Active ingredients: Methylprednisolone (Methylprednisolone sodium succinate)
SOLU-MEDROL 40mg / ml powder and solvent for solution for injection
SOLU-MEDROL 125mg / 2ml powder and solvent for solution for injection
SOLU-MEDROL 500mg / 8ml powder and solvent for solution for injection
SOLU-MEDROL 1000mg / 16ml powder and solvent for solution for injection
SOLU-MEDROL 2000mg / 32ml powder and solvent for solution for injection
Why is Solu-Medrol used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Systemic corticosteroids, glucocorticoids
THERAPEUTIC INDICATIONS
1. Endocrine disorders
Acute adrenocortical insufficiency (hydrocortisone or cortisone are the drugs of choice: the addition of mineralocorticoids may be necessary, especially when synthetic analogues are used).
2. Collagen diseases
During an exacerbation or as maintenance therapy in particular cases of systemic lupus erythematosus.
3. Dermatological alterations
to. Pemphigus
b. Severe Erythema Multiforme (Stevens-Johnson Syndrome)
c. Exfoliative dermatitis
4. Allergic states
Control of severe or incapacitating allergic conditions that do not respond to traditional therapy, in case of:
to. Bronchial asthma
b. Contact dermatitis
c. Serum sickness
d. Drug hypersensitivity reactions
And. Angioneurotic edema, urticaria, anaphylactic shock (in addition to adrenaline)
5. Gastrointestinal diseases
Ulcerative colitis (systemic therapy or as a retentive or drip enema to help the patient overcome a particularly critical phase of the disease), segmental ileitis
6. Edematous states
To induce diuresis or remission of proteinuria in nephrotic syndrome without uremia or idiopathic type or due to systemic lupus erythematosus.
7. Central nervous system
Cerebral edema from primary or metastatic tumor and / or associated with surgical or radiation therapy.
Exacerbations of multiple sclerosis.
Acute spinal cord injury. Treatment should begin within 8 hours of the trauma occurring.
8. Neoplastic affections
Palliative treatment of: leukemia and lymphomas in adults, acute childhood leukemia.
Palliative therapy of very advanced tumors.
SOLU-MEDROL can also be used in the following conditions:
to. Generalized neurodermatitis
b. Acute rheumatic fever
c. Severe shock: hemorrhagic, traumatic, surgical
In cases of severe shock, the use of intravenous SOLU-MEDROL can help in restoring the haemodynamic situation. Corticosteroid therapy should not be considered as a replacement for standard methods to combat shock but recent experiences indicate that the concomitant use of massive doses of corticosteroids together with other therapeutic measures, can increase the survival rate.
d. Esophageal burns
In the case of esophageal burns due to ingestion of caustic agents, corticosteroid therapy has decreased the incidence of adhesions and morbidity. Corticosteroids must be administered within 48 hours of the burn. A fast-acting steroid such as SOLU -MEDROL can be given together with fluids and antibiotics as an initial treatment.
After esophagoscopy, the administration of the drug can be interrupted in patients who do not have burns.Treatment of those patients with esophageal damage should continue with injectable methylprednisolone acetate or tablets if tolerated plus antibiotics and drainage.
And. Prevention of nausea and vomiting associated with anticancer chemotherapy
f. Adjuvant therapy of severe Pneumocystis jiroveci lung diseases in subjects affected by A.I.D.S. Administration should be performed within 24 hours of starting antimicrobial treatment.
Contraindications When Solu-Medrol should not be used
Hypersensitivity to the active substance or to any of the excipients.
SOLU-MEDROL is also contraindicated:
- in patients with systemic fungal infections.
- in use by intrathecal administration.
- in use for epidural administration.
Administration of live, live attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids.
Precautions for use What you need to know before taking Solu-Medrol
Since the onset of side effects is related to the dosage and duration of treatment, it is necessary to carefully evaluate these factors in each individual patient. During therapy it is suggested to gradually reduce the dosage in order to find the lowest dose. maintenance.
Immunosuppressive effects / Increased susceptibility to infections
Corticosteroids may increase susceptibility to infections, may mask some signs of infection, and intercurrent infections may occur during their use; evaluate the opportunity to institute adequate antibiotic therapy.
Decreased resistance and inability to localize infection may occur during treatment with corticosteroids. Infections caused by viruses, bacteria, fungi, protozoa and helminth organisms, anywhere in the body may be associated with the use of corticosteroids alone or in association with other immunosuppressive agents that affect cellular, humoral immunity and neutrophil function. These infections can be mild, but also severe and in some cases fatal. Increasing corticosteroid doses increases the incidence rate of infections.
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.
Administration of live or attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids. By decreasing the immune response, methylprednisolone can increase the undesirable effects of living vaccines, leading to the development of diseases due to viral dissemination. 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. Patients should not be vaccinated against smallpox during corticosteroid treatment.
Do not perform other immunization procedures in patients under corticosteroid therapy, particularly at high doses, due to the possible risks of neurological complications and a decreased antibody response. Administration of corticosteroids can reduce or abolish the response to skin tests.
The use of SOLU-MEDROL in active tuberculosis should be limited to those cases of fulminant or disseminated disease in which the corticosteroid is used for the treatment of the disease under an appropriate antituberculous regimen. If corticosteroids are administered to patients with latent or responding tuberculosis positive for tuberculin, close surveillance is necessary as a reactivation of the disease may occur, particularly in immunocompromised patients in whom the opportunity for anti-tuberculosis therapy must be evaluated. The possibility of activation of other latent infections should also be considered in these patients. During prolonged therapy, chemoprophylactic coverage should be established.
Cases of Kaposi's sarcoma have occurred in patients treated with corticosteroids. Discontinuation of treatment can lead to regression of the disease.
Effects on the immune system
Allergic reactions can occur. As there have been rare cases of skin reactions and anaphylactic / anaphylactoid reactions in patients receiving corticosteroid therapy, appropriate precautions should be taken prior to administration, particularly when the patient has a history of allergic to medicinal products.
Effects on the endocrine system
In patients on corticosteroid therapy experiencing unusual stress, an increase in the dosage of fast-acting corticosteroids is indicated before, during and after the stressful situation.
Drug doses of corticosteroids administered for prolonged periods can lead to suppression of the hypothalamic-pituitary adrenal system (HPA) (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. This effect can be minimized with alternate day therapy. In addition, abrupt discontinuation of glucocorticoid therapy. treatment with glucocorticoids can lead to acute adrenocortical insufficiency with a fatal outcome. Drug-induced secondary adrenocortical insufficiency can be minimized by gradual dose reduction. This type of relative insufficiency can persist for months after discontinuation of therapy; therefore, if the patient is subject to stressful conditions during this period, appropriate hormone therapy should be adopted.
A steroid "withdrawal syndrome" apparently unrelated to adrenocortical insufficiency may also occur after abrupt withdrawal of glucocorticoids. This syndrome includes symptoms such as: anorexia, nausea, vomiting, lethargy, headache, fever, joint pain, scaling , myalgia, weight loss and / or hypotension These effects are thought to be due to the abrupt change in glucocorticoid concentration rather than low corticosteroid levels.
