Presentation and Status in Health Basket
1 ml X 40 mg/ml
2 ml X 40 mg/ml
5 ml X 40 mg/ml
The drug may be used by any of the following routes:
– Intra-articular, periarticular, intrabursal or soft tissues
– Intrarectal instillation
This formulation is contra-indicated for I.V. and intrathecal administration.
This formulation is not recommended for epidural, intranasal, intra-ocular or any other unapproved route of administration.
A. I.M. ADMINISTRATION FOR SYSTEMIC EFFECT:
The intramuscular dosage will vary with the condition being treated. When a prolonged effect is desired, the weekly dose may be calculated by multiplying the daily oral dose by 7 and given as a singular intramuscular injection. Dosage must be individualized according to the severity of the disease and response of the patient. In general, the duration of the treatment should be kept as short as possible. Medical surveillance is necessary. For infants and children, the recommended dosage will have to be reduced, but dosage should be governed by the severity of the condition rather than by strict adherence to the ratio indicated by age or body weight. Hormone therapy is adjunct to and not a repLacement for conventional therapy. Dosage must be decreased or discontinued gradually when the drug has been administered for more than a few days. Strict medical surveillance is recommended when a chronic treatment is discontinued. The severity, prognosis and expected duration of the disease and the reaction of the patient to medication are primary factors in determining the dosage. If a period of spontaneous remission occurs in a chronic condition, treatment should be discontinued. Routine laboratory studies, such as urinalysis, two-hour postprandial blood sugar, determination of blood pressure and body weight and a chest x-ray should be made at regular intervals during prolonged therapy. Upper Gl X-rays are desirable in patients with an ulcer history or significant dyspepsia. In patients with the adrenogenital syndrome, a single intramuscular injection of 40 mg every two weeks may be adequate. For maintenance of patients with rheumatoid arthritis, the weekly intramuscular dose will vary from 40 to 120 mg. The usual dosage for patients with dermatologic lesions benefited by systemic corticoid therapy is 40 to 120 mg of methylprednisolone acetate administered intramuscularly at weekly intervals for one to four weeks. In acute severe dermatitis due to poison ivy, relief may result within 8 to 12 hours following intramuscular administration of a single dose of 80 to 120 mg. In chronic contact dermatitis repeated injections at 5 to 10 day intervals may be necessary. In seborrheic dermatitis, a weekly dose of 80 mg may be adequate to control the condition. Following intramuscular administration of 80 to 120 mg to asthmatic patients. relief may result within 6 to 48 hours and persist for several days to two weeks. Similarly in patients with allergic rhinitis (hay fever) an intramuscular dose of 80 to 120 mg may be followed by relief of coryzal symptoms within six hours persisting for several days to three weeks. If signs of stress are associated with the condition being treated, the dosage of the suspension should be increased. If a rapid hormonal effect of maximum intensity is required, the intravenous administration of highly soluble methylprednisolone sodium succinate is indicated.
B. IN SITU ADMINISTRATION FOR LOCAL EFFECT:
Therapy with This formulation does not obviate the need for the conventional measures usually employed. Although this method of treatment will ameliorate symptoms, it is in no sense a cure and the hormone has no effect on the cause of the inflammation.
1. Rheumatoid and osteoarthritis: The dose for intra-articular administration
depends upon the size of the joint and varies with the severity of the condition in the individual patient. In chronic cases, repeated injections, if needed, may be given at intervals of one to five or more weeks, depending on the degree of relief obtained from the initial injection.
These doses are given as a general guide:
Large (knees, ankles, shoulders): 20-80 mg.
Medium (elbows, wrists): 10-40 mg.
Small (Metacarpophalangeal, Interphalangeal, Sternoclavicular, Acromioclavicular): 4-10 mg.
Procedure: It is recommended that the anatomy of the joint involved be reviewed before attempting intra-articular injection. In order to obtain the full anti-inflammatory effect it is important that the injection be made into the synovial space.
