Active ingredients: Methylprednisolone
MEDROL 4 mg tablets
MEDROL 16 mg tablets
Why is Medrol used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Unassociated systemic corticosteroids, glucocorticoids.
THERAPEUTIC INDICATIONS
Endocrine Disorders
Primary or secondary adrenal insufficiency (hydrocortisone or cortisone are the first choice drugs; synthetic analogues can be used in combination with mineralocorticoids when possible; in childhood, integration with mineralocorticoids is of particular importance). Adrenal hyperplasia congenital Hypercalcemia associated with neoplasms Non-suppurative thyroiditis.
Rheumatological pathologies
Short-term administration as additive therapy (to help the patient overcome an acute episode or exacerbation) in the following conditions: psoriatic arthritis; rheumatoid arthritis (special cases may require low-dose maintenance therapy); acute nonspecific tenosynovitis; ankylosing spondylitis; acute and subacute bursitis; acute gouty arthritis.
Collagenopathies
During an exacerbation or as maintenance therapy in special cases of: lupus erythematosus sistemicus; acute rheumatic carditis.
Dermatological pathologies
Pemphigus. Exfoliative dermatitis. Herpetiform dermatitis. Mycosis fungoides. Severe erythema multiforme (Stevens-Johnson syndrome). Severe psoriasis.
Allergic states
To control severe or debilitating allergic conditions that cannot be treated conventionally: seasonal or perennial allergic rhinitis; contact dermatitis, atopic dermatitis; bronchial asthma; serum sickness; angioneurotic edema; urticaria.
Ophthalmic disorders
Chronic and acute, severe inflammatory and allergic processes involving the eye and its appendages, such as: allergic corneal marginal ulcers; allergic conjunctivitis; ophthalmic herpes zoster; keratitis; anterior segment inflammation; chorioretinitis; diffuse posterior uveitis and choroiditis; neuritis optic; iritis and iridocyclitis; sympathetic ophthalmia.
Respiratory pathologies
Sarcoidosis. Loeffler syndrome not treatable with other therapeutic means. Berylliosis. Diffuse or fulminant pulmonary tuberculosis under appropriate antituberculous chemotherapy coverage.
Haematological disorders
Idiopathic and secondary thrombocytopenia in adults. Acquired (autoimmune) haemolytic anemia. Erythroblastopenia. Congenital hypoplastic anemia (erythroid).
Neoplastic pathologies
As palliative therapy in: leukemias and lymphomas in adults; acute leukemia of childhood.
Edematous states
To induce diuresis or remission of proteinuria in nephrotic syndrome, without uremia, of an idiopathic or lupus erythematosus nature.
Various affections
Tuberculous meningitis with active or latent subarachnoid block under antituberculous chemotherapy coverage. Systemic dermatomyositis (polymyositis). Medrol is also applied in case of:
a) Respiratory affections: pulmonary emphysema, in cases where bronchial edema or bronchospasm play a significant role. Diffuse interstitial pulmonary fibrosis (Hamman-Rich syndrome)
b) Edematous states: in association with diuretics to induce diuresis in case of: liver cirrhosis with ascites, congestive heart failure.
c) Gastrointestinal affections: as an adjuvant in the treatment of ulcerative colitis, intractable sprue, regional enteritis.
Contraindications When Medrol should not be used
Hypersensitivity to the active substance or to any of the excipients. Systemic fungal infections.
Administration of live or live attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids.
Precautions for use What you need to know before taking Medrol
Immunosuppressive effects / Increased susceptibility to infections
Corticosteroids can increase susceptibility to infections, mask some signs of infection and during their use new infections can appear: evaluate the opportunity to establish an adequate antibiotic therapy.
Decreased resistance and inability to localize infection during treatment with corticosteroids may occur during corticosteroid use. Infections caused by any pathogen, including viral, bacterial, fungal or protozoal or helminth infections, located anywhere in the body may be associated with the use of corticosteroids alone or in combination with other immunosuppressive agents that affect the " cellular and humoral immunity and on neutrophilic function. These infections can be mild, but also severe and in some cases fatal. As the dose of corticosteroids increases, the incidence of infections increases.
People treated with immunosuppressive drugs are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in non-immune children or adults undergoing corticosteroid therapy.
Patients should not be vaccinated against smallpox during corticosteroid treatment. Do not perform other immunization procedures in patients on corticosteroid therapy, especially at high doses, due to the possible risks of neurological complications and a decreased antibody response.
Administration of live or attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids. Dead or inactive vaccines can be given to patients receiving immunosuppressive doses of corticosteroids, although the response to these vaccines may be diminished. Special immunization procedures may be undertaken in patients receiving non-immunosuppressive doses of corticosteroids.
The use of corticosteroids in active tuberculosis should be limited to cases of fulminant or disseminated disease in which the corticosteroid is used to treat the condition under an appropriate antituberculous regimen. If corticosteroids are administered to patients with latent tuberculosis or a positive response to tuberculin, close observation is required as reactivation of the disease may occur.
During prolonged corticosteroid therapy, these patients should undergo chemoprophylaxis.
Cases of Kaposi's sarcoma have occurred in patients treated with corticosteroids. Discontinuation of treatment could lead to regression of the disease.
Immune system
Allergic reactions may occur, eg. angioedema. Since rare cases of skin reactions and anaphylactic / anaphylactoid reactions have occurred in patients receiving corticosteroids, adequate precautionary measures should be observed prior to administration, especially in the case of patients with a history of allergy to any drug.
Endocrine system
In patients on corticosteroid therapy subject to particular stress, a higher dosage of fast-acting corticosteroids is indicated before, during and after the stressful event.
Drug doses of corticosteroids administered for prolonged periods can lead to suppression of the hypothalamic-pituitary-adrenal (HPA) system (secondary adrenocortical insufficiency). The degree and duration of secondary adrenocortical insufficiency is variable in patients and depends on the dose, frequency, time of administration and duration of glucocorticoid therapy. In addition, abrupt discontinuation of glucocorticoid treatment may lead to acute adrenocortical insufficiency with an fatal outcome. Drug-induced adrenocortical insufficiency can be minimized by a gradual reduction in dosage. This type of relative insufficiency can persist for months after discontinuation of therapy; therefore in any stressful situation that occurs during this period, a suitable hormonal therapy must be adopted. Since the mineralocorticoid secretion can be altered, administer salts and / or mineralocorticoids in combination.
