Depo-medrol

Package leaflet: Information for the patient

DEPO-MEDROL, 40 mg/ml, injection suspension
Methylprednisoloni acetas
Please read all of this leaflet carefully before the medicine is administered, because it contains
important information for you.

• Keep this leaflet. You may need to read it again.
• If you have any further questions, please ask your doctor or pharmacist.
• This medicine has been prescribed for a specific individual. Do not pass it on to others. It may harm other people, even if their symptoms are the same.
• If you experience any adverse reactions, including any not listed in this leaflet, tell your doctor or pharmacist immediately. See section 4.

Table of contents

1. What Depo-Medrol is and what it is used for
2. Important information before using Depo-Medrol
3. How to use Depo-Medrol
4. Possible side effects
5. How to store Depo-Medrol
6. Contents of the pack and other information

1. What Depo-Medrol is and what it is used for

The active substance in Depo-Medrol, methylprednisolone acetate, belongs to a group of drugs called
glucocorticoids intended for systemic and local use.
Like other glucocorticoids, Depo-Medrol affects, among others:

• inflammatory and immunological processes,
• carbohydrate, protein and fat metabolism,
• the circulatory system,
• the cardiovascular system,
• the central nervous system,
• skeletal muscles,
• bone tissue,
• connective tissue,
• skin and mucous membranes,
• the endocrine system,
• kidney function.

Depo-Medrol should be used for symptomatic treatment, except in endocrine disorders, where it is used for substitution therapy.
Depo-Medrol is administered intramuscularly, intra-articularly, into the bursa, periarticularly, into the lesion, or rectally.
A. Intramuscular administration
Endocrine disorders
Primary or secondary adrenal insufficiency;
Acute adrenal insufficiency;
Congenital adrenal hyperplasia;
Hypercalcemia associated with malignancy;
Silent thyroiditis.
Rheumatic diseases
As supportive treatment for short-term use (during episodes of exacerbation or worsening of condition) in:
traumatic osteoarthritis;
epicondylitis;
synovitis in osteoarthritis;
acute non-specific tenosynovitis;
rheumatoid arthritis, including juvenile rheumatoid arthritis
(in some cases, low-dose administration may be required as maintenance therapy);
psoriatic arthritis;
acute gouty arthritis;
ankylosing spondylitis;
acute and subacute bursitis.
Systemic connective tissue diseases
During exacerbations or as maintenance therapy in:
systemic lupus erythematosus;
acute polymyositis and dermatomyositis;
acute rheumatic carditis.
Skin diseases
pemphigus;
bullous pemphigoid;
severe forms of erythema multiforme (Stevens-Johnson syndrome);
severe seborrheic dermatitis;
exfoliative dermatitis;
vegetative pyoderma;
severe psoriasis.
Allergic diseases
Treatment of severe or functionally disabling allergic conditions when conventional therapies are ineffective:
bronchial asthma;
drug hypersensitivity reactions;
contact dermatitis (allergic contact dermatitis);
urticarial reactions following transfusion;
atopic dermatitis;
acute angioedema of the larynx without infection (epinephrine is the first-line treatment);
serum sickness.
Eye diseases
Acute and chronic allergic and inflammatory processes involving the eye and its adnexa, such as:
herpes zoster ophthalmicus;
drug hypersensitivity reactions;
iritis, iridocyclitis;
anterior segment inflammation;
chorioretinitis;
allergic conjunctivitis;
diffuse posterior uveitis;
allergic marginal corneal ulcers;
optic neuritis;
keratitis.
Gastrointestinal diseases
As adjunctive therapy in the acute phase of:
ulcerative colitis (systemic treatment);
Crohn's disease (systemic treatment).
Respiratory diseases
fulminant or disseminated pulmonary tuberculosis, concomitantly with appropriate antituberculous chemotherapy;
symptomatic pulmonary sarcoidosis;
berylliosis (beryllium lung disease);
Loeffler's syndrome unresponsive to other treatments;
aspiration pneumonia.
Blood disorders
secondary thrombocytopenia in adults;
lack of erythroblasts in bone marrow (erythroblastopenia);
acquired (autoimmune) hemolytic anemia;
congenital hypoplastic anemia.
Neoplastic diseases
Palliative treatment:
leukemias and lymphomas in adults;
acute leukemia in children.
Edema
To induce diuresis or remission of proteinuria (proteinuria) in nephrotic syndrome:
non-uremic;
idiopathic;
associated with systemic lupus erythematosus.
Other
tuberculous meningitis in the presence of, or at risk of, spinal block, in combination with appropriate antituberculous treatment;
trichinosis with involvement of the nervous system or myocardium.
B. Intra-articular administration
Administration into the bursa
Periarticular administration
Depo-Medrol is indicated for short-term use as adjunctive therapy in:

• synovitis in osteoarthritis;
• epicondylitis;
• rheumatoid arthritis;
• acute non-specific tenosynovitis;
• acute and subacute bursitis;
• traumatic osteoarthritis;
• acute gouty arthritis.

