HYDROCORTISONE LORIEN 100 mg POWDER FOR INJECTABLE SOLUTION AND FOR INFUSION

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

Do not use Hydrocortisone Lorien

• if you are allergic to hydrocortisone or any of the other ingredients of this medicine (listed in section 6);
• if you have any acute viral, fungal or tropical worm infection. Bacterial infections must be treated first before starting treatment with this medicine;
• if you have a stomach or duodenal ulcer;
• if you have received or need to receive live or attenuated virus vaccines, do not use this medicine in a dose that weakens your immune system.

This medicine must not be injected:

• into the spinal cord (intrathecally) or via the epidural route.

The general conditions for not using adrenal cortex hormones (glucocorticosteroids) and the precautions that apply when using systemic therapy with glucocorticosteroids also apply to this medicine.

Warnings and precautions

Because the risk of side effects with the use of glucocorticosteroids increases as the dose and duration of treatment increase, the benefits and drawbacks of treatment will be carefully weighed against each other when determining the dose and duration of treatment.

The use of this medicine should not be stopped suddenly, but should be gradually withdrawn.

Consult your doctor or pharmacist before starting to use this medicine.

• Patient undergoing surgery, suffering an accident or contracting an infection during or after treatment with hydrocortisone may occasionally need to be treated with fast-acting glucocorticoids.
• Glucocorticoids can suppress the symptoms of an infection and new infections can occur during their use, because resistance may decrease. In case of a bacterial infection, your doctor will first determine the type of bacteria and treat the infection before you receive treatment with glucocorticoids.
• If you are taking medicines that suppress the immune system, you may be more susceptible to infections than healthy individuals.
• If you have a pre-existing risk factor for cardiovascular disease, with high doses and prolonged use of this medicine, the risk of cardiovascular disease may increase. Examples include increased blood pressure and increased and/or decreased lipids in the blood (cholesterol, triglycerides).
• If you have reduced heart pumping strength (congestive heart failure).
• Hydrocortisone may cause increased blood pressure, water and salt retention, and increased potassium excretion. Your doctor may prescribe a low-salt diet with potassium supplements for this. It may be necessary to restrict salt in the diet and administer potassium supplements. All corticosteroids increase calcium excretion.
• If you have septic shock. This is a condition caused by an infection characterized by a sudden drop in blood pressure, paleness, restlessness, rapid and weak pulse, moist skin, and reduced consciousness. In that case, the routine use of this medicine is not recommended.
• You should not be vaccinated with a live virus vaccine during treatment with high doses of hydrocortisone.
• If you have active tuberculosis or are being treated for tuberculosis, your doctor will closely monitor you during treatment with this medicine.
• If you have ever had an allergic reaction to a medicine, your doctor will take the necessary precautions before starting treatment.
• If you have a herpes eye infection, the ophthalmologist should monitor you periodically during treatment.
• Treatment with corticosteroids can cause retinal detachment and cataracts. Contact your doctor if you experience blurred vision or other visual disturbances.
• Corticosteroid therapy can cause retinal detachment and cataracts.
• During treatment, psychiatric changes may occur, such as mood swings, insomnia, irritability, personality changes, and depression.
• There have been reports of fat accumulation in the spinal canal with long-term use of corticosteroids at high doses.
• If you have stomach or intestinal inflammation, increased blood pressure, active or latent stomach ulcers, kidney failure, adrenal gland tumor, Kaposi's sarcoma (a certain type of skin cancer), osteoporosis, severe myasthenia (a muscle disease), or if you have a higher risk of thrombosis, your doctor will be very careful when prescribing this medicine.
• If you have liver disease, your doctor may prescribe a lower dose, as the effect of hydrocortisone may be enhanced.
• If you have Cushing's disease (a disease caused by excessive levels of the hormone cortisol in the blood).
• If you have reduced thyroid function (hypothyroidism).
• If you have diabetes.
• If you have a disease associated with seizures/convulsions (e.g. epilepsy).
• If you are taking certain pain relievers with anti-inflammatory and antipyretic effects (NSAIDs).
• If you have pancreatitis, with severe pain in the upper abdomen that radiates to the back, nausea, and vomiting.
• If hydrocortisone is administered to a premature newborn, it may be necessary to monitor heart function and structure.