A steroid withdrawal syndrome, apparently unrelated to adrenal insufficiency, may also occur following abrupt discontinuation of glucocorticoids. This syndrome presents with symptoms such as: anorexia, nausea, vomiting, lethargy, headache, fever, joint pain, scaling, myalgia, weight loss and / or hypotension. These effects are believed to be due to the sudden change in glucocorticoid concentration rather than low glucocorticoid levels.
Since glucocorticoids can cause or aggravate Cushing's syndrome, their administration should be avoided in patients with Cushing's disease. In hypothyroid patients, there is an enhancement of the effects of corticosteroids. During therapy it is suggested to gradually reduce the dosage in order to find the lowest maintenance dose.
Metabolism and nutrition
Corticosteroids, including methylprednisolone, can increase blood glucose levels, worsen pre-existing diabetes and predispose patients on prolonged corticosteroid therapy to diabetes mellitus.
Psychiatric disorders
Corticosteroids can cause psychiatric disorders such as: euphoria, insomnia, mood swings, personality changes, severe depression up to obvious psychotic manifestations. In addition, pre-existing emotional instability or psychotic tendencies can be aggravated by corticosteroids. Steroids for systemic use can cause potentially severe psychological adverse reactions (See section Undesirable effects). Symptoms typically occur within days or weeks of starting treatment. Most reactions regress with dose reduction or discontinuation of treatment, although specific treatments may be required. Psychological effects have occurred following discontinuation of corticosteroid therapy, but the frequency of these effects is unknown. .
Patients and family members should seek medical advice if the patient exhibits psychological symptoms especially if depression and suicidal thoughts are suspected.
Patients and family members should be informed of possible psychiatric disorders that may occur during or immediately after tapering the dose or after steroid discontinuation.
Nervous system
Corticosteroids should be used with caution in patients with myasthenia gravis (see also Musculoskeletal system section) and in patients with seizures.
Controlled clinical trials have demonstrated the efficacy of corticosteroids in accelerating the resolution of multiple sclerosis exacerbations, but show no effect on the final outcome or natural history of the disease.Studies have shown that relatively high doses of corticosteroids are required to demonstrate a significant effect (see section DOSE, METHOD AND TIME OF ADMINISTRATION). Cases of epidural lipomatosis have been reported in patients taking corticosteroids, usually following prolonged use at high doses.
Ocular effects
Prolonged use of corticosteroids can produce posterior subcapsular cataracts and nuclear cataracts (particularly in children), exophthalmos, or increased intraocular pressure, which can generate glaucoma with possible damage to the optic nerve. Fungal infections can stabilize in patients treated with glucocorticoids. or secondary viral of the eye. Systemic corticosteroids should be used with caution in patients with ocular herpes simplex due to the risk of corneal perforation. Corticosteroid therapy has been associated with central serous chorioretinopathy, which can lead to retinal detachment.
Effects on the cardiovascular system
When high doses are used for long periods in patients with cardiovascular risk factors, adverse events of glucocorticoids on the cardiovascular system, such as dyslipidemia and hypertension, may predispose to further cardiovascular effects. Therefore, corticosteroids should be used with caution. in such patients, paying attention to risk modification and increasing cardiac monitoring if necessary. Use of low doses and administration every other day may reduce the incidence of complications of corticosteroid therapy.
Systemic corticosteroids should be used with caution, and only if strictly necessary, in cases of congestive heart failure. Steroids should be used with caution in hypertension.
Gastrointestinal and hepatobiliary system
There is no universal agreement on whether corticosteroids are directly responsible for peptic ulcers that occur during therapy; however, glucocorticoid therapy can mask the symptoms of peptic ulcer so that bleeding and perforation can occur without significant pain.
The risk of developing gastrointestinal ulcers increases with concomitant use of NSAIDs. Steroids should be used with caution in the following conditions: nonspecific ulcerative colitis, if there is a danger of perforation, abscess or other pyogenic infection; diverticulitis; recent intestinal anastomosis • Active or latent peptic ulcer. In patients with liver cirrhosis the effect of corticosteroids is enhanced.
High doses of corticosteroids can induce acute pancreatitis.
Musculoskeletal system
Acute myopathy has been observed with the use of high doses of corticosteroids, especially in patients with neuromuscular transmission disorders (myasthenia gravis), or in patients receiving concomitant therapy with anticholinergic drugs, such as neuromuscular blockers (pancuronium).
This myopathy is generalized and can involve muscles of the eye and respiratory system causing tetraparesis. Increased creatine kinase may occur. Clinical improvement or recovery following corticosteroid discontinuation may take weeks or years.
Osteoporosis is a common, but not always recognized, side effect associated with prolonged use of high-dose glucocorticoids.
Renal and urinary system
Corticosteroids should be used with caution in patients with renal insufficiency.
Diagnostic tests
Medium or high doses of hydrocortisone and cortisone can cause increased blood pressure, water and salt retention, and increased potassium excretion. These effects are less evident with the use of synthetic derivatives except when used at high doses. A low-salt diet and potassium supplementation may be required. All corticosteroids increase calcium excretion.
Injury, poisoning and procedural complications
High doses of systemic corticosteroids should not be used in cases of traumatic brain injury.
Other
Since the complications of glucocorticoid treatment are related to the dose and duration of therapy, the risk / benefit ratio for each individual patient should be assessed in relation to the dose, duration of therapy and dosing schedule (daily therapy or daily therapy). alternatives) that must be used.
During treatment with corticosteroids, the lowest effective dose should always be used to control the disease being treated, and where it is possible to reduce the dosage it should be done gradually.
Aspirin and non-steroidal anti-inflammatory agents should be used with caution in combination with corticosteroids.
Administration of corticosteroids can reduce or abolish the response to skin tests.
A pheochromocytoma crisis, which can be fatal, has been reported following administration of systemic corticosteroids. In patients with suspected or identified pheochromocytoma, corticosteroids should only be administered after an "appropriate benefit / risk assessment".
Pediatric population
Particular attention must be paid to the growth and development of infants and children undergoing prolonged corticosteroid therapy. Growth retardation may occur in children receiving prolonged daily therapy or divided dose glucocorticoid therapy, and the use of such a regimen should be restricted to the most urgent indications.