C. Injection into the lesion
Depo-Medrol is indicated for direct injection into pathological lesions in the following conditions:

• keloids;
• localized, hypertrophic, infiltrated, inflammatory lesions in:
• lichen planus,
• plaque psoriasis,
• annular granuloma,
• chronic lichen simplex (localized neurodermatitis);
• discoid (localized) lupus erythematosus;
• alopecia areata;
• morphea.

Depo-Medrol may also be used in the treatment of cystic nodules, fasciitis or tendonitis (ganglia).
D. Rectal administration

• Ulcerative colitis.

2. Important information before using Depo-Medrol

When not to use Depo-Medrol

• if the patient is allergic to the active substance or to any of the other ingredients of this medicine (listed in section 6);
• in patients with systemic fungal infection;
• intrathecally;
• epidurally;
• intravenously;
• into the nose or eyeball, as well as into other sites (scalp skin, oropharyngeal cavity, sphenopalatine ganglion).

Administration of live or live attenuated vaccines is contraindicated during treatment with Depo-Medrol at doses causing immunosuppressive effects.

Warnings and precautions

Patients with the following conditions should receive Depo-Medrol treatment for the shortest possible duration and require special medical supervision during treatment:

• Children: In children undergoing long-term treatment with divided daily doses of Depo-Medrol, growth suppression may occur. The physician should limit the use of such treatment to the most severe indications.
• Patients with diabetes: Treatment with Depo-Medrol may reveal latent diabetes or increase the requirement for insulin or oral antidiabetic agents.
• Patients with hypertension: Treatment with Depo-Medrol may exacerbate arterial hypertension.
• Patients with a history of psychiatric disorders: Treatment with Depo-Medrol may worsen existing emotional instability or psychotic tendencies.
• Patients with ocular herpes simplex or herpes zoster ophthalmicus with eye involvement: Treatment with Depo-Medrol may increase the risk of corneal perforation. If the patient experiences blurred vision or other visual disturbances, medical advice should be sought.

If the patient has hyperthyroidism, discuss this with a doctor or pharmacist before starting Depo-Medrol.

Depo-Medrol must not be used as a multi-dose vial. After administering the required dose, any remaining suspension should be discarded.

Immunosuppressive effect/Increased susceptibility to infections

Depo-Medrol may increase susceptibility to infections, may mask some signs of infection, exacerbate existing infections, or cause recurrence or worsening of previous, latent infections. New infections may also occur during treatment with Depo-Medrol. These infections may range from mild to severe and, in some cases, may lead to death. During treatment with Depo-Medrol, decreased immunity and inability to localize infection may occur; some infection symptoms may be atypical. The physician will closely monitor the patient for the development of infection and, if necessary, consider interrupting treatment or reducing the dose.

Use of corticosteroids as monotherapy or in combination with other immunosuppressive agents may be associated with infections caused by pathogenic microorganisms, including viral, bacterial, fungal, protozoal, or parasitic diseases, in any part of the body. Infections occurring during treatment with these drugs may be mild or severe and sometimes fatal. The frequency of infectious complications increases with increasing corticosteroid doses. Patients taking immunosuppressive drugs are more susceptible to infections than healthy individuals. Chickenpox and measles may have a more severe course or even be fatal in non-immune children or adults receiving corticosteroids.

Depo-Medrol must not be administered intra-articularly, intracapsularly, or intratendinously in patients with acute infection for local effect.

Vaccination with live, attenuated virus vaccines is contraindicated in patients receiving immunosuppressive doses of corticosteroids. Inactivated or killed vaccines may be administered to these patients, but the response may be limited or the vaccines may be ineffective. Patients receiving Depo-Medrol at doses that do not have immunosuppressive effects may receive all required vaccinations (see section: Depo-Medrol and other medicines).

Depo-Medrol should be used only in cases of fulminant or disseminated tuberculosis in combination with other appropriate antituberculosis drugs in patients with active tuberculosis.

If administration of Depo-Medrol is necessary in a patient with latent tuberculosis or a positive tuberculin test, close monitoring is essential, as reactivation of the disease may occur. In such patients undergoing long-term corticosteroid therapy, the physician may decide to initiate chemoprophylaxis.

Kaposi's sarcoma has been reported in patients receiving corticosteroids. Discontinuation of these drugs may lead to clinical remission.

Effects on the immune system

Allergic reactions may occur in patients treated with Depo-Medrol. Depo-Medrol should be used with caution, especially in patients with a history of allergic reactions to corticosteroids, due to the possibility of anaphylactic or anaphylactoid reactions.

Skin allergic reactions may occur during treatment, most likely due to excipients in the medicine. Skin tests rarely detect a reaction to methylprednisolone acetate itself.

Endocrine disorders

In patients exposed to significant stress, the physician may recommend appropriate dose increases of Depo-Medrol before, during, and after the stressful period.

Adrenal insufficiency may occur during long-term treatment with Depo-Medrol and may persist for several months after discontinuation of treatment.

The physician may also decide to gradually reduce the dose of Depo-Medrol. Patients should inform the physician of any stressful situations occurring during this period. The physician may consider initiating hormone therapy.

Sudden discontinuation of Depo-Medrol may cause acute adrenal insufficiency leading to death.