Since glucocorticoids can cause or aggravate Cushing's syndrome, their administration should be avoided in patients with Cushing's disease.
In patients with hypothyroidism the effect of corticosteroids is enhanced.
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 which in this case should only be administered in cases of actual need and under close surveillance.
Systemic steroids can cause potentially severe psychiatric adverse reactions. 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.
Effects on the nervous system
Corticosteroids should be used with caution in patients with seizures. Corticosteroids should be used with caution in patients with myasthenia gravis (see also information in the Musculoskeletal System section).
Although some controlled clinical trials have shown the efficacy of corticosteroids in accelerating the resolution of acute exacerbations of multiple sclerosis, they have shown no effects of corticosteroids on the final outcome or natural course of the disease. However, the studies show the need for relatively low doses. elevated corticosteroids to demonstrate a significant effect.
Serious medical events have been reported in association with intrathecal / epidural routes of administration (see section Undesirable effects).
Cases of epidural lipomatosis have been reported in patients treated with corticosteroids, usually with long-term use at high doses.
Ocular effects
Furthermore, these drugs should be used with extreme caution in patients with ocular herpes simplex due to possible corneal perforation. 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.
Corticosteroid therapy has been associated with central serous chorioretinopathy which can cause retinal detachment.
Effects on the cardiovascular system
If high doses and prolonged cycles are used, adverse events of glucocorticoids on the cardiovascular system, such as dyslipidemia and hypertension, can predispose patients with existing cardiovascular risk factors to further cardiovascular effects. Therefore, corticosteroids should be used with judgment in such patients and attention should be paid to risk modification and if necessary to further cardiac monitoring. Low dose and alternate day therapy can reduce the incidence of complications during corticosteroid therapy.
There are reports of cardiac arrhythmias and / or circulatory collapses and / or cardiac arrest following rapid intravenous high doses (greater than 500 mg) of SOLU-MEDROL. These reactions appeared mainly in subjects who had undergone kidney transplants and it seems to be due in some cases to the speed of administration, eg. when the dose is administered in less than 10 minutes.
The use of SOLU-MEDROL in this pathological condition is not among the indications listed, however doctors must be informed of this eventuality.
Bradycardia has been reported during or after administration of high doses of methylprednisolone sodium succinate which may be related to the rate or duration of the infusion.
Systemic corticosteroids should be used with caution in cases of congestive heart failure only if strictly necessary.
Effects on the gastrointestinal system
There is no universal agreement as to whether corticosteroids are directly responsible for peptic ulcers occurring during therapy, however, glucocorticoid therapy can mask the symptoms of peptic ulcer so that bleeding and perforation can occur without significant pain. In combination with NSAIDs, the risk of developing gastrointestinal ulcers increases.
Steroids should be used with caution in non-specific ulcerative colitis if there is a danger of perforation; abscesses or other pyogenic infection; diverticulitis; recent intestinal anastomoses; latent or active peptic ulcer.
Effects on the hepatobiliary system
High doses of corticosteroids can produce acute pancreatitis.
Effects on the 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 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 disorders
Corticosteroids should be used with caution in patients with renal insufficiency.
Laboratory tests
Medium or high doses of hydrocortisone and cortisone can cause increased blood pressure, water and salt retention, and increased potassium excretion. Such effects are less likely with the use of synthetic derivatives except when used in high doses. A low-salt diet and potassium supplementation may be required. All corticosteroids increase calcium excretion.
Injury, poisoning and procedural complications
Methylprednisolone sodium succinate should not be used routinely for the treatment of traumatic brain injury, as demonstrated by the results of a multicenter study. The results of the study revealed increased mortality in the 2 weeks or 6 months after injury in patients given methylprednisolone sodium succinate compared to placebo. A causal association with methylprednisolone sodium succinate treatment has not been established. .
Other
In patients with hypothyroidism or with cirrhosis of the liver, the response to corticosteroids may increase
Since the complications of glucocorticoid treatment are dose-dependent and duration of treatment, a decision on the benefit-risk balance with regard to dose and duration of treatment and whether therapy should be daily or intermittent must be made in each individual case. .
To control the condition under treatment, the lowest possible dose of corticosteroids should be used and, when possible, tapering should be gradual.
Aspirin and non-steroidal anti-inflammatory drugs should be used with caution in combination with corticosteroids in patients with hypoprothrombinemia.
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".
Use in children
Particular attention should be paid to the bodily development of infants and children undergoing prolonged corticosteroid therapy. Growth retardation may occur in children receiving prolonged daily therapy or alternate-day glucocorticoid therapy, and the use of such a regimen should be restricted to the most urgent indications. Alternate-day glucocorticoid therapy generally avoids or minimizes this. collateral effect.
Infants and children on prolonged corticosteroid therapy are particularly at risk of increased intracranial pressure. High doses of corticosteroids can produce pancreatitis in children.
Use in the elderly
Caution is advised with prolonged corticosteroid treatment in the elderly due to a potential increased risk of osteoporosis, as well as an increased risk of fluid retention resulting in possible hypertension.
Interactions Which drugs or foods can modify the effect of Solu-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 drugs) 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 medicinal products, 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, such as methylprednisolone. Co-administration may require an increase in methylprednisolone dose to achieve Expected effects. CYP3A4 substrates: In the presence of another CYP3A4 substrate, hepatic clearance of methylprednisolone may be altered, resulting in the need for dose adjustment. Undesirable effects associated with the use of the single substance may be more likely to occur if the medicines 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.
Concomitant intake of troleandomycin, erythromycin or ketoconazole may enhance the effects of the drug.
The effect of methylprednisolone can also be increased by the administration of methotrexate. Furthermore, methylprednisolone can precipitate myasthenic crises in the presence of anticholinesterase drugs (neostigmine, pyridostigmine).
The glucomineralocorticoid action of methylprednisolone, and in particular the sodium retention and potassium-wasting effect, may reduce the efficacy of pre-existing antihypertensive therapy or enhance the toxicity of diuretics or digoxin. Also the response to hypoglycemic agents ( or insulin) is reduced in diabetic patients.
Finally, methylprednisolone reduces the neuromuscular efficacy of pancuronium, may determine the need for a dose adjustment in subjects being treated with psychotropic drugs (anxiolytics and antipsychotics), increases the response to sympathomimetic agents (such as salbutamol) and can change blood levels of theophylline.
Incompatibility
To avoid compatibility and stability problems, it is recommended that methylprednisolone sodium succinate be administered separately from other substances that are administered intravenously. Drugs that are physically incompatible in solution with methylprednisolone sodium succinate include, but are not limited to: sodium allopurinol, doxapram hydrochloride, tigecycline, diltiazem hydrochloride, but beyond these also include calcium gluconate, vecuronium bromide, rocuronium bromide, cisatracurium besylate, glycopyrrolate, propofol. (see section INSTRUCTIONS FOR USE - Incompatibility)
Warnings It is important to know that:
Fertility, pregnancy and lactation
Ask your doctor or pharmacist for advice before taking any medicine.
Fertility
Corticosteroids have been shown to reduce fertility in animal studies.
