HYDROCORTISONE PHARMIS 100 mg POWDER AND SOLVENT FOR INJECTION AND INFUSION SOLUTION

Introduction

Package Leaflet: Information for the Patient

Hydrocortisone Pharmis 100 mgPowder and solvent for solution for injection

and for EFG perfusion

Read all of this leaflet carefully before you start using this medicine because it contains important information for you.

• Keep this leaflet, you may need to read it again.

If you have any further questions, ask your doctor or nurse.

• This medicine has been prescribed for you only. Do not pass it on to others. It may harm them, even if their signs of illness are the same as yours.
• If you get any side effects, talk to your doctor or nurse. This includes any possible side effects not listed in this leaflet. See section 4.

Contents of the Pack

1. What is Hydrocortisone Pharmis and what is it used for
2. What you need to know before you use Hydrocortisone Pharmis
3. How to use Hydrocortisone Pharmis
4. Possible side effects
5. Storage of Hydrocortisone Pharmis
6. Contents of the pack and other information

1. What is Hydrocortisone Pharmis and what is it used for

This medicine contains hydrocortisone as sodium succinate.

Hydrocortisone belongs to a group of medicines called corticosteroids or steroids.

Corticosteroids are produced naturally in the body and are important for many bodily functions.

The use of extra corticosteroids, such as Hydrocortisone, is an effective way to treat various diseases that involve inflammatory processes in the body. This medicine reduces this inflammation, which could otherwise worsen. You should take this medicine regularly to get the most benefit.

Corticosteroids can also help treat hypersensitivity reactions (anaphylactic) or other stressful conditions. These include inflammatory or allergic conditions that affect:

• lungs, e.g. bronchial asthma or inflammation caused by inhaling (aspirating) vomit or stomach contents,
• skin, e.g. Stevens-Johnson Syndrome (an autoimmune disorder in which the immune system causes the skin to form blisters and peel) or systemic lupus erythematosus (lupus).

This medicine may be prescribed to treat conditions other than those listed above, such as adrenal insufficiency and other medical emergencies such as the treatment of shock associated with this.

You should consult a doctor if you do not feel better or if you feel worse or if you are not sure why you have been given this medicine.

2. What you need to know before you use Hydrocortisone Pharmis

Do not use Hydrocortisone Pharmis

• if you think you have ever had an allergic reaction, or any other type of reaction after receiving this medicine, or any other medicine that contains corticosteroids, or any of the components of this medicine (a list of excipients is included in section 6). An allergic reaction can cause a rash or redness of the skin, swelling of the face or lips or difficulty breathing.
• If you have any fungal infection that is not being treated.
• If you have recently received or are about to receive any vaccine.

This medicine must not be injected:

• Into the spinal cord (intrathecally) [except as part of certain chemotherapy regimens], or by epidural route. This medicine is not recommended for use in the intrathecal route of administration

Children and adolescents

This medicine should be used with caution in children as prolonged use interferes with the child's growth and development and may cause them cataracts.

If hydrocortisone is administered to premature newborns, monitoring of heart function and structure may be necessary.

Consult your doctor immediately in any of the above cases.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before using Hydrocortisone.

Tell your doctor before taking this medicine if you are in any of the following situations. Your doctor may need to monitor your treatment more closely, change your dose, or give you another medicine.

• Chickenpox, shingles, or a herpes eye infection. If you think you have come into contact with someone with chickenpox or shingles and have not had these diseases before, or if you are not sure if you have had them.
• Severe depression or manic depression(bipolar disorder). This includes having depression before or while taking steroid medicines like this, or if any of your close relativeshave had these diseases.
• If you suffer from mood changes, insomnia, and personality changes.
• If you are under unusual stress.
• If you develop adrenal insufficiency.

