SOLU-MODERIN 1 g POWDER AND SOLVENT FOR INJECTABLE SOLUTION

2. What you need to know before you use Solu-Moderín

Do not use Solu-Moderín

• if you are allergic to methylprednisolone or any of the other ingredients of this medicine (listed in section 6).
• if you have fungal infections in different parts of the body.

• by the intrathecal route (injection into the layer that covers the brain and spinal cord).
• by the epidural route (injection around the spinal cord).
• before and after vaccination with live or attenuated microorganisms if immunosuppressive doses of corticosteroids are to be administered.

Warnings and precautions

Consult your doctor, pharmacist or nurse before starting treatment with Solu-Moderín,

• if you have stomach or duodenal ulcers,
• if you have intestinal diseases due to the risk of intestinal perforation with peritonitis, such as non-specific ulcerative colitis with imminent risk of perforation, abscesses or other pyogenic infections, as well as diverticulitis (inflammation of small pouches in the intestinal wall), intestinal anastomosis (reconstitution of the intestine by suture) or peptic ulcer,
• if you have any infection, treatment with Solu-Moderín may decrease your resistance to different infections, mask some signs of infection, worsen existing infections or cause old and latent infections to reappear or worsen. New infections may also appear during the use of Solu-Moderín. Your doctor will closely monitor you to detect the development of infections and consider interrupting treatment or reducing the dose as necessary,
• if you have poliomyelitis (an infectious disease that affects the nervous system), except for bulbar poliomyelitis,
• if you have active, latent or reactive tuberculosis,
• if you are going to receive vaccines with killed or inactivated microorganisms and are using immunosuppressive doses of corticosteroids, as the response to these vaccines may be reduced,
• if during treatment with Solu-Moderín you may come into contact with people with infections such as chickenpox or herpes zoster, even if you do not have any symptoms,
• if you have osteoporosis (severe bone demineralization),
• if you have myasthenia gravis, as you may need a dose adjustment,
• if you have diabetes, as it may increase blood glucose levels,
• if you have congestive heart failure (a disease in which the heart cannot pump oxygen-rich blood),
• if you have ocular herpes simplex due to the risk of corneal perforation,
• if during treatment with this medicine you notice any visual disturbances, including vision loss, blurred vision or other visual changes,
• if you have Cushing's syndrome (a condition characterized by a rounded face, fat accumulation in the cervical area, obesity in the trunk, etc.) as this medicine may produce or worsen the disease,
• if you have hypothyroidism or liver cirrhosis, as you may need a dose reduction.
• in case of hyperthyroidism, corticosteroid levels may decrease,
• if you have hyperthyroidism (overactive thyroid),
• if you experience any symptoms of pancreatitis during treatment,
• if after administration of this medicine by intravenous injection (usually in an initial dose of ≥ 1 g/day) you experience any symptoms of liver damage, such as acute hepatitis or increased liver enzymes, as in these cases, adequate monitoring is required,
• if you have thrombosis or are prone to it,
• if you have hypertension,
• if you have kidney disease,
• if you have scleroderma (also known as systemic sclerosis, an autoimmune disorder), as it may increase the risk of a serious complication called scleroderma renal crisis,
• if you have emotional instability or psychotic tendencies,

• if you are suspected or diagnosed with pheochromocytoma (a rare tumor of the adrenal gland tissue),
• if Solu-Moderín is administered to a premature newborn, it may be necessary to monitor heart function and structure,

Tumor lysis syndrome may occur when corticosteroids are used during cancer treatment. Inform your doctor if you have cancer and symptoms of tumor lysis syndrome such as muscle cramps, muscle weakness, confusion, irregular heartbeats, vision loss or visual disturbances, and difficulty breathing.

Oral anticoagulants (medicines administered orally to prevent blood clotting), if used with Solu-Moderín, may increase the risk of bleeding. In some cases, the effect of oral anticoagulants may also be reduced. Your doctor may need to monitor your bleeding risk more frequently through additional blood tests while you are being treated with Solu-Moderín. They may also adjust the dose of Solu-Moderín if necessary.

Contact your doctor immediately if you experience muscle weakness, muscle pain, cramps, and stiffness while using methylprednisolone. These may be symptoms of a disease called thyrotoxic periodic paralysis that can occur in patients with hyperthyroidism (overactive thyroid) treated with methylprednisolone. You may need additional treatment to alleviate this condition.