Employing the same sterile technique as for a lumbar puncture, a sterile 20 to 24 gauge needle (on a dry syringe) is quickly inserted into the synovial cavity. Procaine infiltration is elective. The aspiration of only a few drops of joint fluid proves the joint space has been entered by the needle. The injection site for each joint is determined by that location where the synovial cavity is most superficial and most free of large vessels and nerves. With the needle in place, the aspirating syringe is removed and replaced by a second syringe containing the desired amount of Depo-Medrol. The plunger is then pulled outward slightly to aspirate synovial fluid and to make sure the needle is still in the synovial space. After injection, the joint is moved gently a few times to aid mixing of the synovial fluid and the suspension. The site is covered with a small sterile dressing. Suitable sites for intra-articular injection are the knee, ankle, wrist, elbow, shoulder, phalangeal and hip joints. Since difficulty is occasionally encountered in entering the hip joint, precautions should be taken to avoid any large blood vessels in the area. Joints not suitable for injection are those that are anatomically inaccessible such as the spinal joints and those like the sacroiliac joints that are devoid of synovial space. Treatment failures are most frequently the result of failure to enter the joint space. Little or no benefit follows injection into surrounding tissue. If failures occur when injections into the synovial spaces are certain, as determined by aspiration of fluid, repeated injections are usually futile. Local therapy does not alter the underlying disease process, and whenever possible comprehensive therapy including physiotherapy and orthopedic correction should be employed.
2. Bursitis: The area around the injection site is prepared in a sterile way and a wheal at the site made with 1% procaine hydrochloride solution. A 20 to 24 gauge needle attached to a dry syringe is inserted into the bursa and the fluid aspirated. The needle is left in place and the aspirating syringe changed for a small syringe containing the desired dose. After injection, the needle is withdrawn and a small dressing applied.
3. Miscellaneous: ganglion, tendinitis, epicondylitis: In the treatment of conditions such as tendinitis or tenosynovitis, care should be taken to inject the suspension into the tendon sheath rather than into the substance of the tendon. The tendon may be readily palpated when placed on a stretch. When treating conditions such as epicondylitis, the area of greatest tenderness should be outlined carefully and the suspension infiltrated into the area. For ganglia of the tendon sheaths, the suspension is injected directly into the cyst. In many cases, a single injection causes a marked decrease in the size of the cystic tumor and may effect disappearance.
The usual sterile precautions should be observed, of course, with each injection (application of a suitable antiseptic to the skin).
The dose in the treatment of the various conditions of the tendinous or bursal structures listed above varies with the condition being treated and ranges from 4 to 30 mg. In recurrent or chronic conditions, repeated injections may be necessary.
4. Injections for local effect in dermatologic conditions: Following cleansing with an appropriate antiseptic such as 70% alcohol, 20 to 60 mg of the suspension is injected into the lesion. It may be necessary to distribute doses ranging from 20 to 40 mg by repeated local injections in the case of large lesions. Care should be taken to avoid injection of sufficient material to cause blanching since this may be followed by a small slough. One to four injections are usually employed, the intervals between injections varying with the type of lesion being treated and the duration of improvement produced by the initial injection.
C. INTRARECTAL ADMINISTRATION:
Depo-Medrol in doses of 40 to 120 mg administered as retention enemas or by continuous drip three to seven times weekly for periods of two or more weeks, have been shown to be a useful adjunct in the treatment of some patients with ulcerative colitis. Many patients can be controlled with 40 mg of methylprednislone acetate administered in from 30-300 ml of water depending upon the degree of involvement of the inflamed colonic mucosa. Other accepted therapeutic measures should, of course, be instituted.
For the treatment of conditions responsive to steroid injection therapy.
