Package leaflet: Information for the patient

LISAMETHYLE 20 mg/2 ml powder and solvent for injectable solution, 40 mg/2 ml powder and solvent for injectable solution, 120 mg/2 ml powder and solvent for injectable solution, 500 mg powder for injectable solution

Methylprednisolone sodium succinate
Generic medicine
Please read all of this leaflet carefully before you start using this medicine, as it contains important information for you.

Keep this leaflet. You may need to read it again.
If you have any questions, ask your doctor or the doctor treating the child or pharmacist.
This medicine has been prescribed for you and/or the child only. Do not give it to other people, even if their symptoms are the same as yours, because it could be dangerous.
If you and/or the child experience any adverse reactions, including those not listed in this leaflet, contact your doctor or the doctor treating the child or pharmacist. See section 4.

Contents of this leaflet

What LISAMETHYLE is and what it is used for
What you need to know before using LISAMETHYLE
How to use LISAMETHYLE
Possible side effects
How to store LISAMETHYLE
Contents of the pack and other information

1. What LISAMETHYLE is and what it is used for

LISAMETHYLE contains the active substance methylprednisolone sodium succinate. Methylprednisolone sodium succinate belongs to a group of medicines called corticosteroids. Corticosteroids are substances naturally produced by the body and are important for many bodily functions.

LISAMETHYLE is used in adults and children over three years of age for the treatment of:

diseases in which the body is unable to produce sufficient amounts of natural corticosteroids, for example due to adrenal gland problems such as adrenal insufficiency;
skin diseases (pemphigus, severe erythema multiforme, exfoliative dermatitis);
allergic diseases (bronchial asthma, contact dermatitis, serum sickness, drug allergies, angioneurotic edema, urticaria, anaphylactic shock);
intestinal diseases (ulcerative colitis, segmental ileitis);
blood cancers (e.g. leukaemia in adults and children);
diseases of the brain (e.g. conditions caused by a tumour or trauma);
lung diseases in patients with AIDS;
cancers affecting the lymph glands (lymphomas in adults);
conditions characterized by fluid accumulation (edematous states);
very advanced-stage cancers (palliative therapy).

LISAMETHYLE may also be used for relapses of symptoms in multiple sclerosis and systemic lupus erythematosus, or for other stressful conditions.

LISAMETHYLE may also be used in the following diseases:

generalized skin disease (neurodermatitis);
acute rheumatic fever ( acute inflammatory disease affecting the joints, heart, skin, and central nervous system);
oesophageal burns;
prevention of nausea and vomiting associated with chemotherapy for cancer treatment;
severe Pneumocystis jiroveci lung infections in patients with A.I.D.S. (adjunctive therapy).

Please consult your doctor if you are unsure about why this medicine has been prescribed for you or your child.

2. What you should know before using LISAMETHYLE

Do not use LISAMETHYLE if you and/or the child:

are allergic to sodium succinylate methylprednisolone or to any of the other ingredients of this medicine (listed in section 6);
have a fungal infection that has spread to certain organs or throughout the body;
if the child was born prematurely, is a newborn, or is under three years of age.

LISAMETHYLE will not be administered to you/the child via injections into the back
(intrathecal/epidural administration).
You and/or the child must not be vaccinated with live or live attenuated vaccines during treatment
with LISAMETHYLE.
Warnings and precautions
Talk to your doctor or pharmacist BEFORE using this medicine if:

you need to undergo skin sensitivity tests;
you have or have previously had tuberculosis;
you are under particular conditions of stress. In such cases, your doctor will prescribe a higher dose of this medicine for you or your child;
you have Cushing's syndrome , a disease characterized by excessive production of natural corticosteroids in the body. LISAMETHYLE may worsen your or your child’s condition;
your thyroid gland is underactive ( hypothyroidism ). In this case, doses of LISAMETHYLE should be reduced;
you have diabetes;
you suffer from epileptic seizures;
you have myasthenia gravis , a disease causing muscle weakness and fatigue, or you are undergoing surgery with general anesthesia requiring muscle-blocking drugs (e.g. pancuronium). In this case, there is an increased risk that LISAMETHYLE may cause muscle problems;
you have an eye infection caused by the Herpes simplex virus;
you have high blood pressure ( hypertension );
you have elevated levels of fats in the blood ( dyslipidemia );
you have heart problems ( heart failure );
you suffer from or are predisposed to developing blood clots in the veins;
you have a stomach ulcer or other serious stomach or intestinal problems (see "How to use LISAMETHYLE");
you have kidney problems;
you have scleroderma (also known as systemic sclerosis, an autoimmune disease), since the use of corticosteroids may increase the risk of a serious complication called scleroderma renal crisis;
you have a brain injury caused by trauma;
you have liver cirrhosis , a liver disease;
you are being treated with non-steroidal anti-inflammatory drugs (e.g. acetylsalicylic acid) (see section “Other medicines and LISAMETHYLE”) and have reduced prothrombin activity, a protein that helps blood to clot;
you have a type of tumor called pheochromocytoma;
you suffer from peritonitis or other gastrointestinal disorders because glucocorticoid therapy may mask symptoms such as perforation, obstruction, or pancreatitis.
If your thyroid is overactive (hyperthyroidism)

If you have cancer, you are at high risk of developing tumor lysis syndrome, which may occur when
corticosteroids are used during cancer treatment. Inform your doctor if you have cancer and
experience symptoms of tumor lysis syndrome such as muscle cramps, muscle weakness, confusion,
irregular heartbeat, vision loss or visual disturbances, and shortness of breath.
Inform your doctor or the doctor treating your child if any of the following conditions appear or worsen DURING treatment with this medicine (also see section 4 “Possible side effects”):

infections. This medicine may increase susceptibility to infections or worsen existing infections. For example, chickenpox and measles may follow a more severe course, sometimes fatal;
Kaposi's sarcoma , a skin tumor. In this case discontinue treatment with LISAMETHYLE;
severe allergic reactions;
onset or worsening of mental disorders (e.g. depression). Inform people living with you about the possible effects of this medicine;
fat accumulation compressing the spinal cord;
eye problems;
changes in heart rhythm ( cardiac arrhythmias ), reduced heart rate ( bradycardia ), circulatory collapse and cardiac arrest;
severe inflammation of the pancreas or liver;
hepatobiliary disorders (reversible after discontinuation);
osteoporosis (fragile bones);
swelling in various parts of the body, especially in the legs and ankles, or changes in normal levels of minerals in the blood;
blurred vision or other visual disturbances.

You or your child must not be vaccinated with live or live attenuated vaccines during treatment
with LISAMETHYLE (see section “Do not use LISAMETHYLE if you and/or the child”). However, you may
receive vaccination with killed or inactivated vaccines , although the effectiveness of these vaccines may be
reduced.
If you experience muscle weakness, muscle pain, cramps, or stiffness while taking methylprednisolone,
contact your doctor immediately. These may be symptoms of a condition called thyrotoxic periodic paralysis, which may occur in patients with overactive thyroid (hyperthyroidism) treated with
methylprednisolone. Additional treatment may be required to relieve this condition.
For those engaged in sports
Using the drug without therapeutic need constitutes doping and may lead to a positive anti-doping test.
Children
This medicine must not be given to premature infants, newborns, or children under three years of age.
Long-term or high-dose treatment with LISAMETHYLE may cause growth retardation, increased intracranial pressure, and pancreatitis in children.
The use of methylprednisolone in premature newborns may induce the development of hypertrophic cardiomyopathy (thickening of the heart walls).
Elderly
If you are elderly, long-term treatment with LISAMETHYLE may increase the risk of developing osteoporosis, excessive fluid retention, and high blood pressure.
Your doctor will assess your condition and administer this medicine cautiously.
Other medicines and LISAMETHYLE
Inform your doctor or pharmacist if you and/or the child are taking, have recently taken, or might take any other medicines, including those obtained without a prescription.
Some medicines may enhance the effects of LISAMETHYLE, and your doctor may wish to monitor you closely if you are taking these medicines.
The following medicines may affect the activity of LISAMETHYLE or LISAMETHYLE may
affect the efficacy and/or toxicity of the following medicines:

isoniazid, troleandomycin, clarithromycin, and erythromycin (antibiotics);
methotrexate, used for the treatment of tumors and autoimmune diseases;
rifampicin (antibiotic for tuberculosis);
phenobarbital, phenytoin, and carbamazepine (medicines for seizures);
aprepitant and fosaprepitant (medicines for vomiting);
itraconazole, ketoconazole, and amphotericin B (medicines for fungal infections);
HIV treatments such as indinavir, ritonavir, and cobicistat (medicines against HIV virus);
aminoglutethimide (medicine for excessive production of natural corticosteroids);
diltiazem (medicine used for heart problems or high blood pressure);
ethinylestradiol/norethindrone (hormones used in combination as oral contraceptives);
cyclosporine, cyclophosphamide, and tacrolimus, medicines to prevent organ transplant rejection and for autoimmune diseases;
oral anticoagulants, medicines used to thin the blood;
neuromuscular blockers such as pancuronium and vecuronium (medicines causing muscle relaxation);
anticholinesterases such as pyridostigmine and neostigmine (medicines for muscle diseases like myasthenia gravis and Alzheimer's disease);
antidiabetics (medicines for diabetes);
aspirin (acetylsalicylic acid);
diuretics (medicines that increase urine production);
xanthines (e.g. theophylline) and beta-2 agonists (e.g. salbutamol), medicines for asthma;
antihypertensives, medicines used to lower blood pressure;
digoxin, used for treatment of heart failure and/or irregular heartbeat;
psychotropic drugs (anxiolytics and antipsychotics), medicines used to treat anxiety and mental illnesses.

LISAMETHYLE and beverages
You and/or the child must not drink grapefruit juice during treatment with LISAMETHYLE, as
the efficacy and toxicity of this medicine could increase.
Pregnancy, breastfeeding, and fertility
If you are pregnant, suspect you may be pregnant, planning to become pregnant, or breastfeeding, consult your doctor or pharmacist before using/receiving this medicine.
Pregnancy
If you use this medicine during pregnancy, especially at high doses and for a prolonged period, the baby may experience adverse effects at birth. Therefore, if you are pregnant, your doctor will prescribe LISAMETHYLE only if strictly necessary.
Breastfeeding
LISAMETHYLE passes into breast milk and this may cause adverse effects in the infant. If you are breastfeeding, your doctor will prescribe LISAMETHYLE only if strictly necessary.
Fertility
Based on currently available information, this medicine may reduce fertility.
Driving and operating machinery
Do not drive or operate machinery if you experience dizziness, vertigo, visual disturbances, fatigue, euphoria, or mood disturbances during treatment with LISAMETHYLE.
LISAMETHYLE contains sodium
LISAMETHYLE 20 mg/2 ml, 40 mg/2 ml, 120 mg/2 ml: contains less than 1 mmol (23 mg) of sodium per vial, i.e., practically "sodium-free".

3. How to use LISAMETHYLE

Use this medicine exactly as instructed by your doctor or pharmacist. If you have any doubts,
consult your doctor or pharmacist.
Your doctor will determine the dose of LISAMETHYLE to be administered based on the severity of the
condition to be treated and your health status (yours or your child's).
During treatment, your response to therapy will be monitored, and therefore the dose may be
adjusted. Your doctor will explain how to reduce the dose prior to discontinuation of LISAMETHYLE.

Adults
The recommended initial dose ranges from 10 mg to 40 mg, administered intravenously (into a vein)
over several minutes.
Subsequent doses may be administered intravenously or intramuscularly (into a muscle).
LISAMETHYLE may be given in high doses for up to a maximum of 48–72 hours.
In such cases, the recommended dose is 30 mg/kg of body weight administered intravenously
over a 30-minute period. The dose may be repeated every 4–6 hours over 48 hours.