Use in sports

This medicine contains substances that may result in a positive doping control test.

Children and adolescents

Long-term treatment with glucocorticoids can cause growth retardation in children and adolescents. Therefore, the doctor will generally treat children with alternate-day doses.

Babies and children treated with corticosteroids for a long time have a higher risk of developing increased intracranial pressure.

High doses of corticosteroids can cause pancreatitis in children.

Other medicines and Hydrocortisone Lorien

Tell your doctor or pharmacist if you are taking, have recently taken or might take any other medicines, including those bought without a prescription.

You should inform your doctor about any other medicine, such as:

• Isoniazid: used to treat bacterial infections.
• Rifampicin: an antibiotic used to treat tuberculosis.
• Substances that counteract blood clotting (oral anticoagulants).
• Barbiturates, carbamazepine, and phenytoin used to treat epilepsy.
• Substances used to treat certain nervous system diseases (anticholinergics).
• Substances used to treat myasthenia gravis (anticholinesterases).
• Substances used to treat diabetes (antidiabetics).
• Aprepitant and fosaprepitant: used to prevent nausea and vomiting.
• Itraconazole and ketoconazole: used to treat fungal infections.
• Some medicines may increase the effects of hydrocortisone and your doctor may want to monitor you closely if you are taking these medicines (including some medicines for HIV: indinavir, ritonavir, cobicistat).
• Aminoglutethimide and cyclophosphamide: used to treat cancer.
• Tacrolimus: used after organ transplantation to prevent organ rejection.
• Diltiazem: used to treat heart problems or high blood pressure.
• Digoxin: a heart medicine that belongs to a group of medicines called cardiac glycosides.
• Estrogens (including oral contraceptives that contain estrogens).
• Cyclosporin: used to treat conditions such as severe joint inflammation (rheumatoid arthritis), severe skin conditions associated with dry and scaly skin rashes (psoriasis), and to prevent organ rejection after transplantation.
• Clarithromycin, erythromycin, and/or troleandomycin: substances used to prevent/combating certain infections.
• Aspirin (acetylsalicylic acid) and a certain group of pain relievers that also have anti-inflammatory and antipyretic effects (NSAIDs).
• Potassium-reducing substances, such as diuretics.

Hydrocortisone Lorien with food and drinks

Grapefruit juice may change the effects of this medicine. Always consult your doctor or pharmacist about drinking grapefruit juice 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.

Pregnancy

This medicine can be used according to the approved indications. Chronic use of higher doses should be avoided as much as possible.

Breastfeeding

Corticosteroids pass into breast milk. Therefore, breastfeeding is not recommended during treatment with corticosteroids, unless you consult your doctor.

Fertility

There is no evidence that corticosteroids interfere with fertility.

Driving and using machines

Various possible side effects of this medicine, such as blurred vision, mood changes, muscle weakness, and involuntary muscle contractions, may negatively affect your ability to drive and use machines.

Hydrocortisone Lorien contains sodium

This medicine contains less than 1 mmol of sodium (23 mg) per vial (9.46 mg per dose); it is essentially "sodium-free". This should be taken into account in patients on a controlled sodium diet.

3. How to use Hydrocortisone Lorien

Your doctor or nurse will inject this medicine. It can be administered into a vein (with a syringe or by infusion) or into the muscle (with a syringe).

Your doctor will determine the suitable dose for you based on your disease and situation.

If you use more Hydrocortisone Lorien than you should

No data are available on the acute overdose of this medicine. Hydrocortisone is dialyzable. This means that in case of overdose, excess hydrocortisone can be removed from the blood with the help of an artificial kidney. With repeated use over a long period (daily or several times a week), Cushing's syndrome (including moon face) may occur.

If you forget to use Hydrocortisone Lorien

Normally, your doctor will make sure you receive the next dose on time. Do not take a double dose to make up for forgotten doses.

