Active ingredients: Methylprednisolone (Methylprednisolone acetate)
DEPO MEDROL 40 mg / mL
Why is Depo Medrol used? What is it for?
PHARMACOTHERAPEUTIC CATEGORY
Systemic corticosteroids, glucocorticoids
THERAPEUTIC INDICATIONS
Intramuscular administration
When it is not possible to practice oral therapy and the dosage, the pharmaceutical form and the route of administration of the drug make the preparation suitable for the treatment of the pathological condition, the intramuscular use of DEPO-MEDROL suspension of methylprednisolone acetate is indicated in the following cases :
- Endocrine disorders Primary and secondary adrenocortical insufficiency (hydrocortisone or cortisone remain the first choice drugs; synthetic analogues can be used, when applicable, in association with mineralocorticoids; integration with mineralocorticoids is of particular importance in childhood) . Acute adrenocortical insufficiency (hydrocortisone or cortisone remain the first choice drugs; integration with mineralocorticoids may be necessary, particularly when synthetic analogues are used). Before surgery and in case of trauma or serious illness, in patients in whom adrenal insufficiency is known or in whom adrenocortical reserve is questionable, congenital adrenal hyperplasia, tumor-associated hypercalcemia, non-suppurative thyroiditis.
- Rheumatological conditions As adjunctive therapy for short-term administration (to help the patient overcome an acute episode or "exacerbation) in the following cases: Post-traumatic osteoarthritis, synovitis in the course of osteoarthritis, rheumatoid arthritis, including juvenile rheumatoid arthritis, special cases may require low-dose maintenance therapy, acute and subacute bursitis, epicondylitis, acute nonspecific tenosynovitis, acute gouty arthritis, psoriatic arthritis, ankylosing spondylitis.
- Collagen diseases During exacerbation or as maintenance therapy in special cases of: systemic lupus erythematosus, systemic dermatomyositis (polymyositis), acute rheumatic carditis.
- Dermatological conditions Pemphigus, severe erythema multiforme (Steven-Johnson syndrome), exfoliative dermatitis, bullous herpetiformis dermatitis, severe seborrheic dermatitis, severe psoriasis, mycosis fungoides.
- Allergic states For the control of severe or disabling allergic conditions, not treatable with conventional therapy in cases of: Bronchial asthma, contact dermatitis, atopic dermatitis, serum sickness, seasonal or perennial allergic rhinitis, hypersensitivity reactions to drugs, urticarial reactions from transfusion, acute uninfected laryngeal edema (adrenaline is the drug of choice).
- Ophthalmic affections Acute and chronic severe inflammatory and allergic processes affecting the eye and its appendages such as: Ophthalmic herpes zoster, iritis and iridocyclitis, chorioretinitis, diffuse posterior uveitis and choroiditis, optic neuritis, sympathetic ophthalmia, inflammation of the anterior segment, allergic conjunctivitis , corneal marginal ulcers
- Gastrointestinal affections To make the patient overcome a critical period of illness in the following cases: Ulcerative colitis, segmental enteritis. - Respiratory affections Symptomatic sarcoidosis, berylliosis, fulminant or diffuse pulmonary tuberculosis, in association with appropriate antituberculous chemotherapy, Loeffler's syndrome not otherwise treatable, "ab ingestis" pneumonia.
- Haematological disorders Acquired (autoimmune) haemolytic anemia, secondary thrombocytopenia in adults, erythroblastopenia (red cell anemia), congenital (erythrocyte) hypoplastic anemia.
- Neoplastic diseases For the palliative treatment of: Leukemia and lymphomas in adults, acute childhood leukemia.
- Edematous states To induce diuresis or remission of proteinuria from nephrotic syndrome, without uremia, of idiopathic type or lupus erythematosus.
- Nervous system Acute exacerbations of multiple sclerosis
- Other indications Tuberculous meningitis with subarachnoid block or impending block, in association with appropriate antituberculous therapy, trichiniasis with neurological or myocardial involvement.
B. Intra-synovial, periarticular and intrabursal administration - See
PRECAUTIONS FOR USE.DEPO-MEDROL is indicated as adjunct therapy for short-term administration (to help the patient overcome an acute episode or "exacerbation) in the following cases: Osteoarthritis synovitis, rheumatoid arthritis, acute and subacute bursitis, acute gouty arthritis, epicondylitis, acute nonspecific tenosynovitis, post-traumatic osteoarthritis.
C. Intralesional administration
DEPO-MEDROL is indicated for intralesional use in the following conditions: keloids, inflammatory lesions, infiltrates, localized hypertrophic (lichen planus, psoriatic plaques, annular granuloma and chronic lichen simplex, discoid lupus erythematosus, lipoid necrobiosis in diabetics, alopecia areata). DEPO-MEDROL can also be administered intralesionally into the tendon and aponeurotic.
Contraindications When Depo Medrol should not be used
Hypersensitivity to the active substance or to any of the excipients.
- Systemic fungal infections.
- Intravenous and intrathecal administration.
- Epidural administration.
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 Depo Medrol
This product is not suitable for multi-dose use. After administration of the desired dose, the remaining suspension should be discarded.
Tell your doctor or pharmacist if you have recently taken any other medicines, even those without a prescription.
Corticosteroids injected into the dermis can give rise to the formation of crystals which, by suppressing inflammatory reactions, can induce the destruction of cellular elements and physico-chemical modifications in the basal substance of the connective tissue.
These rarely occurring changes in the dermis and subcutaneous tissue can result in skin depressions at the injection site.
The extent of these reactions depends on the amount of steroid injected.
Regeneration is usually complete within a few months or after all corticosteroid crystals have been absorbed.
To minimize the incidence of atrophy of the dermis and subcutaneous tissue, the utmost care must be taken not to exceed the recommended doses for injections. Whenever possible, give multiple injections of small amounts within the wound area.
The intra-synovial and intramuscular administration technique must avoid injection and infiltration of the product into the dermis.
Injection into the deltoid muscle should be avoided due to the high incidence of subcutaneous atrophy.
DEPO-MEDROL is not indicated for intrathecal, epidural, intranasal, intraocular and any other unapproved route (see Therapeutic indications). When administering methylprednisolone acetate it is essential to use appropriate technique and to be careful to ensure correct placement of the drug.
Serious medical events have been reported in association with routes of administration other than those indicated, particularly intrathecal / epidural (see section Undesirable effects reported following non-recommended routes of administration). Adequate measures should be taken to avoid intravascular injection.
Observe the following additional precautions for parenteral corticosteroids.
The intrasynovial injection of a corticosteroid can induce both systemic and local effects. It is therefore necessary to carefully examine the joints to rule out a septic process. A marked increase in pain accompanied by local swelling, further restriction of joint movement, fever and malaise are indicative of a "septic arthritis; in this case, institute" appropriate antibiotic therapy.
Avoid local injection of a steroid into a joint previously affected by septic process.
Corticosteroids should not be injected into joints with ongoing inflammatory processes.
It is necessary to operate with sterile techniques to prevent infection or contamination. It should be borne in mind that the rate of absorption after intramuscular administration is slower.
Immunosuppressive effects / increased susceptibility to infections
Corticosteroids can increase susceptibility to infections, mask some signs of infection, and new infections can occur during their use.
Decreased resistance and inability to localize infection may occur during use of corticosteroids. Infections caused by any pathogen, including viral, bacterial, fungal, or protozoal or helminth infections, anywhere in the body, can be associated with the use of corticosteroids alone or in combination with other immunosuppressive agents that affect immunity cellular, humoral immunity or neutrophil function. These infections can be mild, but they can also be serious and sometimes fatal. With increasing doses of corticosteroids, the rate of occurrence of infectious complications increases. In the presence of acute infection do not use intrasynovial, intrabursal or intratendinous administration to obtain a local effect.