During treatment with corticosteroids the lowest effective dose should always be used and dose reduction, if possible, should be gradual.
Infants and children on long-term corticosteroid therapy are at particular risk of increased intracranial pressure.
High doses of corticosteroids can induce pancreatitis in children.
Use in the elderly
Caution is advised with prolonged corticosteroid treatments in the elderly due to a potential increased risk of osteoporosis, as well as an increased risk of fluid retention, possibly resulting in hypertension.
Interactions What medications or foods may change the effect of Medrol
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Methylprednisolone is a substrate of the cytochrome P450 (CYP) enzyme and is primarily metabolised by the CYP3A4 enzyme. The CYP3A4 enzyme is the dominant enzyme of the more abundant CYP subfamily in the adult human liver. This catalyzes the 6β-hydroxylation of steroids, a critical step in phase I metabolism for both synthetic and endogenous corticosteroids. Many others. substances are substrates of CYP3A4, some of which (as well as other medicinal products) have been shown to alter glucocorticoid metabolism by induction (upregulation) or inhibition of the CYP3A4 enzyme.
CYP3A4 inhibitors: Medicinal products that inhibit CYP3A4 activity generally decrease hepatic clearance and increase plasma concentration of CYP3A4 substrate drugs, including methylprednisolone. In the presence of a CYP3A4 inhibitor, the dose of methylprednisolone may need to be titrated to avoid steroid toxicity.
CYP3A4 inducers: Medicinal products that induce CYP3A4 activity generally increase hepatic clearance, resulting in decreased plasma concentrations of CYP3A4 substrate medicinal products, including methylprednisolone. Co-administration may require an increase in methylprednisolone dose to achieve the expected effects.
CYP3A4 substrates: In the presence of another CYP3A4 substrate the hepatic clearance of methylprednisolone may be impaired, resulting in the need for dose adjustment. It is possible that the undesirable effects associated with the use of the single substance are more likely to occur if the drugs are co-administered.
Non-CYP3A4 Dependent Mediation Effects: Other interactions or effects that may occur with methylprednisolone are described in Table 1 below. Table 1 provides a list and description of the most common or clinically important interactions and effects that may occur with methylprednisolone.
Table 1. Effects and interactions of drugs and substances with methylprednisolone
- FENOBARBITAL
- PHENITOIN
Warnings It is important to know that:
Fertility, pregnancy and breastfeeding
Ask your doctor or pharmacist for advice before taking any medicine.
Fertility
There is no evidence of impaired fertility by corticosteroids
Pregnancy
Studies in laboratory animals have shown that corticosteroids, given to mothers in high doses, can induce fetal malformations.
Adequate reproductive studies with the use of corticosteroids have not been conducted in humans, they are not available.
As there is no evidence on the safety of use in pregnancy, this drug should only be used when strictly necessary. Some corticosteroids cross the placenta. A retrospective study has shown an increased incidence of underweight babies born to mothers receiving corticosteroids.
Although adrenal insufficiency appears to be rare in infants exposed to corticosteroids during pregnancy, infants of mothers treated with particularly high doses of corticosteroids during pregnancy should be closely monitored for signs of adrenal insufficiency.
Cases of cataracts have been observed in infants of mothers undergoing long-term corticosteroid treatment during pregnancy.
Effects of corticosteroids during labor or delivery are unknown.
Feeding time
Corticosteroids are excreted in breast milk. Corticosteroids in breast milk can retard growth and interfere with the production of endogenous glucocorticoids in infants.
Since adequate human reproductivity studies are not available for the use of glucocorticoids, this drug should only be given to nursing mothers if the benefit of therapy outweighs the potential risk to the baby.
In pregnant women and in women who are breastfeeding the medicine must be administered in cases of real need under the direct supervision of the doctor.
Effects on ability to drive and use machines
Should euphoria and mood disturbances occur with the use of glucocorticoids, such activities should be avoided. The effect of corticosteroids on the ability to drive and use machines has not been systematically evaluated.
After treatment with corticosteroids, side effects such as dizziness, vertigo, visual disturbances and fatigue may occur. If affected, patients should not drive or operate machinery.
Important information about some of the ingredients
If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicinal product
For those who carry out sporting activities
For those who carry out sporting activities: the use of the drug without therapeutic necessity constitutes doping and can in any case determine positive anti-doping tests.
Dosage and method of use How to use Medrol: Dosage
The starting dosage of Medrol (Methylprednisolone) can range from 4 to 48 mg per day depending on the severity of the disease. The initial dosage should be maintained or adjusted until a satisfactory response is noted. If after a reasonable period of time the clinical response is unsatisfactory, Medrol should be discontinued and the patient re-initiated.
It should be emphasized that dosage needs are variable and must be individualized on the basis of the disease being treated and on the basis of the patient's response.
Following a favorable response, it is necessary to determine an appropriate maintenance dosage by decreasing the initial dosage of the drug with small decreases at appropriate intervals until the minimum effective dosage is reached to maintain an adequate clinical response.
It must be remembered that constant monitoring and adjustment of the drug dosage is necessary. Situations that may require dosage adjustments include changes in secondary clinical status with remissions or worsening of the disease process, individual drug response, the effect of patient exposure to stressful situations not directly related to the extent of the disease. disease being treated; in this latter situation it may be necessary to increase the dosage of Medrol for a period of time according to the patient's condition. rather than abrupt.
Overdose What to do if you have taken too much Medrol
There are no corticosteroid overdose syndromes. In case of acute overdose, cardiac arrhythmias and / or cardiovascular collapse may occur. Cases of acute toxicity and / or death from corticosteroid overdose are rare. There are no specific antidotes for corticosteroid overdose; the treatment is supportive and symptomatic.
Methylprednisolone is hemodialysable.
In case of accidental ingestion / intake of an overdose of Medrol, notify your doctor or pharmacist immediately.
If you have any questions about the use of Medrol, ask your doctor and pharmacist.
Side Effects What are the side effects of Medrol
Like all medicines, Medrol can cause side effects, although not everybody gets them.