If you stop treatment with Hydrocortisone Lorien

If treatment with this medicine is stopped suddenly or if you have to undergo surgery during treatment, have an accident, or contract a severe infection, it is possible that your adrenal cortex may not function as well. This would allow the symptoms of the disease for which you are being treated to recur. Epileptic seizures, dizziness, and headache, especially in children, may occur if treatment is stopped too quickly. Therefore, your doctor will generally gradually reduce treatment with this medicine.

If you have any further questions on the use of this medicine, ask your doctor or pharmacist.

4. Possible Adverse Effects

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

The following side effects have been reported with unknown frequencies, which means that the frequency cannot be determined based on the available data:

• Hydrocortisone suppresses the symptoms of an inflammatory response, so infections are difficult to detect, latent infections can be activated, and new infections can occur.
• Infections that are normally rare (opportunistic infection) may occur.
• A type of skin cancer (Kaposi's sarcoma).
• Severe increase in blood pressure due to inflammation of the adrenal gland (pheochromocytoma).
• More white blood cells in the blood than normal (leukocytosis).
• Severe allergic reaction to certain substances, involving a sudden drop in blood pressure, paleness, restlessness, rapid and weak pulse, sweaty skin, and reduced consciousness after significant and sudden vasodilation (anaphylactic reaction).
• Sudden drop in blood pressure, paleness, restlessness, rapid and weak pulse, sweaty skin, and reduced consciousness due to significant and sudden vasodilation without a pre-existing allergy (anaphylactoid reaction).
• Hypersensitivity to medicines.
• Development of obesity (head, trunk), moon face, and arterial hypertension (Cushing's syndrome).
• Lack of one or more hormones secreted by the pituitary gland (suppression of the hypothalamic-pituitary-adrenal axis).
• Syndrome associated with withdrawal symptoms that may appear after stopping treatment with corticosteroids (steroid withdrawal syndrome).
• Acidification of the blood (metabolic acidosis).
• Sodium retention by the kidneys (sodium retention).
• Retention of excess fluid in the body (fluid retention).
• Alteration of fat metabolism (dyslipidemia).
• Altered acid-base balance of the blood due to excessive potassium loss (hypokalemic alkalosis).
• Reduced ability to tolerate glucose (reduced glucose tolerance).
• Disruption of blood sugar regulation that allows latent diabetes to be detected or increases the need for insulin or other medications to reduce blood sugar.
• Increased appetite.
• Accumulation of fatty tissue in different parts of the body (lipomatosis).
• Psychotic disorders, such as excessive lightheartedness associated with having a lot of energy (mania), delusions, observation of things that do not exist (hallucinations), and severe mental illness (schizophrenia) characterized by a gradual change in personality.
• Mood disorders such as depressed mood, extreme feeling of joy (euphoria), emotional lability, drug dependence, suicidal thoughts.
• Mental disorder.
• Confusion.
• Fear.
• Personality change.
• Mood swings.
• Abnormal behavior.
• Insomnia.
• Irritability.
• Worsening of pre-existing psychotic behavior.
• Accumulation of fat in the spinal canal (epidural lipomatosis).
• Increased intracranial pressure.
• Increased pressure in the brain with inflammation of the mucous membranes (benign intracranial hypertension).
• Loss of consciousness with muscle spasms (convulsions).
• Memory loss (amnesia).
• Alteration of cognitive functions such as perception, attention, concentration, memory, orientation, language use, and skills (cognitive impairment).
• Dizziness.
• Headache.
• Retinal and choroidal disease (chorioretinopathy).
• Blurred vision.
• Cloudy lens (cataracts).
• Increased eye pressure (glaucoma).
• Abnormal bulging of the eye (exophthalmia).
• Vertigo.
• The heart's pumping force may be reduced in at-risk patients (congestive heart failure).
• Increased blood coagulation (thrombosis).
• Reduced blood pressure (hypotension).
• Increased blood pressure (hypertension).
• Pulmonary embolism.
• Persistent hiccups.
• Gastric/duodenal ulcers with possible perforation and bleeding.
• Bleeding and injury to the intestinal wall (intestinal perforation).
• Gastric bleeding.
• Inflammation of the pancreas with severe pain in the upper abdomen that radiates to the back, nausea, and vomiting (pancreatitis).
• Inflammation of the esophagus with or without ulcers (esophagitis).
• Abdominal pain (abdominal pain).
• Swollen stomach (abdominal distension).
• Diarrhea.
• Altered digestion with a feeling of fullness in the upper stomach, stomach pain, belching, nausea, vomiting, and heartburn (dyspepsia).
• Nausea.
• Sudden accumulation of fluid in the skin and mucous membranes (e.g., throat or tongue), difficulty breathing, and/or itching and skin rash, often as an allergic reaction (angioedema).
• Excessive hair growth in women (hirsutism).
• Small spots of bruising under the skin (petechiae).
• Small spots of bruising on a mucous membrane (ecchymosis).
• Thin, fragile, and wrinkled skin (skin atrophy).
• Redness of the skin (erythema).
• Excessive sweating (hyperhidrosis).
• Striae on the skin (striae).
• Skin rash.
• Itching (pruritus).
• Skin rash with intense itching and bump formation (urticaria).
• (Adolescents) Acne.
• Muscle weakness.
• Muscle pain (myalgia).
• Muscle disease (myopathy).
• Reduction of muscle tissue because a muscle is not used or can no longer be used due to a nervous system disease (muscle atrophy).
• Bone fracture (osteonecrosis).
• Bone decalcification (osteoporosis).
• Bone fracture (pathological fracture).
• Joint disease due to a nervous system disorder (neuropathic arthropathy).
• Joint pain (arthralgia).
• Growth retardation.
• Collapsed vertebrae (spinal compression fracture).
• Tendon tears.
• Irregular menstruation.
• Altered wound healing.
• Accumulation of fluid in arms and legs (peripheral edema).
• Fatigue.
• Feeling of general malaise.
• Reactions at the injection site.
• Increased intraocular pressure.
• Decreased ability to process sugars (carbohydrates), which may lead to a greater need for insulin or other substances to reduce blood sugar levels.
• Decrease in blood potassium levels, severely recognizable by muscle spasms or weakness and muscle fatigue (hypokalemia).
• Increased calcium levels in the urine.
• Abnormal blood test results (increased alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase in blood).
• Increased amount of waste products in the blood due to protein degradation (increased urea in blood).
• Suppression of skin allergy test reactions.
• Thickening of the heart muscle (hypertrophic cardiomyopathy) in premature newborns.
• Weight gain.