Interference with laboratory tests

If you are going to undergo any diagnostic tests (including blood tests, urine tests, skin tests using allergens, etc.) during the administration of medium and high doses of glucocorticoids, inform your doctor that you are using this medicine, as it may alter the results.

Use in athletes

If you are going to undergo doping control tests, as methylprednisolone may result in a positive test.

Children and adolescents

Prolonged use of corticosteroids has been associated with growth and development delay in children. Therefore, it will only be used when there are important medical reasons for it.

When corticosteroids are used for prolonged periods in infants and children, there is a greater risk of suffering from increased intracranial pressure.

If high doses of corticosteroids are administered in this population, it may cause severe acute pancreatitis.

Other medicines and Solu-Moderín

Tell your doctor or pharmacist if you are using, have recently used or might use any other medicines.

It may be necessary to adjust the dose of one of your medicines and monitor the appearance of adverse reactions. This is especially important if you are taking:

Medicines that may increase methylprednisolone levels:aprepitant, fosaprepitant, cyclosporin, diltiazem, erythromycin, clarithromycin, ethinyl estradiol, norethindrone, itraconazole, ketoconazole, troleandomycin, and pharmacokinetic enhancers (cobicistat).

Medicines that may decrease methylprednisolone levels:phenobarbital, phenytoin, primidone, carbamazepine, rifampicin.

Medicines that may increase or decrease methylprednisolone levels:tacrolimus, cyclophosphamide, carbamazepine, aprepitant, fosaprepitant, itraconazole, ketoconazole, diltiazem, ethinyl estradiol, norethindrone, erythromycin, clarithromycin, phenobarbital, cyclosporin.

Medicines whose blood levels and/or effects may be affected by the administration of methylprednisolone:amphotericin B, xanthines or beta-2 agonists, oral anticoagulants (medicines administered orally to prevent blood clotting), anticholinesterases, isoniazid, antidiabetics, non-steroidal anti-inflammatory drugs, salicylates, anticholinergics (neuromuscular blockers), HIV protease inhibitors, aromatase inhibitors, immunosuppressants, potassium eliminators, antihypertensives, toxoids, and vaccines.

Some medicines may increase the effects of Solu-Moderín, so your doctor may decide to monitor you closely if you are taking medicines such as antivirals (ritonavir, indinavir) and pharmacokinetic enhancers (cobicistat) used to treat HIV.

Using Solu-Moderín with food and drinks

You should avoid consuming grapefruit juice as it may interfere with this medicine.

Pregnancy, breastfeeding, and fertility

If you are pregnant or breastfeeding, think you may be pregnant or are planning to have a baby, ask your doctor or pharmacist for advice before using this medicine, weighing the risk-benefit ratio.

Pregnancy

This medicine may be used during pregnancy only if your doctor considers it necessary.

Children born to mothers who received high doses of corticosteroids during pregnancy should be carefully monitored for possible signs of adrenal insufficiency. Cataracts have been observed in children born to mothers treated with corticosteroids for prolonged periods during pregnancy.

The risk of low birth weight has been associated with the dose and can be minimized by administering low doses of corticosteroids.

Breastfeeding

Solu-Moderín passes into breast milk.

Driving and using machines

Treatment with corticosteroids may cause dizziness, vertigo, visual disturbances, and fatigue.

Therefore, do not drive or operate machinery if you experience these effects while being treated with Solu-Moderín.

Solu-Moderín 500 mg contains sodium

This medicine contains 58.3 mg of sodium (a major component of table salt/cooking salt) per vial. This is equivalent to 2.92% of the maximum recommended daily sodium intake for an adult.

Solu-Moderín 1 g contains sodium

This medicine contains 116.8 mg of sodium (a major component of table salt/cooking salt) per vial. This is equivalent to 5.84% of the maximum recommended daily sodium intake for an adult.

3. How to use Solu-Moderín

Follow exactly the instructions for administration of this medicine as indicated by your doctor or pharmacist. If you are unsure, consult your doctor or pharmacist again.

Solu-Moderín can be administered by intravenous injection (by injection or infusion) or by intramuscular injection.

The intravenous route is the preferred route of administration in case of shock or other acute situations.

The open route for the administration of methylprednisolone should not be used for the administration of any other medicine. A different intravenous route should be used for infusion.

The dose will be individual for each patient and may be modified depending on the severity of the condition and the patient's response. The effective dose should be used to control the disease, and treatment should be prolonged for the shortest possible time.

It should also be evaluated whether administration will be daily or intermittent.

Dose reduction should be done gradually, particularly with relatively high doses.

Your doctor will decide when to switch to oral therapy.