The onset of undesirable effects is related to the dosage and duration of treatment, it is therefore necessary to carefully evaluate these factors in each individual patient. During therapy with methylprednisolone, especially if intense and prolonged, the following undesirable effects have been reported with the following frequencies: very common (≥1 / 10); common (≥1 / 100,
Infections and infestations:
common: infections
not known: opportunistic infections.
Immune system disorders:
not known: drug hypersensitivity (including anaphylactic and anaphylactoid reaction), suppression of reactions to skin tests.
Metabolism and nutrition disorders:
common: sodium retention, fluid retention
not known: hypokalemic alkalosis, metabolic acidosis, impaired glucose tolerance, increased appetite (which may result in weight gain), increased need for insulin or hypoglycemic agents in diabetics.
Decreased tolerability to carbohydrates and possible manifestation of latent diabetes mellitus as well as increased need for hypoglycemic drugs in diabetics.
Cardiac disorders:
not known: Alterations of the hydroelectrolytic balance which in rare cases and in predisposed patients can lead to hypertension and congestive heart failure.
Vascular disorders:
common: hypertension
not known: hypotension.
Respiratory, thoracic and mediastinal disorders:
not known: hiccups
Musculoskeletal and connective tissue disorders:
common: muscle weakness, growth retardation
not known: arthralgia, muscle atrophy, myalgia, osteoporosis, neuropathic arthropathy, osteonecrosis, myopathy, pathological fractures.
Gastrointestinal disorders:
common: complications affecting the gastrointestinal tract which can lead to the appearance or activation of a peptic ulcer (with possible peptic ulcer with perforation and hemorrhagic peptic ulcer)
not known: abdominal distension, abdominal pain, diarrhea, dyspepsia, gastric haemorrhage, intestinal perforation, nausea, oesophagitis, ulcerative oesophagitis, pancreatitis.
Skin and subcutaneous tissue disorders:
common: acne, skin atrophy
not known: angioedema, ecchymosis, erythema, hirsutism, hyperhidrosis, petechiae, pruritus, skin rash and striae, urticaria.
Reproductive system and breast disorders:
not known: menstrual irregularity.
Nervous system disorders:
not known: amnesia, cognitive disorders, convulsions, dizziness, headache and increased intracranial pressure (with papilledema benign intracranial hypertension), epidural lipomatosis.
Psychiatric disorders:
common: affective disorders (including depressed mood, euphoria)
not known: psychotic disorders (including mania, delirium, hallucination and aggravation of schizophrenia) psychotic behavior, affective disorders (including affective lability, psychological dependence, suicidal thoughts), mental disorder, personality changes, mood swings, confusion, anxiety , abnormal behavior, insomnia, irritability.
Endocrine disorders:
common: Cushingoid-like appearance
not known: hypopituitarism, steroid withdrawal syndrome. Interference with the function of the pituitary-adrenal axis, particularly in times of stress. Changes in growth in children.
Eye disorders:
common: subcapsular cataract
not known: exophthalmos, glaucoma, central serous chorioretinopathy
Ear and labyrinth disorders:
not known: dizziness
General disorders and administration site conditions:
common: delays in healing processes
not known: tiredness, malaise
Diagnostic tests:
common: decreased levels of potassium in the blood
not known: increased alanine aminotransferase, increased aspartate aminotransferase, increased blood alkaline phosphatase, decreased tolerance to carbohydrates, increased intraocular pressure, increased urine calcium levels. Negativization of the nitrogen balance.
Injury, poisoning and procedural complications:
not known: spinal compression fractures, tendon rupture (especially the Achilles tendon).
Compliance with the instructions contained in the package leaflet reduces the risk of undesirable effects.
Reporting of suspected adverse reactions
If you get any side effects, talk to your doctor or pharmacist. This includes any possible side effects not listed in this leaflet. Side effects can also be reported directly via the national reporting system at https://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects you can help provide more information on safety of this medicine
Expiry and Retention
Expiry: see the expiry date printed on the package.
The expiry date refers to the product in intact and correctly stored packaging. Warning: do not use the medicine after the expiry date shown on the package.
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.
KEEP THIS MEDICINAL PRODUCT OUT OF THE SIGHT AND REACH OF CHILDREN.
Composition and pharmaceutical form
COMPOSITION
Each 4 mg tablet contains: 4 mg methylprednisolone.
Excipients: lactose, corn starch, dried corn starch, sucrose, calcium stearate.
Each 16 mg tablet contains: 16 mg methylprednisolone.
Excipients: lactose monohydrate; sucrose; liquid paraffin; calcium stearate; cornstarch.
PHARMACEUTICAL FORM AND CONTENT
10-30 tablets of 4 mg
20 tablets of 16 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.
01.0 NAME OF THE MEDICINAL PRODUCT
MEDROL
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
One 4 mg tablet contains: methylprednisolone 4 mg.
One 16 mg tablet contains: methylprednisolone 16 mg.
Excipients with known effects:
Medrol 4 mg: lactose, sucrose
Medrol 16 mg: lactose monohydrate, sucrose.
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Tablets for oral use.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
Endocrine Disorders
Primary or secondary adrenal insufficiency (hydrocortisone or cortisone are the drugs of first choice; synthetic analogues can be used in combination with mineralocorticoids when possible; in childhood integration with mineralocorticoids is of particular importance).
• Congenital adrenal hyperplasia.
• Hypercalcemia associated with cancer.
• Non-suppurative thyroiditis.
Rheumatological pathologies
Short-term administration as additive therapy (to help the patient overcome an acute episode or exacerbation) under the following conditions:
• Psoriatic arthritis;
• Rheumatoid arthritis (special cases may require low dose maintenance therapy);
• Acute nonspecific tenosynovitis.
• Ankylosing spondylitis.
• Acute and subacute bursitis.
• Acute gouty arthritis.
Collagenopathies
During an exacerbation or as maintenance therapy in special cases of:
• Systemic lupus erythematosus.
• Acute rheumatic carditis.
Dermatological pathologies
• Pemphigus.
• Exfoliative dermatitis.
• Herpetiform dermatitis.
• Mycosis fungoides.
• Severe Erythema Multiforme (Stevens-Johnson Syndrome).
• Severe psoriasis.
Allergic states
To control severe or debilitating allergic conditions that cannot be treated conventionally:
• seasonal or perennial allergic rhinitis;
• contact dermatitis, atopic dermatitis;
• bronchial asthma;
• serum sickness;
• angioneurotic edema;
• hives.