After abrupt discontinuation of Depo-Medrol, a "steroid withdrawal syndrome" may also occur. This syndrome includes the following symptoms: anorexia, nausea, vomiting, lethargy, headache, fever, joint pain, desquamation, muscle pain, weight loss, and/or hypotension.

Depo-Medrol may cause or exacerbate Cushing's syndrome; therefore, patients with Cushing's disease should not use it.

Enhanced effects of Depo-Medrol are observed in patients with hypothyroidism.

Seek immediate medical advice if weakness or muscle pain, cramps, and stiffness occur during methylprednisolone treatment. These may be symptoms of thyrotoxic periodic paralysis, which may occur in patients with hyperthyroidism treated with methylprednisolone. Additional treatment may be required to alleviate this condition.

Effects on metabolism and nutrition

Corticosteroids, including methylprednisolone, may increase blood glucose levels, worsen pre-existing diabetes, and predispose patients on long-term corticosteroid therapy to develop diabetes.

Psychiatric disorders

During and after treatment with Depo-Medrol, psychiatric disorders ranging from euphoria, insomnia, mood swings, personality changes, and severe depression to early and severe psychotic disorders may occur. These usually appear within a few days or weeks after starting treatment with Depo-Medrol. Most resolve after dose reduction or discontinuation of Depo-Medrol. Patients and caregivers should seek medical advice if psychiatric symptoms develop, especially if depressive mood or suicidal thoughts are suspected. Patients and caregivers should pay particular attention to psychiatric disorders that may occur during treatment, immediately after dose reduction, or after discontinuation of Depo-Medrol.

Effects on the nervous system

Depo-Medrol should be used with caution in patients with seizure disorders.

Depo-Medrol should be used with caution in patients with myasthenia.

In patients receiving Depo-Medrol, usually after long-term use of high doses, cases of subcapsular cataract have been reported.

Effects on the eyes

Long-term use of Depo-Medrol may lead to the development of posterior subcapsular cataract and nuclear cataract (especially in children), exophthalmos, or increased intraocular pressure, which may cause glaucoma with potential damage to the optic nerves. Secondary fungal and viral eye infections may also occur more frequently in patients receiving Depo-Medrol.

Depo-Medrol should be used with caution in patients with ocular herpes simplex or herpes zoster with ocular symptoms due to the risk of corneal perforation.

Visual disturbances may occur following systemic or local administration of the drug. If such disturbances occur, the patient should contact a physician to determine possible causes, including cataract, glaucoma, or rare diseases such as central serous chorioretinopathy.

Central serous chorioretinopathy may lead to retinal detachment.

Effects on the heart

When using high doses and long-term treatment with Depo-Medrol in patients with cardiovascular risk factors, caution is required, and additional monitoring of the cardiovascular system may be necessary.

In patients with congestive heart failure, Depo-Medrol should be administered with caution and only if absolutely necessary.

Vascular disorders

Thrombosis, including venous thromboembolic disease, has been reported during treatment with Depo-Medrol. Therefore, caution is required in patients with thromboembolic disorders or those who may be susceptible to their occurrence.

Depo-Medrol should be used with caution in patients with arterial hypertension.

Effects on the stomach and intestines

Acute pancreatitis may occur after administration of high doses of Depo-Medrol.

During long-term therapy, the physician may recommend appropriate routine tests. In patients with a history of peptic ulcer disease or with pronounced dyspeptic symptoms, the physician may recommend radiological examination of the upper gastrointestinal tract.

Treatment with Depo-Medrol may mask symptoms of peptic ulcers, so perforation or hemorrhage may occur without significant accompanying pain. Treatment with Depo-Medrol may mask peritonitis or other symptoms associated with gastrointestinal disorders such as perforation, constipation, or pancreatitis. Concurrent use of Depo-Medrol with non-steroidal anti-inflammatory drugs (NSAIDs) increases the risk of gastric and intestinal ulcer disease.

Depo-Medrol should be used with caution in patients with ulcerative colitis if there is a risk of perforation or abscess formation or other forms of suppurative infection. Caution is also required in diverticulitis, recent intestinal anastomoses, active or latent peptic ulcer disease, renal failure, osteoporosis, and myasthenia when steroids are used as primary or adjunctive therapy.

Effects on the liver and biliary tract

Intermittent, cyclic intravenous administration of Depo-Medrol (usually at initial doses ≥1 g per day) may cause drug-induced liver injury, including acute hepatitis or increased liver enzyme activity. Rare cases of hepatotoxicity have been reported. Symptoms may appear after several weeks or later. In most cases, adverse events resolved after discontinuation of treatment. Therefore, appropriate monitoring is necessary.

Effects on the musculoskeletal system

Acute myopathy may occur during administration of high doses of Depo-Medrol, particularly in patients with neuromuscular transmission disorders (e.g., myasthenia) or in patients concurrently treated with anticholinergic drugs, including neuromuscular blockers (e.g., pancuronium). Myopathy may affect eye and respiratory muscles and may lead to quadriparesis. Increased creatine kinase activity may occur. Clinical improvement or complete recovery after discontinuation of Depo-Medrol may take several weeks or even years.