In life-threatening situations, it is recommended to start treatment with doses of 250 mg to 1,000 mg of methylprednisolone.

• Adrenal insufficiency: 16 to 32 mg in intravenous infusion, followed by another 16 mg over 24 hours.

In these crises and in Waterhouse/Friderichsen syndrome, simultaneous administration of mineralocorticoids is indicated.

• Anaphylactic shock and situations mediated by immediate hypersensitivity mechanisms: 250 mg to 500 mg of methylprednisolone.

• Severe inflammatory respiratory diseases: 30 to 90 mg/day.

In status asthmaticus, it is recommended to administer 250 to 500 mg of methylprednisolone.

• Acute exacerbations of multiple sclerosis: administer 500 mg/day or 1 g/day for 3 or 5 days, intravenous injection.

• Cerebral edema: 250 to 500 mg of methylprednisolone.

• Acute spinal cord injury: 30 mg of methylprednisolone per kg of body weight in a bolus IV dose over a minimum of 15 minutes. After a 45-minute pause, a continuous intravenous infusion of 5.4 mg/kg/hour will be administered for 23 hours for patients in whom treatment was started before 3 hours had passed since the injury occurred, and for 47 hours for those patients in whom treatment was started after 3-8 hours had passed since the injury occurred.

• Rejection crisis: up to 30 mg/kg of body weight.

Use in children and adolescents

The dose should be based on the severity of the disease and the patient's response, rather than their age or weight.

In any case, the pediatric dose should not be less than 0.5 mg/kg every 24 hours.

In life-threatening situations, it is recommended to start treatment with single doses of 4 to 20 mg/kg of body weight in children.

If you use more Solu-Moderín than you should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicology Information Service, phone 91 562 04 20, indicating the medicine and the amount ingested.

If you forget to use Solu-Moderín

Do not use a double dose to make up for forgotten doses.

If you stop using Solu-Moderín

Do not stop using this medicine without consulting your doctor.

If you have any other questions about the use of this medicine, ask your doctor, pharmacist, or nurse.

4. Possible Adverse Effects

Like all medicines, this medicine can cause adverse effects, although not all people suffer from them.

The following adverse reactions have been reported with the following contraindicated routes of administration: intrathecal/epidural: arachnoiditis, functional gastrointestinal disorders/bladder dysfunction, headache, meningitis, paraparesis/paraplegia, epileptic seizures, sensory disturbances.

Reported adverse effects are classified according to their frequency as frequent adverse effects (may affect up to 1 in 10 people) and unknown frequency (cannot be estimated from available data).

Infections and Infestations

Frequent: infection.

Unknown frequency: opportunistic infection, peritonitis (may be the first sign or symptom present in a digestive disorder such as perforation, obstruction, or pancreatitis).

Blood and Lymphatic System Disorders

Unknown frequency: elevated white blood cell count (leucocytosis).

Immune System Disorders

Unknown frequency: drug hypersensitivity, anaphylactic reaction, anaphylactoid reaction.

Endocrine Disorders

Frequent: Cushing's syndrome.

Unknown frequency: suppression of the hypothalamic-pituitary-adrenal axis, steroid suppression syndrome.

Metabolic and Nutrition Disorders

Frequent: sodium retention, fluid retention.

Unknown frequency: metabolic acidosis, epidural lipomatosis, hypokalemic alkalosis, dyslipidemia, decreased glucose tolerance, increased need for insulin (or oral hypoglycemics in diabetics), accumulation of fatty tissue in localized areas of the body (lipomatosis), increased appetite (which may lead to weight gain).

Psychiatric Disorders

Frequent: affective disorder (including depressed mood, euphoric mood).

Unknown frequency: affective disorder (including mood lability, drug dependence, suicidal ideation), psychotic disorder (including mania, delirium, hallucination, and schizophrenia), mental disorder, personality change, confusional state, anxiety, mood changes, abnormal behavior, insomnia, irritability.

Nervous System Disorders

Unknown frequency: increased intracranial pressure (with papilledema [benign intracranial hypertension]), epileptic seizures, amnesia, cognitive disorder, dizziness, headache.

Eye Disorders

Frequent: cataract.

Unknown frequency: retinal and choroidal disease (chorioretinopathy), glaucoma, exophthalmos, blurred vision.

Ear and Labyrinth Disorders

Unknown frequency: vertigo.

Cardiac Disorders

Unknown frequency: congestive heart failure (in susceptible patients), arrhythmia.

Vascular Disorders

Frequent: hypertension.