Pregnancy
Studies in laboratory animals have shown that corticosteroids, given to mothers in high doses, can induce fetal malformations. In humans, insufficient reproductive studies have been conducted. Since human studies cannot exclude the possibility of harm, methylprednisolone sodium succinate should only be used during pregnancy if strictly necessary. Some corticosteroids easily cross the placenta. A retrospective study found an increased incidence of low birth weight in children born to mothers receiving corticosteroids. Babies born to mothers treated with high doses of corticosteroids during pregnancy should be monitored and signs of adrenal insufficiency evaluated, although neonatal adrenal insufficiency appears to be rare in infants who have been exposed to corticosteroids in utero.
Cases of cataracts have been observed in infants born to mothers treated with long-term corticosteroids during pregnancy. Benzyl alcohol can pass the placenta (see section Important information about some excipients).
There are no known effects of corticosteroids on labor and delivery.
Feeding time
Corticosteroids are excreted in breast milk, therefore breastfeeding should be discontinued during corticosteroid therapy. Corticosteroids present in breast milk may retard growth and interfere with the production of endogenous glucocorticoids in infants. As adequate reproductivity studies in infants are not available. For the use of glucocorticoids, this drug should be given to nursing mothers only if the benefit of therapy outweighs the potential risk to the infant.
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
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 tiredness, euphoria or mood disturbances are possible after treatment with corticosteroids. If such undesirable effects occur, patients should not drive or operate machinery.
Important information about some of the ingredients
SOLU-MEDROL contains 9 mg / ml of benzyl alcohol. This medicine should not be given to premature babies or newborns. It can cause toxic and allergic reactions in children up to 3 years of age. Due to the risk of fatal toxic reactions resulting from exposure to benzyl alcohol in quantities greater than 90 mg / kg / day, this medicine should not be given to children up to 3 years of age.
Premature babies and those born underweight may be more likely to develop toxicity.
The benzyl alcohol preservative has been associated with serious adverse events and death in pediatric patients including neonates characterized by central nervous system depression, metabolic acidosis, wheezing, cardiovascular insufficiency, haematological abnormalities "gasping syndrome". Although normal therapeutic doses of this product usually carry amounts of benzyl alcohol that are substantially less than those reported in association with "gasping syndrome", the minimum amount of benzyl alcohol at which toxicity can occur is not known. When given in volumes. elevated, in subjects with hepatic or renal insufficiency, should be used with caution and preferably for short-term treatment due to the risk of accumulation and toxicity (metabolic acidosis). Use only if strictly necessary and if there are no other possible alternatives
SOLU-MEDROL 40 mg / ml and SOLU-MEDROL 125 mg / 2 ml contain less than 1 mmol (23mg) sodium per vial, ie they are practically "sodium free"
SOLU-MEDROL 500 mg / 8 ml contains 2.43 mmol per sodium ampoule. To be taken into consideration in people with reduced kidney function or who follow a low sodium diet.
SOLU-MEDROL 1000 mg / 16 ml contains 4.85 mmol per sodium ampoule. To be taken into consideration in people with reduced kidney function or who follow a low sodium diet.
SOLU-MEDROL 2000 mg / 32 ml contains 9.70 mmol per sodium ampoule. To be taken into consideration in people with reduced kidney function or who follow a low sodium diet.
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 Solu-Medrol: Dosage
When high dose treatment is required, the recommended dose of SOLU-MEDROL (methylprednisolone sodium succinate) is 30 mg / kg administered intravenously over a period of at least 30 minutes. This dose can be repeated every 4-6 hours for a period of 48 hours. The initial dose should be administered intravenously over several minutes. In general, high-dose corticosteroid therapy should only be continued until the patient's condition has stabilized, usually no later than 48 to 72 hours. Although side effects associated with short-term high-dose corticoid therapy are rare, a "peptic ulcer" can occur. Prophylactic anti-acid therapy may be indicated.
When treatment is required through the administration of intravenous boluses of SOLU-MEDROL for pathological states in exacerbation and / or no longer responsive to standard therapy, such as those listed below, the recommended dosages are as follows:
- Multiple sclerosis: 1 g / day i.v. for 3 days or for 5 days
- Edematous states (glomerulonephritis, lupus nephritis): 30 mg / kg i.v. every other day or 1 g / day i.v. for 3, 5 or 7 days
These schedules can be repeated if no improvement is noticed within the week following the end of treatment, or if the patient's condition suggests it.
- Acute Spinal Cord Injuries:
The following dosing schedules refer only to the indication of acute spinal cord injury.
For patients treated within 3 hours of trauma:
administer 30 mg / kg of methylprednisolone sodium succinate as a venous bolus over 15 minutes, followed by a 45 minute interval and then a maintenance infusion of 5.4 mg / kg per hour for the next 23 hours. A separate intravenous site should be used for the infusion pump.
For patients treated between 3 and 8 hours after trauma:
administer 30 mg / kg of methylprednisolone sodium succinate as a venous bolus over 15 minutes, followed by a 45 minute interval and then a maintenance infusion of 5.4 mg / kg per hour for the next 47 hours.
Treatment should begin within 8 hours of the trauma occurring.
- Palliative therapy in very advanced cancer:
125 mg / day i.v. for up to 8 weeks, they have been shown to significantly improve pain, nausea / vomiting, anorexia, asthenia and anxiety.
- In the prevention of nausea and vomiting associated with anticancer chemotherapy, the following dosage regimens are recommended:
In mild to moderately emetizing chemotherapy, administer:
125-250 mg of methylprednisolone sodium succinate alone or in combination with a chlorinated phenothiazine one "hour before chemotherapy, followed by a second dose of methylprednisolone sodium succinate at the time of chemotherapy, and a final dose of methylprednisolone sodium succinate to be administered before the patient is discharged to ensure extended anti-emetic coverage after the patient has left the hospital
In highly emetizing chemotherapy, administer:
250 mg of methylprednisolone sodium succinate + 1-2.5 mg of droperidol or 1.5-2 mg / kg of metoclopramide one "hour before chemotherapy.
A second dose of methylprednisolone sodium succinate given at the time of chemotherapy.
A final dose of methylprednisolone sodium succinate to be administered before the patient is discharged to ensure prolonged anti-emetic coverage after the patient has left the hospital.
- Adjuvant therapy of severe Pneumocystis jiroveci pneumonia in patients with A.I.D.S.
0.5 mg / kg every 6 hours for a period of 10 days.
Administration should take place within 24 hours of starting antimicrobial therapy.
In the other indications the starting dose can vary from 10 to 40 mg of methylprednisolone depending on the clinical condition to be treated. Higher doses may be required for short-term treatment of acute and severe conditions. The initial dose should be administered intravenously over several minutes. Subsequent doses may be administered intravenously or intramuscularly at intervals determined by the patient's response and clinical condition. Corticosteroid therapy is adjuvant and not a substitute for conventional therapy.
The dose may be reduced in infants and children, but should primarily be determined based on the severity of the condition and the patient's response rather than his age and weight. It must not be less than 0.5 mg / kg / day. The dosage should be gradually decreased when the drug has been administered over several days. If, during the treatment of a chronic disease, a period of spontaneous remission is noted, the drug must be discontinued (see section SPECIAL WARNINGS).
SOLU-MEDROL can be administered by intravenous or intramuscular injection or by drip. For initial emergency treatment, the preferred route of administration is intravenous.