Osteoporosis may occur in patients on long-term, high-dose Depo-Medrol therapy.

Effects on the kidneys and urinary system

Caution is required in patients with systemic sclerosis, as an increased incidence of scleroderma renal crisis has been observed with corticosteroids, including methylprednisolone.

Depo-Medrol should be used with caution in patients with renal impairment.

Injury, poisoning, and procedural complications

Depo-Medrol should not be used in the treatment of traumatic brain injury.

Diagnostic tests

Administration of medium and high doses of Depo-Medrol may increase blood pressure, sodium and water retention, and potassium loss. Therefore, dietary sodium restriction and potassium supplementation may be necessary. All glucocorticoids, including Depo-Medrol, increase calcium excretion.

Children

In children receiving long-term treatment with divided daily doses of Depo-Medrol, growth suppression may occur. This treatment regimen should be limited to the most severe indications. Patients should remain under close medical supervision. Infants and children receiving Depo-Medrol long-term are particularly susceptible to increased intracranial pressure.

High doses of Depo-Medrol may cause pancreatitis in children.

Other warnings

Complications of glucocorticoid therapy depend on dose size and duration of treatment. The physician will decide on dosing and duration of treatment individually for each patient.

If long-term treatment is discontinued, the physician will recommend monitoring the patient's condition (see also section 3: Discontinuation of Depo-Medrol).

Inform the physician about all medicines currently or recently taken by the patient, including those available without a prescription.

Some medicines may enhance the effect of Depo-Medrol, and the physician may wish to monitor the patient closely when such medicines are used (including some HIV medications: ritonavir, cobicistat).

Patients should exercise caution when using acetylsalicylic acid and non-steroidal anti-inflammatory drugs (NSAIDs) concurrently with Depo-Medrol.

Oral anticoagulants (medicines taken orally to prevent blood clotting) used together with Depo-Medrol may increase the risk of bleeding. In some cases, the effect of oral anticoagulants may also be reduced.

During treatment with Depo-Medrol, frequent monitoring of bleeding risk by the physician through additional blood tests may be necessary. If needed, the physician may also adjust the dose of Depo-Medrol.

Due to the possibility of skin and subcutaneous tissue atrophy, the physician will recommend appropriate dosing and injection technique to minimize these complications.

Corticosteroids may affect results of biological tests (e.g., skin tests, thyroid hormone measurements).

After administration of Depo-Medrol, pheochromocytoma crisis has been reported, sometimes fatal. In patients in whom pheochromocytoma is suspected or confirmed, the physician will decide on using Depo-Medrol only after appropriate benefit-risk assessment.

Tumor lysis syndrome may occur during corticosteroid treatment of tumors. Inform the physician if the patient has cancer and experiences symptoms of tumor lysis syndrome such as muscle cramps, muscle weakness, confusion, irregular heartbeat, vision loss or disturbances, and shortness of breath.

INTRA-ARTICULAR ADMINISTRATION

To prevent infections, aseptic techniques must be followed.

After intra-articular administration of corticosteroids, the patient should avoid overloading joints in which symptoms have been relieved. Failure to do so may exacerbate joint destruction, outweighing the benefits of steroid administration.

Injections should not be made into unstable joints. In some cases, repeated intra-articular injections may cause joint instability. In selected cases, the physician may decide to perform a control X-ray to detect possible joint deterioration.

If a local anesthetic is used before injection of Depo-Medrol, the physician should read the package leaflet of that medicine and follow all recommended precautions.

THE FOLLOWING ADDITIONAL PRECAUTIONS SHOULD BE TAKEN WHEN ADMINISTERING CORTICOSTEROIDS BY PARENTERAL ROUTES:

Intramuscular injection of corticosteroids may cause systemic and local effects.

Appropriate examination of joint fluid is necessary to exclude possible infection.

Significant increase in pain intensity with accompanying local swelling, limited joint mobility, fever, and worsening general condition are potential signs of acute septic arthritis. If this complication occurs and sepsis is confirmed, the physician will recommend discontinuing local glucocorticoid injections and initiate appropriate antimicrobial treatment.

Local administration of steroids into joints previously affected by infection should be avoided.

Glucocorticoids should not be injected into unstable joints. Sterile technique must be used to prevent infections and contamination.

Depo-Medrol and other medicines

Inform the physician about all medicines currently or recently taken by the patient, as well as any medicines the patient plans to take.

Depo-Medrol may affect the action of other medicines, and other medicines may affect the action of Depo-Medrol.