Unknown frequency: blood clots (thrombotic events), hypotension, skin heat and redness (rubefaction).

Respiratory, Thoracic, and Mediastinal Disorders

Unknown frequency: pulmonary embolism, hiccups.

Gastrointestinal Disorders

Frequent: peptic ulcer (with possible perforation and hemorrhage).

Unknown frequency: intestinal perforation, gastric hemorrhage, pancreatitis, ulcerative esophagitis, esophagitis, abdominal distension, abdominal pain, diarrhea, dyspepsia, nausea.

Hepatobiliary Disorders

Unknown frequency: methylprednisolone may damage your liver; cases of hepatitis and increased liver enzymes have been reported.

Skin and Subcutaneous Tissue Disorders

Frequent: ecchymosis, skin atrophy, acne.

Unknown frequency: angioedema, hirsutism, petechiae, erythema, hyperhidrosis, skin striae, rash, pruritus, urticaria, skin hypopigmentation.

Musculoskeletal and Connective Tissue Disorders

Frequent: muscle weakness, osteoporosis, growth retardation.

Unknown frequency: myalgia, myopathy, muscle atrophy, osteonecrosis, pathological fracture, neuropathic arthropathy, arthralgia.

Reproductive System and Breast Disorders

Unknown frequency: irregular menstruation.

General Disorders and Administration Site Conditions

Frequent: impaired wound healing.

Unknown frequency: peripheral edema, fatigue, general malaise, injection site reaction.

Investigations

Frequent: decreased blood potassium.

Unknown frequency: increased intraocular pressure, decreased carbohydrate tolerance, elevated urine calcium, elevated alanine aminotransferase (ALT), elevated aspartate aminotransferase (AST), elevated blood alkaline phosphatase (FA), elevated blood urea.

Injury, Poisoning, and Procedural Complications

Unknown frequency: vertebral compression fracture, tendon rupture (especially Achilles tendon rupture).

Other Adverse Effects in Children

The following reactions were more frequent in children: mood changes, abnormal behavior, insomnia, irritability.

Reporting of Adverse Effects

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect that does not appear in this prospectus. You can also report them directly through the Spanish Pharmacovigilance System for Human Use Medicines: https://www.notificaram.es. By reporting adverse effects, you can contribute to providing more information on the safety of this medicine.

5. Storage of Solu-Moderin

No special storage conditions are required.

Validity period after reconstitution: 48 hours.

Keep this medicine out of the sight and reach of children.

Do not use this medicine after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Medicines should not be thrown away through wastewater or household waste. Deposit the packaging and medicines you no longer need at the pharmacy's SIGRE point. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Solu-Moderin 500 mg and Solu-Moderin 1 g powder and solvent for injectable solution

• The active ingredient is methylprednisolone (sodium succinate). Each vial of powder contains 500 mg and 1 g (1000 mg), respectively, of methylprednisolone (as sodium succinate)
• The other components (excipients) are: monobasic monohydrate sodium phosphate, anhydrous dibasic sodium phosphate, and water for injectable preparations.

Appearance of the Product and Package Contents

Solu-Moderin 500 mg and Solu-Moderin 1 g are presented in powder and solvent for injectable solution.

Vial of lyophilized powder, white in color, and vial of transparent and colorless solvent.

Solu-Moderin 500 mg and Solu-Moderin 1 g are packaged in containers of 1 vial with powder and 1 vial with solvent and containers of 50 vials with powder and 50 vials with solvent.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Pfizer, S.L.

Avda. de Europa, 20-B. Parque Empresarial La Moraleja - 28108 Alcobendas (Madrid)

Manufacturer

Pfizer Manufacturing Belgium NV

Rijksweg 12

2870 Puurs-Sint-Amands

Belgium

Date of the Last Revision of this Prospectus: July 2024

Detailed and updated information on this medicine is available on the website of the Spanish Agency for Medicines and Health Products (AEMPS) http://www.aemps.gob.es/.

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This information is intended only for healthcare professionals:

Solu-Moderin must be reconstituted before use. An aseptic technique is required for its preparation.

• Reconstitution of the injection solution:

The powder contained in the vial must be reconstituted with the solvent included in the solvent vial. Shake well until a clear solution is obtained.

• Reconstitution of the solution for infusion:

First, the powder contained in the vial must be reconstituted as previously indicated. The reconstituted solution can be administered in diluted solutions of 5% dextrose in water, isotonic saline solution, or 5% dextrose solution in 0.45% or 0.9% sodium chloride.