Overdose What to do if you have taken too much Solu-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 is no antidote to corticosteroid overdose, the treatment is supportive and symptomatic. In case of accidental intake of an excessive dose of SOLU-MEDROL, notify your doctor immediately or go to the nearest hospital.
IF IN ANY DOUBT ABOUT USING SOLU-MEDROL, CONTACT YOUR DOCTOR OR PHARMACIST.
Side Effects What are the side effects of Solu-Medrol
Like all medicines, SOLU-MEDROL can cause side effects, although not everybody gets them.
The following adverse reactions have been reported with the intrathecal / epidural routes of administration: arachnoiditis, functional gastrointestinal disorder / bladder dysfunction, headache, meningitis, paraparesis / paraplegia, convulsions, sensory disturbances. The frequency of these adverse reactions is unknown.
The onset of side effects is related to the dosage and duration of treatment, it is therefore necessary to carefully evaluate these factors in each individual patient.
During corticosteroid therapy, especially if intense and prolonged, some of the following side effects may arise:
* not MedDRA PT
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. Undesirable effects can also be reported directly through 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 the 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 packaging, correctly stored.
Warning: do not use the medicine after the expiry date shown on the package.
Warnings: Once in solution, SOLU-MEDROL must be used within 48 hours.
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 medicine out of the sight and reach of children.
COMPOSITION
SOLU-MEDROL 40 mg / ml powder and solvent for solution for injection:
Each 1 ml double chamber bottle contains: methylprednisolone sodium succinate 53.03 mg (equivalent to 40 mg of methylprednisolone).
Excipients:
Powder: lactose monohydrate, sodium bisphosphate, sodium phosphate, Solvent: benzyl alcohol, water for injections.
SOLU-MEDROL 125 mg / 2 ml powder and solvent for solution for injection:
Each 2ml double chamber bottle contains: methylprednisolone sodium succinate 165.72 mg (equivalent to 125 mg of methylprednisolone).
Excipients:
Powder: sodium bisphosphate, sodium phosphate, benzyl alcohol Solvent: water for injections.
SOLU-MEDROL 500 mg / 8 ml powder and solvent for solution for injection:
Each 8 ml bottle contains: methylprednisolone sodium succinate 662.88 mg (equivalent to 500 mg of methylprednisolone).
Excipients:
Powder: sodium bisphosphate, sodium phosphate, Solvent: benzyl alcohol, water for injections.
SOLU-MEDROL 1000 mg / 16 ml powder and solvent for solution for injection:
Each 16 ml bottle contains: methylprednisolone sodium succinate 1325.77 mg (equivalent to 1000 mg of methylprednisolone).
Excipients:
Powder: sodium bisphosphate, sodium phosphate Solvent: benzyl alcohol, water for injections.
SOLU-MEDROL 2000mg / 32ml powder and solvent for solution for injection:
Each 32 ml bottle contains: methylprednisolone sodium succinate 2651.5 mg (equivalent to 2000 mg of methylprednisolone).
Excipients: Powder: sodium bisphosphate, sodium phosphate Solvent: benzyl alcohol, water for injections.
PHARMACEUTICAL FORM AND CONTENT
Powder and solvent for solution for injection.
1 double chamber bottle of 40 mg / ml
1 double chamber bottle of 125 mg / 2 ml
1 bottle of 500 mg / 8 ml
1 bottle of 1000 mg / 16 ml
1 bottle of 2000 mg / 32 ml
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
SOLU-MEDROL, POWDER AND SOLVENT FOR INJECTABLE SOLUTION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
For the full list of excipients, see section 6.1.
03.0 PHARMACEUTICAL FORM
Powder and solvent for solution for injection.
INTRAMUSCULAR AND INTRAMUSCULAR USE.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
1. Endocrine disorders
Acute adrenocortical insufficiency (hydrocortisone or cortisone are the drugs of choice: the addition of mineralocorticoids may be necessary, especially when synthetic analogues are used).
2. Collagen diseases
During an exacerbation or as maintenance therapy in particular cases of systemic lupus erythematosus.
3. Dermatological alterations
to. pemphigus
b. severe erythema multiforme (Stevens-Johnson syndrome)
c. exfoliative dermatitis
4. Allergic states
Control of severe or incapacitating allergic conditions that do not respond to traditional therapy, in case of:
to. bronchial asthma
b. contact dermatitis
c. serum sickness
d. drug hypersensitivity reactions
And. angioneurotic edema, urticaria, anaphylactic shock (in addition to adrenaline)
5. Gastrointestinal diseases
Ulcerative colitis (systemic therapy or as a retentive or drip enema to help the patient overcome a particularly critical phase of the disease), segmental ileitis.
6. Edematous states
To induce diuresis or remission of proteinuria in nephrotic syndrome without uremia or idiopathic type or due to systemic lupus erythematosus.
7. Central nervous system
Cerebral edema from primary or metastatic tumor and / or associated with surgical or radiation therapy, exacerbations of multiple sclerosis, acute spinal cord injury. Treatment should begin within 8 hours of the trauma occurring.
8. Neoplastic affections
Palliative treatment of: leukemia and lymphomas in adults, acute childhood leukemia.
Palliative therapy of very advanced tumors.
SOLU-MEDROL can also be used in the following conditions:
to. Generalized neurodermatitis
b. Acute rheumatic fever
c. Severe shock: hemorrhagic, traumatic, surgical
In cases of severe shock, the use of intravenous SOLU-MEDROL can help in restoring the haemodynamic situation. Corticosteroid therapy should not be considered as a replacement for standard methods to combat shock but recent experiences indicate that the concomitant use of massive doses of corticosteroids, along with other therapeutic measures, can increase the survival rate.
d. Esophageal burns
In the case of esophageal burns due to ingestion of caustic agents, corticosteroid therapy has decreased the incidence of adhesions and morbidity. Corticosteroids must be administered within 48 hours of the burn. A fast-acting steroid such as SOLU -MEDROL can be given together with fluids and antibiotics as an initial treatment.
After esophagoscopy, the administration of the drug can be interrupted in patients who do not have burns. Treatment of those patients with esophageal damage should continue with DEPO-MEDROL (methylprednisolone acetate) or MEDROL tablets (methylprednisolone acetate), if tolerated, plus antibiotics and drainage.
And. Prevention of nausea and vomiting associated with anticancer chemotherapy
f. Adjuvant therapy in severe pneumocystis carinii lung diseases in subjects affected by A.I.D.S.
Administration should be performed within 24 hours of starting antimicrobial treatment.
04.2 Posology and method of administration
When high dose treatment is required, the recommended dose of SOLU-MEDROL (methylprednisolone sodium succinate) is 30 mg / kg administered intravenously over a period of at least 30 minutes. This dose can be repeated every 4-6 hours for a period of 48 hours. The initial dose should be administered intravenously over several minutes. In general, high-dose corticosteroid therapy should only be continued until the patient's condition has stabilized, usually no later than 48 to 72 hours. Although side effects associated with short-term high-dose corticoid therapy are rare, a "peptic ulcer" can occur. Prophylactic anti-acid therapy may be indicated.