Dose adjustment of Depo-Medrol may be necessary when used concomitantly with the following medicines or products:

• antibacterial agents: isoniazid
• antituberculosis antibiotic: rifampicin
• oral anticoagulants
• anticonvulsants: carbamazepine, phenobarbital, phenytoin
• anticholinergic agents: neuromuscular blocking agents
• muscle relaxants, e.g., pancuronium, vecuronium
• cholinesterase inhibitors
• antidiabetic agents
• antiemetics: aprepitant, fosaprepitant
• antifungal agents: itraconazole, ketoconazole
• antiviral agents: HIV protease inhibitors: indinavir and ritonavir
• aromatase inhibitor: aminoglutethimide
• calcium channel antagonist: diltiazem
• oral contraceptives: ethinylestradiol/norethisterone
• grapefruit juice
• immunosuppressive agents: cyclosporine, cyclophosphamide, tacrolimus
• macrolide antibacterial agents: clarithromycin, erythromycin, troleandomycin
• non-steroidal anti-inflammatory drugs (NSAIDs): high-dose acetylsalicylic acid
• medicines reducing potassium concentration

Use of Depo-Medrol in patients with renal or hepatic impairment

Depo-Medrol should be used with caution in patients with renal impairment.

Pregnancy, breastfeeding, and effects on fertility

If the patient is pregnant or breastfeeding, suspects she may be pregnant, or is planning to have a child, she should consult a doctor or pharmacist before using this medicine.

Fertility

Animal studies have shown that Depo-Medrol has adverse effects on fertility.

Pregnancy

Some animal studies have shown that corticosteroids administered to mothers may cause developmental abnormalities in the fetus.

However, Depo-Medrol does not appear to cause congenital malformations in the fetus when administered to pregnant women. Until adequate studies on the effects of Depo-Medrol on human reproduction are conducted, this medicine should not be given to pregnant women unless a careful benefit-risk assessment for mother and fetus has been performed.

If during pregnancy there is a need to discontinue chronic use of Depo-Medrol, it should be done gradually. In some cases (e.g., replacement therapy in adrenal insufficiency treatment), continuation or even dose increase may be necessary.

Corticosteroids readily cross the placental barrier. In one retrospective study, an increased incidence of low birth weight in infants born to mothers receiving corticosteroids was observed. In humans, the risk of low birth weight is dose-dependent. This risk may be reduced by using lower doses of corticosteroids.

Infants born to mothers who received significant doses of Depo-Medrol during pregnancy should be closely observed and examined for adrenal insufficiency, although adrenal insufficiency in newborns appears to be rare in infants exposed to corticosteroids in utero.

Cataracts have been observed in infants born to mothers who received long-term corticosteroid therapy during pregnancy.

The effect of corticosteroids on labor is unknown.

Breastfeeding

Corticosteroids pass into human milk.

In infants breastfed by mothers receiving Depo-Medrol, which passes into breast milk, growth suppression and effects on endogenous glucocorticoid production may occur. This medicine may be used by breastfeeding women only after a careful benefit-risk assessment for mother and infant.

Driving and using machines

The effect of Depo-Medrol on the ability to drive or use machines has not been studied. Patients experiencing dizziness, visual disturbances, or fatigue during treatment with Depo-Medrol should not drive or operate machinery.

Depo-Medrol contains sodium.
The medicine contains less than 1 mmol (23 mg) of sodium per vial, meaning the medicine is considered "sodium-free".

3. How to use Depo-Medrol

This medicine should always be used as directed by the physician. If in doubt, consult your doctor or pharmacist.
Dosage and administration instructions intended solely for professional medical personnel are provided at the end of this leaflet.
The physician will determine the appropriate dose, route, and site of administration of Depo-Medrol.

A. ADMINISTRATION FOR SYSTEMIC EFFECT
The physician will adjust the dose of the medicine administered intramuscularly according to the severity of the disease being treated and the patient's response to therapy.
The usual recommended doses range from 40 mg to 120 mg.
The duration of treatment should be as short as possible. The patient must remain under medical supervision. In infants and children, the recommended doses should be reduced; however, dosing should depend more on the severity of the disease than on precise calculations based on age or body weight.
Hormonal therapy is an adjunct to conventional treatment but does not replace it.
After administration for more than several days, the physician will decide whether to gradually reduce the dose or taper off the medicine. If the physician decides to discontinue long-term treatment, the patient should remain under close medical observation. If spontaneous remission occurs during chronic illness, the medicine should be discontinued gradually under medical supervision.
During long-term treatment, the physician will order regular routine follow-up examinations.

B. LOCAL ADMINISTRATION (FOR LOCAL EFFECT)
Treatment with Depo-Medrol does not eliminate the need for conventional therapies. Although this treatment method may alleviate symptoms, it does not in any way ensure complete cure, and the hormone does not affect the underlying cause of inflammation.

1. Rheumatoid arthritis and osteoarthritis
   The dose for intra-articular administration depends on the size of the joint and the severity of the condition in the individual patient. The usual recommended doses range from 4 mg to 80 mg. In chronic conditions, injections may be repeated at intervals of one to five or more weeks, depending on the degree of symptom relief achieved after the initial injection.

2. Tenosynovitis
   The physician will appropriately adjust the dose of the medicine administered into the tendon sheath according to the course of the disease and the patient's response to treatment.

3. Other conditions: ganglion, tendinitis, epicondylitis
   The physician will appropriately adjust the dose of the medicine according to the severity of the condition and the patient's response to treatment. The usual recommended doses range from 4 mg to 30 mg. In the treatment of recurrent or chronic conditions, repeat injections may be necessary.

Each injection must be performed under sterile conditions.