Those who take drugs that suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more severe or even fatal course in non-immune children or adults who take corticosteroids.
The use of DEPO-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 a positive response to tuberculin, close observation is required as reactivation of the disease may occur. During prolonged therapy, these patients should receive chemoprophylactic coverage.
Kaposi's sarcoma has been reported in patients receiving corticosteroids.
Withdrawal of corticosteroids can lead to clinical remission.
Effects on the immune system
Allergic skin reactions may occur. Since rare cases of skin and anaphylactic / anaphylactoid reactions have occurred in patients treated with corticosteroid therapy, adequate precautionary measures should be taken prior to administration, especially when the patient has a history of drug allergy. Patients should not be vaccinated against smallpox during corticosteroid treatment. Killed or inactivated vaccines can be administered to patients receiving immunosuppressive doses of corticosteroids, however, the response to such vaccines may be reduced. The indicated immunization procedures can be undertaken in patients receiving non-immunosuppressive doses of corticosteroids. 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.
Endocrine effects
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 given over prolonged periods can cause suppression of the hypothalamic-pituitary-adrenal axis (HPA) (secondary adrenal insufficiency). The degree and duration of adrenal insufficiency produced varies among patients and is dependent on dosage, frequency. , the time of administration and the duration of glucocorticoid therapy. This effect can be reduced thanks to a therapy to be followed every other day.
In addition, acute adrenal insufficiency with fatal outcome may occur if glucocorticoids are abruptly discontinued. Drug-induced secondary adrenal insufficiency can then be minimized by gradual dose reduction. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any stressful situation occurring during this period, hormone therapy must be resumed. Steroid "withdrawal syndrome", apparently unrelated to adrenal insufficiency. This syndrome includes symptoms such as: anorexia, nausea, vomiting, lethargy, headache, fever, joint pain, scaling, myalgia, weight loss and / or hypotension These effects are likely due to the sudden change in glucocorticoid concentration rather than low corticosteroid levels.
Since glucocorticoids can produce or aggravate Cushing's syndrome, glucocorticoids should be avoided in patients with Cushing's disease. In patients with hypothyroidism or with cirrhosis of the liver, the response to corticosteroids is increased.
Metabolism and nutrition
Corticosteroids, including methylprednisolone, can raise blood sugar, worsen pre-existing diabetes, and predispose patients on long-term corticosteroid therapy to diabetes mellitus.
The lowest possible dose capable of controlling the disease state should be used during therapy and when dose reduction is feasible, it should be done gradually.
Psychiatric Effects
Corticosteroids can give rise to psychic alterations such as euphoria, insomnia, emotional instability, personality changes, severe depressions up to frankly psychotic manifestations. Additionally, pre-existing emotional instability or psychotic tendencies can be aggravated by corticosteroids.
Potentially serious psychiatric adverse reactions can occur with systemic steroids. Symptoms typically emerge within a few days or weeks of starting treatment. Most reactions disappear after dose reduction or discontinuation, although specific treatment may be required. Psychological effects have been reported on discontinuation of corticosteroids; frequency is not known. Patients or caregivers should be encouraged to seek medical attention if the patient develops psychological symptoms, especially if depression or suicidal ideation is suspected. Patients or caregivers should be alert for possible psychiatric disorders that may occur during or immediately after reducing / discontinuing the dose of systemic steroids.
Effects on the nervous system
Corticosteroids should be used with caution in patients with seizure disorders.
Corticosteroids should be used with caution in patients with myasthenia gravis (see myopathy part in the Musculoskeletal Effects section).
Although it has emerged from controlled clinical studies that corticosteroids are able to accelerate the resolution of acute exacerbations of multiple sclerosis, they have not been found to affect the final response or the natural evolution of the disease.
These studies show that relatively high doses of corticosteroids are required for a significant effect to be achieved (see DOSE, METHOD AND TIME OF ADMINISTRATION).
There have been reports of seizures following a combined treatment of cyclosporine with high doses of methylprednisolone.
Cases of epidural lipomatosis have been reported in patients taking corticosteroids, usually in high doses and for prolonged periods.
Ocular effects
Prolonged use of corticosteroids can cause subcapsular posterior cataracts and nuclear cataracts (particularly in children), exophthalmos or an increase in intraocular pressure, which can cause glaucoma with possible damage to the optic nerves and can promote the onset of secondary ocular infections due to fungi or viruses.
Corticosteroids should be used with caution in patients with ocular herpes simplex due to the possibility of causing corneal perforation.
Corticosteroid therapy has been associated with central serous chorioretinopathy, which can lead to retinal detachment.
Cardiac effects
Adverse effects of glucocorticoids on the cardiovascular system, such as dyslipidemia and hypertension, in the event of prolonged cycles or high doses, may predispose patients treated with existing cardiovascular risk factors to an increase in such cardiovascular effects. Consequently, corticosteroids should be used judiciously in such patients and attention should be paid to the variation in risk and further cardiac monitoring should be performed if necessary.Systemic corticosteroids should be used with caution, and only as strictly necessary, in cases of congestive heart failure.
Vascular effects
Corticosteroids should be used with caution in patients with hypertension.
Gastrointestinal effects
There is no universal agreement on whether corticosteroids are in themselves responsible for the peptic ulcers found during therapy; however, glucocorticoid therapy can mask the symptoms of peptic ulcer and, consequently, perforation or bleeding can occur without significant pain. In combination with NSAIDs, the risk of developing gastrointestinal ulcers is increased.
Steroids should be used with caution in case of nonspecific ulcerative colitis, if there is a risk of perforation, abscess or other pyogenic infection. When steroids are used as direct or in combination therapy, care should also be taken in the presence of diverticulitis, recent intestinal anastomosis, latent or active peptic ulcer. Effects on the hepatobiliary system High doses of corticosteroids can produce acute pancreatitis.
Musculoskeletal effects
Acute myopathy has been reported with the use of high doses of corticosteroids; this occurs more frequently in patients with neuromuscular transmission disorders (eg, myasthenia gravis), or in patients receiving concomitant anticholinergic therapy, such as eg neuromuscular blockers (eg pancuronium) (See Effects on the nervous system). This acute myopathy is generalized, can involve the ocular and respiratory muscles, and can cause tetraparesis. Creatine kinase increases may occur. For clinical improvement or recovery after discontinuation of corticosteroids may take weeks to years.
Osteoporosis is a common but rarely recognized adverse effect associated with long-term use of high doses of glucocorticoids.
Renal and urinary tract disorders
Corticosteroids should be used with caution in patients with renal insufficiency.
Diagnostic tests
Prolonged therapy and high doses of corticosteroids can lead to increased blood pressure, alterations in the water-electrolyte balance and increased potassium excretion. These effects are less likely to occur with synthetic derivatives, except when used in large doses. Dietary sodium restrictions and potassium supplementation may be necessary. All corticosteroids increase calcium excretion.
Injuries, poisoning and procedural complications
High doses of systemic corticosteroids should not be used to treat traumatic brain injuries.
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. Aspirin and non-steroidal anti-inflammatory agents should be used with caution in combination with corticosteroids. Acetylsalicylic acid should be used with caution during corticosteroid therapy 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 can be suppressed in children treated with glucocorticoids with long-term divided daily therapy.
The use of this regime must be limited to the most serious indications.
Infants and children undergoing prolonged corticosteroid therapy are particularly at risk of increased intracranial pressure. High doses of corticosteroids can cause 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 can change the effect of Depo 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 CYP3A enzyme. CYP3A4 is the dominant enzyme of the CYP subfamily most abundant in the liver of adult humans. It catalyzes 6β-hydroxylation of steroids, the Phase I metabolic step essential for both endogenous and synthetic corticosteroids. Many other compounds are also 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 (Table 1).
The drug interactions of DEPO-MEDROL are those of corticosteroids.