When treatment is required through the administration of intravenous boluses of SOLU-MEDROL for pathological states in exacerbation and / or no longer responsive to standard therapy, such as those listed below, the recommended dosages are as follows:
Multiple sclerosis: 1 g / day i.v. for 3 days or for 5 days.
Edematous states (glomerulonephritis, lupus nephritis): 30 mg / kg i.v. every other day or 1 g / day i.v. for 3, 5 or 7 days
These schedules can be repeated if no improvement is noticed within the week following the end of treatment, or if the patient's condition suggests it.
Acute spinal cord injury
The following dosing schedules refer only to the indication of acute spinal cord injury.
For patients treated within 3 hours of trauma: administer 30 mg / kg of methylprednisolone sodium succinate as a venous bolus over 15 minutes, followed by an interval of 45 minutes and then a maintenance infusion of 5.4 mg / kg per hour for the next 23 hours.
For patients treated between 3 and 8 hours after trauma: administer 30 mg / kg of methylprednisolone sodium succinate as a venous bolus over 15 minutes, followed by an interval of 45 minutes and then a maintenance infusion of 5.4 mg / kg per hour for the next 47 hours.
A separate intravenous site should be used for the infusion pump.
Treatment should begin within 8 hours of the trauma occurring.
Palliative therapy in very advanced cancer: 125 mg / day i.v. up to 8 weeks have been shown to significantly improve pain, nausea / vomiting, anorexia, asthenia and anxiety.
In the prevention of nausea and vomiting associated with anticancer chemotherapy, the following dosage regimens are recommended:
• in mild to moderately emetic chemotherapy, administer:
125-250 mg of methylprednisolone sodium succinate alone or in combination with a chlorinated phenothiazine one "hour before chemotherapy, followed by a second dose of methylprednisolone sodium succinate at the time of chemotherapy, and a final dose of methylprednisolone sodium succinate to be administered before the patient is discharged to ensure extended anti-emetic coverage after the patient has left the hospital
• in highly emetizing chemotherapy, administer:
250 mg of methylprednisolone sodium succinate + 1-2.5 mg of droperidol or 1.5-2 mg / kg of metoclopramide one "hour before chemotherapy.
A second dose of methylprednisolone sodium succinate given at the time of chemotherapy.
A final dose of methylprednisolone sodium succinate to be administered before the patient is discharged to ensure prolonged anti-emetic coverage after the patient has left the hospital.
Adjuvant therapy of severe Pneumocystis carinii pneumonia in patients with A.I.D.S .: 0.5 mg / kg every 6 hours for a period of 10 days.
Administration should take place within 24 hours of starting antimicrobial therapy.
In the other indications the starting dose can vary from 10 to 40 mg of methylprednisolone depending on the clinical condition to be treated. Higher doses may be required for short-term treatment of acute and severe conditions. The initial dose should be administered intravenously over several minutes. Subsequent doses may be administered intravenously or intramuscularly at intervals determined by the patient's response and clinical condition. Corticosteroid therapy is adjuvant and not a substitute for conventional therapy.
The dose may be reduced in infants and children, but should primarily be determined according to the severity of the condition and the patient's response, rather than his age and weight. It should not be less than 0.5 mg / kg / day. The dosage should be gradually decreased when the drug has been administered over several days. If, during the treatment of a chronic disease, a period of spontaneous remission is noted, the drug should be discontinued.
SOLU-MEDROL can be administered by intravenous or intramuscular injection or by drip. For initial emergency treatment, the preferred route of administration is intravenous (see section 6.6 "Special precautions for disposal and handling").
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Solu-medrol is contraindicated:
• in patients with systemic fungal infections.
• when used for intrathecal administration.
Administration of live, live attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids.
04.4 Special warnings and appropriate precautions for use
Since the onset of side effects is related to the dosage and duration of treatment, it is necessary to carefully evaluate these factors in each individual patient.During therapy it is suggested to gradually reduce the dosage in order to find the lowest maintenance dose.
Immunosuppressive effects / Increased susceptibility to infections
Corticosteroids may increase susceptibility to infections, may mask some signs of infection, and intercurrent infections may occur during their use; evaluate the opportunity to institute adequate antibiotic therapy.
Decreased resistance and inability to localize infection may occur during treatment with corticosteroids. Infections caused by viruses, bacteria, fungi, protozoa, and helminthic organisms throughout the body may be associated with the use of corticosteroids alone or in combination. to other immunosuppressive agents that affect cellular, humoral immunity and neutrophil function. These infections can be mild, but also severe and in some cases fatal. Increasing corticosteroid doses increases the incidence rate of infections.
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.
Corticosteroids should be used with caution in patients with known or suspected parasitic infections such as Strongyloidiasis (roundworm infestation). In these patients, corticosteroid-induced immunosuppression can lead to strongyloidiasis hyperinfection and widespread dissemination of larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia.
The role of corticosteroids in septic shock is controversial; initial studies reported both harmful effects and benefits. The use of corticosteroids has recently been suggested to be of benefit in patients with septic shock who present with adrenal insufficiency.
The routine use of corticosteroids in septic shock is not recommended, and systematic reviews of the literature do not support their use at high doses for short periods.
However, meta-analyzes and publications suggest that prolonged use (5-11 days) of low-dose corticosteroids can reduce mortality.
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. Administration of corticosteroids can reduce or abolish the response to skin tests. Patients should not be vaccinated against smallpox during corticosteroid treatment.
Do not perform other immunization procedures in patients under corticosteroid therapy, particularly at high doses, due to the possible risks of neurological complications and a decreased antibody response. The use of SOLU-MEDROL in active tuberculosis should be limited to those cases of fulminant or disseminated disease in which the corticosteroid is used for the treatment of the disease under an appropriate antituberculous regimen.
If corticosteroids are administered to patients with latent tuberculosis or with a positive response to tuberculin, close surveillance is necessary as a reactivation of the disease may occur, particularly in immunocompromised patients in whom the appropriateness of antituberculous therapy must be evaluated. in these patients the possibility of activation of other latent infections should also be considered.Chemoprophylactic coverage should be established during prolonged therapy.
Cases of Kaposi's sarcoma have occurred in patients treated with corticosteroids. Discontinuation of treatment could lead to regression of the disease.
Blood and lymphatic system
Aspirin and non-steroidal anti-inflammatory agents should be used with caution in combination with corticosteroids in patients with hypoprothrombinemia.
Effects on the immune system
Allergic reactions may occur. As there have been rare cases of skin reactions and anaphylactic / anaphylactoid reactions in patients receiving corticosteroid therapy, appropriate precautions should be taken prior to administration, particularly when the patient has a history of allergic to medicinal products.
Effects on the endocrine system
Drug doses of corticosteroids administered for prolonged periods may 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. This effect can be minimized with alternate day therapy. In addition, abrupt discontinuation of glucocorticoid therapy. treatment with glucocorticoids can lead to acute adrenocortical insufficiency with a fatal outcome. Drug-induced secondary adrenocortical insufficiency can be minimized by gradual dose reduction. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, if the patient is subject to stressful conditions during this period, appropriate hormone therapy should be adopted. Since mineralocorticoid secretion can be altered, administer in combination. salts and / or drugs with mineralocorticoid activity.
