastinal); weight gain.
sodium retention and accumulation of water in the tissues, increased potassium excretion with possible hypokalaemia, increased pulmonary congestion in heart attack patients, hypertension.
alteration in the secretion of sex hormones (possible amenorrhea, increased hair growth, decreased sexual potency); inactivation or atrophy of corticoadrenal activity, growth retardation in children.
increased blood sugar, steroid diabetes, changes in serum lipid fraction.
tendon rupture (Achilles tendon), especially in patients with metabolic disorders such as: uremia or diabetes mellitus.
muscle weakness. Weakening of muscle weakness and severe myasthenic crises can occur in patients with myasthenia gravis. Acute myopathies can be aggravated by the use of non-depolarizing relaxants.
development of gastric and duodenal ulcers; gastric and duodenal perforations, with peritonitis.
blood diseases, delays in healing processes, increase in protein metabolism accompanied by the "increase of" urea.
skin changes (atrophy, striae, acne and bleeding).
in rare cases hypersensitivity reactions and skin rash may occur. Hypersensitivity reactions include shock which may arise after parenteral administration and particularly in patients with bronchial asthma or who have undergone a kidney transplant.
decreased immune response and increased risk of infections. Some viral diseases such as: chickenpox, herpes simplex and shingles can become serious.
cerebral convulsions, increased intracranial pressure with papilloedema (pseudotumor cerebri), development or aggravation of mental disorders such as: euphoria, mood swings, personality change, severe depression, psychosis, dizziness, headache and sleep disturbances.
leukocytosis (initially returns to normal during therapy), tendency to thrombocytosis, increased risk of thrombosis.
clouding of the lens, increased intraocular pressure, chorioretinopathy (see section "Special warnings").

Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.

Reporting of side effects

If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. You can also report side effects directly via the national reporting system of the Italian Medicines Agency, website: https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects you can help to provide more information on the safety of this medicine.

Expiry and Retention

Expiry: see the expiry date indicated on the package.

The expiry date indicated refers to the product in intact and correctly stored packaging.

WARNING: do not use the medicine after the expiry date indicated on the package.

Do not store above 30 ° C.

Keep out of the reach and sight of children.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

Composition and pharmaceutical form

COMPOSITION

1 tablet contains:

Active ingredient: methylprednisolone 4 mg.

Excipients: lactose, corn starch, talc, colloidal silicon dioxide and magnesium stearate.

PHARMACEUTICAL FORM AND CONTENT

Tablets

Box of 10 tablets of 4 mg.

Source Package Leaflet: AIFA (Italian Medicines Agency). Content published in January 2016. The information present may not be up-to-date.
To have access to the most up-to-date version, it is advisable to access the AIFA (Italian Medicines Agency) website. Disclaimer and useful information.

Further information on Urbason can be found in the "Summary of Characteristics" tab. 01.0 NAME OF THE MEDICINAL PRODUCT 02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION 03.0 PHARMACEUTICAL FORM 04.0 CLINICAL PARTICULARS 04.1 Therapeutic indications 04.2 Posology and method of administration 04.3 Contraindications 04.4 Special warnings and appropriate precautions for use 04.5 Interactions with other medicinal products and other forms of interaction 04.6 Pregnancy and lactation 04.7 Effects on ability to drive and use machines 04.8 Undesirable effects 04.9 Overdose 05.0 PHARMACOLOGICAL PROPERTIES 05.1 Pharmacodynamic properties 05.2 Pharmacokinetic properties 05.3 Preclinical safety data 06.0 PHARMACEUTICAL PARTICULARS 06.1 Excipients 06.2 Incompatibilities 06.3 Shelf life 06.4 Special precautions for storage 06.5 Nature of the primary packaging and contents of the package 06.6 Instructions for use and handling 07.0 MARKETING AUTHORIZATION HOLDER 08.0 MARKETING AUTHORIZATION NUMBER CIO 09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION 10.0 DATE OF REVISION OF THE TEXT 11.0 FOR RADIO DRUGS, FULL DATA ON INTERNAL RADIATION DOSIMETRY 12.0 FOR RADIO DRUGS, FURTHER DETAILED INSTRUCTIONS ON PREPARATION AND QUALITY CONTROL

01.0 NAME OF THE MEDICINAL PRODUCT

URBASON

02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION

URBASON 4 mg tablets

1 tablet contains: methylprednisolone 4 mg.

URBASON 8 mg prolonged-release tablets

1 tablet contains: methylprednisolone 8 mg.

URBASON 4 mg prolonged-release tablets

1 tablet contains: methylprednisolone 4 mg.

For the full list of excipients, see section 6.1.

03.0 PHARMACEUTICAL FORM

URBASON 4 mg tablets

Round tablets marked "IVD" on one face and the Hoechst logo on the other.