A. For (intramuscular administration): Methylprednisolone acetate (This formulation) is not suitable for the treatment of acute life threatening conditions. If a rapid hormonal effect of maximum intensity is required, the l.V administration of highly soluble methylprednisolone sodium succinate (Solu-Medrol) is indicated. When oral therapy is not feasible and the strength, dosage form, and route of administration of the drug reasonably lend this preparation to the treatment of the condition, the intramuscular use of this formulation is indicated as follows:
1. Rheumatic disorders: As adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in: Psoriatic arthritis, Ankylosing spondylitis. For the following indications, preference should be given to in situ administration if possible: Post-traumatic osteoarthritis, Synovitis of osteoarthritis, Rheumatoid arthritis, including juvenile rheumatoid arthritis (selected cases may require low- dose maintenance therapy), Acute and subacute bursitis, Epicondylitis, Acute nonspecific tenosynovitis, Acute gouty arthritis.
2. Collagen diseases: During an exacerbation or as maintenance therapy in selected cases of: Systemic lupus erythematosus, Systemic dermatomyositis (polymyositis), Acute rheumatic carditis.
3. Dermatological diseases: Pemphigus, Bullous dermatitis herpetiformis (sulfone is the drug of first choice and systemic administration of glucocorticoids is an adjuvant), Severe erythema multiforme (Stevens-Johnson syndrome), Exfoliative dermatitis, Mycosis fungoides, Severe psoriasis
4. Allergic states: Control of severe or incapacitating allergic conditions intractable to adequate trials of conventional treatment in: Bronchial asthma, Contact dermatitis, Atopic dermatitis, Serum sickness, Seasonal or perennial allergic rhinitis. Drug hypersensitivity reactions, Urticarial transfusion reactions, Acute noninfectious laryngeal edema (epinephrine is the drug of first choice).
5. Gastro-intestinal diseases: To tide the patient over a critical period of the disease in: Ulcerative colitis (systemic therapy). Crohn disease (systemic therapy).
6. Respiratory diseases: Symptomatic pulmonary sarcoidosis, Berylliosis, Fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous chemotherapy, Loeffler’s syndrome not manageable by other means, Aspiration pneumonitis.
7. Hematologic disorders: Acquired (autoimmune) hemolytic anemia, Secondary thrombocytopenia in adults, Erythroblastopenia (RBC anemia), Congenital (erythroid) hypoplastic anemia.
8. Oncological diseases: For palliative management of: Leukemias and lymphomas, Acute leukemia of childhood.
9. Endocrine disorders: Primary or secondary adrenocortical insufficiency (hydrocortisone or cortisone is the drug of choice. Synthetic analogues may be used in conjunction with mineralocorticoids where applicable; in infancy mineralocorticoid supplementation is of particular importance), Acute adrenocortical insufficiency (hydrocortisone or cortisone is the drug of choice, mineralocorticoid supplementation may be necessary, particularly when synthetic analogs are used).In infancy mineralocorticoid supplementation is of particular importance. Congenital adrenal hyperplasia, Hypercalcemia associated with cancer, Nonsuppurative thyroiditis.
10. Opthalmic diseases dermatological diseases: Severe acute and chronic allergic and inflammatory processes involving the eye, such as: Herpes zoster ophthalmicus, Drug hypersensitivity reactions, Iritis, iridocyclitis, Anterior segment inflammation, Chorioretinitis, Allergic conjunctivitis, Diffuse posterior uveitis, Allergic corneal marginal ulcers, Optic neuritis, Keratitis.
11. Edematous states: To induce diuresis or remission of proteinuria in the nephrotic syndrome, without uremia, of the idiopathic type or that due to lupus erythematosus.
12. Nervous system: Acute exacerbations of multiple sclerosis.
13. Miscellaneous: Tuberculous meningitis with subarachnoid block or impending block when used concurrently with appropriate antituberculous chemotherapy. Trichinosis with neurologic or myocardial involvement.