Ophthalmic disorders
Chronic and acute, severe inflammatory and allergic processes involving the eye and its appendages, such as:
• allergic corneal marginal ulcers;
• allergic conjunctivitis;
• ophthalmic herpes zoster;
• keratitis;
• inflammation of the anterior segment;
• chorioretinitis;
• diffuse posterior uveitis and choroiditis;
• optic neuritis; iritis and iridocyclitis;
• sympathetic ophthalmia.
Respiratory pathologies
• Sarcoidosis.
• Loeffler's syndrome not treatable with other therapeutic means.
• Berylliosis.
• Diffuse or fulminant pulmonary tuberculosis under appropriate antituberculous chemotherapy coverage.
Haematological disorders
• Idiopathic and secondary thrombocytopenia in adults.
• Acquired (autoimmune) haemolytic anemia.
• Erythroblastopenia.
• Congenital hypoplastic anemia (erythroid).
Neoplastic pathologies
As palliative therapy in:
• leukemias and lymphomas in adults;
• acute childhood leukemia.
Edematous states
To induce diuresis or remission of proteinuria in nephrotic syndrome, without uremia, of an idiopathic or lupus erythematosus nature.
Various affections
• Tuberculous meningitis with active or latent subarachnoid block under antituberculous chemotherapy coverage.
• Systemic dermatomyositis (polymyositis).
MEDROL is also applied in case of:
to) Respiratory diseases:
pulmonary emphysema, in cases where bronchial edema or bronchospasm play a significant role.
Diffuse interstitial pulmonary fibrosis (Hamman-Rich syndrome)
b) Edematous states:
in combination with diuretics to induce diuresis in case of:
cirrhosis of the liver with ascites, congestive heart failure.
c) Gastrointestinal diseases:
as an adjuvant in the treatment of ulcerative colitis, intractable sprue, regional enteritis.
04.2 Posology and method of administration
Dosage
The starting dosage of MEDROL (Methylprednisolone) can range from 4 to 48 mg per day depending on the severity of the disease. The initial dosage should be maintained or adjusted until a satisfactory response is noted.
If after a reasonable period of time the clinical response is unsatisfactory, MEDROL should be discontinued and the patient re-initiated.
It should be emphasized that dosage needs are variable and must be individualized on the basis of the disease being treated and on the basis of the patient's response.
Following a favorable response, it is necessary to determine an appropriate maintenance dosage by decreasing the initial dosage of the drug with small decreases at appropriate intervals until the minimum effective dosage is reached to maintain an adequate clinical response. constant control and adaptation of drug dosage.
Situations that may require dosage adjustments include changes in the clinical status secondary to remission or aggravation of the disease process, individual response to the drug, the effect of patient exposure to stressful situations not directly related to the extent of the disease in progress. treatment; in this latter situation it may be necessary to increase the dosage of MEDROL for a period of time according to the patient's condition. If drug administration is to be discontinued after long-term therapy, gradual rather than abrupt tapering is recommended.
04.3 Contraindications
• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
• Systemic fungal infections.
Administration of live or live attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids.
04.4 Special warnings and appropriate precautions for use
Immunosuppressive effects / Increased susceptibility to infections
Corticosteroids can increase susceptibility to infections, mask some signs of infection and during their use new infections can appear: evaluate the opportunity to establish an adequate antibiotic therapy.
Decreased resistance and inability to localize infection during treatment with corticosteroids may occur during corticosteroid use. Infections caused by any pathogen, including viral, bacterial, fungal or protozoal or helminth infections, located anywhere in the body may be associated with the use of corticosteroids alone or in combination with other immunosuppressive agents that affect the " cellular and humoral immunity and on neutrophilic function. These infections can be mild, but also severe and in some cases fatal. As the dose of corticosteroids increases, the incidence rate of infections increases.
People treated with immunosuppressive drugs are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in non-immune children or adults undergoing corticosteroid therapy.
Patients should not be vaccinated against smallpox during corticosteroid treatment. Do not perform other immunization procedures in patients on corticosteroid therapy, especially at high doses, due to the possible risks of neurological complications and a decreased antibody response.
Administration of live or attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids. Dead or inactive vaccines can be given to patients receiving immunosuppressive doses of corticosteroids, although the response to these vaccines may be diminished. Special immunization procedures may be undertaken in patients receiving non-immunosuppressive doses of corticosteroids.
The use of corticosteroids in active tuberculosis should be limited to cases of fulminant or disseminated disease in which the corticosteroid is used to treat the condition under an appropriate antituberculous regimen.
If corticosteroids are administered to patients with latent tuberculosis or a positive response to tuberculin, close observation is required as reactivation of the disease may occur. During prolonged corticosteroid therapy, these patients should undergo chemoprophylaxis.
Cases of Kaposi's sarcoma have occurred in patients treated with corticosteroids. Discontinuation of treatment could lead to regression of the disease.
Immune system
Allergic reactions may occur, eg. angioedema.
Since rare cases of skin reactions and anaphylactic / anaphylactoid reactions have occurred in patients receiving corticosteroids, adequate precautionary measures should be observed prior to administration, especially in the case of patients with a history of allergy to any drug.
Endocrine system
In patients on corticosteroid therapy subject to particular stress, a higher dosage of fast-acting corticosteroids is indicated before, during and after the stressful event.
Drug doses of corticosteroids administered for prolonged periods can lead to suppression of the hypothalamic-pituitary-adrenal (HPA) system (secondary adrenocortical insufficiency). The degree and duration of secondary adrenocortical insufficiency is variable in patients and depends on the dose, frequency, time of administration and duration of glucocorticoid therapy.
Furthermore, abrupt discontinuation of glucocorticoid treatment can lead to acute adrenocortical insufficiency with a fatal outcome.
Drug-induced adrenocortical insufficiency can be minimized by gradually reducing the dosage. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any stressful situation that arises during this period, a " suitable hormone therapy. Since mineralocorticoid secretion can be impaired, salts and / or mineralocorticoids should be administered in combination.
