Hydrocortisone pharmline

Package leaflet: Information for the user

Hydrocortisone PHARMLINE, 100 mg, powder for solution for
injection/infusion
Hydrocortisonum (as sodium succinate)
Please read all of this leaflet carefully before using this medicine, because it contains
important information for you.

• Keep this leaflet, as 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 someone else, even if their symptoms are the same.
• If you experience any adverse effects, including any not listed in this leaflet, inform your doctor or pharmacist. See section 4.

Leaflet contents

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

1. What Hydrocortisone is and what it is used for

The active substance in Hydrocortisone, hydrocortisone, is a glucocorticoid (a natural hormone) produced in the human adrenal cortex. The main action of hydrocortisone is to suppress inflammatory and immunological reactions (the immune system's response to foreign substances). In addition, it affects, among other things, carbohydrate and protein metabolism.

Hydrocortisone may be used in combination with other adrenal cortex hormones when the adrenal cortex does not function properly, for example in Addison's disease or congenital adrenal hyperplasia. It may also be used when adrenal cortex function is impaired due to another illness.

Additionally, Hydrocortisone may be used for a short period when other treatments are ineffective or insufficiently effective:

• in severe exacerbations of asthma, chronic bronchitis, or pulmonary emphysema;
• in status asthmaticus (persistent asthma attack);
• in combination with other medicines for severe allergic reactions.

2. Important information before using Hydrocortisone

When not to use Hydrocortisone

• if the patient is allergic to hydrocortisone or any of the other ingredients of this medicine (listed in section 6).
• if the patient has acute viral, fungal, or tropical parasitic infections. Bacterial infections should be treated before starting therapy with Hydrocortisone.
• in cases of peptic ulcer of the stomach or duodenum.
• if the patient has received or is due to receive vaccines containing live or attenuated viruses, Hydrocortisone should not be used at doses that suppress the immune system.

This medicine should not be injected:

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

General contraindications for corticosteroids (glucocorticoids) and
precautions applicable during systemic glucocorticoid therapy also apply to Hydrocortisone.
Warnings and precautions
The risk of adverse effects with glucocorticoids increases with higher doses and prolonged treatment duration. Therefore, benefits and risks of treatment will be carefully weighed when determining the dose and duration of therapy.
Treatment with Hydrocortisone should not be stopped abruptly, but the dose should be gradually reduced.
Before starting treatment, discuss the following with your doctor or pharmacist:

• Patients undergoing surgery, those who have had an accident, or those with an infection during or after hydrocortisone treatment may require treatment with fast-acting glucocorticoids.
• Glucocorticoids may mask signs of infection, and new infections may occur during treatment due to reduced immunity. In cases of bacterial infection, the doctor will first identify the type of bacteria and treat the infection before initiating glucocorticoid therapy.
• While taking immunosuppressive drugs, patients may be more susceptible to infections than healthy individuals.
• If the patient already has a cardiovascular disease risk factor, they may be at increased risk of further cardiovascular complications with high-dose and long-term use of Hydrocortisone. Examples include elevated blood pressure and increased levels (and/or decreased levels) of one or more blood lipids (lipids, cholesterol, triglycerides).
• If the patient has reduced cardiac ability to pump blood (congestive heart failure).
• Hydrocortisone may cause elevated blood pressure, salt and water retention, and increased potassium excretion. The doctor may recommend a low-salt diet with potassium supplementation. Dietary salt restriction and potassium supplementation may be necessary. All corticosteroids increase calcium excretion.
• In patients with septic shock—a condition caused by infection characterized by a sudden drop in blood pressure, pallor, anxiety, weak and rapid pulse, moist skin, and reduced level of consciousness—routine use of Hydrocortisone is not recommended.
• Patients should not be vaccinated with live virus vaccines during high-dose hydrocortisone therapy.
• If the patient has active tuberculosis or is being treated for tuberculosis, the doctor should closely monitor the patient during Hydrocortisone treatment.
• If allergic reactions have previously occurred due to medications, the doctor will take necessary precautions before starting treatment.
• If the patient has ocular herpes infections, regular ophthalmological examinations should be performed during treatment.
• Corticosteroid treatment may cause retinal detachment and cataracts. If blurred vision or other visual disturbances occur, contact your doctor.
• Corticosteroid treatment may lead to retinal detachment and cataracts.
• During treatment, psychiatric changes may occur, such as excessive happiness, insomnia, irritability, personality changes, and depression.
• Cases of fat accumulation in the spinal canal have been reported during long-term, high-dose corticosteroid therapy.
• If the patient has gastrointestinal inflammation, high blood pressure, active or inactive ulcers, kidney dysfunction, adrenal gland tumors, Kaposi's sarcoma (a type of skin cancer), osteoporosis, myasthenia (certain muscle disorders), or thrombosis or is at increased risk of thrombosis, the doctor should exercise special caution when prescribing Hydrocortisone.
• If the patient has liver disease, the doctor may prescribe a lower dose, as hydrocortisone may have enhanced effects in such patients.
• If the patient has Cushing's disease (a condition caused by excess cortisol hormone in the blood).
• If the patient has reduced thyroid function (hypothyroidism).
• If the patient has diabetes.
• If the patient has a condition associated with seizures or fits (e.g., epilepsy).
• When using certain anti-inflammatory and antipyretic painkillers (NSAIDs).
• If the patient has pancreatitis, characterized by severe upper abdominal pain radiating to the back, accompanied by nausea and vomiting.