B. For intrasynovial, periartlcular, intrabursal or soft tissue administration:
The drug is indicated as adjunctive therapy for short-term administration (to tide the patient over an acute episode or exacerbation) in: Synovitis of osteoarthritis, Rheumatoid arthritis, Acute and subacute bursitis, Acute gouty arthritis, Epicondylitis, Acute nonspecific tenosynovitis, Post-traumatic osteoarthritis.
C. For intralesional administration: This formulation is indicated for intralesional use in the following conditions: Keloids, Localized hypertropic, infiltrated, inflammatory lesions of: Lichen planus, psoriatic plaques, Necrobiosis lipodica diabeticorum, Granuloma annulare, Lichen Simplex chronicus (neurodermatitis), Discoid lupus erythematosus, Alopecia areata, This formulation may also be useful in cystic tumors or an aponeurosis or tendon (ganglia).
D. For intrarectal installation: Ulcerative colitis.
– In patients with known hypersensitivity to the active substance or to any of the excipients.
– In patients who have systemic infection unless specific anti-infective therapy is employed.
– For use by the intrathecal route (due to its potential for neurotoxicity)
– For use by the intravenous route.
– Administration of live or live, attenuated vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids.
Undesirable effects may be minimised by using the lowest effective dose for the minimum period. Frequent patient review is required to appropriately titrate the dose against disease activity.
The vials are intended for single dose use only. Any multidose use of the product may lead to contamination.
Severe medical events have been reported in association with the intrathecal/epidural routes of administration. Appropriate measures must be taken to avoid intravascular injection.
Due to the absence of a true tendon sheath, the Achilles tendon should not be injected with this formulation.
While crystals of adrenal steroids in the dermis suppress inflammatory reactions, their presence may cause disintegration of the cellular elements and physiochemical changes in the ground substance of the connective tissue. The resultant infrequently occurring dermal and/or subdermal changes may form depressions in the skin at the injection site. The degree to which this reaction occurs will vary with the amount of adrenal steroid injected. Regeneration is usually complete within a few months or after all crystals of the adrenal steroid have been absorbed.
In order to minimize the incidence of dermal and subdermal atrophy, care must be exercised not to exceed recommended doses in injections. Multiple small injections into the area of the lesion should be made whenever possible. The technique of intra-articular and intramuscular injection should include precautions against injection or leakage into the dermis. Injection into the deltoid muscle should be avoided because of a high incidence of subcutaneous atrophy.
Intralesional doses should not be placed too superficially, particularly in easily visible sites in patients with deeply pigmented skins, since there have been rare reports of subcutaneous atrophy and depigmentation.
Systemic absorption of methylprednisolone occurs following intra-articular injection of This formulation. Systemic as well as local effects can therefore be expected.
Adrenal cortical atrophy develops during prolonged therapy and may persist for months after stopping treatment. In patients who have received more than physiological doses of systemic corticosteroids (approximately 6 mg methylprednisolone) for greater than 3 weeks, withdrawal should not be abrupt. How dose reduction should be carried out depends largely on whether the disease is likely to relapse as the dose of systemic corticosteroids is reduced. Clinical assessment of disease activity may be needed during withdrawal. If the disease is unlikely to relapse on withdrawal of systemic corticosteroids, but there is uncertainty about HPA suppression, the dose of systemic corticosteroid may be reduced rapidly to physiological doses. Once a daily dose of 6 mg methylprednisolone is reached, dose reduction should be slower to allow the HPA-axis to recover.
The following precautions apply for parenteral corticosteroids: Following intra-articular injection, the occurrence of a marked increase in pain accompanied by local swelling, further restriction of joint motion, fever, and malaise are suggestive of septic arthritis. If this complication occurs and the diagnosis of sepsis is confirmed, appropriate antimicrobial therapy should be instituted.
Local injection of a steroid into a previously infected joint is to be avoided.