4. Local injections for the treatment of skin disorders
   The physician will appropriately adjust the dose of the medicine according to the severity of the condition and the patient's response to treatment. After cleansing the skin with an appropriate antiseptic agent such as 70% alcohol, 20 to 60 mg of methylprednisolone acetate is injected into the lesion. In larger lesions, the physician may decide to administer doses of 20 to 40 mg divided into several separate local injections. Injection of amounts that may cause skin discoloration should be avoided, as such doses may lead to small areas of necrosis. Usually, the medicine is administered in one to four injections. The interval between injections depends on the type of lesion and the duration of improvement achieved after the first injection.

C. RECTAL ENEMA ADMINISTRATION
The physician will appropriately adjust the dose of the medicine according to the severity of the condition and the patient's response to treatment.
Administration via rectal enema is used as adjunctive therapy in the treatment of certain patients with ulcerative colitis. The usual doses range from 40 mg to 120 mg, administered as rectal enemas (e.g., 40 mg of the medicine in 30 to 300 ml of water) or continuous rectal infusion, three to seven times weekly for two or more weeks. The physician will also decide on the use of other established therapeutic agents.

Use of a higher than recommended dose of Depo-Medrol
There is no clinical syndrome of acute overdose with methylprednisolone acetate.
Prolonged use of the medicine in frequently repeated doses (once daily or several times weekly) may lead to Cushing's syndrome.

Missed dose of Depo-Medrol
Do not use a double dose to make up for a missed dose.

Discontinuation of Depo-Medrol
In the case of interrupting long-term treatment, patient monitoring is recommended. The risk of post-treatment secondary adrenal insufficiency can be minimized by gradually reducing or tapering the dose. After discontinuation of long-term treatment, adrenal cortex function should be evaluated. The most important symptoms of insufficiency are weakness, orthostatic hypotension, and depression.

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everyone will experience them.
Following administration of the product by contraindicated routes (intrathecally/intracranially), the following adverse reactions have been reported:
meningitis, gastrointestinal or urinary bladder dysfunction, headache, meningitis, paraplegia/paraparesis, seizures, sensory disturbances.

Possible adverse reactions associated with the use of Depo-Medrol include:
Frequency unknown (frequency cannot be estimated from available data)

• Opportunistic infections, infections, peritonitis, injection site infections
• Leukocytosis (increased number of white blood cells in blood)
• Hypersensitivity to the drug, anaphylactic reaction – a type of immediate allergic reaction upon re-exposure to an allergen, anaphylactoid reaction – an immediate systemic reaction that may occur even after first contact with the drug
• Cushing's syndrome, suppression of the hypothalamic-pituitary-adrenal (HPA) axis, steroid withdrawal syndrome
• Metabolic acidosis, subcutaneous lipomatosis, sodium retention (accumulation of sodium in the body), fluid retention, hypokalemic alkalosis (alkalosis with low potassium ion concentration in blood), dyslipidemia (abnormal fasting serum concentration of one or more lipoprotein fractions or their composition), impaired glucose tolerance, increased insulin requirement (or need for oral antidiabetic drugs in diabetic patients), redistribution of body fat, increased appetite (which may lead to weight gain)
• Affective disorders (including depressive mood, euphoric mood, emotional lability, drug dependence, suicidal thoughts), psychotic disorders (including mania, delusions, hallucinations, schizophrenia), mental disorders, personality changes, confusion, anxiety disorders, mood swings, abnormal behavior, insomnia, irritability
• Increased intracranial pressure (with papilledema [benign intracranial hypertension]), seizures, amnesia, cognitive disorders, dizziness, headache
• Chorioretinopathy (disorders of retina and choroid), blindness†, cataract, glaucoma, exophthalmos, rarely - blurred vision
• Vertigo of labyrinthine origin
• Congestive heart failure (in susceptible patients)
• Increased blood coagulability, arterial hypertension, hypotension
• Feeling of warmth and skin flushing (hot flushes)
• Pulmonary embolism, hiccups
• Gastrointestinal ulcers (with possible gastrointestinal ulcer perforation, bleeding from gastrointestinal ulcers), intestinal perforation, gastric bleeding, pancreatitis, ulcerative esophagitis, esophagitis, abdominal distension, abdominal pain, diarrhea, dyspepsia, nausea
• Methylprednisolone may cause liver damage. Cases of hepatitis and increased liver enzyme activity (elevated alanine aminotransferase and aspartate aminotransferase activity) have been reported
• Angioedema, hirsutism, petechiae, subcutaneous or intradermal hemorrhages, skin atrophy, erythema, excessive sweating, striae, rash, pruritus, urticaria, acne, skin discoloration, loss of skin pigment
• Inflammation of subcutaneous fat tissue, which may cause skin induration and the appearance of painful red nodules or skin lesions (subcutaneous panniculitis). Subcutaneous panniculitis has been reported after dose reduction or discontinuation of long-term high-dose treatment. In most cases, it resolves spontaneously
• Muscle weakness, myalgia, myopathy, muscle atrophy, osteoporosis, osteonecrosis, pathological fractures, neuropathic joint degeneration, joint pain, growth suppression
• Transient increase in pain after injection (temporary intensification of pain at the site of administration)
• Irregular menstruation
• Sterile abscess, impaired wound healing, peripheral edema, fatigue, malaise, irritability, injection site reactions
• Increased intraocular pressure, decreased carbohydrate tolerance, decreased blood potassium concentration, increased urinary calcium concentration, increased serum alkaline phosphatase activity, increased blood urea concentration, suppression of skin test reactions
• Vertebral compression fractures, tendon rupture