A "withdrawal syndrome" can also develop following abrupt discontinuation of glucocorticoids. from steroids, apparently unrelated to adrenal insufficiency. This syndrome presents with symptoms such as: anorexia, nausea, vomiting, lethargy, headache, fever, joint pain, scaling, myalgia, weight loss and / or hypotension. These effects are believed to be due to the sudden change in glucocorticoid concentration rather than low glucocorticoid levels.
Since glucocorticoids can cause or aggravate Cushing's syndrome, their administration should be avoided in patients with Cushing's disease.
In hypothyroid patients there is an enhancement of the effects of corticosteroids.
During therapy it is suggested to gradually reduce the dosage in order to find the lowest maintenance dose.
Metabolism and nutrition
Corticosteroids, including methylprednisolone, can increase blood glucose levels, worsen pre-existing diabetes and predispose patients on prolonged corticosteroid therapy to diabetes mellitus.
Psychiatric disorders
Corticosteroids can cause psychiatric disorders such as: euphoria, insomnia, mood swings, personality changes, severe depression up to obvious psychotic manifestations. In addition, pre-existing emotional instability or psychotic tendencies can be aggravated by corticosteroids.
Steroids for systemic use can cause potentially severe psychiatric adverse reactions (see section 4.8). Symptoms typically occur within days to weeks of starting treatment. Most reactions subside with dose reduction or discontinuation, although specific treatments may be required.
Psychological effects have occurred following discontinuation of corticosteroid therapy, but the frequency of these effects is unknown.
Patients and family members should seek medical advice if the patient exhibits psychological symptoms especially if depression and suicidal thoughts are suspected.
Patients and family members should be informed of possible psychiatric disorders that may occur during or immediately after tapering the dose or after steroid discontinuation.
Nervous system
Corticosteroids should be used with caution in patients with myasthenia gravis (see also section Musculoskeletal effects) and in patients with seizures.
Controlled clinical trials have demonstrated the efficacy of corticosteroids in accelerating the resolution of MS exacerbations, but show no effect on the final outcome or natural history of the disease. Studies have shown that doses are required to demonstrate a significant effect. relatively high corticosteroids (see section 4.2).
Cases of epidural lipomatosis have been reported in patients taking corticosteroids, usually following prolonged use at high doses.
Ocular effects
Prolonged use of corticosteroids can produce posterior subcapsular cataracts and nuclear cataracts (particularly in children), exophthalmos, or increased intraocular pressure, which can generate glaucoma with possible damage to the optic nerve.
In patients treated with glucocorticoids, secondary fungal or viral infections of the eye may stabilize.
Systemic corticosteroids should be used with caution in patients with ocular herpes simplex due to the risk of corneal perforation.
Corticosteroid therapy has been associated with central serous chorioretinopathy, which can lead to retinal detachment.
Effects on the cardiovascular system
When high doses are used for long periods in patients with cardiovascular risk factors, adverse events of glucocorticoids on the cardiovascular system, such as dyslipidemia and hypertension, may predispose to further cardiovascular effects. Therefore, corticosteroids should be used with caution. in such patients, paying attention to risk modification and increasing cardiac monitoring if necessary. Use of low doses and administration every other day may reduce the incidence of complications of corticosteroid therapy.
Systemic corticosteroids should be used with caution, and only if strictly necessary, in cases of congestive heart failure.
Steroids should be used with caution in hypertension.
Gastrointestinal and hepatobiliary system
There is no universal agreement on whether corticosteroids are directly responsible for the peptic ulcers that occur during therapy; however, glucocorticoid therapy can mask the symptoms of the peptic ulcer so that bleeding and perforation can occur without significant pain. The risk of developing gastrointestinal ulcers increases with concomitant use of NSAIDs.
Steroids should be used with caution in the following conditions: nonspecific ulcerative colitis, if there is a danger of perforation, abscess or other pyogenic infection; diverticulitis; recent intestinal anastomoses; active or latent peptic ulcer.
In patients with liver cirrhosis the effect of corticosteroids is enhanced.
High doses of corticosteroids can induce acute pancreatitis.
Musculoskeletal system
Acute myopathy has been observed with the use of high doses of corticosteroids, especially in patients with neuromuscular transmission disorders (myasthenia gravis), or in patients receiving concomitant therapy with anticholinergic drugs, such as neuromuscular blockers (pancuronium) (see Effects on the system This myopathy is generalized and may involve eye and respiratory muscles causing tetraparesis. Creatine kinase elevation may occur. Clinical improvement or healing following corticosteroid discontinuation may take weeks or years.
Osteoporosis is a common, but not always recognized, side effect associated with prolonged use of high-dose glucocorticoids.
Renal and urinary system
Corticosteroids should be used with caution in patients with renal insufficiency.
Diagnostic tests
Medium or high doses of hydrocortisone and cortisone can cause increased blood pressure, water and electrolyte retention, and increased potassium excretion. Such effects are less likely with the use of synthetic derivatives except when used in high doses. Dietary restrictions on salt and potassium supplementation may be necessary. All corticosteroids increase calcium excretion.
Injury, poisoning and procedural complications
High doses of systemic corticosteroids should not be used in cases of traumatic brain injury.
Other
Since the complications due to glucocorticoid treatment are related to the dose and duration of therapy, the risk / benefit ratio should be evaluated for each individual patient in relation to the dose, duration of therapy and dosing schedule (daily therapy or daily therapy). alternatives) that must be used.
During treatment with corticosteroids, the lowest effective dose should always be used to control the disease being treated, and where it is possible to reduce the dosage it should be done gradually.
Aspirin and non-steroidal anti-inflammatory agents should be used with caution in combination with corticosteroids.
Administration of corticosteroids can reduce or abolish the response to skin tests.
A pheochromocytoma crisis, which can be fatal, has been reported following administration of systemic corticosteroids. In patients with suspected or identified pheochromocytoma, corticosteroids should only be administered after an "appropriate benefit / risk assessment".
Pediatric population
Particular attention must be paid to the growth and development of infants and children undergoing prolonged corticosteroid therapy.
Growth retardation may occur in children receiving prolonged daily therapy or divided dose glucocorticoid therapy, and the use of such a regimen should be restricted to the most urgent indications.
Infants and children on long-term corticosteroid therapy are at particular risk of increased intracranial pressure.
High doses of corticosteroids can induce pancreatitis in children.