However, due to the particular modes of absorption of DEPO-MEDROL, the clinical manifestations of these interactions may be altered.
Corticosteroids interact mainly with: rifampicin, phenytoin, barbiturates (decreased corticosteroid effect); estrogen, ketoconazole, troleandomycin, erythromycin (increased corticosteroid effect); salicylates (decreased effect of salicylates); ethacrynic acid, thiazides, furosemide (increased loss of potassium); ethacrynic acid, indomethacin, acetylsalicylic acid, NSAIDs (increased risk of gastric ulceration); cyclophosphamide (decreased effect of cyclophosphamide); amphotericin (hypokalemia); antidiabetics (decreased blood sugar control).
CYP3A4 INHIBITORS - Medicinal products that inhibit CYP3A4 activity generally decrease hepatic clearance and increase the plasma concentration of CYP3A4 substrate drugs, such as methylprednisolone. In the presence of a CYP3A4 inhibitor, the dose of methylprednisolone may need to be titrated to avoid steroid toxicity (Table 1).
CYP3A4 INDUCTORS - Medicinal products that induce CYP3A4 activity generally increase hepatic clearance, resulting in decreased plasma concentrations of medicinal products that are CYP3A4 substrates. Co-administration may require an increase in methylprednisolone dosage to achieve the desired result ( Table 1).
CYP3A4 SUBSTRATES - In the presence of another CYP3A4 substrate, effects on hepatic clearance of methylprednisolone may occur, resulting in necessary dose adjustments. Adverse events associated with single drug use alone may be more likely to occur with co-administration (Table 1).
EFFECTS NOT MEDIATED BY CYP3A4 - Other interactions and effects occurring with methylprednisolone are described in Table 1 below.
Table 1. Important drug or substance interactions / effects 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
Adequate human reproduction studies with corticosteroids have not been performed. Corticosteroids have been shown to reduce fertility in animal studies.
Pregnancy
Some studies conducted in experimental animals have shown that corticosteroids administered to mothers can induce fetal malformations. As there are no clinical data on the effects of corticosteroid therapy on reproduction, the use of corticosteroids in known or presumed pregnant women must be reserved for cases of real need under the direct supervision of the doctor. If prolonged or high-dose corticosteroid treatment during pregnancy is not delayed, the neonate should be carefully monitored for hypoadrenalism. Although neonatal adrenal insufficiency appears to be rare in infants who have been exposed to corticosteroids in utero. A retrospective study found an increased incidence of low birth weight in infants born to mothers receiving corticosteroids. Cases of cataracts have been observed in infants born to mothers treated with long-term corticosteroids during pregnancy. The effects of corticosteroids on labor from delivery are not known.
Feeding time
Corticosteroids are excreted in breast milk, therefore breastfeeding should be discontinued during corticosteroid therapy. Corticosteroids distributed in breast milk may inhibit growth and interfere with endogenous glucocorticoid production in infants. Since adequate studies have not been performed. on reproduction in humans with glucocorticoids, these drugs should only be given to nursing mothers if the benefits of therapy are judged to outweigh the potential risks to the newborn. 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
DEPO-MEDROL contains less than 1 mmol (23mg) sodium (per dose) ie practically "sodium free".
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 Depo Medrol: Dosage
The lowest possible dose that can control should be used during therapy
the pathological state and when the reduction of the dosage is feasible, it must be done gradually.
Local administration
This therapy should be understood as symptomatic and not causal.
1. Rheumatoid arthritis and osteoarthritis.
The dose for intra-articular administration depends on the size of the joint and varies with the severity of the condition in the individual patient. In chronic cases, infiltrations can be repeated at intervals ranging from 1 to 5 or more weeks depending on the degree of improvement obtained from the first administration The doses in the following table are given as a general guide:
Table 2. Medicinal product dosage
Method of administration: a revision of the anatomy of the joint to be treated is recommended before proceeding with intra-articular infiltration. To achieve complete anti-inflammatory activity, it is important that infiltration is performed in the synovial space.
Using the same sterile technique used for lumbar puncture, quickly insert a sterile 20-24 needle, mounted on a dry syringe, into the synovial cavity. Procaine infiltration is optional. Aspiration of a few drops of synovial fluid ensures complete entry of the needle into the joint space.
The injection site for each joint is determined by the location of the most superficial synovial cavity and most devoid of large vessels and nerves.
By leaving the needle at the injection site, you will replace the syringe containing the drops of aspirated liquid with another syringe containing the desired amount of DEPO MEDROL. Further check by suction that the needle is always in place.
After infiltration, move the joint slightly to help disperse the suspension in the synovial fluid. Cover the infiltration site with sterile gauze. Suitable sites for intra-articular infiltration are the knee, ankle, wrist, elbow, shoulder, phalangeal and hip joints.
Since occasionally it is possible to encounter difficulties in penetrating the hip joint, precautions must be taken to avoid the large vessels in the area.
Joints unsuitable for infiltration are those anatomically inaccessible, such as spinal and sacroiliac joints with no synovial space. Treatment failures are most frequently due to failed drug introduction into the joint space. Infiltration into surrounding tissue leads to poor or no benefit. If the failure occurs after an injection surely made into the synovial space (verified by aspiration of the liquid), it is superfluous to repeat the infiltration.
Local therapy is not able to modify the underlying disease process, therefore, when possible, practice a comprehensive therapy including physiotherapy and orthopedic revision.
After intra-articular therapy with corticosteroids, take particular care to avoid abuse of the joint, favored by the symptomatic benefit obtained.
Neglect of this circumstance may allow for increased joint damage which nullifies the benefit of the steroid.
There must be no infiltrations in the joints with inflammatory processes in place.
Repeated infiltrations can sometimes induce "inflammation of the joint". In particular cases it is advisable to check the damage by X-rays. If a local anesthetic is used before the infiltration of DEPO MEDROL, first read the package leaflet carefully and observe all the recommended precautions.
2. Bursitis
Sterilize the area surrounding the site to be infiltrated and anesthetize with 1% procaine hydrochloride solution. Attach a 20-24 size needle to a dry syringe, insert it into the bag and aspirate the fluid. Leave the needle in place and replace the syringe used to draw with a smaller syringe containing the desired dose of DEPO MEDROL. After the injection, pull the needle and apply a small dressing.
Use the same technique indicated for intra-articular infiltration.
3. Tendon cysts, tendinitis, epicondylitis
In the treatment of these conditions inject the suspension into the tendon sheath rather than its thickness. Properly sterilize the overlying skin before infiltration. The tendon can be easily palpated when it is stretched. To treat epicondylitis it is advisable to carefully delineate the area of greatest pain for infiltration into the area. Tendon cysts must be infiltrated directly. In many cases, a single infiltration is sufficient to induce a significant decrease in the size of the cysts and the elimination of the effect.
The dose to be administered in the treatment of these forms varies from 4 to 30 mg. In chronic or recurrent diseases, more infiltrations may be necessary. For each infiltration, the usual precautions for operating in sterility must be observed. 4.
Local treatment of dermatological diseases
After adequate antiseptic treatment, infiltrate the lesion with doses of 20-60 mg. Sometimes it may be useful to perform a series of small periwound infiltrations of doses of 20 to 40 mg.
Pay attention to avoid the infiltration of material that could induce a reaction which could be followed by a small eschar.
Normally 1 to 4 infiltrations are performed at variable intervals according to the type of lesion to be treated and the duration of the improvement achieved with the first injection.
Systemic intramuscular administration
The dosage varies according to the morbid condition to be treated.
When a prolonged effect is required, only one injection per week of DEPO MEDROL can be given intramuscularly, calculating the dosage by multiplying the daily oral dose of methylprednisolone x 7.
Dosage must be identified for each patient. The basic criteria for determining the dosage are the severity, prognosis, expected duration of the disease and the patient's reaction to treatment.