LOCAL ADMINISTRATION
Due to systemic absorption of the drug from the site of administration, the physician should monitor the patient for the above-mentioned systemic adverse reactions.
Local injection of the drug may cause atrophy of the skin and subcutaneous tissue. Although corticosteroid crystals in the dermis inhibit inflammatory reactions, their presence may lead to disintegration of cellular components and physicochemical changes in the ground substance of connective tissue.
As a result, rare skin and/or subcutaneous tissue changes may occur, leading to the formation of skin depressions at the injection site. The severity of this reaction depends on the amount of corticosteroid injected. Complete recovery usually occurs within several months or after complete absorption of all corticosteroid crystals.

Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor. Adverse reactions can be reported directly to the Department of Monitoring of Adverse Drug Reactions, Office for Registration of Medicinal Products, Medical Devices and Biocidal Products
Al. Jerozolimskie 181C
02-222 Warsaw
Tel. +48 22 49 21 301
Fax: +48 22 49 21 309
Website: https://smz.ezdrowie.gov.pl
Adverse reactions can also be reported to the marketing authorization holder or its representative.
Reporting adverse reactions allows the collection of additional information on the safety of the medicine.

5. How to store Depo-Medrol

Keep this medicine out of the sight and reach of children.
Store below 25°C.
Do not use this medicine after the expiry date stated on the packaging after: EXP.
The expiry date refers to the last day of the stated month.
Medicines must 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.

6. Contents of the pack and other information

What Depo-Medrol contains

• The active substance is methylprednisolone acetate. 1 ml of injection suspension contains 40 mg of methylprednisolone.
• The other ingredients are: macrogol 3350, sodium chloride, myristyl-gamma pyridinium chloride, water for injections, sodium hydroxide (for pH adjustment) (see section 2 “Depo-Medrol contains sodium”) and hydrochloric acid (for pH adjustment).

What Depo-Medrol looks like and contents of the pack
A white suspension.
Pack contains 1 or 5 vials.
Marketing Authorisation Holder:
Pfizer Europe MA EEIG
Boulevard de la Plaine 17
1050 Bruxelles
Belgium
Manufacturer:
Pfizer Manufacturing Belgium NV
Rijksweg 12
2870 Puurs-Sint-Amands
Belgium
For further information, contact the local representative of the Marketing Authorisation Holder:
Pfizer Polska Sp. z o.o.
tel. 22 335 61 00

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Information intended exclusively for healthcare professionals

Depo-Medrol must not be diluted with other solutions or mixed with other solutions.
Before administration, inspect the vial for the presence of solid particles or discoloration. To prevent iatrogenic infections, strict aseptic technique must be observed. The drug is not suitable for intravenous or intrathecal administration. It must not be used as a multi-dose vial. After administering the required dose, any remaining suspension must be discarded.
Shake vigorously before use to obtain a uniform suspension.

ADMINISTRATION FOR SYSTEMIC EFFECT
The intramuscular dose depends on the severity of the condition being treated and must be individually adjusted according to disease severity and the patient's response to treatment.
When prolonged action is desired, the weekly dose is calculated by multiplying the daily oral dose by 7 and administered as a single injection.
The duration of treatment should be as short as possible. The patient must remain under medical supervision. In infants and children, recommended doses should be reduced; however, dosing should depend more on disease severity than on precise age- or weight-based calculations.
Hormonal therapy is an adjunct to conventional treatment but does not replace it.
After administration for more than a few days, the physician will decide whether to gradually reduce the dose or taper the drug. If the physician decides to discontinue chronic therapy, the patient should remain under close medical supervision. If spontaneous remission occurs in a chronic condition, treatment should be discontinued gradually under medical supervision.
During long-term treatment, the physician may order regular routine tests, such as: urinalysis, blood glucose measurement two hours after meals, blood pressure and body weight monitoring, and chest X-ray. In patients with a history of peptic ulcer disease or with pronounced dyspeptic symptoms, a radiographic examination of the upper gastrointestinal tract is advisable.

Example dosages:
Adrenogenital syndrome:

• single intramuscular injections of 40 mg every two weeks.

Rheumatoid arthritis, maintenance treatment:

• 40 to 120 mg once weekly, administered intramuscularly.

Skin disorders:

• 40 to 120 mg of methylprednisolone acetate administered intramuscularly over one to four weeks.

Severe dermatitis caused by poison ivy:

• symptom relief may be achieved within 8 to 12 hours after a single intramuscular dose of 80 to 120 mg.

Chronic contact dermatitis:

• repeated injections at intervals of 5 to 10 days may be necessary.

Seborrheic dermatitis:

• 80 mg once weekly.