• Cushing's syndrome(a hormonal disorder caused by high levels of cortisol in the blood).
• Diabetes(or if there is a family history of diabetes).
• Epilepsy, seizures, or convulsions.
• Glaucoma(increased pressure in the eye) or if there is a family history of glaucoma.
• Cataracts.
• Contact your doctor if you experience blurred vision or other visual disturbances.
• Heart problems, including heart failure or infections.
• Hypertension(high blood pressure).
• Fluid retention in the body.
• Hypothyroidism(an underactive thyroid).
• Pancreatitis(inflammation of the pancreas that causes severe abdominal and back pain).
• Peritonitis(inflammation of the thin lining (peritoneum) around the intestine and stomach).
• Joint infection.
• Kidney or liver disease.
• You have had muscle problems(pain or weakness) while taking steroids in the past.
• Myasthenia gravis(a condition that causes tired and weak muscles).
• Osteoporosis(brittle bones – bones that break easily).
• Pheochromocytoma(a rare tumor of the adrenal gland tissue. The adrenal glands are located above the kidneys).
• Skin abscess.
• Stomach ulcer, diverticulitis(inflammation of the intestinal wall) or other serious stomach or intestinal problems.
• Thrombophlebitis: vein problems due to thrombosis (blood clots in the veins) resulting in phlebitis (red, swollen, and sensitive veins).
• Head injury.
• Tuberculosis(TB) or if you have had tuberculosis in the past.

Corticosteroids should be used with caution, as they can cause an eye condition (central serous chorioretinopathy), in which a buildup of fluid forms under the layer of light-sensitive tissue in the back of the inner eye (retina), causing visual impairment and potentially leading to retinal detachment.

Long-term therapy with corticosteroids at high doses may cause an abnormal amount of fat deposit in or outside the lining of the spinal column (epidural lipomatosis).

Use in athletes:

Athletes are warned that this medicine contains a component that may result in a positive doping control test.

Tell your doctor if you suspect that an infection has occurred, as corticosteroids are known to increase susceptibility to infections and may mask their signs.

Other medicines and Hydrocortisone Pharmis

Tell your doctor or pharmacist if you are taking or have recently taken any other medicines.

You should tell your doctor if you are using any of the following medicines, which may affect how Hydrocortisone works or any other medicine:

• Acetazolamide- used to treat glaucoma and epilepsy.
• Anticoagulants- used to "thin" the blood, such as acenocoumarol, phenindione, and warfarin.
• Anticholinergics- medicines called neuromuscular blockers used in some surgical procedures.
• Anticholinesterases- used to treat myasthenia gravis (a muscle condition), such as distigmine and neostigmine.
• Antibacterials- such as isoniazid, erythromycin, clarithromycin, troleandomycin.
• Antidiabetics- medicines used to treat high blood sugar levels.
• Anti-emetic- such as Aprepitant and Fosaprepitant to prevent nausea and vomiting.
• Antifungal- Ketoconazole or itraconazole.
• Antitubercular- rifampicin and rifabutin: antibiotics used to treat tuberculosis (TB).

• Antiviral- used to treat HIV infections.
• Aromatase inhibitor- aminoglutethimide - used to treat cancer.
• NSAIDs- aspirin (high dose) and non-steroidal anti-inflammatory medicines, such as ibuprofen, used to treat mild to moderate pain.
• Antiepileptics/anticonvulsants- barbiturates, carbamazepine, and phenytoin, used to treat epilepsy.
• Carbenoxolone- used for stomach acidity.
• Ciclosporin- used to treat conditions such as severe rheumatoid arthritis, severe psoriasis, or after an organ or bone marrow transplant.
• Calcium channel blockers - Diltiazem.
• Cardiac glycosides- Digoxin - used for heart failure and/or irregular heartbeats.
• Immunosuppressants- tacrolimus and cyclophosphamide: used after an organ transplant to prevent organ rejection.
• Neuroblocking agents - pancuronium, used in some surgical procedures.
• Oral contraceptives- products containing estrogen.
• Pharmacokinetic enhancers: products containing cobicistat
• Potassium-lowering agents, such as diuretics, amphotericin B, xanthines, or beta2 agonists (e.g., medicines used to treat asthma).
• Vaccines- tell your doctor or nurse if you have recently been vaccinated or are about to be vaccinated. You must nothave "live" vaccines while using this medicine. Other vaccines may be less effective.
• Grapefruit juice.

If you are taking medication continuously

If you are being treated for diabetes, high blood pressure, or fluid retention (edema), tell your doctor, as you may need to adjust the dose of the medicines used to treat these conditions.

Before undergoing surgery, tell your doctor, dentist, or anesthetist to indicate that you are taking this medicine.