Use in the elderly
Caution is advised with prolonged corticosteroid treatments in the elderly due to a potential increased risk of osteoporosis, as well as an increased risk of fluid retention, possibly resulting in hypertension.
Important information about some of the ingredients
This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose-galactose malabsorption should not take this medicine.
This medicinal product contains sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption and sucrase isomaltase insufficiency should not take this medicine.
04.5 Interactions with other medicinal products and other forms of interaction
Methylprednisolone is a substrate of the cytochrome P450 (CYP) enzyme and is primarily metabolised by the CYP3A4 enzyme. The CYP3A4 enzyme is the dominant enzyme of the more abundant CYP subfamily in the adult human liver. This catalyzes the 6β-hydroxylation of steroids, a critical step in phase I metabolism for both synthetic and endogenous corticosteroids. Many others. substances are substrates of CYP3A4, some of which (as well as other medicinal products) have been shown to alter glucocorticoid metabolism by induction (up-regulation) or inhibition of the CYP3A4 enzyme.
CYP3A4 inhibitors: Medicinal products that inhibit CYP3A4 activity generally decrease hepatic clearance and increase plasma concentration of CYP3A4 substrate drugs, including methylprednisolone. In the presence of a CYP3A4 inhibitor, the dose of methylprednisolone may need to be titrated to avoid steroid toxicity.
CYP3A4 inducers: Medicinal products that induce CYP3A4 activity generally increase hepatic clearance, resulting in decreased plasma concentrations of CYP3A4 substrate medicinal products, including methylprednisolone. Co-administration may require an increase in methylprednisolone dose to achieve the expected effects.
CYP3A4 substrates: In the presence of another CYP3A4 substrate the hepatic clearance of methylprednisolone may be impaired, resulting in the need for dose adjustment. It is possible that the undesirable effects associated with the use of the single substance are more likely to occur if the drugs are co-administered.
Non-CYP3A4 Dependent Mediation Effects: Other interactions or effects that may occur with methylprednisolone are described in Table 1 below.
Table 1 provides a list and description of the most common or clinically important interactions and effects that may occur with methylprednisolone.
Table 1. Effects and interactions of drugs and substances with methylprednisolone
04.6 Pregnancy and lactation
Fertility
There is no evidence of impaired fertility by corticosteroids (see section 5.3).
Pregnancy
Studies in laboratory animals have shown that corticosteroids, given to mothers in high doses, can induce fetal malformations (see section 5.3).
Adequate reproductive studies with the use of corticosteroids have not been conducted in humans.
As there is no evidence on the safety of use in pregnancy, this drug should only be used if strictly necessary. Some corticosteroids cross the placenta. A retrospective study has shown an increase in the incidence of low birth weight in infants born to mothers treated with corticosteroids. Although adrenal insufficiency appears to be rare in infants exposed to corticosteroids during pregnancy, infants of mothers treated with particularly high doses of corticosteroids during pregnancy should be closely monitored for signs of adrenal insufficiency.
Cases of cataracts have been observed in infants of mothers undergoing long-term corticosteroid treatment during pregnancy.
The effects of corticosteroids during labor or delivery are not known.
Feeding time
Corticosteroids are excreted in breast milk. Corticosteroids in breast milk can retard growth and interfere with the production of endogenous glucocorticoids in infants.
As adequate human reproductivity studies are not available for the use of glucocorticoids, this drug should only be given to nursing mothers if the benefit of therapy outweighs the potential risk to the newborn.
In pregnant women and in women who are breastfeeding the medicine must be administered in cases of real need under the direct supervision of the doctor.
04.7 Effects on ability to drive and use machines
The effect of corticosteroids on the ability to drive and use machines has not been systematically evaluated.
Undesirable effects such as dizziness, vertigo, visual disturbances and fatigue are possible following treatment with corticosteroids. In the presence of such effects, patients should not drive or use machines.
04.8 Undesirable effects
During methylprednisolone therapy, especially if intense and prolonged, the following undesirable effects have been reported with the following frequencies: very common (≥1 / 10);
common (≥1 / 100,
Infections and infestations:
common: infections
not known: opportunistic infections.
Disorders of the immune system:
not known: drug hypersensitivity (including anaphylactic and anaphylactoid reaction), suppression of reactions to skin tests.
Metabolism and nutrition disorders:
common: sodium retention, fluid retention
not known: hypokalemic alkalosis, metabolic acidosis, impaired glucose tolerance, increased appetite (which can result in weight gain), increased need for insulin or hypoglycemic agents in diabetics.
Decreased tolerability to carbohydrates and possible manifestation of latent diabetes mellitus as well as increased need for hypoglycemic drugs in diabetics.
Cardiac pathologies:
not known: alterations in the hydroelectrolytic balance which in rare cases and in predisposed patients can lead to hypertension and congestive heart failure.
Vascular pathologies:
common: hypertension
not known: hypotension.
Respiratory, thoracic and mediastinal disorders:
not known: hiccup
Musculoskeletal and connective tissue disorders:
common: muscle weakness, growth retardation,
not known: arthralgia, muscle atrophy, myalgia, osteoporosis, neuropathic arthropathy, osteonecrosis, myopathy, pathological fractures.
Gastrointestinal disorders:
common. complications affecting the gastrointestinal system that can lead to the appearance or activation of a peptic ulcer (with possible peptic ulcer with perforation and hemorrhagic peptic ulcer)
not known: abdominal distension, abdominal pain, diarrhea, dyspepsia, gastric haemorrhage and intestinal perforation, nausea, oesophagitis, ulcerative oesophagitis, pancreatitis.
Skin and subcutaneous tissue disorders:
common: acne, skin atrophy
not known: angioedema, ecchymosis, erythema, hirsutism, hyperhidrosis, petechiae, pruritus, rash, and skin striae, urticaria.
Diseases of the reproductive system and breast:
not known: menstrual irregularity.
Nervous system disorders:
not known: amnesia, cognitive disorders, convulsions, dizziness, headache and increased intracranial pressure (with papilledema benign intracranial hypertension), epidural lipomatosis.
Psychiatric disorders:
common: emotional disorders (including depressed mood, euphoria)
not known: psychotic disorders (including mania, delirium, hallucination and aggravation of schizophrenia), psychotic behavior, affective disorders (including affective lability, psychological dependence, suicidal thoughts), mental disorder, personality changes, mood swings, confusion, anxiety, abnormal behavior, insomnia, irritability.