Asthma:

• after intramuscular administration of 80 to 120 mg, symptom reduction may occur within 6 to 48 hours. The effect may last from several days to two weeks.

If the condition being treated is associated with stress symptoms, the suspension dose should be increased.
If rapid achievement of maximum hormonal effect is required, intravenous administration of a highly soluble sodium succinate salt of methylprednisolone is indicated.

LOCAL ADMINISTRATION (FOR LOCAL EFFECT)
Treatment with Depo-Medrol does not eliminate the need for conventional measures. Although this method of treatment leads to symptom relief, it does not provide a complete cure under any circumstances, and the hormone does not affect the underlying cause of inflammation.

1. Rheumatoid arthritis and osteoarthritis

The dose for intra-articular administration depends on the size of the joint and the severity of the condition in the individual patient. In chronic conditions, injections may be repeated at intervals of one to five or more weeks, depending on the degree of symptom relief achieved after the first injection. The following table provides approximate dosage guidelines:
Joint size Examples Dosage range
Large Knee joints 20 to 80 mg
Ankle joints
Shoulder joints
Medium Elbow joints 10 to 40 mg
Wrists
Small Metacarpophalangeal joints 4 to 10 mg
Interphalangeal joints
Sternoclavicular joints
Acromioclavicular joints
It is recommended that the anatomy of the joint be thoroughly reviewed before performing an intra-articular injection. To achieve optimal anti-inflammatory effect, the injection should be administered into the synovial space. Using sterile technique typical for lumbar puncture, a sterile needle of size 20 to 24 (attached to a dry syringe) should be rapidly introduced into the synovial space. Infiltration anesthesia with procaine may be considered. To confirm correct needle placement within the joint space, aspirate a few drops of synovial fluid. Each injection should be administered at the site where the joint cavity is most superficial and furthest from major vessels and nerves. After needle placement, remove the syringe used for aspiration and replace it with a second syringe containing the desired amount of Depo-Medrol. Aspirate a small amount of synovial fluid again to confirm that the needle remains within the synovial space. After injection, gently move the joint several times to help mix the suspension with synovial fluid. The injection site should then be covered with a small sterile dressing.
Appropriate sites for intra-articular injections include knee, ankle, wrist, elbow, shoulder, finger, and hip joints. Needle insertion into the hip joint is often difficult; care must be taken not to puncture large blood vessels in this area. Anatomically inaccessible joints, such as spinal joints and sacroiliac joints, which lack a synovial space, are not suitable for injection. Treatment failure is most commonly due to failure to deliver the drug into the joint space. Injections into surrounding tissues are minimally effective or ineffective. When treatment fails despite correct intra-articular injection (confirmed by fluid aspiration), subsequent injections are usually ineffective. Local treatment does not affect the underlying disease process; therefore, whenever possible, it should be supplemented with physiotherapy and orthopedic correction.
After intra-articular corticosteroid administration, joints in which symptoms have improved should not be overused.
Injections should not be performed into unstable joints. Repeated intra-articular injections may in some cases lead to joint instability. In selected cases, radiological monitoring may be indicated to detect progressive joint damage.
If a local anesthetic is to be used prior to injection of Depo-Medrol, refer to the package insert of the anesthetic product and follow recommended precautions.

2. Bursitis
   Carefully clean the skin around the injection site and inject 1% procaine hydrochloride solution to form a fluid bleb. Insert a sterile 20 to 24 gauge needle (attached to a dry syringe) into the bursa and aspirate fluid. Leave the needle in place and replace the syringe with another containing the drug dose. After injection, remove the needle and apply a small dressing.

3. Other conditions: ganglion, tendonitis, epicondylitis
   In treating conditions such as tendonitis or tenosynovitis, after applying an appropriate antiseptic, care must be taken to inject the suspension into the tendon sheath, not into the tendon tissue itself. The tendon is more easily palpated in a stretched position. In treating epicondylitis, carefully identify the area of maximum tenderness and inject the suspension into this region. For tendon sheath ganglia, inject the suspension directly into the cyst. In many cases, a single injection significantly reduces the size of the joint cyst or may even cause it to disappear. Depending on the severity of the condition, doses may range from 4 to 30 mg. In recurrent or chronic conditions, repeat injections may be necessary.

Each injection must be performed under sterile conditions (an appropriate antiseptic should be applied to the skin).

4. Local injections for the treatment of skin disorders
   After thorough antiseptic cleansing of the skin (e.g., with 70% alcohol), inject 20 to 60 mg of methylprednisolone acetate directly into the lesion. For larger lesions, doses of 20 to 40 mg may need to be divided into several local injections. Avoid injecting amounts that may cause skin discoloration, as this may lead to small areas of necrosis. Usually, the drug is administered in one to four injections. The interval between injections depends on the type of lesion and the duration of improvement following the first injection.

RECTAL ADMINISTRATION (RETENTION ENEMA)
Supplementary treatment in the therapy of certain patients with ulcerative colitis:
40 to 120 mg as rectal enemas (e.g., 40 mg of drug in 30 to 300 ml of water) or continuous rectal infusion three to seven times weekly for two or more weeks. Other established therapeutic measures should also be used.