Children and adolescents
Long-term glucocorticoid therapy may suppress growth in children. Therefore, doctors usually prescribe alternate-day dosing in children.
Infants and children receiving long-term corticosteroid therapy are particularly at risk of increased intracranial pressure.
High doses of corticosteroids may cause pancreatitis in children.
If hydrocortisone is administered to premature infants, monitoring of cardiac function and myocardial imaging may be necessary.

Hydrocortisone and other medicines
Inform your doctor or pharmacist about all medicines currently or recently used, as well as any medicines you plan to take, including over-the-counter medicines.
Tell your doctor about any of the following medicines you are taking:

• Isoniazid: used to treat bacterial infections.
• Rifampicin: an antibiotic used to treat tuberculosis.
• Anticoagulants (oral anticoagulants).
• Barbiturates, carbamazepine, and phenytoin used to treat epilepsy.
• Medicines used to treat certain nervous system disorders (anticholinergic drugs).
• Medicines used in the treatment of myasthenia (muscle disease) (anticholinesterases).
• Medicines used to treat diabetes (antidiabetic drugs).
• Aprepitant and fosaprepitant: used to prevent nausea and vomiting.
• Itraconazole and ketoconazole: used to treat fungal infections.
• Some medicines may enhance the effect of Hydrocortisone, and the doctor may wish to closely monitor patients taking these medicines (including certain anti-HIV drugs: indinavir, ritonavir, cobicistat).
• Aminoglutethimide and cyclophosphamide: used in cancer treatment.
• Tacrolimus: a medicine used after organ transplantation to prevent rejection.
• Diltiazem: used to treat heart conditions or high blood pressure.
• Digoxin: a cardiac glycoside used for heart conditions.
• Estrogens (including estrogen-containing oral contraceptives).
• Cyclosporine; used to treat, among others, severe inflammatory joint disease (rheumatoid arthritis), severe skin disorders associated with scaly, dry skin rash (psoriasis), and to prevent rejection of transplanted organs.
• Clarithromycin, erythromycin, and/or troleandomycin: medicines used to prevent or treat certain infections.
• Aspirin (acetylsalicylic acid) and a specific group of painkillers that also have anti-inflammatory and antipyretic effects (NSAIDs).
• Medicines that reduce potassium levels, such as diuretics.

Hydrocortisone with food and drink
Grapefruit juice may alter the effect of Hydrocortisone. Consult your doctor or pharmacist before using this medicine and consuming grapefruit juice simultaneously.

Pregnancy, breastfeeding, and fertility
If the patient is pregnant, breastfeeding, suspects she may be pregnant, or plans to become pregnant, she should consult her doctor or pharmacist before using this medicine.

Pregnancy
Hydrocortisone may be used according to approved indications.
Prolonged use of higher doses should be avoided whenever possible.

Breastfeeding
Corticosteroids pass into breast milk. Therefore, breastfeeding during corticosteroid therapy is not recommended unless advised by a doctor.

Fertility
There is no evidence that corticosteroids affect fertility.

Driving and operating machinery
Many potential adverse effects of Hydrocortisone, such as blurred vision, mood changes, muscle weakness, and involuntary muscle contractions, may negatively affect the ability to drive and operate machinery.

Hydrocortisone contains sodium
This medicine contains 9.46 mg of sodium (the main component of table salt) per vial. Patients controlling their dietary sodium intake should take this into account.