Intra-articular corticosteroids are associated with a substantially increased risk of inflammatory response in the joint, particularly bacterial infection introduced with the injection. Charcot-like arthropathies have been reported particularly after repeated injections. Appropriate examination of any joint fluid present is necessary to exclude any bacterial infection, prior to injection.
Corticosteroids should not be injected into unstable joints.
Sterile technique is necessary to prevent infections or contamination.
The slower rate of absorption by intramuscular administration should be recognised.
Immunosuppressant Effects/Increased Susceptibility to Infections:
Corticosteroids may increase susceptibility to infection, may mask some signs of infection, and new infections may appear during their use. Suppression of the inflammatory response and immune function increases the susceptibility to fungal, viral and bacterial infections and their severity. The clinical presentation may often be atypical and may reach an advanced stage before being recognised. With increasing doses of corticosteroids, the rate of occurrence of infectious complications increases.
Do not use intra-synovially, intrabursally or intratendinous administration for local effect in the presence of acute infection.
Persons who are on drugs which suppress the immune system 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 on corticosteroids.
Chickenpox is of serious concern since this normally minor illness may be fatal in immunosuppressed patients. Patients (or parents of children) without a definite history of chickenpox should be advised to avoid close personal contact with chickenpox or herpes zoster and if exposed they should seek urgent medical attention. Passive immunization with varicella/zoster immunoglobin (VZIG) is needed by exposed non-immune patients who are receiving systemic corticosteroids or who have used them within the previous 3 months; this should be given within 10 days of exposure to chickenpox. If a diagnosis of chickenpox is confirmed, the illness warrants specialist care and urgent treatment. Corticosteroids should not be stopped and the dose may need to be increased.
Live vaccines should not be given to individuals with impaired immune responsiveness. The antibody response to other vaccines may be diminished. The use of this formulation in active tuberculosis should be restricted to those cases of fulminating or disseminated tuberculosis in which the corticosteroid is used for the management of the disease in conjunction with an appropriate antituberculous regimen. If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary as reactivation of the disease may occur. During prolonged corticosteroid therapy, these patients should receive chemoprophylaxis.
The role of corticosteroids in septic shock has been controversial, with early studies reporting both beneficial and detrimental effects. More recently, supplemental corticosteroids have been suggested to be beneficial in patients with established septic shock who exhibit adrenal insufficiency. However, their routine use in septic shock is not recommended. A systematic review of short-course high-dose corticosteroids did not support their use. However, meta-analyses and a review suggest that longer courses (5-11 days) of low-dose corticosteroids might reduce mortality, especially in patients with vasopressor-dependent septic shock.
Immune System Effects: Allergic reactions may occur. Because rare instances of skin reactions and anaphylactic/anaphylactoid reactions have occurred in patients receiving corticosteroid therapy, appropriate precautionary measures should be taken prior to administration, especially when the patient has a history of drug allergy.
Endocrine Effects: Pharmacologic doses of corticosteroids administered for prolonged periods may result in hypothalamic-pituitary-adrenal (HPA) suppression (secondary adrenocortical insufficiency). The degree and duration of adrenocortical insufficiency produced is variable among patients and depends on the dose, frequency, time of administration, and duration of glucocorticoid therapy. This effect may be minimized by use of alternate-day therapy.
In addition, acute adrenal insufficiency leading to a fatal outcome may occur if glucocorticoids are withdrawn abruptly. Drug-induced secondary adrenocortical insufficiency may therefore be minimized by gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, in any situation of stress occurring during that period, hormone therapy should be reinstituted. Salt and/or a mineralocorticoid are only needed if mineralocorticoid secretion is impaired.
A steroid “withdrawal syndrome,” seemingly unrelated to adrenocortical insufficiency, may also occur following abrupt discontinuance of glucocorticoids. This syndrome includes symptoms such as: anorexia, nausea, vomiting, lethargy, headache, fever, joint pain, desquamation, myalgia, weight loss, and/or hypotension. These effects are thought to be due to the sudden change in glucocorticoid concentration rather than to low corticosteroid levels.
