Package Insert: Information for the User

Fortecortin 40 mg/5 ml Injectable Solution

Dexamethasone Phosphate

Read this entire package insert carefully before starting to use the medication, as it contains important information for you.

• Keep this package insert, as you may need to refer to it again.
• If you have any questions, consult your doctor or pharmacist.
• This medication has been prescribed only for you and should not be given to others who may have the same symptoms as you, as it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are not listed in this package insert. See section 4.

Dexamethasone phosphate contained in Fortecortín is a corticosteroid (glucocorticoid) that is obtained from cortisone. It intervenes by regulating many of the body's metabolic processes with anti-inflammatory and immunosuppressive activity.

Fortecortín is used by intravenous or intramuscular route for the treatment of:

• Inflammatory processes derived from brain tumors or head trauma.
• Severe traumatic shock (shock state after severe injuries).
• Anaphylactic shock (severe generalized allergic reaction).

No use Fortecortín:

• If you are allergic or have had an allergic reaction to dexamethasone or any of the other components of this medication (listed in section 6). These reactions are more common in patients with a history of allergy to any medication.

• By intravenous administration if you have any systemic infection, unless you receive specific anti-infective treatment.

Warnings and precautions

The administration of Fortecortín may induce adrenal insufficiency, especially if high doses are administered for a prolonged period.

Avoid sudden suspension of treatment, especially in prolonged treatments, as it may cause a corticosteroid withdrawal syndrome characterized by general malaise, weakness, and muscle pain, difficulty breathing, loss of appetite, nausea, vomiting, fever, decreased blood pressure, and decreased blood glucose levels.

In certain special situations of physical stress during treatment with Fortecortín (e.g., febrile disorders, accidents, operations, childbirth), it may be necessary to temporarily increase the daily dose of corticosteroid.

Fortecortín may increase the risk of infection as well as mask the signs of an infection and/or make its diagnosis difficult. Latent infections may reactivate during the use of corticosteroids.

In the following cases, close monitoring of treatment by your doctor will be necessary:

• Acute and chronic bacterial infections.
• If you have lymph node inflammation (lymph nodes that help defend the body) after receiving the tuberculosis vaccine.
• If you have a history of tuberculosis.
• Patients with chronic hepatitis (inflammation of the liver).
• Acute viral infections (hepatitis B, herpes, varicella, poliomyelitis, measles).
• Infections caused by fungi or parasites.
• If you need to be vaccinated or have been vaccinated between approximately 8 weeks before and 2 weeks after.
• If you have diabetes, peptic ulcer, or inflammatory diseases of the digestive system, osteoporosis (loss of calcium in the bones), heart failure, high blood pressure, and psychiatric disorders.
• If you have glaucoma (increased intraocular pressure), ulcers, or lesions of the cornea, blurred vision, or other visual disturbances.

The long-term treatment with Fortecortín will only be established when it is strictly necessary and should be associated with specific treatment that corresponds to each case.

The administration of Fortecortín may alter the values of certain laboratory tests.

Especially with long-term treatment with high doses of Fortecortín, it is necessary to consider a sufficient intake of potassium and a restricted intake of salt and monitor potassium levels in the blood.

The administration of high doses of dexamethasone may cause a decrease in heart rate in some patients.

Severe anaphylactic reactions (hypersensitivity of the immune system) may occur.

If you have myasthenia gravis (severe muscle weakness), it may initially worsen during treatment with Fortecortín.

If the intravenous administration of Fortecortín is too rapid, a sensation of tingling or numbness may occur, which may last for a few minutes.

If Fortecortín is administered locally (intramuscularly), unwanted systemic effects may occur.

In postmenopausal women, Fortecortín may increase the risk of osteoporosis.

You should inform your doctor if you have any of the following symptoms of tumor lysis syndrome (TLS) such as muscle cramps, muscle weakness, confusion, visual loss or alteration, and difficulty breathing, in the case that you suffer from a malignant hematological process.

Children and adolescents

In children, the doctor should evaluate the benefits of treatment, as the use of glucocorticoids may affect their growth.Dexamethasone should not be used routinely in premature neonates with respiratory problems.

If dexamethasone is administered to a premature baby, it is necessary to monitor the function and structure of the heart.

Older adults

In patients over 65 years old, the doctor should evaluate the benefits of treatment and possible risks, as these patients may be more susceptible to adverse effects, such as osteoporosis.

Use of Fortecortín with other medications

Inform your doctor or pharmacist if you are taking or have recently taken any other medication, including those acquired without a prescription, homeopathic, herbal, and other health-related products, as it may be necessary to interrupt treatment or adjust the dose of some of them. Note that these instructions may also apply to medications that have been used before or may be used later.