If you need to have a test or be in the hospital, it is important that you tell your doctor or nurse that you are taking this medicine. This medicine may affect the results of some tests.

Pregnancy and breastfeeding

Pregnancy

If you are pregnant, think you may be pregnant, or plan to become pregnant, consult your doctor before using this medicine, as it may delay the growth of the baby.

Corticosteroids can cross the placenta, which is a risk associated with low birth weight.

Cataracts have been observed in babies born to mothers treated with corticosteroids for long periods during pregnancy.

Breastfeeding

Tell your doctor if you are breastfeeding, as small amounts of corticosteroids may be found in breast milk. If you continue breastfeeding while being treated, your baby will need to have extra tests to make sure they are not being affected by this medicine.

Consult your doctor or pharmacist before taking any medicine.

Driving and using machines

The effect of this class of medicines on the ability to drive or use machines has not been studied. Since side effects such as seizures can occur with the use of corticosteroids, you should not drive or use machines if you have these symptoms.

HydrocortisonePharmis contains sodium.

This medicine contains 9.36 mg of sodium (the main component of table salt) in each vial. This is equivalent to 0.5% of the maximum recommended daily intake of sodium for an adult.

3. How to use Hydrocortisone Pharmis

Follow the instructions for administration of this medicine exactly as indicated by your doctor. Consult your doctor or nurse if you are not sure.

Dosing information

Your doctor will decide the site of injection, the amount of medicine, and how many injections you will receive, depending on the condition being treated and its severity. Your doctor will inject the lowest dose for the shortest time possible to obtain effective relief of your symptoms. Your doctor may also want you to take a second type of steroid or a salt supplement to help you balance the salt.

Adults

Your doctor or nurse will administer this medicine to you as an injection, either into a vein (intravenously) or into a muscle (intramuscularly). The first dose is usually given into a vein, especially in an emergency.

It will be administered slowly over a period of 1 - 10 minutes. Depending on your situation, a repeated dose may be injected at intervals of 2 to 6 hours. Normally, high doses can only be used for two or three days.

This medicine is first dissolved in sterile water for injectable preparations. If the medicine is to be administered by perfusion (via pump or drip), it is also mixed with another suitable liquid. Other medicines must not be mixed.

Elderly population

Treatment will normally be the same as for younger adults. However, your doctor may want to see you more regularly to check how you are getting on with this medicine.

Use in children and adolescents

Corticosteroids can affect the growth of children, so your doctor will prescribe the lowest effective dose (not less than 25 mg per day).

If you use more Hydrocortisone Pharmis than you should

If you think you have had more injections of this medicine than you should, talk to your doctor immediately.

If you forget to use Hydrocortisone Pharmis

Since this medicine will be administered under close medical supervision, it is unlikely that you will not be given a dose. However, you should inform your doctor if you think you have not been given a dose.

If you stop treatment with Hydrocortisone Pharmis

Your doctor will decide when it is time to stop your treatment. You will need to come off this treatment slowly if:

• you have received corticosteroids, such as this medicine, for a long time,
• you have been given high doses of corticosteroids, such as this medicine,
• you have had treatment with corticosteroid tablets or injections in the last year,
• you already have problems with your adrenal glands (adrenocortical insufficiency) before starting this treatment.

You will need to come off this medicine slowly to avoid withdrawal symptoms. These symptoms can include skin itching, fever, muscle and joint pain, runny nose, sticky eyes, sweating, and weight loss.

If your symptoms seem to return or worsen as the dose of this medicine is reduced, tell your doctor immediately.

Mental health problems while taking this medicine

Mental health problems can occur while taking steroids like this medicine (see also section 4, Possible side effects).

• These diseases can be serious.
• They usually start a few days or weeks after starting to take the medicine.
• They are more likely to occur with high doses.
• Most of these problems go away if the dose is reduced or the medicine is stopped. However, if problems occur, they may need treatment.

Talk to a doctor if you (or someone taking this medicine) show signs of mental problems. This is particularly important if you are depressed or could be thinkingabout suicide. In some cases, mental problems have occurred when doses were reduced or stopped.