URBASON 8 mg prolonged-release tablets

Round, prolonged-release tablets with a gastro-resistant core and marked "IVR".

URBASON 4 mg prolonged-release tablets

Round, prolonged-release tablets with a gastro-resistant core and marked "IVM".

04.0 CLINICAL INFORMATION

04.1 Therapeutic indications

Acute joint rheumatism (rheumatic fever) and chronic polyarthritis, rheumatic and rheumatoid manifestations of internal organs, vessels, eyes, skin and serous; uric arthritis; psoriatic arthropathy; bronchial asthma, hay fever, serum sickness, hypersensitivity to drugs and other allergic and toxic-allergic reactions; urticaria, generalized eczema, dermatitis; erythroderma, disseminated erythematodes, dermatomyositis, pemphigus, exfoliative dermatitis; agranulocytosis, thrombocytopenia, acquired haemolytic anemia, myeloblastosis, lymphadenosis, lymphogranulomatosis; hepatitis, ulcerative colitis, adrenogenital syndrome; nephrotic syndrome (also in association with the saluretic Lasix).

04.2 Posology and method of administration

Dosage:

URBASON 4 mg tablets

In bronchial asthma and allergic diseases, starting doses between 16-40 mg per day are recommended, while the maintenance dose is mostly 4-16 mg per day.

In mild cases of chronic polyarthritis, 8-16 mg may be sufficient to initiate therapy, while in severe cases 16-40 mg is required. A daily dose of 4-16 mg is usually sufficient to maintain therapeutic success.

According to the most recent experience, high doses of steroids are required in acute rheumatic fever. Therefore the daily dose of 40-80-120 mg (in children under the age of 14, 1.2-1.6 mg / kg) should be administered as long as the erythrocyte sedimentation rate has remained normal for at least one week; then the dosage is gradually decreased.

Significantly higher dosages, up to daily doses of 100 mg and more, are sometimes required in acute Erythematodes, pemphigus vulgaris and various haemopathies.

In patients treated with prednisone or prednisolone, when switching to Urbason, the maintenance dose is usually 80% of the previously administered dose, i.e. one Urbason 4 mg tablet corresponds to one prednisone 5 mg tablet. or prednisolone.

URBASON 8 mg prolonged-release tablets and URBASON 4 mg prolonged-release tablets.

It is certainly possible to start oral corticosteroid therapy immediately with Urbason 8 mg prolonged-release tablets or Urbason 4 mg prolonged-release tablets; usually starting with a daily dose of between 20 and 40 mg and then moving on, possibly as soon as possible. and in the judgment of the physician, at a lower dose.

The maintenance posology must always be the minimum capable of controlling the symptoms; the dosage reduction must always be done gradually.

Method of administration

The tablets should not be swallowed on an empty stomach.

The prolonged-release tablets should be swallowed whole, without chewing.

The distribution of the dose during the day and the duration of the therapy are left to the judgment of the doctor who will decide, as in any therapy with glucocorticoids, based on the severity of the disease and the different response of the patients to the treatment.

It is recommended that the once daily dose be taken early in the morning. Once the maintenance dose has been established it is recommended that the patient take a double daily dose every other day at once in the morning. The duration of the treatment depends from patient to patient.

04.3 Contraindications

It must not be used in patients with hypersensitivity to methylprednisolone or to other glucocorticoids or to any of the excipients (see "6.1 List of excipients").

Except in replacement or emergency therapy, Urbason should not be administered in:

- patients with gastric or duodenal ulcers;

- patients with bone demineralization (osteoporosis);

- patients with mental disorders;

- patients with open and closed angle glaucoma;

- patients with herpetic keratitis;

- patients with some viral diseases such as: Chickenpox, herpes simplex, and during the viral phase of herpes zoster;

- patients with latent or manifest tuberculosis and even if only suspected (risk of onset of the disease until then latent or worsening of the disease already in progress);

- patients with lymphadenopathy following BCG vaccinations;

- patients suffering from amoebiasis;

- patients with systemic mycosis;

- patients with poliomyelitis (with the exception of the encephalitic bulbar form);

- for approximately 8 weeks before and 2 weeks after vaccinations.

Due to the risk of stunted growth Urbason should only be given to children when clearly needed.

04.4 Special warnings and appropriate precautions for use

The use of glucocorticoids can weaken the immune system causing the onset of infections, some microorganisms can be activated with consequent manifestation of latent infections.

Glucocorticoids can hide the signs of an infection making the diagnosis of its existence or development more difficult.

In patients receiving systemic glucocorticoids, certain viral diseases such as chicken pox, herpes simplex and during the viral phase of herpes zoster can also become severe in replacement therapies.