3. How to use Hydrocortisone

Hydrocortisone is administered by a doctor or nurse. It can be given intravenously (by injection or infusion) or intramuscularly (by injection).
The appropriate dose will be determined by the doctor, depending on the disease and individual circumstances.

Use of a higher than recommended dose of Hydrocortisone
There is no information available on acute overdose of Hydrocortisone.
Hydrocortisone can be removed by dialysis. This means that in case of overdose, excess hydrocortisone can be removed from the blood using an artificial kidney. After prolonged, repeated use (daily or several times per week), the patient may develop Cushing's syndrome (characterized, among other features, by moon face – "full moon").

Missing a dose of Hydrocortisone
The doctor will ensure that the patient receives the next dose at the appropriate time. Do not use a double dose to make up for a missed dose.

Stopping treatment with Hydrocortisone
If treatment with Hydrocortisone is stopped suddenly, or if surgery becomes necessary during treatment, or a severe infection occurs, the adrenal cortex may become less effective. This may cause the symptoms of the disease being treated to reappear. Especially in children, seizures, dizziness, and headache may occur if treatment is discontinued too rapidly. Therefore, the doctor will usually gradually reduce the dose of Hydrocortisone.

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

4. Possible adverse reactions

Like all medicines, this medicine can cause adverse reactions, although not everybody gets them.
The following adverse reactions have been reported at an unknown frequency (frequency cannot be determined
from the available data):

• Hydrocortisone suppresses inflammatory response symptoms, which may in turn make diagnosis of infection more difficult, and may lead to the emergence of previously inactive infections and the occurrence of new infections.
• Infections may occur, which usually are rare (opportunistic infections).
• Skin cancer (Kaposi's sarcoma).
• Significant increase in blood pressure due to adrenal medulla swelling (pheochromocytoma).
• Increased number of white blood cells in the blood (leukocytosis).
• Severe allergic reaction to certain substances, including sudden drop in blood pressure, pallor, restlessness, weak and rapid pulse, moist skin, and reduced level of consciousness due to sudden, intense vasodilation (anaphylactic reaction).
• Hypersensitivity to medicines.
• Development of obesity (head, trunk), moon-shaped face (moon face), and high blood pressure (Cushing's syndrome).
• Deficiency of one or more hormones secreted by the pituitary gland (suppression of the hypothalamic-pituitary-adrenal axis).
• Withdrawal syndrome, which may occur after discontinuation of corticosteroid treatment (steroid withdrawal syndrome).
• Blood acidification (metabolic acidosis).
• Sodium retention by the kidneys (sodium retention).
• Fluid accumulation in the body (fluid retention).
• Fat metabolism disorders (dyslipidemia).
• Acid-base imbalance in the blood due to excessive potassium loss (hypokalemic alkalosis).
• Reduced ability to tolerate glucose (impaired glucose tolerance).
• Disruption of blood sugar regulation, allowing detection of latent diabetes or increasing the need for insulin or other blood sugar-lowering medicines.
• Increased appetite.
• Accumulation of fat tissue in various parts of the body (lipomatosis).
• Psychiatric disorders such as excessive happiness associated with high energy levels (mania), delusions, perception of things that are not present (hallucinations), and severe mental illness (schizophrenia) characterized by progressive personality changes.
• Mood disorders such as depressed mood, extreme feelings of joy (euphoria), emotional lability, drug dependence, suicidal thoughts.
• Mental disorder.
• Disorientation.
• Anxiety.
• Personality change.
• Mood swings.
• Unusual behavior.
• Insomnia.
• Irritability.
• Exacerbation of pre-existing psychotic behaviors.
• Fat accumulation in the spinal canal (epidural lipomatosis).
• Increased intracranial pressure.
• Increased intracranial pressure with mucosal edema (benign intracranial hypertension).
• Loss of consciousness with muscle tremors (seizures).
• Memory loss (amnesia).
• Cognitive function disorders, such as perception, attention, concentration, memory, orientation, language use, and skills (cognitive disorders).
• Dizziness.
• Headache.
• Retinal and choroidal disorders (chorioretinopathy).
• Visual disturbances.
• Clouding of the lens (cataract).
• Increased intraocular pressure (glaucoma).
• Abnormal protrusion of the eyeballs (exophthalmos).
• Dizziness with balance disturbances (vertigo).
• In patients at risk, reduced ability of the heart to pump blood (congestive heart failure) may occur.
• Increased blood coagulation (thrombosis).
• Low blood pressure (hypotension).
• High blood pressure (hypertension).
• Pulmonary embolism.
• Persistent hiccups.
• Gastric and/or duodenal ulcers, possibly with perforation and bleeding.
• Bleeding and intestinal wall damage (intestinal perforation).
• Gastrointestinal bleeding.
• Pancreatitis with symptoms of severe upper abdominal pain radiating to the back, nausea, and vomiting (pancreatitis).
• Esophagitis with or without ulcers.
• Abdominal pain.
• Abdominal distension.
• Diarrhea.
• Digestive disturbances with a feeling of fullness in the upper abdomen, stomach pain, belching, nausea.
• Vomiting and heartburn (dyspepsia).
• Nausea.
• Sudden accumulation of fluid in the skin and mucous membranes (e.g., throat or tongue), breathing difficulties, and/or itching and skin rash, often as an allergic reaction (angioedema).
• Excessive hair growth in women (hirsutism).
• Small bruises under the skin (petechiae).
• Small bruises on mucous membranes (petechiae).
• Thin, fragile, and wrinkled skin (skin atrophy).
• Skin redness (erythema).
• Excessive sweating.
• Skin scars (striae).
• Skin rash.
• Itching (pruritus).
• Skin rash with intense itching and bumps (urticaria).
• Acne-like skin eruptions ("adolescent acne") (acne).
• Muscle weakness.
• Muscle pain (myalgia).
• Muscle diseases (myopathy).
• Reduction of muscle tissue due to disuse or inability to use muscle due to neurological disease (muscle atrophy).
• Bone necrosis.
• Bone demineralization (osteoporosis).
• Bone fractures (pathological fractures).
• Joint diseases caused by neurological disorders (neuropathic arthropathy).
• Joint pain (arthralgia).
• Growth delay.
• Vertebral collapse (compression fracture of the spinal column).
• Tendon rupture.
• Irregular menstruation.
• Impaired wound healing.
• Fluid retention in the limbs (peripheral edema).
• Fatigue.
• General malaise, nausea.
• Skin reactions at the injection site.
• Increased intraocular pressure.
• Reduced ability to metabolize sugars (carbohydrates), which may lead to increased need for insulin or other blood sugar-lowering medicines.
• Reduced potassium levels in the blood, in severe cases manifesting as muscle cramps or muscle weakness and fatigue (hypokalemia).
• Increased calcium levels in urine.
• Abnormal blood test results (increased alanine aminotransferase activity, increased aspartate aminotransferase activity, increased alkaline phosphatase activity in blood).
• Increased levels of protein breakdown products in blood (elevated blood urea nitrogen).
• Disturbances in skin allergy test results.
• Weight gain.