This is especially important if you are taking the following medications:

• Nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin and salicylates, as they increase the risk of ulcer and gastrointestinal bleeding.
• Oral antidiabetic drugs and insulin, as their effect may be reduced.
• Antiepileptic drugs (carbamazepine), antiarrhythmic drugs (phenytoin), antihistamines, and bronchodilators (ephedrine), antibiotics (rifampicin), barbiturates, and primidone, as they may reduce the effects of dexamethasone.
• Medications that slow down degradation in the liver, such as some antifungal medications (ketoconazole, itraconazole) and certain antiretroviral medications, as they may increase the action of corticosteroids.Therefore, your doctor will perform close monitoring if you are taking these medications (including some for HIV: ritonavir, cobicistat).
• Coumarin derivatives (oral anticoagulants), as their anticoagulant effect may be modified.
• Estradiol (e.g., for contraceptive use) may increase the action of dexamethasone.
• Atropine and other anticholinergic medications, as they may increase intraocular pressure.
• Medications used to treat heart disease, such as cardiac glycosides, as their effect may be increased by decreases in potassium levels.
• Diuretics/laxatives, as they may increase the elimination of potassium.
• Praziquantel, as glucocorticoids may cause a decrease in praziquantel levels in the blood.
• Antihypertensive medications (ACE inhibitors), as they may increase the risk of alterations in blood components.
• Antimalarial medications (chloroquine, hydroxychloroquine, mefloquine), as they may increase the risk of muscle diseases or heart muscle diseases (myopathies, cardiomyopathies).
• Immunosuppressive medications, as they may increase the risk of infections. Additionally, in the case of cyclosporine, they may increase cyclosporine levels in the blood, which increases the risk of seizures.
• Non-depolarizing muscle relaxants, as muscle relaxation may be prolonged.
• Protirelin, as its effects on thyroid-stimulating hormone (TSH) may be affected.
• Fluoroquinolones, as they may increase the risk of tendon alterations.
• Anidulafungin, as it may increase the risk of hypokalemia (low potassium levels).
• Albendazole, as it may increase the levels of its active metabolite in the blood.
• Vaccines, as the immune response to the vaccine may be inadequate.

Pregnancy, lactation, and fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication.

Pregnancy

Dexamethasone crosses the placenta. During pregnancy, especially in the first three months, treatment should only be administered after carefully weighing the risk-benefit ratio. Therefore, women should inform their doctor about an existing or impending pregnancy. With long-term treatment with glucocorticoids during pregnancy, fetal growth disorders cannot be ruled out. If glucocorticoids are administered at the end of pregnancy, the newborn may have a deficient functioning of the adrenal glands, which requires initiation of a reduced-dose treatment in the newborn.

Newborns of mothers who received Fortecortín near the end of pregnancy may have low blood sugar levels after birth.

Lactation

Glucocorticoids, including dexamethasone, pass into breast milk. So far, no damage to the infant has been reported. However, the need for administration during breastfeeding should be carefully examined. If high doses are necessary for medical reasons, breastfeeding should be interrupted. Consult your doctor immediately.

Fertility

The effects of Fortecortín on fertility have not been studied.

Driving and operating machinery

No data are available on how Fortecortín affects driving or operating machinery, so try not to perform tasks that require special attention until you check how you tolerate the medication.

Fortecortín contains sodium

This medication contains less than 23 mg (1 mmol) of sodium per ampoule, so it is considered essentially "sodium-free".

Influence on laboratory results

This medication may alter the values of certain laboratory tests. Additionally, skin reactions may be masked in allergy tests.

Use in athletes

This medication contains a component that may produce a positive result in doping control tests.

Follow exactly the administration instructions for this medication as indicated by your doctor. Your doctor will set the doses on an individual basis. In case of doubt, consult your doctor or pharmacist again.

The dosing requirements are variable and should be individualized based on the disease and the patient's response.

Fortecortín is usually injected slowly (over 2-3 minutes) intravenously, but it can also be administered intramuscularly. The dose and duration of treatment depend on the indication and severity of the disease being treated. After obtaining an initial favorable response, your doctor will establish the most suitable maintenance dose for you. Reducing the dose and suspending treatment should always be done progressively.

Renal and Hepatic Insufficiency

No specific dose adjustment is necessary for patients with renal insufficiency.

In patients with hepatic insufficiency, lower doses may be sufficient or the dose may need to be reduced.

Use in Children and Adolescents

Generally, the recommended daily dose in children is 0.08-0.3 mg/kg, depending on the severity and type of disease.

If You Use More Fortecortín Than You Should

In case of overdose or accidental ingestion, consult your doctor or pharmacist immediately or call the Toxicological Information Service, phone: 91 562 04 20, indicating the medication and the amount used.

No acute intoxications with dexamethasone have been reported. In the case of overdose, it is expected that the adverse reactions described in this prospectus will occur to a greater extent.

If You Discontinue Treatment with Fortecortín

Do not stop treatment before your doctor indicates or abruptly, as this could worsen your disease.

The dose reduction should be done progressively. Similarly, the suspension of treatment should always be done progressively.

Excessively rapid dose reduction after long-term treatment may cause symptoms such as muscle and joint pain. Your doctor will reduce your dose progressively.

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

Like all medicines, this medicine may cause side effects, although not everyone will experience them.

The terms used to describe the frequency of side effects are adjusted to the following definitions: Very common (may affect more than 1 in 10 people), common (may affect up to 1 in 10 people), uncommon (may affect up to 1 in 100 people), rare (may affect up to 1 in 1,000 people), very rare (may affect up to 1 in 10,000 people), frequency not known (cannot be estimated from available data).