In patients on corticosteroid therapy experiencing unusual stress, an increase in the dosage of fast-acting corticosteroids is indicated before, during and after the stressful situation.
A steroid "withdrawal syndrome" apparently unrelated to adrenocortical insufficiency may also occur after abrupt withdrawal of glucocorticoids. This syndrome includes symptoms such as: anorexia, nausea, vomiting, lethargy, headache, fever, joint pain, scaling , myalgia, weight loss and / or hypotension These effects are thought to be due to the abrupt change in glucocorticoid concentration rather than low corticosteroid levels.
Since glucocorticoids can cause or aggravate Cushing's syndrome, their administration should be avoided in patients with Cushing's disease.
In patients with hypothyroidism, the effect of corticosteroids is enhanced.
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 which in this case should only be administered in cases of actual need and under close surveillance.
Systemic steroids can cause potentially severe psychiatric adverse reactions. Symptoms typically occur within days to weeks of starting treatment. Most reactions regress 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.
Effects on the nervous system
Corticosteroids should be used with caution in patients with seizures. Corticosteroids should be used with caution in patients with myasthenia gravis (see also information in the Musculoskeletal System section).
Ocular effects
Furthermore, these drugs should be used with extreme caution in patients with ocular herpes simplex due to possible corneal perforation.
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.
Effects on the cardiovascular system
If high doses and prolonged cycles are used, adverse glucocorticoid events on the cardiovascular system, such as dyslipidemia and hypertension, may predispose patients with pre-existing cardiovascular risk factors to further cardiovascular effects. Consequently, corticosteroids should be used. used judiciously in such patients and attention should be paid to risk modification and, if necessary, further cardiac monitoring. Low doses and alternate day therapy can reduce the incidence of complications during corticosteroid therapy.
There are reports of cardiac arrhythmias and / or circulatory collapses and / or cardiac arrest following rapid intravenous high doses (greater than 500 mg) of SOLU-MEDROL. These reactions appeared mainly in subjects who had undergone kidney transplants and it seems to be due in some cases to the speed of administration, eg. when the dose is administered in less than 10 minutes.
The use of SOLU-MEDROL in this pathological condition is not among the indications listed, however doctors must be informed of this eventuality.
Bradycardia has been reported during or after administration of high doses of methylprednisolone sodium succinate which may be related to the rate or duration of the infusion. Systemic corticosteroids should be used with caution in cases of congestive heart failure, only if strictly necessary.
Effects on the gastrointestinal system
There is no common agreement that 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.
Steroids should be used with caution in non-specific ulcerative colitis if there is a danger of perforation; of abscesses or other pyogenic infection; diverticulitis; recent intestinal anastomoses; latent or active peptic ulcer.
Effects on the hepatobiliary system
High doses of corticosteroids can produce acute pancreatitis.
Effects on the 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 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 disorders
Corticosteroids should be used with caution in patients with renal insufficiency.
Laboratory tests
Medium or high doses of hydrocortisone and cortisone can cause increased blood pressure, water and salt retention, and increased potassium excretion. Such effects are less likely with the use of synthetic derivatives except when used in high doses. A low-salt diet and potassium supplementation may be required. All corticosteroids increase calcium excretion.
Injury, poisoning and procedural complications
Methylprednisolone sodium succinate should not be used routinely for the treatment of head injuries, as demonstrated by the results of a multicenter study. The study results revealed increased mortality in the 2 weeks or 6 months after injury in patients given methylprednisolone sodium succinate compared to placebo. A causal association with methylprednisolone sodium succinate treatment has not been established. .
Other adverse events
Caution is advised with prolonged corticosteroid treatment in the elderly due to a potential increased risk of osteoporosis, as well as an increased risk of fluid retention resulting in possible hypertension. In patients with hypothyroidism or with cirrhosis of the liver, the response to corticosteroids may increase. Since the complications of glucocorticoid treatment are dose- and duration-dependent, a decision on the benefit / risk ratio for dose and duration of treatment and on the use of daily or intermittent therapy must be made in each individual case.
The lowest possible dose of corticosteroids should be used to control the treatment condition and, when possible, dose reduction should be gradual.
Use in children
Particular attention should be paid to the bodily development of infants and children undergoing prolonged corticosteroid therapy. Growth retardation may occur in children receiving prolonged daily therapy or alternate-day glucocorticoid therapy, and the use of such a regimen should be restricted to the most urgent indications. Alternate-day glucocorticoid therapy generally avoids or minimizes this. side effect Infants and children on prolonged corticosteroid therapy are particularly at risk of increased intracranial pressure.
High doses of corticosteroids can produce pancreatitis in children.
In pregnant women and in very early childhood, the product must be administered in cases of real need under the direct supervision of the doctor.
Important information about some of the ingredients
SOLU-MEDROL contains 9 mg / ml of benzyl alcohol. This medicine should not be given to premature babies or newborns. It can cause toxic and anaphylactic reactions in children up to 3 years of age.
An "association" of benzyl alcohol with fatal "Gasping Syndrome" has been reported in premature infants. Due to the presence of benzyl alcohol, the product should not be administered to premature babies or newborns. Due to the risk of fatal toxic reactions resulting from exposure to benzyl alcohol in quantities greater than 90 mg / kg / day, this medicine should not be given to children up to 3 years of age.
SOLU-MEDROL 40 mg and SOLU-MEDROL 125 mg contain less than 1 mmol (23mg) sodium per vial, ie it is essentially "sodium-free".
SOLU-MEDROL 500 mg contains 2.43 mmol per sodium ampoule. To be taken into consideration in people with reduced kidney function or who follow a low sodium diet.
SOLU-MEDROL 1000 mg contains 4.85 mmol per sodium ampoule. To be taken into consideration in people with reduced kidney function or who follow a low sodium diet.
SOLU-MEDROL 2000 mg contains 9.70 mmol per sodium ampoule. To be taken into consideration in people with reduced kidney function or who follow a low sodium diet.
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 drugs) have been shown to alter glucocorticoid metabolism by induction (up-regulation) or inhibition of the CYP3A4 enzyme.
CYP3A4 inhibitors
Drugs 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
Drugs that induce CYP3A4 activity generally increase hepatic clearance, resulting in a decrease in plasma concentration of CYP3A4 substrate drugs. Co-administration may require an increase in the dose of methylprednisolone to achieve the expected effects.
CYP3A4 substrates
In the presence of another CYP3A4 substrate, hepatic clearance of methylprednisolone may be inhibited or induced, 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
Concomitant intake of troleandomycin, erythromycin or ketoconazole may enhance the effects of the drug.
The effect of methylprednisolone can also be enhanced by the administration of methotrexate.
Furthermore, methylprednisolone can precipitate myasthenic crises in the presence of anticholinesterase drugs (neostigmine, pyridostigmine).
The glucomineralocorticoid action of methylprednisolone, and in particular the sodium retention and potassium-wasting effect, may reduce the efficacy of pre-existing antihypertensive therapy or enhance the toxicity of diuretics or digoxin. Also the response to hypoglycemic agents ( or insulin) is reduced in diabetic patients.
By decreasing the immune response, methylprednisolone can increase the undesirable effects of living vaccines, leading to the development of diseases due to viral dissemination.