Additional adverse reactions that may occur in children and adolescents up to 18 years of age
In children, growth suppression may occur. In premature infants, hypertrophy of the heart muscle may occur (hypertrophic cardiomyopathy).
Reporting of adverse reactions
If any adverse reactions occur, including any not listed in this leaflet, inform your doctor or pharmacist. Adverse reactions can be reported directly to the Department of Monitoring Adverse Drug Reactions of the 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.
Reporting adverse reactions helps to provide more information on the safety of the medicine.

5. How to store Hydrocortisone PHARMLINE

Keep this medicine out of sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and label following: EXP.
The expiry date refers to the last day of the stated month.
Do not store above 25°C. Keep the vial in the outer packaging to protect it from light.
After mixing the medicine with sterile water for injection, the solution should be used immediately.
Any unused solution should be safely discarded.
Before administration, the doctor will check whether the solution contains any particles and whether it has discolored.
Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. This helps protect the environment.

6. Contents of the packaging and other information

What Hydrocortisone contains

• The active substance is hydrocortisone. One vial for injection contains 100 mg of hydrocortisone in the form of hydrocortisone sodium succinate.
• Other ingredients are: disodium dihydrogen phosphate dihydrate, disodium dihydrogen phosphate anhydrous, sodium hydroxide.

What Hydrocortisone looks like and contents of the pack
Hydrocortisone is a white or almost white powder for solution for injection/infusion. It is contained in a type I colourless glass vial closed with a rubber stopper and sealed with an aluminium cap, containing 100 mg of hydrocortisone.
Hydrocortisone is available in packs containing 1 or 10 vials.
One vial or two protective trays made of PVC covered with PET/PE foil, each containing 5 vials, are packed in a cardboard box.
Not all pack sizes may be marketed.