In infancy, the recommended dosage must be reduced, but favoring the severity of the condition with respect to the age / body weight ratio for the choice of dosage.
Hormone therapy is a support and not a replacement for conventional therapy.
After administration of the drug for several days, the dosage should be gradually reduced or discontinued.
If a period of spontaneous remission occurs during a chronic disease, the treatment should be stopped.
During prolonged therapy, normal blood and urinary parameters, post-prandial glycaemia, blood pressure and body weight should be monitored; in addition, a chest x-ray is advisable at regular intervals.
In patients with a history of ulcers or significant dyspepsia, an X-ray examination of the upper gastrointestinal tract is recommended.
In patients with adrenogenital syndrome, a single intramuscular injection of 40 mg of DEPO-MEDROL every two weeks may be sufficient. The weekly intramuscular maintenance dose of DEPO-MEDROL for rheumatoid arthritis patients will range from 40 to 120 mg. The usual dosage for patients with skin conditions is 40-120 mg intramuscularly at one week intervals for a period of one to four weeks.
In severe acute dermatitis caused by Canada Ivy, intramuscular administration of a single dose of 80-120 mg can bring relief within 8-12 hours.
In chronic contact dermatitis, repeated injections may be needed at intervals of 5-10 days.
In seborrheic dermatitis, a weekly dose of 80 mg of DEPO MEDROL may be suitable for controlling the pathological condition.
After intramuscular administration of 80-120 mg of DEPO-MEDROL to asthmatic patients, relief may be achieved within a period of 6 to 48 hours with persistent effect for several days and up to two weeks.Similarly, in patients suffering from allergic rhinitis, the intramuscular administration of 80-120 mg of DEPO-MEDROL can induce relief within 6 hours with persistent effect for a period of several days up to three weeks.
If the condition being treated is accompanied by symptoms of stress, the doses of DEPO-MEDROL should be increased. If a rapid and maximum intensity effect is desired, the administration of the soluble salt (methylprednisolone sodium succinate) intravenously is suggested.
Rectal administration in ulcerative colitis
The administration of DEPO-MEDROL in dosages of 40-120 mg, by retentive enema or continuous drip from 3 to 7 times a week, for two and / or more weeks has proved to be a "useful adjuvant therapy in the treatment of some cases of colitis ulcerative.
Many patients can be controlled with 40 mg of DEPO-MEDROL administered in 30-300 ml of water depending on the extent of the inflamed colonic mucosa. However, other suitable therapeutic measures must also be undertaken.
Instructions for Use
Before administering parenteral preparations, the contents should be visually inspected for the presence of particles or discolouration.
Incompatibility
Methylprednisolone acetate 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 DEPO-MEDROL with other solutions.
Overdose What to do if you have taken too much Depo Medrol
Reports of acute toxicity and / or death following corticosteroid overdose are rare. In the event of an overdose, no specific antidotes are available; treatment is symptomatic and supportive.
The use of repeated doses frequently, daily or several times a week, for a prolonged period over time can induce the onset of a Cushingoid syndrome. Methylprednisolone is dialysable.
In case of accidental ingestion / intake of an excessive dose of DEPO-MEDROL, notify your doctor immediately or go to the nearest hospital. If you have any questions about the use of DEPO-MEDROL, ask your doctor or pharmacist.
Side Effects What are the side effects of Depo Medrol
Like all medicines, DEPO-MEDROL can cause side effects, although not everybody gets them.
The following undesirable effects have been observed during treatment with methylprednisolone with the following frequencies: very common (≥1 / 10); common (≥1 / 100 to
* Not a preferred MedDRA term
UNDESIRABLE EFFECTS OBSERVED WITH NOT RECOMMENDED ROUTES OF ADMINISTRATION
- Intrathecal / epidural route Arachnoiditis, meningitis, paraparesis, paraplegia, sensory disturbances, intestinal / bladder dysfunctions, headache, seizures, convulsions, sensory disturbances. The frequency of these adverse reactions is not known.
- Intranasal route Temporary / permanent changes in vision including blindness, allergic reactions, rhinitis
- Ophthalmic route Temporary / permanent changes in vision including blindness, increased intraocular pressure, ocular and periocular inflammation including allergic reactions, infections, residues or scabs at the injection site
- Other injection sites (scalp, palatine tonsils, sphenopalatine ganglia) Blindness
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. 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 indicated 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.
Storage: Do not freeze.
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 and pharmaceutical form
COMPOSITION
Each 1 mL bottle contains: methylprednisolone acetate 40 mg (equivalent to 36 mg of methylprednisolone).
Excipients: Macrogol 3350; sodium chloride; myristyl gamma picolinium chloride; sodium hydroxide; hydrochloric acid; water for injections.
PHARMACEUTICAL FORM AND CONTENT
Suspension for injection 40 mg / ml.
1 bottle of 1 ml
3 bottles of 1 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
DEPO-MEDROL 40 MG INJECTABLE SUSPENSION
02.0 QUALITATIVE AND QUANTITATIVE COMPOSITION
A 1ml bottle contains: principle active: methylprednisolone acetate 40 mg.
Excipients with known effects: sodium chloride.
For the full list of excipients see section 6.1.
03.0 PHARMACEUTICAL FORM
Suspension for injection.
04.0 CLINICAL INFORMATION
04.1 Therapeutic indications
A. Intramuscular administration
When it is not possible to practice oral therapy and the dosage, the pharmaceutical form and the route of administration of the drug make the preparation suitable for the treatment of the pathological condition, the intramuscular use of DEPO-MEDROL suspension of methylprednisolone acetate is indicated in the following cases :
- Endocrine disorders
Primary and secondary adrenocortical insufficiency (hydrocortisone or cortisone remain the first choice drugs; synthetic analogues can be used, when applicable, in association with mineralocorticoids; integration with mineralocorticoids is of particular importance in childhood).
Acute adrenocortical insufficiency (hydrocortisone or cortisone remain the drugs of choice; supplementation with mineralocorticoids may be necessary, particularly when synthetic analogues are used).
Before surgery and in case of trauma or serious illness, in patients with known adrenal insufficiency or in whom adrenocortical reserve is questionable.
Congenital adrenal hyperplasia, tumor-associated hypercalcemia, non-suppurative thyroiditis.
- Rheumatological affections
As adjunctive therapy for short-term administration (to help the patient overcome an acute episode or "exacerbation) in the following cases:
Post-traumatic osteoarthritis, synovitis in the course of osteoarthritis, rheumatoid arthritis, including juvenile rheumatoid arthritis, special cases may require low-dose maintenance therapy, acute and subacute bursitis, epicondylitis, acute nonspecific tenosynovitis, acute gouty arthritis, arthritis psoriatic, ankylosing spondylitis.
- Collagen diseases
During exacerbation or as maintenance therapy in special cases of: systemic lupus erythematosus, systemic dermatomyositis (polymyositis), acute rheumatic carditis.
- Dermatological affections
Pemphigus, severe erythema multiforme (Steven-Johnson syndrome), exfoliative dermatitis, bullous herpetiformis dermatitis, severe seborrheic dermatitis, severe psoriasis, mycosis fungoides.
- Allergic states
For the control of severe or disabling allergic conditions, not treatable with conventional therapy in cases of: bronchial asthma, contact dermatitis, atopic dermatitis, serum sickness, seasonal or perennial allergic rhinitis, hypersensitivity reactions to drugs, transfusion urticarial reactions, acute uninfected laryngeal edema (adrenaline is the drug of choice).
- Ophthalmic affections
Acute and chronic severe inflammatory and allergic processes affecting the eye and its appendages such as: Ophthalmic herpes zoster, iritis and iridocyclitis, chorioretinitis, diffuse posterior uveitis and choroiditis, optic neuritis, sympathetic ophthalmia, anterior segment inflammation, allergic conjunctivitis, ulcers allergic corneal margins, keratitis.