Other Adverse Effects in Children and Adolescents

Growth inhibition may occur in children.

Reporting of Adverse Effects

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

5. Storage of Hydrocortisone Lorien

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

Do not use this medicine after the expiration date shown on the box and label after CAD. The expiration date is the last day of the month indicated.

Do not store at a temperature above 25°C. Keep the vials in the original packaging to protect them from light.

Once the medicine has been mixed with sterile water for injectable preparations, the solution must be used immediately. Any unused liquid must be disposed of safely.

Your doctor will check that the solution does not contain particles and does not discolor before using it.

Medicines should not be thrown away through drains or into the trash. Ask your pharmacist how to dispose of the packaging and medicines that are no longer needed. This will help protect the environment.

6. Package Contents and Additional Information

Composition of Hydrocortisone Lorien

• The active ingredient is hydrocortisone. Each vial contains 100 mg of hydrocortisone (as hydrocortisone sodium succinate).
• The other ingredients are: sodium dihydrogen phosphate dihydrate, disodium hydrogen phosphate anhydrous, and sodium hydroxide.

Appearance of Hydrocortisone Lorien and Package Contents

Hydrocortisone Lorien is a white or almost white powder for injectable/infusion solution. It is presented in a colorless glass vial containing 100 mg of hydrocortisone, closed with a rubber stopper and sealed with an aluminum cap.

Hydrocortisone Lorien is available in the following package sizes:

Cardboard box with 1 vial or cardboard box with 2 protective PVC trays covered with a PET/PE sheet with 5 vials each and a prospectus.

.

Not all package sizes may be marketed.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder:

Laboratorios Lorien, S.L.