The antibody response to killed vaccines, on the other hand, may be reduced.
Finally, methylprednisolone reduces the neuromuscular efficacy of pancuronium, may determine the need for a dose adjustment in subjects being treated with psychotropic drugs (anxiolytics and antipsychotics), increases the response to sympathomimetic agents (such as salbutamol) and can change blood levels of theophylline.
Incompatibility
To avoid compatibility and stability problems, it is recommended that methylprednisolone sodium succinate be administered separately from other substances that are administered intravenously. Drugs that are physically incompatible in solution with methylprednisolone sodium succinate include sodium allopurinol, doxapram hydrochloride, tigecycline, diltiazem hydrochloride, but beyond these also include calcium gluconate, vecuronium bromide, rocuronium bromide, cisatracurium besylate, glycopyrrolate (see section 6.2 "Incompatibility).
04.6 Pregnancy and lactation
Fertility
There is no evidence that corticosteroids reduce fertility.
Pregnancy
Studies in laboratory animals have shown that corticosteroids, given to mothers in high doses, can induce fetal malformations. However, corticosteroids do not appear to cause birth defects when administered to pregnant women. However, since human studies cannot rule out the possibility of harm, methylprednisolone sodium succinate should only be used during pregnancy if strictly necessary. Some corticosteroids cross the placenta easily. A retrospective study found an increased incidence of low birth weight in babies born to mothers in Corticosteroid Treatment Although neonatal adrenal insufficiency appears to be rare in infants who have been exposed to corticosteroids in utero, those exposed to substantial doses of corticosteroids should be carefully observed and signs of adrenal insufficiency evaluated. There are no known effects of corticosteroids on labor and delivery. Cataracts have been observed in infants born to mothers treated with long-term corticosteroids during pregnancy.
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 baby.
The use of this drug in pregnancy, lactation, or by women of childbearing age requires that the benefits of the drug be weighed against the potential risks to the mother, embryo or fetus.
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 tiredness, euphoria or mood disturbances are possible after treatment with corticosteroids. If such undesirable effects occur, patients should not drive or operate machinery.
04.8 Undesirable effects
During corticosteroid therapy, especially if intense and prolonged, some of the following side effects may arise:
Infections and infestations
Infections, opportunistic infections.
Disorders of the immune system
Hypersensitivity to the drug, (including anaphylactoid and anaphylactic reactions with or without circulatory collapse, cardiac arrest and bronchospasm), urticaria.
Endocrine pathologies
Cushingoid aspect, Hypopituitarism, Steroid withdrawal syndrome.
Metabolism and nutrition disorders
Impaired glucose tolerance, hypokalaemic alkalosis, dyslipidemia, increased need for insulin (or oral hypoglycemic agents in diabetics), sodium retention, water retention, negative nitrogen balance (due to protein catabolism), blood urea, increased blood appetite (which can translate into weight gain), lipomatosis.
Alterations of the hydroelectrolytic balance, in particular sodium retention and potassium loss, which in rare cases and in predisposed patients can lead to hypertension and congestive heart failure.
Psychiatric disorders
Affective disorders (including affective instability, depressed mood, euphoria, psychological dependence, suicidal ideation), psychotic disorders (including mania, delirium, hallucinations, schizophrenia [aggravation of]), confusion, mental disorders, anxiety, personality changes, swings mood, abnormal behavior, insomnia, irritability.
Nervous system disorders
Neurological alterations such as increased intracranial pressure (with papilledema [benign intracranial hypertension]), convulsions, amnesia, cognitive disturbances, dizziness, headache.
Eye disorders
Posterior subcapsular cataracts and increased intraocular pressure, glaucoma, exophthalmos.
Ear and labyrinth disorders
Dizziness.
Pathologies cardiac
Congestive heart failure (in sensitive patients), cardiac arrhythmias.
Vascular pathologies
Hypotension or arterial hypertension.
Respiratory, thoracic and mediastinal disorders
Hiccup.
Gastrointestinal disorders
Complications affecting the gastrointestinal tract that can reach up to gastric haemorrhage, intestinal perforation, peptic ulcer (with possible perforation and peptic ulcer haemorrhage), pancreatitis, peritonitis, ulcerative esophagitis, esophagitis, abdominal pain, abdominal distension, diarrhea, dyspepsia, nausea and vomit.
Skin and subcutaneous tissue disorders
Skin alterations such as delays in the healing processes, thinning and fragility of the skin, hyperpigmentation or hypopigmentation; atrophy of the skin and skin appendages, sterile abscesses. Angioedema, peripheral edema, ecchymosis, petechiae, skin striae, skin hypopigmentation, hirsutism, rash, erythema, pruritus, urticaria, acne, hyperhidrosis.
Musculoskeletal and connective tissue disorders
Musculoskeletal alterations such as osteoporosis, myopathy, muscle weakness, bone fragility, osteonecrosis of the femoral head and humerus, pathological fracture, growth retardation (in children), muscle atrophy, neuropathic arthropathies, arthralgia, myalgia.
Diseases of the reproductive system and breast
Menstrual irregularities.
General disorders and administration site conditions
Difficulty in healing, injection site reaction, fatigue, malaise.
Diagnostic tests
Increased alanine aminotransaminase, aspartate aminotransaminase, increased blood alkaline phosphatase, increased intraocular pressure, decreased tolerance to carbohydrates, decreased blood potassium concentration, increased calcium in urine, suppression of skin test reactions.
Injury, poisoning and procedural complications
Vertebral compression fracture. Rupture of the tendon (especially the Achilles tendon).
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.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: systemic corticosteroids, glucocorticoids
ATC: H02AB04
SOLU-MEDROL, sodium salt of the succinic ester of methylprednisolone, is a synthetic steroid with a powerful anti-inflammatory action superior to that of prednisolone and a lower tendency to sodium and water retention.
Methylprednisolone sodium succinate has the same metabolism and anti-inflammatory action as methylprednisolone. Parenterally administered in equimolar quantities, the two molecules demonstrate equivalent biological activity. The relative potency of methylprednisolone sodium succinate and hydrocortisone sodium succinate, as demonstrated by the decrease in eosinophil counts after intravenous administration, is four to one.
05.2 Pharmacokinetic properties
The pharmacokinetics of methylprednisolone are linear and independent of the route of administration.
Plasma concentrations of methylprednisolone were measured by HPLC. After a 40 mg intramuscular dose of methylprednisolone sodium succinate to fourteen healthy adult male volunteers, the plasma concentration at 1 hour was 425 ng / mL and at 12 hours it dropped to 31.9 ng / mL. The mean peak concentration was 454 ng / mL. No trace of methylprednisolone was detected 18 hours after administration. The intramuscular dose of methylprednisolone sodium succinate was equivalent to the same dose administered intravenously with reference to the area under the time-concentration curve indicating the total amount of methylprednisolone absorbed. The results of one study showed that the methylprednisolone sodium ester succinate is rapidly and extensively converted to the active part of methylprednisolone after any route of administration. The degree of absorption of free methylprednisolone administered intramuscularly and intravenously was equivalent to and significantly higher than the degree of absorption after administration of oral solution and oral methylprednisolone tablets. The degree of methylprednisolone absorbed after intramuscular and intravenous treatment was equivalent. Even if after intravenous administration a greater quantity of the hemisuccinate ester had reached the circulation it would appear that the ester is converted into the tissue after intramuscular injection with subsequent absorption as free methylprednisolone.