- Gastrointestinal affections
To make the patient overcome a critical period of illness in the following cases:
Ulcerative colitis, segmental enteritis.
- Respiratory affections
Symptomatic sarcoidosis, berylosis, fulminant or diffuse pulmonary tuberculosis, in association with appropriate antituberculous chemotherapy, Loeffler's syndrome not otherwise treatable, "ab ingestis" pneumonia.
- Hematological affections
Acquired (autoimmune) haemolytic anemia, secondary thrombocytopenia in adults, erythroblastopenia (red cell anemia), congenital (erythrocyte) hypoplastic anemia.
- Neoplastic diseases
For the palliative treatment of:
Leukemia and lymphomas in adults, acute childhood leukemia.
- Edematous states
To induce diuresis or remission of nephrotic syndrome proteinuria, without uremia, idiopathic or lupus erythematosus type.
- Nervous system
Acute exacerbations of multiple sclerosis.
- Other indications
Tuberculous meningitis with subarachnoid block or impending block, in association with appropriate antituberculous therapy, trichiniasis with neurological or myocardial involvement.
B. Intra-synovial or soft tissue administration
(including the periarticular and intraborsal route) - see section 4.4.
DEPO-MEDROL is indicated as an adjunct therapy for short-term administration (to help the patient overcome an acute episode or "exacerbation) in the following cases:
osteoarthritis synovitis, rheumatoid arthritis, acute and subacute bursitis, acute octose arthritis, epicondylitis, acute nonspecific tenosynovitis, post-traumatic osteoarthritis.
C. Intralesional administration
DEPO-MEDROL is indicated for intralesional use in the following conditions:
keloids, inflammatory, infiltrated, localized hypertrophic lesions (lichen planus, psoriatic plaques, granuloma annulare and chronic lichen simplex, discoid lupus erythematosus, lipoid necrobiosis of diabetics, alopecia areata).
DEPO-MEDROL can also be administered intralesionally in tendon and aponeurotic cysts.
04.2 Posology and method of administration
Due to possible physical incompatibilities, DEPO-MEDROL must not be diluted or mixed with other solutions.
Before administering parenteral preparations, the contents should be visually inspected for the presence of particles or discolouration.
Local administration
This therapy should be understood as symptomatic and not causal.
1. Rheumatoid arthritis and osteoarthritis
The dose for intra-articular administration depends on the size of the joint and varies with the severity of the condition in the individual patient. In chronic cases, infiltrations can be repeated at intervals ranging from 1 to 5 or more weeks depending on the degree of improvement obtained from the first administration The doses in the following table are given as a general guide:
Method of administration: a revision of the anatomy of the joint to be treated is recommended before proceeding with intra-articular infiltration. To achieve complete anti-inflammatory activity, it is important that infiltration is performed in the synovial space.
Using the same sterile technique used for lumbar puncture, quickly insert a sterile 20-24 needle, mounted on a dry syringe, into the synovial cavity.
Procaine infiltration is optional.
The aspiration of a few drops of synovial fluid ensures the complete entry of the needle into the joint space.
The injection site for each joint is determined by the location of the most superficial synovial cavity and most devoid of large vessels and nerves.
By leaving the needle at the injection site, you will replace the syringe containing the drops of aspirated liquid with another syringe containing the desired amount of DEPO MEDROL. Further check by suction that the needle is always in place.
After infiltration, move the joint slightly to help disperse the suspension in the synovial fluid.
Cover the infiltration site with sterile gauze.
Suitable sites for intra-articular infiltration are the knee, ankle, wrist, elbow, shoulder, phalangeal and hip joints.
Since occasionally it is possible to encounter difficulties in penetrating the hip joint, precautions must be taken to avoid the large vessels in the area.
Joints unsuitable for infiltration are those anatomically inaccessible, such as spinal and sacroiliac joints without synovial space.
Treatment failures are most frequently due to the failed introduction of the drug into the joint space.
Infiltration into surrounding tissue leads to little or no benefit.
If the failure occurs after an injection surely made into the synovial space (verified by aspiration of the liquid), it is superfluous to repeat the infiltration. Local therapy is not able to modify the underlying disease process, therefore, when possible, practice a comprehensive therapy including physiotherapy and orthopedic revision.
After intra-articular therapy with corticosteroids, take particular care to avoid abuse of the joint, favored by the symptomatic benefit obtained.
Neglect of this circumstance may allow for increased joint damage which nullifies the benefit of the steroid.
There must be no infiltrations in the joints with inflammatory processes in place.
Repeated infiltrations can sometimes induce "inflammation of the joint".
In special cases it is advisable to check the damage by X-rays.
If a local anesthetic is used before DEPO MEDROL infiltration, first read the package leaflet carefully and observe all suggested precautions.
2. Bursitis
Sterilize the area surrounding the site to be infiltrated and anesthetize with 1% procaine hydrochloride solution. Attach a 20-24 size needle to a dry syringe, insert it into the bag and aspirate the fluid. Leave the needle in place and replace the syringe used to draw with a smaller syringe containing the desired dose. After the injection, pull the needle and apply a small dressing.
Use the same technique indicated for intra-articular infiltration.
3. Tendon cysts, tendinitis, epicondylitis
In the treatment of these conditions inject the suspension into the tendon sheath rather than its thickness. Properly sterilize the overlying skin before infiltration. The tendon can be easily palpated when it is stretched. To treat epicondylitis it is advisable to carefully delineate the area of greatest pain for infiltration into the area.
Tendon cysts must be infiltrated directly.
In many cases a single infiltration is sufficient to induce a significant decrease in the size of the cysts and the elimination of the effect.
For each infiltration, the usual precautions for operating in sterility must be observed.
The dose to be administered in the treatment of these forms varies from 4 to 30 mg.
In chronic or recurrent diseases, more infiltrations may be necessary.
4. Local treatment of dermatological diseases
After adequate antiseptic treatment, infiltrate the lesion with doses of 20-60 mg.
Sometimes it may be useful to perform a series of small periwound infiltrations of doses of 20 to 40 mg.
Pay attention to avoid the infiltration of material that could induce a reaction which could be followed by a small eschar.
Normally 1 to 4 infiltrations are performed at variable intervals according to the type of lesion to be treated and the duration of the improvement achieved with the first injection.
Systemic intramuscular administration
The dosage varies according to the morbid condition to be treated.
When a prolonged effect is required, only one injection per week of DEPO MEDROL can be given intramuscularly, calculating the dosage by multiplying the daily oral dose of methylprednisolone x 7.
The dosage must be identified for each patient according to the severity of the disease and the response to treatment.
In infancy, the recommended dosage must be reduced, but favoring the severity of the condition with respect to the age / body weight ratio for the choice of dosage.
Hormone therapy is a support and not a replacement for conventional therapy. After administration of the drug for several days, the dosage should be gradually reduced or discontinued.
The basic criteria for determining the dosage are the severity, prognosis, expected duration of the disease and the patient's reaction to treatment.
If a period of spontaneous remission occurs during a chronic disease, the treatment should be stopped.
During prolonged therapy, normal blood and urinary parameters, post-prandial glycaemia, blood pressure and body weight should be monitored; in addition, a chest x-ray is advisable at regular intervals.
In patients with a history of ulcers or severe dyspepsia, an X-ray examination of the upper gastrointestinal tract is recommended.
In patients with adrenogenital syndrome, a single intramuscular injection of 40 mg of DEPO-MEDROL every two weeks may be sufficient. The weekly intramuscular maintenance dose of DEPO-MEDROL for rheumatoid arthritis patients will range from 40 to 120 mg. The usual dosage for patients with skin conditions is 40-120 mg intramuscularly at one week intervals for a period of one to four weeks. In severe acute dermatitis caused by Canadian ivy, intramuscular administration of a single dose of 80-120 mg can bring relief within 8-12 hours. In chronic contact dermatitis, repeated injections at intervals of 5-10 may be necessary. days.