Marketing Authorisation Holder
Pharmline Company Sp. z o.o.
Juliana Ursyna Niemcewicza Street 17/11
02-306 Warsaw
Tel: +48 780 008 085
E-mail: [email protected]

Manufacturer
S.C. Rompharm Company S.R.L.
1A Eroilor Street
075100 Otopeni, Ilfov County
Romania

This medicinal product is authorised in the European Economic Area member states under the following names:
Austria Hydrocortison Inresa 100 mg Powder for solution for injection/infusion
Bulgaria Hydrocortisone Rompharm 100 mg powder for injection/infusion solution
Spain Hidrocortisona Lorien 100 mg powder for solution for injection and perfusion EFG
Germany Hydrocortison Inresa 100 mg Powder for solution for injection/infusion
Poland Hydrocortisone PHARMLINE
Romania Hidrocortizon Rompharm 100 mg pulbere pentru soluție injectabilă/perfuzabilă
Hungary 100 mg por oldatos injekcióhoz vagy infúzióhoz

Information intended exclusively for healthcare professionals:

Dosage and administration
Hydrocortisone may be administered by intravenous or intramuscular injection, or by intravenous infusion. The preferred route for initial administration in emergency situations is intravenous injection. After initial emergency intervention, consideration should be given to switching to a longer-acting injectable formulation or an oral formulation. The duration of infusion depends on the dose; it may range from 30 seconds (e.g., 100 mg) to 10 minutes (e.g., 500 mg or more).
In general, high-dose corticosteroid therapy should be continued until the patient's condition stabilizes (usually no longer than 48 to 72 hours).
Although adverse effects associated with short-term, high-dose corticosteroid therapy are not very common, gastrointestinal ulcers may occur. Prophylactic treatment with acid-neutralizing agents may therefore be indicated.
When hydrocortisone treatment must be continued beyond 48 to 72 hours, hypernatremia may occur; therefore, it may be preferable to replace Hydrocortisone with a corticosteroid such as sodium succinate of methylprednisolone, which causes minimal or no sodium retention.
The initial dose of Hydrocortisone ranges from 100 mg to 500 mg or more, depending on the severity of the condition. This dose may be repeated every 2, 4, or 6 hours, depending on the patient's clinical status. Corticosteroid therapy is an adjunct to conventional therapy and should not replace it.
Hydrocortisone may have a stronger effect in patients with liver disease. Therefore, dose reduction should be considered (see section 4.4).

Children and adolescents
The dose of Hydrocortisone in children should be determined based on the severity of the disease and the patient's response, rather than on body weight or age. In these patients, the dose may be reduced but should not be less than 25 mg per day (see section 4.4).

Preparation of solution
Parenteral medicinal products should be inspected visually for particulate matter and discoloration prior to administration.
After reconstitution, the solution is clear and free of visible particles or precipitate.
The product contains no preservative and is intended for single use only. After opening the vial, its contents should be used immediately (see section 6.3).

Instructions:
Add no more than 2 mL of sterile water for injection to one vial containing sterile powder, under aseptic conditions.

For intravenous or intramuscular injection:
Prepare the solution as described above. Further dilution is not required for intravenous or intramuscular injection; shake and withdraw for use.

Intravenous infusion:
First, prepare the solution as described above by adding no more than 2 mL of sterile water for injection to the vial. The resulting solution containing 100 mg of hydrocortisone may then be added to 100–1000 mL (but not less than 100 mL) of one of the following solutions:

• 5% glucose solution in water
• 0.9% sodium chloride solution

If the patient is on a sodium-restricted diet, 5% glucose solution may be used.
After reconstitution according to instructions, the pH of the solution ranges from 7.0 to 8.0.

Shelf life
Unopened vial:
2 years

The stability of the solution after reconstitution with 2 mL of sterile water for injection has not been studied. Therefore, the reconstituted solution should be used immediately.

After reconstitution and dilution:
After reconstitution and subsequent dilution in 100 mL and 1000 mL of 0.9% sodium chloride for injection, chemical and physical stability has been demonstrated for 4 hours at 25°C.
After reconstitution and subsequent dilution in 100 mL and 1000 mL of 5% glucose for injection, chemical and physical stability has been demonstrated for 4 hours at 25°C.
From a microbiological standpoint, the medicinal product should be used immediately. If not used immediately, the user is responsible for the storage conditions and duration.

Special precautions for storage
Do not store above 25°C.
Keep the vial in the outer packaging to protect from light.

More information can be found in the Summary of Product Characteristics.