Systemic glucocorticoid treatment can cause chorioretinopathy which can lead to visual disturbances including vision loss. Prolonged use of systemic glucocorticoid treatment even at low doses can cause chorioretinopathy (see section 4.8).

Due to the risk of intestinal perforation with peritonitis, Urbason should only be used when clearly needed and with adequate monitoring of patients with:

- severe ulcerative colitis with risk of perforation, abscess or purulent inflammation;

- diverticulitis;

- recent intestinal anastomoses.

Unless they have already had chickenpox, children and adults should avoid having contact with people with chickenpox or shingles. If they are exposed to such infections while taking Urbason they should contact a doctor immediately even in the absence of symptoms.

Patients with tuberculin reactivity should be monitored due to the risk of reactivation. In these patients, chemoprophylaxis is recommended during long-term glucocorticoid therapy.

In patients with myasthenia gravis, particularly if they are receiving high doses of glucocorticoids, there is a risk of the disease getting worse, usually within the first two weeks of starting glucocorticoid therapy. It is therefore recommended that Urbason doses are low at the start of therapy and gradually increased.

The metabolic conditions of diabetic patients should be monitored and antidiabetic therapy adjusted if necessary.

Possible worsening of hypertension and heart disease should be taken into consideration, therefore appropriate monitoring of patients is required.

In long-term treatment with glucocorticoids, medical checks include ophthalmological ones.

In hypothyroid patients or patients with liver cirrhosis, the response to corticosteroids may be increased and therefore dose reduction and patient monitoring are required.

Important information about some of the ingredients of URBASON

URBASON contains lactose.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.

04.5 Interactions with other medicinal products and other forms of interaction

- Digitalis glucosides: the action of glucosides could be enhanced by hypokalemia.

- Diuretics: increased potassium excretion.

- Antidiabetics: the hypoglycemic effect may be decreased.

- Coumarin derivatives: anticoagulant effects could be reduced.

- Rifampicin, phenytoin and barbiturates: the corticosteroid effect may be decreased (see "Undesirable effects").

- Non-depolarizing muscle relaxants: muscle relaxation could be prolonged.

- Estrogens (contraceptive products): concomitant use of estrogen can reduce the metabolism of corticosteroids including methylprednisolone.

- Non-steroidal anti-inflammatories increase the risk of gastrointestinal bleeding.

- Ciclosporin: inhibition of metabolism; increased risk of seizures.

- Allergy tests: skin reactions to allergy tests may be suppressed.

- Diltiazem: inhibition of the metabolism of methylprednisolone (CYP3A4) and inhibition of P-glycoprotein. The patient should be monitored when starting methylprednisolone therapy. Dosage adjustment may be required.

04.6 Pregnancy and breastfeeding

Methylprednisolone crosses the placenta and passes into breast milk.

04.7 Effects on ability to drive and use machines

04.8 Undesirable effects

During corticosteroid therapy, especially for intense and prolonged treatments, some of the following effects may occur:

- abnormal distribution of body fat as in the case of lunar facies, obesity and very rarely also a distribution of fat in the vertebral canal (epidural) or in the thoracic cavity (epicardial, mediastinal); weight gain.

- sodium retention and accumulation of water in the tissues, increased potassium excretion with possible hypokalaemia, increased pulmonary congestion in heart attack patients, hypertension.

- alteration in the secretion of sex hormones (possible amenorrhea, increased hair growth, decreased sexual potency); inactivation or atrophy of corticoadrenal activity, growth retardation in children.

- increased blood sugar, steroid diabetes, changes in the serum fraction of lipids.

- rupture of the tendon (Achilles tendon), especially in patients with metabolic disorders such as: uremia or diabetes mellitus.

- muscle weakness.

- worsening of muscle weakness and severe myasthenic crises can occur in patients with myasthenia gravis. Acute myopathies can be aggravated by the use of non-depolarizing relaxants.

- development of gastric and duodenal ulcers; gastric and duodenal perforations, with peritonitis.

- blood diseases, delays in the healing process, increase in protein metabolism accompanied by the "increase in" urea.

- skin changes (atrophy, striae, acne and bleeding).

- in rare cases, hypersensitivity reactions and skin rash may occur. Hypersensitivity reactions include shock which may arise after parenteral administration and particularly in patients with bronchial asthma or who have undergone a kidney transplant.

- decreased immune response and increased risk of infections. Some viral diseases such as: chickenpox, herpes simplex and shingles can become serious.

- cerebral convulsions, increased intracranial pressure with papilloedema (pseudotumor cerebri), development or aggravation of mental disorders such as: euphoria, mood swings, personality change, severe depression, psychosis, dizziness, headache and sleep disturbances .

- leukocytosis (initially, it returns to normal during therapy), tendency to thrombocytosis, increased risk of thrombosis.