In seborrheic dermatitis, a weekly dose of 80 mg of DEPO MEDROL may be suitable for controlling the pathological condition.
After intramuscular administration of 80-120 mg of DEPO-MEDROL to asthmatic patients, relief may be achieved within a period of 6 to 48 hours with persistent effect for several days and up to two weeks. Similarly, in patients suffering from allergic rhinitis, the intramuscular administration of 80-120 mg of DEPO-MEDROL can induce relief within 6 hours with persistent effect for a period of several days up to three weeks.
If the condition being treated is accompanied by symptoms of stress, the doses of DEPO-MEDROL must be increased. If a rapid and maximum intensity effect is desired, the administration of the soluble salt (methylprednisolone sodium succinate - SOLU-MEDROL) is suggested for intravenously.
Rectal administration in ulcerative colitis
The administration of DEPO-MEDROL in dosages of 40-120 mg, by retentive enema or continuous drip from 3 to 7 times a week, for two and / or more weeks has proved to be a "useful adjuvant therapy in the treatment of some cases of colitis. Many patients can be controlled with 40 mg of DEPO-MEDROL administered in 30-300 ml of water depending on the extent of the inflamed colonic mucosa. However, other suitable therapeutic measures must also be undertaken.
04.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients, listed in section 6.1 Systemic fungal infections. Intravenous administration. Intrathecal administration.
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
Corticosteroids injected into the dermis can give rise to the formation of crystals which, by suppressing inflammatory reactions, can induce the destruction of cellular elements and physico-chemical modifications in the basal substance of the connective tissue. These rarely occurring changes in the dermis and subcutaneous tissue can result in skin depressions at the injection site.
The extent of these reactions depends on the amount of steroid injected.
Regeneration is usually complete within a few months or after all corticosteroid crystals have been absorbed.
To minimize the incidence of atrophy of the dermis and subcutaneous tissue, the utmost care must be taken not to exceed the recommended doses for injections. Whenever possible, perform multiple injections of small quantities within the lesion area. The intra-synovial and intramuscular administration technique must avoid injection and infiltration of the product into the dermis.
Injection into the deltoid muscle should be avoided due to the high incidence of subcutaneous atrophy.
DEPO-MEDROL is not indicated for intrathecal, epidural, intranasal, intraocular and any other unapproved route (see UNDESIRABLE EFFECTS reported following non-recommended routes of administration).
In patients on corticosteroid therapy, subjected to particular stress, it is essential to adjust the dose according to the extent of the stressful condition.
Immunosuppressive effects / increased susceptibility to infections
Corticosteroids can increase susceptibility to infections, mask some signs of infection, and new infections can occur during their use.
Decreased resistance and inability to localize infection may occur during use of corticosteroids. Infections caused by any pathogen, including viral, bacterial, fungal, or protozoal or helminth infections, anywhere in the body, may be associated with the use of corticosteroids alone or in combination with other immunosuppressive agents that affect immunity cellular, humoral immunity or neutrophil function. These infections can be mild, but they can also be serious and sometimes fatal. With increasing doses of corticosteroids, the rate of occurrence of infectious complications increases. Those who take drugs that suppress the immune system are more susceptible to infections than healthy individuals. Chickenpox and measles, for example, can have a more severe or even fatal course in non-immune children or adults who take corticosteroids. In the presence of acute infection, do not administer intra-synovial, intra-borsal or intra-tendon route due to the local effect. The role of corticosteroids in septic shock is controversial: the first studies report both beneficial and harmful effects. More recently, it has been suggested that corticosteroid supplementation offers benefit in patients with septic shock who present with adrenal insufficiency. However, their routine use in septic shock is not recommended. A systematic review of a short course of high-dose corticosteroids did not support their use. However, meta-analyzes and a review suggest that longer courses (5-11 days) of low-dose corticosteroids could reduce mortality.
Killed or inactivated vaccines can be administered to patients receiving immunosuppressive doses of corticosteroids, however, the response to such vaccines may be reduced. The indicated immunization procedures can be undertaken in patients receiving non-immunosuppressive doses of corticosteroids.
Kaposi's sarcoma has been reported in patients receiving corticosteroids.
Withdrawal of corticosteroids can lead to clinical remission.
Effects on the immune system
Allergic skin reactions may occur. Since rare cases of skin and anaphylactic / anaphylactoid reactions have occurred in patients treated with corticosteroid therapy, adequate precautionary measures should be taken prior to administration, especially when the patient has a history of drug allergy.
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 DEPO-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 a positive response to tuberculin, close observation is required as reactivation of the disease may occur. During prolonged therapy, these patients should receive chemoprophylactic coverage.
Since there have been rare cases of anaphylactoid reactions in patients undergoing parenteral therapy with corticosteroids, appropriate precautions should be taken prior to administration, particularly when the patient has a history of allergy to any drug.
Endocrine effects
Drug-induced secondary adrenal 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 hormonal therapy should be adopted. Drug doses of corticosteroids given over prolonged periods can cause suppression of the hypothalamic-pituitary-adrenal axis (HPA) (secondary adrenal insufficiency). The degree and duration of adrenal insufficiency produced varies among patients and is dependent on dosage, frequency. , the time of administration and the duration of glucocorticoid therapy. This effect can be reduced thanks to a therapy to be followed every other day.
In addition, acute adrenal insufficiency with fatal outcome may occur if glucocorticoids are abruptly discontinued. Drug-induced secondary adrenal insufficiency can then be minimized by gradual dose reduction. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any stressful situation occurring during this period, hormone therapy must be resumed. Since mineralocorticoid secretion may be impaired, a concomitant administration of a salt and / or a mineralocorticoid.
Steroid "withdrawal syndrome", apparently unrelated to adrenal insufficiency, can also occur following 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 likely due to the sudden change in glucocorticoid concentration rather than low corticosteroid levels.
Since glucocorticoids can produce or aggravate Cushing's syndrome, glucocorticoids should be avoided in patients with Cushing's disease. As the secretion of mineralocorticoids can be altered, administer salts and / or drugs with mineralocorticoid activity in combination. In patients with hypothyroidism or with cirrhosis of the liver, the response to corticosteroids is increased.
Metabolism and nutrition
Corticosteroids, including methylprednisolone, can raise blood sugar, worsen pre-existing diabetes, and predispose patients on long-term corticosteroid therapy to diabetes mellitus.
The lowest possible dose capable of controlling the disease state should be used during therapy and when dose reduction is feasible, it should be done gradually.
Psychiatric Effects
Corticosteroids can give rise to psychic alterations such as euphoria, insomnia, emotional instability, personality changes, severe depressions up to frankly psychotic manifestations. Additionally, pre-existing emotional instability or psychotic tendencies can be aggravated by corticosteroids.
Potentially serious psychiatric adverse reactions can occur with systemic steroids. Symptoms typically emerge within days to weeks of starting treatment. Most reactions disappear after dose reduction or discontinuation, although specific treatment may be required. Psychological effects have been reported on discontinuation of corticosteroids; frequency is not known. Patients or caregivers should be encouraged to seek medical attention if the patient develops psychological symptoms, especially if depression or suicidal ideation is suspected. Patients or caregivers should be alert for possible psychiatric disorders that may occur during or immediately after reduction / discontinuation of the dose of systemic steroids.
Acetylsalicylic acid should be used with caution during corticosteroid therapy in patients with hypoprothrombinemia.
Effects on the nervous system
Corticosteroids should be used with caution in patients with seizure disorders.
Corticosteroids should be used with caution in patients with myasthenia gravis (see myopathy part in the Musculoskeletal Effects section below).