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

4. Possible Adverse Effects

Like all medications, this medication can produce adverse effects, although not all people suffer from them. Your doctor may have prescribed this medication because your illness is not being treated properly and could worsen.

In certain medical conditions, medications like Hydrocortisone (steroids) should not be abruptly discontinued. If you experience any of the following symptoms, seek immediate attention.

Your doctor will then decide whether you should continue taking your medication.

• Allergic reactions, such as skin rash, swelling of the face, or wheezing and difficulty breathing. This type of side effect is rare but can be severe.
• Acute pancreatitis, stomach pain that can extend to the back, possibly accompanied by vomiting, shock, and loss of consciousness.
• Ulcers or bleeding ulcers, whose symptoms are severe stomach pain that can extend to the back and may be associated with anal bleeding, black or bloody stools, and/or vomiting with blood.
• Infections.This medication can hide or change the signs and symptoms of some infections or reduce your resistance to infection, making it difficult to diagnose them at an early stage. Symptoms may include elevated temperature and malaise. Symptoms of a flare-up of a previous TB infection may include coughing up blood or chest pain. This medication can also make you more prone to developing a severe infection. It can also increase your susceptibility to infections that can hide or change the usual reactions to skin tests, such as the tuberculosis test.

• The symptoms of pulmonary embolism(blood clot in the lung) include acute and sudden chest pain, difficulty breathing, and coughing up blood.
• Increased pressure in the skullof children (pseudotumor cerebri) whose symptoms are headaches with vomiting, lack of energy, and drowsiness. This side effect usually occurs after treatment is suspended.
• Thrombophlebitis(blood clots or thrombosis in a leg vein), whose symptoms include painful, swollen, red, and sensitive veins.

If you experience any of the following adverse effects, or if you notice any other unusual effect not mentioned in this leaflet, inform your doctor immediately.

The frequency of side effects is unknown. The frequency cannot be estimated from the available data.

Blood, heart, and circulation.

• Problems with your heart's pumping (heart failure) whose symptoms are swollen ankles, difficulty breathing.
• High blood pressure (hypertension), whose symptoms are headaches or general malaise.
• Increased white blood cell count (leukocytosis).
• Low blood pressure.
• Thickening of the heart muscle (hypertrophic cardiomyopathy) in premature babies.

Body water and salts

• Swelling and high blood pressure, caused by high levels of water and salt content.
• Swelling of the body's extremities, e.g., ankles.
• Cramps and spasms due to potassium loss from your body. In rare cases, this can cause congestive heart failure (when the heart cannot pump properly).

Digestive system

• Nausea (feeling of dizziness) or vomiting (being dizzy).
• Ulcers or sores in the throat (discomfort when swallowing).
• Indigestion.
• Bloated stomach.
• Abdominal pain.
• Diarrhea.

Ears

• Feeling of dizziness or spinning (vertigo).

Eyes

• Glaucoma (increased pressure inside the eye, causing eye pain and headaches).

• Inflammation of the optic nerve (causing a condition called papilledema, which can cause vision changes).
• Damage to the optic nerve or cataracts (indicated by vision failure).
• Thinning of the clear front part of the eye (cornea) or the white part of the eye (sclera).
• Worsening of viral or fungal eye infections.
• Protrusion of the eyeballs (exophthalmos).
• Visual impairment, such as a blind spot, decreased or blurred vision, and distortion of shapes, caused by fluid accumulation under the tissue covering the back of the eye (retina).
• Blurred vision.

General disorders

• Feeling of fatigue or malaise.
• Skin reactions at the injection site.

Hormones and metabolic system

• Slowing of normal growth in babies, children, and adolescents, which can be permanent.
• Irregular or absent periods in women.
• Round or moon-shaped face (Cushingoid facies).
• Increased appetite and weight.
• Diabetes or worsening of existing diabetes.
• Prolonged therapy may lead to lower levels of certain hormones, which can cause low blood pressure and dizziness. This effect can persist for months.
• Increased urea in the blood.
• The amount of certain chemicals (enzymes) called alanine transaminase, aspartate transaminase, and alkaline phosphatase that help the body digest medications and other substances in your body may increase after treatment with a corticosteroid. The change is usually small, and enzyme levels return to normal after your medication has been naturally eliminated from your system. You will not notice any symptoms if this happens, but it will appear if a blood test is done.
• The drug withdrawal syndrome includes symptoms such as runny nose, fever, headache, loss of appetite, fatigue, joint pain, skin peeling, weight loss, and low blood pressure.
• Abnormal level of fats, e.g., cholesterol in the blood.
• Abnormal fat deposition in the body.