Endocrine pathologies:
common: Cushingoid-like appearance.
Not known: hypopituitarism, steroid withdrawal syndrome.
Interference with the functionality of the pituitary-adrenal axis, particularly in times of stress.
Impaired growth in children.
Eye disorders:
common: subcapsular cataract
not known: exophthalmos, glaucoma, central serous chorioretinopathy
Ear and labyrinth disorders:
not known: dizziness
General disorders and administration site conditions:
common: delays in the healing process
not known: tiredness, malaise.
Diagnostic tests:
common: decrease in potassium levels in the blood
not known: increased alanine aminotransferase, increased aspartate aminotransferase, increased blood alkaline phosphatase, decreased tolerance to carbohydrates, increased intraocular pressure, increased urine calcium levels.
Negativization of the nitrogen balance.
Injury, poisoning and procedural complications:
not known: Spinal compression fractures, tendon rupture (especially the Achilles tendon).
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. "address: www.agenziafarmaco.gov.it/it/responsabili.
04.9 Overdose
There are no corticosteroid overdose syndromes. In case of acute overdose, cardiac arrhythmias and / or cardiovascular collapse may occur. Cases of acute toxicity and / or death from corticosteroid overdose are rare. There is no antidote to corticosteroid overdose, the treatment is supportive and symptomatic.
Methylprednisolone is dialyzable.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
MEDROL contains a synthetic glycocorticoid, methylprednisolone, a 6-methyl derivative of prednisolone.
Medicinal product category: non-associated systemic corticosteroids - glucocorticoids.
ATC: H02AB04.
Methylprednisolone is a potent steroid anti-inflammatory. It has greater anti-inflammatory power than prednisolone and induces less sodium and water retention than prednisolone. The relative potency of methylprednisolone compared to hydrocortisone is at least four to one.
Natural glucocorticoids (hydrocortisone and cortisone), which also have salt and water retention properties, are used as replacement therapy in states of adrenocortical insufficiency. Their synthetic analogues are mainly used in many ailments for their powerful anti-inflammatory action. Glycocorticoids induce important and various metabolic effects and also modify the immune responses to various stimuli.
05.2 Pharmacokinetic properties
The pharmacokinetics of methylprednisolone are linear regardless of the route of administration.
Absorption
Methylprednisolone is rapidly absorbed and the maximum plasma concentration is reached approximately 1.5-2.3 hours after oral administration in healthy adult volunteers. The absolute bioavailability of methylprednisolone after oral administration in healthy volunteers is generally high (between 82% and 89%).
Distribution
Methylprednisolone is widely distributed to tissues, crosses the blood brain barrier and is excreted in breast milk. The apparent volume of distribution is approximately 1.4 l / kg. Plasma protein binding of methylprednisolone is approximately 77%.
Metabolism
In humans, methylprednisolone is metabolised in the liver to inactive metabolites, the main ones being 20α-hydroxymethylprednisolone and 20β-hydroxymethylprednisolone.
Hepatic metabolism occurs mainly by the CYP3A4 enzyme (for a list of interactions with substances subject to CYP3A4 mediated metabolism see section 4.5).
Methylprednisolone, as well as other substrates of the CYP3A4 enzyme, may also be a substrate for the p-glycoprotein of the ATP binding cassette (ABC) transporter family, affecting tissue distribution and interactions with other medicinal products.
Elimination
The mean elimination half-life for total methylprednisolone is 1.8 to 5.2 hours. Total clearance is approximately 5-6 mL / min / kg.
Methylprednisolone is mainly excreted via the kidney and bile.
No dosage adjustment is necessary in renal insufficiency; methylprednisolone is haemodialysable.
05.3 Preclinical safety data
No unexpected risks were identified based on conventional safety pharmacology studies for repeated toxic dose administration.
Toxicities observed in repeat dose studies are those expected with continued exposure to exogenous adrenocortical steroids.
Carcinogenic potential
Since the drug is indicated for short-term treatment only, no long-term animal studies have been conducted to evaluate carcinogenic potential.
Mutagenic potential
Limited studies performed in mammalian cells have shown no signs of potential genetic and chromosomal mutations.
Teratogenic toxicity
Reproductive fertility studies in animals have not been performed to specifically assess the potential for impaired fertility. There is no evidence that corticosteroids cause impairment of fertility.
Corticosteroids have been shown to be teratogenic in numerous animal species when administered at doses equivalent to the human dose. In animal reproduction studies glucocorticoids such as methylprednisolone have been shown to induce malformations (cleft palate, genetic malformations, cardiovascular defects, hydrocephalus, encephalocele, central nervous system abnormalities) and to delay intrauterine growth (see section 4.6).
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Tablets 4 mg: lactose, corn starch, dried corn starch, sucrose, calcium stearate.
Tablets 16 mg: lactose monohydrate, sucrose, vaseline oil, calcium stearate, corn starch.
06.2 Incompatibility
While it does not apply to the pharmaceutical form of MEDROL, however, methylprednisolone is incompatible in solution with various drugs. Compatibility in fact depends on various factors such as, for example, the concentration of the drugs, the pH of the solution and the temperature. Therefore it is advisable not to dilute and not to mix methylprednisolone with other solutions.
06.3 Period of validity
60 months.
06.4 Special precautions for storage
This medicinal product does not require any special storage conditions.
06.5 Nature of the immediate packaging and contents of the package
Amber glass bottle containing 10 tablets of 4 mg;
Blister packs of laminated opaque PVC and aluminum:
30 tablets of 4 mg.
20 tablets of 16 mg.
06.6 Instructions for use and handling
Unused medicine and waste derived from this medicine must be disposed of in accordance with local regulations.
07.0 MARKETING AUTHORIZATION HOLDER
Pfizer Italia S.r.l. - via Isonzo, 71 - 04100 Latina
08.0 MARKETING AUTHORIZATION NUMBER
10 tablets of 4 mg, AIC 014159014
30 tablets of 4 mg, AIC 014159026
20 tablets of 16 mg, AIC 014159040
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
May 31, 2005
10.0 DATE OF REVISION OF THE TEXT
AIFA determination of 5 May 2014