Although it has emerged from controlled clinical trials that corticosteroids are able to accelerate the resolution of acute exacerbations of multiple sclerosis, they have not been found to affect the final response or the natural evolution of the disease.
These studies show that relatively high doses of corticosteroids are required for a significant effect to be achieved (see section 4.2).
There have been reports of seizures following a combined treatment of cyclosporine with high doses of methylprednisolone.
Ocular effects
Prolonged use of corticosteroids can cause subcapsular posterior cataracts and nuclear cataracts (particularly in children), exophthalmos or an increase in intraocular pressure, which can cause glaucoma with possible damage to the optic nerves and can promote the onset of secondary ocular infections due to fungi or viruses.
Corticosteroids should be used with caution in patients with ocular herpes simplex due to possible corneal perforation.
Cardiac effects
Adverse effects of glucocorticoids on the cardiovascular system, such as dyslipidemia and hypertension, in the event of prolonged cycles or high doses, may predispose patients treated with existing cardiovascular risk factors to an increase in such cardiovascular effects. Consequently, corticosteroids should be used judiciously in such patients and attention should be paid to the variation in risk and further cardiac monitoring should be performed if necessary.
Systemic corticosteroids should be used with caution, and only if strictly necessary, in cases of congestive heart failure.
Vascular effects
Corticosteroids should be used with caution in patients with hypertension.
Gastrointestinal effects
Care should also be taken in the presence of diverticulitis, recent intestinal anastomosis, latent or active peptic ulcer. There is no universal agreement on whether corticosteroids are in themselves responsible for the peptic ulcers found during therapy; however, glucocorticoid therapy can mask the symptoms of peptic ulcer and, consequently, perforation or bleeding can occur without significant pain; Steroids should be used with caution in case of nonspecific ulcerative colitis, if there is a risk of perforation, abscess or other pyogenic infection.
Effects on the hepatobiliary system
High doses of corticosteroids can produce acute pancreatitis.
Musculoskeletal effects
Acute myopathy has been reported with the use of high doses of corticosteroids; this occurs more frequently in patients with neuromuscular transmission disorders (eg, myasthenia gravis), or in patients receiving concomitant anticholinergic therapy, such as eg neuromuscular blockers (eg pancuronium). This acute myopathy is generalized, can involve ocular and respiratory muscles, and can cause tetraparesis. Creatine kinase increases may occur. Clinical improvement or recovery after discontinuation of corticosteroids may be required. weeks to years.
Osteoporosis is a common but rarely recognized adverse effect associated with long-term use of high doses of glucocorticoids.
Renal and urinary tract disorders
Corticosteroids should be used with caution in patients with renal insufficiency.
Diagnostic tests
Prolonged therapy and high doses of corticosteroids can lead to increased blood pressure, alterations in the water-electrolyte balance and increased potassium excretion. These effects are less likely to occur with synthetic derivatives, except when used in large doses. Dietary sodium restrictions and potassium supplementation may be necessary. All corticosteroids increase calcium excretion.
Other warnings and precautions
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.
Aspirin and non-steroidal anti-inflammatory agents should be used with caution in combination with corticosteroids.
Use in children
Particular attention should be paid to the bodily development of infants and children undergoing prolonged corticosteroid therapy. Infants and children undergoing prolonged corticosteroid therapy are particularly at risk of increased intracranial pressure. High doses of corticosteroids can cause pancreatitis in children.
Growth can be suppressed in children treated with glucocorticoids with long-term divided daily therapy. The use of this regime must be limited to the most serious indications.
Observe the following additional precautions for parenteral corticosteroids.
Intrasynovial injection of a corticosteroid can induce both systemic and local effects.
It is therefore necessary to carefully examine the joints in order to exclude a septic process. A marked increase in pain accompanied by local swelling, "further limitation of joint movement, fever and malaise are indicative of" septic arthritis; in this case, institute an "appropriate antibiotic therapy.
Avoid local injection of a steroid into a joint previously affected by septic process.
Corticosteroids should not be injected into joints with ongoing inflammatory processes.
It is necessary to operate with sterile techniques to prevent infection or contamination. It should be borne in mind that the rate of absorption after intramuscular administration is slower.
The complications resulting from treatment with glucocorticoids are dependent on the extent of the dosage and duration, therefore a risk / benefit assessment must be made and the dose and duration of treatment identified for each individual case.
Important information about some of the ingredients
DEPO-MEDROL contains less than 1 mmol (23mg) sodium (per dose) ie practically "sodium free".
04.5 Interactions with other medicinal products and other forms of interaction
Methylprednisolone is a substrate cytochrome P450 (CYP) enzyme and is primarily metabolised by the CYP3A enzyme. CYP3A4 is the dominant enzyme of the most abundant CYP subfamily in the liver of adult humans. It catalyzes 6β-hydroxylation of steroids, the metabolic phase Phase I essential for both endogenous and synthetic corticosteroids. Many other compounds are also 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 (Table 1).
The drug interactions of DEPO-MEDROL are those of corticosteroids.
However, due to the particular modes of absorption of DEPO-MEDROL, the clinical manifestations of these interactions may be altered.
Corticosteroids interact mainly with: rifampicin, phenytoin, barbiturates (decreased corticosteroid effect); estrogen, ketoconazole, troleandomycin, erythromycin (increased corticosteroid effect); salicylates (decreased effect of salicylates); ethacrynic acid, thiazides, furosemide (increased loss of potassium); ethacrynic acid, indomethacin, acetylsalicylic acid, NSAIDs (increased risk of gastric ulceration); cyclophosphamide (decreased effect of cyclophosphamide); amphotericin (hypokalemia); antidiabetics (decreased blood sugar control).
CYP3A4 INHIBITORS - Drugs that inhibit CYP3A4 activity generally decrease hepatic clearance and increase the plasma concentration of CYP3A4 substrate drugs, such as methylprednisolone. In the presence of a CYP3A4 inhibitor, the dose of methylprednisolone may need to be titrated to avoid steroid toxicity (Table 1).
CYP3A4 INDUCTORS - Drugs that induce CYP3A4 activity generally increase hepatic clearance, resulting in decreased plasma concentrations of drugs that are CYP3A4 substrates. Co-administration may require an increase in methylprednisolone dosage to achieve the desired result ( Table 1).
CYP3A4 SUBSTRATES - In the presence of another CYP3A4 substrate, hepatic clearance of methylprednisolone may be inhibited or induced, resulting in necessary dosage adjustments. Adverse events associated with single drug use alone may be more likely to occur with co-administration (Table 1).
EFFECTS NOT MEDIATED BY CYP3A4 - Other interactions and effects occurring with methylprednisolone are described in Table 1 below.
Table 1. Important drug or substance interactions / effects with methylprednisolone
04.6 Pregnancy and lactation
Fertility
There is no evidence that corticosteroids are carcinogenic, mutagenic or that they impair fertility.
Pregnancy
Some studies conducted in experimental animals have shown that corticosteroids administered to mothers in high doses can induce fetal malformations.
Sufficient reproductive studies have not been conducted in humans, therefore the use of the drug during ascertained or presumed pregnancy and during lactation requires a careful evaluation of the benefits with respect to the potential risk for the mother and fetus.
As there is insufficient evidence on the safety of use of the drug in pregnant women, it should only be used if undoubtedly necessary.
Corticosteroids readily cross the placenta, therefore infants from mothers who have received substantial doses of the drug during pregnancy should be carefully observed and evaluated for manifestations of adrenal insufficiency. 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 monitored and evaluated for signs of adrenal insufficiency. A retrospective study found an increase in corticosteroids. incidence of low birth weight in infants born to mothers receiving corticosteroids.
Cataracts have been observed in infants born to mothers treated with long-term corticosteroids during pregnancy.