Methylprednisolone is widely distributed in tissues, crosses the blood-brain barrier and is excreted in breast milk. The plasma protein binding of methylprednisolone in humans is approximately 77%.
In humans, methylprednisolone is metabolised in the liver to inactive metabolites, the major ones being 20α-hydroxymethylprednisolone and 20β-hydroxymethylprednisolone. Metabolism in the liver occurs mainly via CYP3A4 (for a list of drug interactions based on CYP3A4 mediated metabolism, see section 4.5 Interactions with other medicinal products and other forms of interaction). The total elimination half-life of methylprednisolone is in the range of 1.8 to 5.2 hours. The apparent volume of distribution is approximately 1.4 mL / kg and its total clearance is approximately 5 to 6 mL / min / kg. Methylprednisolone, like many CYP3A4 substrates, may also be a substrate for the ATP-binding cassette (ABC), p-glycoprotein transport protein, which affects tissue distribution and interactions with other drugs. No adjustments are required. dosage in case of renal insufficiency Methylprednisolone is hemodialysable.
After i.v. in healthy volunteers of 30 mg / kg of SOLU-MEDROL in a time of 20 minutes, there is a mean peak concentration of 19.9 mcg / ml.
Methylprednisolone is metabolised and inactivated in the liver and is excreted primarily via the kidney and bile.
05.3 Preclinical safety data
No unexpected risks were identified based on conventional safety pharmacology studies of repeated toxic dose administration in mice, rats, rabbits and dogs intravenously, intraperitoneally, subcutaneously, intramuscularly and orally.
Methylprednisolone is a potent steroid, with pharmacological activity consistent with that of glucocorticoids, including effects on carbohydrate metabolism, electrolytes, water balance, blood morphological elements, lymphoid tissue and protein metabolism, which lead to decreased body weight or lack of weight gain, lymphopenia, atrophy of the spleen, thymus, lymph nodes, adrenal cortex and testes, as well as changes in liver lipids and enlargement of pancreatic islet cells. 30-day reversibility test conducted on rats treated with methylprednisolone indicated that organ function returned to normal within approximately 1 month of drug discontinuation.After 52 weeks of methylprednisolone suleptanate treatment in rats, many parameters returned to normal after a 9-week period. Toxicity observed in repeat dose studies is that expected with continued exposure to exogenous adrenocortical steroids. Carcinogenic Potential: Long-term animal studies have not been conducted to evaluate carcinogenic potential as the drug is indicated for treatment of short term and there are no indicative signs of carcinogenic activity. There is no evidence that corticosteroids are carcinogenic. Mutagenic potential:
There is no evidence of a potential for genetic or chromosomal mutation when testing for DNA damage with the Alkaline Elution Test on Chinese Hamster V-79 cells. Methylprednisolone did not induce chromosomal damage in the absence of a liver activation system. Teratogenic potential: In animal studies to evaluate the embryotoxic effects of methylprednisolone, no teratogenic effect was observed in mice or rats treated at daily intraperitoneal doses at 125 mg / kg / day or 100 mg / kg / day, respectively. In rats, methylprednisolone was found to be teratogenic when administered subcutaneously at a dose of 20 mg / kg / day. Methylprednisolone aceponate was teratogenic when administered subcutaneously to rats at a dosage of 1.0 mg / kg / day.
The acute toxicity data relating to the experimental animal are as follows:
SOLU-MEDROL, at doses of 15-150 mg / kg / day for 50 days, does not cause significant changes in the normal course of body weight and anatomical-functional parameters of the main organs in the adult rat.
Studies conducted on rabbits have shown good local tolerability at the level of the conjunctival mucosa, skin tissue and veins. In the rat a satisfactory muscular tolerability was observed.
Teratogenic studies have shown changes commonly observed with corticosteroids (cleft palate, encephalocele and hydrocephalus) in rabbits.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
SOLU-MEDROL 40 mg: lactose monohydrate; sodium bisphosphate; sodium phosphate; benzyl alcohol; water for injections.
SOLU-MEDROL 125-500-1000-2000 mg: sodium bisphosphate; sodium phosphate; benzyl alcohol; water for injections.
06.2 Incompatibility
Since the compatibility and stability of methylprednisolone sodium succinate in solution for intravenous administration with other drugs depend on various factors (final pH of the solutions, concentration, temperature, etc.), it is recommended, where possible, to administer SOLU-MEDROL separately.
06.3 Period of validity
With intact packaging
SOLU-MEDROL 40 mg / 1 ml -1 double-chamber bottle: 2 years.
SOLU-MEDROL 125 mg / 2 ml - 1 double chamber bottle: 2 years.
SOLU-MEDROL 500 mg / 8 ml - powder + solvent bottle: 5 years.
SOLU-MEDROL 1000 mg / 16 ml - powder + solvent bottle: 5 years.
SOLU-MEDROL 2000 mg / 32 ml - powder + solvent bottle: 5 years.
After reconstitution of the solution: 48 hours.
06.4 Special precautions for storage
For storage conditions of the reconstituted medicinal product see section 6.3 "Shelf life".
06.5 Nature of the immediate packaging and contents of the package
Neutral glass bottles with rubber stopper.
SOLU-MEDROL 40 mg / 1 ml: 1 double chamber bottle.
SOLU-MEDROL 125 mg / 2 ml: 1 double chamber bottle.
SOLU-MEDROL 500 mg / 8 ml: powder + solvent bottle.
SOLU-MEDROL 1000 mg / 16 ml: powder + solvent bottle.
SOLU-MEDROL 2000 mg / 32 ml: powder + solvent bottle.
06.6 Instructions for use and handling
A) Double chamber bottle: press the cap firmly to introduce the solvent into the lower compartment of the bottle containing the lyophilisate. Shake the bottle until completely dissolved. Remove the plastic cover that protects the central part of the rubber stopper and sterilize appropriately. Insert the needle directly through the center of the cap until the tip is just visible. Turn the bottle upside down and aspirate the contents.
B) Bottle with separate sterile solvent: remove the protective cap of the bottle and proceed in the usual way.
For intramuscular and intravenous injections, no further dilution is necessary: for infusions with SOLU-MEDROL, use a volume of 100 to 1000 ml (never less than 100 ml) of 5% glucose solution or of physiological or glucose solution 5% in physiological solution (if the patient is not on a low-sodium diet) and dilute SOLU-MEDROL in this solution.
Warnings: Once in solution, SOLU-MEDROL must be used within 48 hours.
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
SOLU-MEDROL 40 mg - AIC 023202017
SOLU-MEDROL 125 mg - AIC 023202043
SOLU-MEDROL 500 mg - AIC 023202056
SOLU-MEDROL 1000 mg - AIC 023202068
SOLU-MEDROL 2000 mg - AIC 023202070
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
AIC: December 31, 1984
Renewal: May 31, 2005
10.0 DATE OF REVISION OF THE TEXT
AIFA determination of 20 September 2012