Abrupt withdrawal of systemic corticosteroid treatment, which has continued up to 3 weeks is appropriate if it considered that the disease is unlikely to relapse. Abrupt withdrawal of doses up to 32 mg daily of methylprednisolone for 3 weeks is unlikely to lead to clinically relevant HPA-axis suppression, in the majority of patients. In the following patient groups, gradual withdrawal of systemic corticosteroid therapy should be considered even after courses lasting 3 weeks or less:
– Patients who have had repeated courses of systemic corticosteroids, particularly if taken for greater than 3 weeks.
– When a short course has been prescribed within one year of cessation of long-term therapy (months or years).
– Patients who may have reasons for adrenocortical insufficiency other than exogenous corticosteroid therapy.
– Patients receiving doses of systemic corticosteroid greater than 32 mg daily of methylprednisolone.
– Patients repeatedly taking doses in the evening.
Because glucocorticoids can produce or aggravate Cushing’s syndrome, glucocorticoids should be avoided in patients with Cushing’s disease.
There is an enhanced effect of corticosteroids on patients with hypothyroidism.
Metabolism and Nutrition: Corticosteroids, including methylprednisolone, can increase blood glucose, worsen pre-existing diabetes, and predispose those on long-term corticosteroid therapy to diabetes mellitus.
See prescribing information for full details.
Usual systemic corticoid adverse reactions, headache, meningismus, meningitis, paraparesis/paraplegia, spinal fluid abnormalities, nausea, vomiting, sweating, arachnoiditis, functional gastrointestinal disorder/bladder dysfunction, seizure, sensory disturbance.
See prescribing information for full details.
Methylprednisolone is a cytochrome P450 enzyme (CYP) substrate and is mainly metabolized 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 essential Phase I metabolic step 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 (upregulation) or inhibition of the CYP3A4 enzyme.
CYP3A4 INHIBITORS: Drugs that inhibit CYP3A4 activity generally decrease hepatic clearance and increase the plasma concentration of CYP3A4 substrate medications, such as 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 decreased plasma concentration of medications that are substrates for CYP3A4. Coadministration may require an increase in methylprednisolone dosage to achieve the desired result.
CYP3A4 SUBSTRATES: In the presence of another CYP3A4 substrate, the hepatic clearance of methylprednisolone may be affected, with corresponding dosage adjustments required. It is possible that adverse events associated with the use of either drug alone may be more likely to occur with coadministration.
See prescribing information for full details.
Pregnancy and Lactation
Pregnancy: The ability of corticosteroids to cross the placenta varies between individual drugs, however, methylprednisolone does cross the placenta. One retrospective study found an increased incidence of low birth weights in infants born of mothers receiving corticosteroids. In humans, the risk of low birth weight appears to be dose related and may be minimized by administering lower corticosteroid doses.
However, corticosteroids do not appear to cause congenital anomalies when given to pregnant women.
Lactation: Corticosteroids are excreted in small amounts in breast milk, however, doses of up to 40 mg daily of methylprednisolone are unlikely to cause systemic effects in the infant. Infants of mothers taking higher doses than this may have a degree of adrenal suppression, but the benefits of breast-feeding are likely to outweigh any theoretical risk.
Corticosteroids distributed into breast milk may interfere with endogenous glucocorticoid production in nursing infants. This medicinal product should be used during breast feeding only after a careful assessment of the benefit‑risk ratio to the mother and infant.
See prescribing information for full details.
Following overdosage the possibility of adrenal suppression should be guarded against by gradual diminution of dose levels over a period of time. In such event the patient may require to be supported during any further traumatic episode.
Reports of acute toxicity and/or death following overdosage of corticosteroids are rare. In the event of overdosage, no specific antidote is available; treatment is supportive and symptomatic. Methylprednisolone is dialyzable.
Storage: Store below 25°C. Do not freeze.