The effects of corticosteroids on labor from delivery are not known.
Feeding time
Corticosteroids are excreted in milk, therefore breastfeeding should be discontinued during treatment.
Corticosteroids distributed in breast milk can inhibit growth and interfere with the endogenous production of glucocorticoids in infants. Since adequate human reproduction studies with glucocorticoids have not been performed, these drugs should only be given to nursing mothers if the benefits of therapy are judged to outweigh the potential risks to the infant.
Adequate human reproduction studies with conticosteroids have not been performed.
For the use of this drug in pregnancy, lactation, or on women of childbearing age, it is necessary that the benefits of the drug are weighed against the potential risk to the mother and to the embryo or fetus.
In pregnant women and in very early childhood, the product should 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 or use machines has not been systematically evaluated. After treatment with corticosteroids, undesirable effects such as dizziness, vertigo, visual disturbances and fatigue may occur. Patients should not drive if affected. or use machinery.
04.8 Undesirable effects
UNDESIRABLE EFFECTS OBSERVED WITH NOT RECOMMENDED ROUTES OF ADMINISTRATION
• Intrathecal / epidural route
Arachnoiditis, meningitis, paraparesis, paraplegia, sensory disturbances, bowel / bladder dysfunction, headache, seizures
• Intranasal route
Temporary / permanent changes in vision including blindness, allergic reactions, rhinitis
• Ophthalmic route
Temporary / permanent changes in vision including blindness, increased intraocular pressure, ocular and periocular inflammation including allergic reactions, infections, residues or scabs at the injection site
• Other injection sites (scalp, palatine tonsils, sphenopalatine ganglia)
Blindness
04.9 Overdose
There are no reports of acute overdose with DEPO-MEDROL.
Reports of acute toxicity and / or death following corticosteroid overdose are rare. In the event of an overdose, no specific antidotes are available; treatment is symptomatic and supportive.
Methylprednisolone is dialyzable.
05.0 PHARMACOLOGICAL PROPERTIES
05.1 Pharmacodynamic properties
Pharmacotherapeutic group: systemic corticosteroids, glucocorticoids.
ATC: H02AB04.
DEPO-MEDROL contains a synthetic glycocorticoid, methylprednisolone acetate, a 6-methyl derivative of prednisolone.
Methylprednisolone is a potent anti-inflammatory steroid. It has greater anti-inflammatory potency than prednisolone and a lower tendency than prednisolone to induce sodium and water retention. Natural glucocorticoids (hydrocortisone and cortisone) 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. Glucocorticoids induce important and various metabolic effects and also modify the immune responses to various stimuli.
05.2 Pharmacokinetic properties
After IM administration of 40 mg methylprednisolone acetate, a mean plasma peak of 14.8 ± 8.6 ng / ml was observed within 7.25 ± 1.04 hours. Plasma concentrations were determinable up to 11-17 days. The mean area under the curve (AUC) was 1354.2 ± 424.1 ng / mL x hours (Day 1-21). After intra-articular administration, the absorption of DEPO-MEDROL in the joint is significantly lower. than the IM route of administration and occurs within a few days.
A peak concentration of 178.9 nmol / l was observed after 2-12 hours after intra-articular administration of 40 mg of DEPO-MEDROL.
Methylprednisolone acetate is hydrolyzed by serum cholinesterases and is mainly metabolised and inactivated by the liver. The major inactive metabolites are 20 alpha-hydroxy-methylprednisolone, 20 beta-hydroxy-methylprednisolone and 20 beta-hydroxy-6-alpha-methylprednisolone. Metabolism in the liver occurs mainly via CYP3A4 (for a list of interactions mediated by CYP3A4 metabolism see section 4.5).
Excretion occurs through the renal emunctorium and bile.
The mean elimination half-life for total methylprednisolone is in the range of 1.8 - 5.2 hours. The apparent volume of distribution is approximately 1.4 L / kg and the total clearance is approximately 5 - 6 mL / min / kg.
Methylprednisolone, like many CYP3A4 substrates, may also be a substrate for the ATP-binding cassette (ABC), p-glycoprotein transport protein, influencing tissue distribution and interactions with other medicinal products.
The clearance of methylprednisolone is impaired by concomitant administration of troleandomycin, erythromycin, rifampicin, anticonvulsants and theophylline. No dosage adjustment is necessary in renal insufficiency; methylprednisolone is haemodialysable.
Methylprednisolone is widely distributed in tissues, rapidly crosses the blood brain barrier and placenta, and is excreted in breast milk. The plasma protein binding of methylprednisolone in humans is approximately 77%.
05.3 Preclinical safety data
The acute toxicity data relating to the experimental animal are as follows:
Based on conventional safety pharmacology studies, repeated dose toxicity in mice, rats, rabbits and dogs using intravenous, intraperitoneal, subcutaneous, intramuscular and oral routes of administration, no unexpected hazards were identified. Toxicities seen in repeat dose studies are those expected even with continued exposure to exogenous adrenal steroids.
Repeated dose toxicity studies in rats and dogs (0.8-8 mg / kg / day and 48-480 mg / kg / day administered IM for 30 consecutive days) did not show toxic effects and tolerability is generally good.
DEPO-MEDROL is well tolerated by rats and dogs even at doses of 0.08-0.8-8 mg / kg / day administered IM for 180 consecutive days. Local tolerability was assessed both in rabbits, by injecting 10 mg of DEPO-MEDROL into the femoral-tibial joint, and in rats and dogs by IM administration of 0.08-0.8-8 mg / kg / day.
There were no significant changes in the various structures of the joint and tolerability in the muscle mass was satisfactory.
Carcinogenic potential:
Long-term animal studies have not been conducted to evaluate carcinogenic potential, as the drug is indicated for short-term treatment only and there were no indicative signs of carcinogenic activity. There is no evidence that corticosteroids are carcinogenic.
Mutagenic potential:
There was no evidence of a potential for genetic and chromosomal mutations when tested in an alkaline elution / DNA damage assay in Chinese hamster V79 cells. Methylprednisolone did not induce chromosomal damage in the absence of a cell activation system liver.
Teratogenic studies have shown changes commonly observed with corticosteroids (cleft palate, encephalocele and hydrocephalus) in rabbits and rats.
Teratogenic potential:
In animal studies on the embryotoxic effects of methylprednisolone, no teratogenic effects were observed in mice or rats at daily intraperitoneal doses of 125 mg / kg / day or 100 mg / kg / day, respectively. In rats, methylprednisolone was 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.
06.0 PHARMACEUTICAL INFORMATION
06.1 Excipients
Macrogol 3350; sodium chloride; myristyl gamma picolinium chloride; sodium hydroxide; hydrochloric acid; water for injections q.s.
06.2 Incompatibility
Methylprednisolone acetate 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 DEPO-MEDROL with other solutions.
06.3 Period of validity
5 years.
06.4 Special precautions for storage
To be stored at a temperature not lower than 0 ° C.
06.5 Nature of the immediate packaging and contents of the package
Neutral glass bottle closed by a rubber stopper.
- DEPO-MEDROL 40 mg / ml, 1 bottle of 1 ml.
- DEPO-MEDROL 40 mg / ml, 3 bottles of 1 ml.
06.6 Instructions for use and handling
07.0 MARKETING AUTHORIZATION HOLDER
Pfizer Italia S.r.l. - Via Isonzo, 71 - 04100 Latina
08.0 MARKETING AUTHORIZATION NUMBER
DEPO-MEDROL 40 mg / ml,
- 1 bottle of 1 ml, AIC 017932017
- 3 bottles of 1 ml, AIC 017932029
09.0 DATE OF FIRST AUTHORIZATION OR RENEWAL OF THE AUTHORIZATION
May 31, 2005
10.0 DATE OF REVISION OF THE TEXT
Aifa Resolution of May 2013