Muscles and bones

• Muscle pain.
• Muscle weakness or wasting.
• Brittle bones (bones that break easily).
• Broken or fractured bones.
• Fracture of bones and joints due to poor blood circulation, causing hip pain.
• Torn muscle tendons causing pain and/or inflammation.
• Muscle cramps or spasms.

Nerves and mood problems

Steroids, including this medication, can cause serious mental health problems.

These are common in both adults and children. They can affect approximately 5 out of 100 people taking medications like this.

• Feeling depressed, even with suicidal thoughts.
• Feeling of euphoria (mania) or mood swings.
• Feeling anxious, having trouble sleeping, difficulty thinking, or being confused and losing memory.

Feeling, seeing, or hearing things that do not exist. Having strange and frightening thoughts, changing your behavior, or having feelings of being alone. If you notice any of these problems, talk to a doctor immediately.

Other nervous system side effects may include:

• Seizures (attacks), dizziness, drowsiness, difficulty breathing, irritability, feeling of cold, heat, or numbness, tinnitus, or loss of consciousness.
• Headache.
• Back pain, decreased strength or sensation in the legs, or imbalance, caused by fat accumulation inside the spinal canal (epidural lipomatosis).

Skin

• Abscess, especially near injection sites.
• Acne.
• Poor wound healing.
• Thinning of the skin with stretch marks.
• Stretch marks (stretch marks on the skin).
• Bruises.
• Small purple/red spots on the skin.
• Pale or dark spots on your skin or increased unusual color spots.
• Excessive growth of body and facial hair.
• Rash, itching, hives.
• Increased sweating.

Adverse effect reporting

If you experience any type of adverse effect, consult your doctor, pharmacist, or nurse, even if it is a possible adverse effect not listed in this leaflet. You can also report them directly through the Spanish Medication Pharmacovigilance System: https://www.notificaRAM.es.

By reporting adverse effects, you can contribute to providing more information on the safety of this medication.

5. Storage of Hydrocortisone Pharmis

Keep this medication out of sight and reach of children.

Do not use this medication after the expiration date shown on the vials and carton. The expiration date refers to the last day of the indicated month.

Store below 25°C.

Keep in the original packaging to protect it from light.

Solution after reconstitution and dilution:

Do not refrigerate.

The chemical and physical stability of the solution has been demonstrated for 24 hours when stored at 2-8°C.

From a microbiological point of view, unless the method of reconstitution excludes the risk of microbial contamination, the product must be used immediately.

If not used immediately, the storage times and conditions are the responsibility of the user.

Medications should not be thrown down the drain or into the trash. Ask your pharmacist how to dispose of the packaging and medications you no longer need. These measures will help protect the environment.

Environmental risk assessment studies showed that dexamethasone had endocrine side effects in fish species.

6. Package Contents and Additional Information

Composition of Hydrocortisone Pharmis

• The active ingredient is sodium succinate hydrocortisone.

Each vial contains 100 mg of hydrocortisone (equivalent to 133.7 mg of sodium succinate hydrocortisone).

• The other ingredients are sodium dihydrogen phosphate monohydrate and disodium phosphate.

Each ampoule of solvent contains 2 ml of water for injectable preparations.

The solvent does not contain excipients.

Appearance of the Product and Package Contents

This medication is presented in vials containing a white lyophilized powder of hydrocortisone (as sodium succinate) and ampoules containing a solvent, water for injectable preparations.

The lyophilized powder is presented in 4 ml type I colorless glass vials, and the solvent in 2 ml type I colorless glass ampoules.

This medication is available in clinical packages containing 50 vials and 50 solvent ampoules.

Marketing Authorization Holder

Pharmis Biofarmacêutica, Lda.