- clouding of the lens, increased intraocular pressure, chorioretinopathy (see section 4.4).

Reporting of suspected adverse reactions.

Reporting of suspected adverse reactions occurring after authorization of the medicinal product is important as it allows continuous monitoring of the benefit / risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system. "Italian Medicines Agency, website: www.agenziafarmaco.gov.it/it/responsabili.

04.9 Overdose

There are no known cases of acute intoxication. However, if necessary, gastric lavage should be performed and any symptoms checked.

05.0 PHARMACOLOGICAL PROPERTIES

05.1 Pharmacodynamic properties

Pharmacotherapeutic group: systemic corticosteroids, glucocorticoids.

ATC code: H02AB04.

Mechanism of action:

Methylprednisolone has a dose-dependent influence on the metabolism in almost all tissues; in the physiological range of concentration, these effects are essential to maintain the body's homeostasis at rest and under stressful conditions and also to regulate the immune system. .

Replacement therapy:

Physiological doses of methylprednisolone replace the endogenous cortisol in case of adrenocortical dysfunction; at these doses there is also an influence on the metabolism of carbohydrates, proteins and lipids. 8 mg of methylprednisolone is equivalent to 40 mg of cortisol. Given the almost total absence of mineralocorticoid effects of methylprednisolone, a mineralocorticoid must be administered simultaneously in replacement therapies when there is a total block of adrenocorticotropic functions.

When it is necessary to administer high doses of Urbason in replacement therapy, methylprednisolone has a rapid anti-inflammatory effect and a delayed immunosuppressive effect.

It inhibits chemotaxis and the activity of cells of the immune system as well as the release and effects of mediators of immune reactions, for example the lysosomal enzyme and leukotrienes. In bronchial obstruction the effects of beta-mimetic bronchodilators are enhanced.

Long and high-dose therapies induce a reduction in the function of the immune system and the cortical part of the adrenal gland.

The mineralotropic effects of methylprednisolone are very limited.

Effects on obstructive airway pathologies:

The effect of methylprednisolone in these pathologies is completely attributable to its ability to inhibit inflammatory processes, to the suppression or prevention of mucosal edema, to the inhibition of bronchoconstriction, to the inhibition or limitation of mucus production and also to the reduction of viscosity of the mucus itself. These effects are based on the following mechanism: membrane stabilization, improvement of the bronchial muscle response to sympathomimetic b2, reduction of type I reactions after one week of therapy.

Duration of effects:

The duration of the effect is higher than the residence time in the serum; in fact the effect persists for intermediate doses, from 12 to 36 hours following oral or intravenous administration.

05.2 Pharmacokinetic properties

After oral administration of Urbason the peak serum concentration of methylprednisolone is reached within 1.5 hours and t½ is approximately 2/3 hours. 77% of the drug is bound to proteins, regardless of the dosage. The binding occurs with albumin and not with transcortin.

Methylprednisolone is metabolised mostly in the liver, the metabolites (11-keto and 20 hydroxy derivatives) are inactive as hormones and excreted primarily via the kidney (approximately 85% of the administered dose appears in the urine within 10 hours and approximately 10% in faeces.) Following oral administration of Urbason, less than 10% of methylprednisolone is excreted unchanged.

05.3 Preclinical safety data

Acute toxicity:

The LD50 of oral methylprednisolone is greater than 40 mg / kg in dogs while in rats it is greater than 4000 mg / kg of body weight.

Chronic toxicity:

The following pharmacodynamic effects have been observed in animal studies: polycythemia, lymphopenia, atrophy of the thymus and cortical part of the adrenal gland and increased hepatic storage of glycogen.

Chronic treatments with high doses (3-10 mg / kg of body weight per day) induce the reduction of the immune response, reduce the activity of the bone marrow, cause the atrophy of the skeletal muscles, affect the weight of the testicles and ovaries ( dogs: reduced testicular weights, rat: increased testicular and ovarian weights) and decreased weight of the prostate (dog) and spermatocyst (rat), polydipsia, diarrhea and worsening of general conditions.

Carcinogenesis

There are no long-term animal studies regarding the carcinogenic effects of methylprednisolone.

Mutagenesis

The mutagenicity of methylprednisolone has not been fully investigated. The AMES test is negative.

06.0 PHARMACEUTICAL INFORMATION

06.1 Excipients

URBASON 4 mg tablets

lactose, corn starch, talc, colloidal silicon dioxide and magnesium stearate.

URBASON 8 mg prolonged-release tablets

corn starch, lactose, talc, magnesium stearate, sucrose, gum arabic, gelatin, liquid glucose, calcium carbonate, glycerin, methacrylic acid copolymer, triethyl citrate, E 127, E 110, polyethylene glycol 6000.

URBASON 4 mg prolonged-release tablets