Av. Josep Tarradellas, 8, Ático 1ª 08029 Barcelona, España

Manufacturer:

S.C. Rompharm Company S.R.L.

Eroilor Street, no. 1A, Otopeni, Ilfov County, 075100, Romania

This medicine is authorized in the Member States of the European Economic Area under the following names:

Names:

Hungary: Hydrocortison Rompharm 100 mg oldatos injekcióhoz/infúzióhoz

Romania: Hidrocortizon Rompharm 100 mg pulbere pentru soluție injectabilă/perfuzabilă

Bulgaria: ????????????? ??????? 100 mg ???? ?? ???????????/?????????? ???????

Spain: Hidrocortisona Lorien 100 mg polvo para solución inyectable y para perfusión EFG

Date of the last revision of this prospectus:May 2023

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

This information is intended only for healthcare professionals:

Dosage and Administration:

This medicine can be administered by intravenous or intramuscular injection, or by intravenous infusion. Intravenous injection is the preferred method for emergency use.

After the initial emergency period, the possibility of using a long-acting injectable preparation or an oral preparation should be considered. The duration of intravenous administration depends on the dose; it can range from 30 seconds (e.g., 100 mg) to 10 minutes (e.g., 500 mg or more).

In general, only high doses of corticosteroids should be administered until the patient's condition has stabilized (usually within 48-72 hours).

Although adverse effects associated with short-term treatment with high doses of corticoids are rare, peptic ulcers may occur. Prophylactic therapy with antacids is indicated.

If it is necessary to continue therapy with hydrocortisone for periods longer than 48-72 hours, hypernatremia may occur, so it may be preferable to replace this medicine with another corticosteroid, such as methylprednisolone sodium succinate, since little or no sodium retention occurs.

The initial dose of this medicine is 100 mg to 500 mg or more, depending on the severity of the condition. This dose may be repeated at intervals of 2, 4, or 6 hours as indicated by the patient's clinical situation. Corticosteroid therapy is a complement and not a replacement for conventional therapy.

In patients with liver disease, there may be an increased effect, and a dose reduction may be considered.

Pediatric Population

The dose of this medicine in pediatrics is governed more by the severity of the condition and the patient's response than by age or body weight. The dose may be reduced for these patients, but it should not be less than 25 mg per day.

Preparation of Solutions:

Parenteral medicines must be visually inspected for particles and color changes before administration.

After reconstitution, the solution is clear without visible particles or precipitates. The formulation does not contain preservatives and is for single use. Once opened, the contents of a vial should normally be used immediately.

Instructions:

Do not add more than 2 ml of sterile water for injectable preparations to the contents of a vial with sterile powder, under aseptic conditions.

For intravenous or intramuscular injection:

Prepare the solution as described above. For intravenous or intramuscular injection, no further dilution is required; shake and withdraw for use.

For intravenous infusion:

First, prepare the solution as described above, adding no more than 2 ml of sterile water for injectable preparations to the vial. This solution containing 100 mg of hydrocortisone can be added to 100-1000 ml (but not less than 100 ml) of one of the following solutions:

• 5% glucose solution
• 0.9% sodium chloride solution

If the patient is on a low-sodium diet, the 5% glucose solution can be used.

When reconstituted as indicated, the pH of the solution will range from 7.0 to 8.0.

Validity Period

Unopened vial:

2 years.

The stability of the solution after reconstitution with 2 ml of sterile water for injectable preparations was not investigated. Therefore, the reconstituted solution must be used immediately.

After reconstitution and dilution:

After reconstitution and dilution with 100 ml and 1000 ml of 0.9% sodium chloride injectable solution, chemical and physical stability has been demonstrated for 4 hours at 25°C.

After reconstitution and dilution with 100 ml and 1000 ml of 5% glucose injectable solution, chemical and physical stability has been demonstrated for 4 hours at 25°C.

From a microbiological point of view, the product must be used immediately. If not used immediately, the storage times and conditions are the responsibility of the user.

Special Precautions for Storage:

Do not store at a temperature above 25°C.

Keep the vial in the outer packaging to protect it from light.

For more information, consult the Medicinal Product Characteristics.