Due to the wide range of therapeutic use, dosage, and duration of treatment, the frequency of side effects of Fortecortin is not known.

Blood and lymphatic system disorders: Alteration of blood cells (white blood cells and lymphocytes among others).

Endocrine disorders: Adrenal suppression and induction of symptoms similar to Cushing's syndrome (moon face, truncal obesity).

Eye disorders: Glaucoma (increased intraocular pressure), cataracts, worsening of symptoms of corneal ulcers; eye infections, ptosis, pupil dilation (mydriasis), burning, perforation of the sclera, in rare cases reversible exophthalmos.

Visual disturbances, blurred vision, loss of vision, frequency not known.

Gastrointestinal disorders: Gastrointestinal discomfort, ulcers, gastrointestinal bleeding, pancreatitis inflammation.

Immune system disorders: Hypersensitivity reactions, severe allergic reactions such as: cardiac rhythm problems, bronchospasm, blood pressure alterations, circulatory failure, cardiac arrest.

Infections and infestations: Masking of infections, existing infections may worsen or reactivate and new infections may appear, activation of intestinal parasitic diseases (strongyloidiasis).

Metabolism and nutrition disorders: Fluid retention (edema), potassium loss (which may cause arrhythmias), weight gain, increased blood sugar, diabetes mellitus, hypercholesterolemia, hypertriglyceridemia, increased appetite.

Musculoskeletal and connective tissue disorders: Muscle atrophy and weakness, myopathy, tendon alterations, osteoporosis, aseptic osteonecrosis, growth retardation in children, epidural lipomatosis.

Note: Excessive rapid reduction in dose after long-term treatment may cause symptoms such as muscle and joint pain.

Nervous system disorders: Increased intracranial pressure (pseudotumor cerebri), increased spasms in epileptic patients or appearance of epilepsy (seizures).

Psychiatric disorders: Psychosis, mania, depression, hallucinations, emotional instability, irritability, increased activity, euphoria, anxiety, sleep disturbances, suicidal thoughts.

Reproductive and mammary system disorders: Alteration of sex hormone secretion (amenorrhea, excessive hair growth, impotence).

Skin and subcutaneous tissue disorders: Acne, dermatitis around the mouth, striae, skin atrophy, petechiae, telangiectasias, ecchymoses, hypertrichosis, skin color changes.

Cardiac disorders: Heart failure.

Frequency not known: Hypertrophic cardiomyopathy in premature babies, which usually returns to normal after treatment is discontinued.

Vascular disorders: Hypertension, increased risk of arteriosclerosis and thrombosis, vasculitis (also as a symptom of withdrawal after long-term treatment), fragility of small blood vessels.

General disorders and administration site conditions: Delayed wound healing, hiccups.

Reporting of side effects

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

Do not store at a temperature above 25°C. Store the ampoules in the outer packaging to protect them from light.

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

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

This medication is for single use and must be administered immediately after opening. Any unused portion must be discarded.

Only transparent and particle-free solutions should be used.

Do not use this medication if you observe visible signs ofdegradation.

Medications should not be disposed of through drains or in the trash. Dispose of the containers and medications you no longer need at the SIGREcollection point at the pharmacy. If in doubt, ask your pharmacist how to dispose of the containers and medications you no longer need. By doing so, you will help protect the environment.

Composition of Fortecortin 40 mg/5 ml

• The active ingredient is dexamethasone phosphate. Each ampoule of injectable solution (5 ml) contains 40 mg of dexamethasone phosphate (as sodium phosphate of dexamethasone, 43.72 mg).

Each ml of injectable solution contains 8 mg of dexamethasone phosphate (as sodium phosphate of dexamethasone, 8.75 mg)

• The other components are: sodium citrate, creatinine, disodium edetate, sodium hydroxide, and water for injectable preparations.

Appearance of the product and content of the container

It is presented in the form of type I glass ampoules that are colorless. Containers containing 5, 25, and 50 ampoules of injectable solution.

Holder of the marketing authorization

LABORATORIOS ERN, S.A.

Perú, 228

08020 Barcelona

Spain

Responsible for manufacturing

LABORATORIOS ERN, S.A.

Gorgs Lladó, 188

08210 Barberá del Vallés, Barcelona. Spain

Date of the last review of this leaflet: January 2022

The detailed and updated information of this medicine is available on the website of the Spanish Agency for Medicines and Medical Devices (AEMPS) http://www.aemps.gob.es/

--------------------------------------------------------------------------------------------------------------------

This information is intended solely for healthcare professionals:

Fortecortin should not be mixed with other medications due to lack of compatibility data. Preferably, it should be administered directly by intravenous injection or injected into the infusion line. However, the injectable solution of Fortecortin is compatible with the following infusion solutions (250 ml and 500 ml each) and must be used within 24 hours: isotonic saline solution, Ringer's solution, and 5% glucose solution.

If Fortecortin is used combined with infusion solutions, attention should be paid to the information related to compatibility, contraindications, adverse reactions, and interactions provided by the manufacturers of the solutions.