Praceta do Farol, 77

2750-610 Cascais

Portugal

Tel.: +351 214823850

Fax: +351 214823859

e-mail: [email protected]

You can request more information about this medication by contacting the local representative of the marketing authorization holder in Spain:

Local Representative:

Pharmis Biofarmacéutica, S.L.

C/ San Germán, nº 52, piso 1º D,

28020 - Madrid.

Tel.: 91 640 22 88

Fax: 91 640 08 45

Email: [email protected]

Manufacturer

Infosaúde – Instituto de Formação e Inovação em Saúde, S.A.

Rua das Ferrarias Del Rei, nº6,

Urbanização da Fábrica da Pólvora,

2730-269 Barcarena

Portugal

This medication is authorized in the Member States of the European Economic Area with the following names:

France: Hydrocortisone Pharmis

Poland: Hydrocortisone Pharmis

Portugal: Hidrocortisona Pharmis

Spain: Hidrocortisona Pharmis 100 mg powder and solvent for injectable and perfusion solution EFG

Date of the last revision of this leaflet:{MM/YYYY}

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The following information is intended only for healthcare professionals.

For more information, consult the Summary of Product Characteristics.

Dosage and administration.

This medication can be administered by intravenous injection, intravenous infusion, or intramuscular injection. The preferred method for initial emergency use is intravenous injection. After the initial emergency period, the use of a long-acting injectable preparation or an oral preparation should be considered.

The dose generally ranges from 100 mg to 500 mg, depending on the severity of the condition, administered by intravenous injection over a period of 1 to 10 minutes. The dose may be repeated at intervals of 2, 4, or 6 hours as indicated by the response and the patient's clinical condition.

Dose requirements are variable and must be individualized based on the disease being treated, its severity, and the patient's response throughout the duration of treatment. A risk/benefit decision must be made in each individual case on a continuous basis.

The appropriate maintenance dose should be determined by decreasing the initial dose of the medication in small decrements at appropriate time intervals until the lowest dose is reached, which will maintain an adequate clinical response.

In general, treatment with high doses of corticosteroids should only be continued until the patient's condition has stabilized, which is usually no more than 48 to 72 hours. When treatment with high doses of hydrocortisone needs to be continued beyond 72 hours, hypernatremia may occur. In such circumstances, it may be necessary to replace this medication with another corticosteroid such as sodium succinate methylprednisolone, as it causes little or no sodium retention.

If the medication needs to be discontinued after long-term treatment, it should be gradually withdrawn rather than abruptly (see section 4.4 of the datasheet).

Adverse effects can be minimized by using the effective dose for the minimum period (see section 4.4 of the datasheet).

Treatment with corticosteroids is a complement and not a replacement for conventional treatment.

In patients with liver disease, there may be an increased effect (see section 4.4 of the datasheet), so a dose reduction should be considered.

Elderly population: Hydrocortisone is mainly used in acute short-term conditions. When used according to the instructions, there is no information that justifies a change in dosage in these people. However, treatment of elderly patients should be planned taking into account the more serious consequences of common corticosteroid side effects in this age group, and closer clinical monitoring is required (see section 4.4 of the datasheet).

Pediatric population: While the dose may be reduced for babies and children, it is more governed by the severity of the condition and the patient's response than by age or body weight, but it should not be less than 25 mg per day (see Section 4.4 of the datasheet).

It is not recommended to use this medication via the intrathecal route.

Administration method

Preparation of solutions:

For intravenous or intramuscular administration, prepare the solution aseptically by adding up to 2 ml of sterile water for injectable preparations to the vial containing the lyophilized powder, shaking, and withdrawing the amount to be used.

The reconstituted solution is isotonic or almost isotonic.

For intravenous perfusion, first prepare the solution by adding up to 2 ml of sterile water for injectable preparations to the vial. This solution can be added to 100 ml - 1000 ml (but not less than 100 ml) of 5% dextrose in water (or isotonic saline solution if the patient has no sodium restriction).

This medication should not be mixed with other medications, except those mentioned in section 6.6 of the Datasheet.

When reconstituted, the pH of the solution will vary from 7.0 to 8.0.

Parenteral pharmaceutical products should be visually inspected for particles and discoloration before administration. The reconstituted solution should be clear without visible particles.

Disposal:

Any unused medication or waste material should be disposed of in accordance with local requirements.