Children over 3 years of age
The doctor will determine the dose based on the severity of the child's condition, response to therapy,
age, and body weight.
The recommended dose should not be less than 0.5 mg/kg of body weight per day.

Method of administration
LISAMETHYLE is administered intravenously (by injection into a vein), intramuscularly (into a muscle),
by intravenous infusion (into a vein), or via an infusion pump (intravenous infusion using an electronic device).
In an emergency, the intravenous route is preferred.
Intravenous administration must be performed by trained healthcare personnel.

If you use/administer more LISAMETHYLE than you should
If a dose of this medicine much higher than prescribed is used/administered, acute toxicity and even death
may occur, although rarely.
Seek immediate medical advice or go to the nearest hospital if you and/or your child have accidentally taken
an excessive dose of LISAMETHYLE.

If you forget to use LISAMETHYLE
Do not use a double dose to make up for the forgotten dose.
If you realize you have missed a dose, consult your doctor.

If you stop treatment with LISAMETHYLE
You or your child must not stop taking LISAMETHYLE suddenly.
LISAMETHYLE may cause reduced function of the adrenal glands, which produce natural corticosteroids, and abrupt discontinuation may lead to death.
Moreover, sudden interruption of LISAMETHYLE treatment may lead to withdrawal symptoms such as:
anorexia, nausea, vomiting, excessive drowsiness, headache, fever, muscle and joint pain, skin desquamation, weight loss, low blood pressure, and mental disturbances.
When stopping treatment, doses must be gradually reduced. Your doctor will advise you on the correct way to do this (see "How to use LISAMETHYLE").

If you have any doubts about how to use this medicine, consult your doctor or pharmacist.

4. Possible side effects

Like all medicines, this medicine can cause side effects, although not everybody will experience them.
Contact your doctor if you experience any of the following side effects:

Frequency not known (frequency cannot be estimated from the available data):

infections, including infections occurring when the body's immune defences are very low
increased number of white blood cells in the blood
hypersensitivity to the medicine
severe allergic reaction, e.g. swelling of the face, tongue and throat with difficulty swallowing and breathing (angioedema)
urticaria
round or moon-shaped face (Cushingoid appearance)
reduced hormone secretion from the pituitary gland (a gland located at the base of the brain)
withdrawal syndrome (see section 3 “If you stop treatment with LISAMETHYLE”)
metabolic acidosis
glucose metabolism disorder and worsening of pre-existing diabetes
increased loss or retention of acidic substances from the body
elevated levels of fats in the blood
fluid and sodium retention in the body
increased blood urea levels
increased appetite and body weight
accumulation of fatty tissue in specific body areas
increased body fat
psychiatric disorders such as: depression, euphoria, manic behaviour, delirium, hallucinations, schizophrenia, altered perception of reality and thought disorders, disturbances in emotional experience (e.g. mood swings, emotional dependency, suicidal ideation), personality changes, confusion, anxiety, abnormal behaviour, insomnia, irritability
increased pressure of the fluid within the skull
seizures
memory difficulties
disturbances in thought processes affecting awareness of reality
dizziness
headache
fat accumulation compressing the spinal cord
cataract
increased intraocular pressure
protruding eyes
reduced central vision
retinal and choroidal membrane disease
heart problems (heart failure) in susceptible patients
irregular heartbeat
formation of blood clots in veins and lungs
increased blood coagulation
increased or decreased blood pressure
warmth and redness of the skin (flushing)
hiccup
stomach and intestinal ulcers with possible bleeding and perforation
inflammation of the pancreas
abdominal inflammation (peritonitis)
inflammation of the oesophagus with or without ulcers
abdominal distension and pain
difficulty digesting
nausea, vomiting and diarrhoea
inflammation of the liver
delayed wound healing
thinning and fragility of the skin
skin patches of unusual colour
atrophy of the skin and its appendages (hair, nails)
pus formation
swelling
bruising
appearance of small red spots or thin purplish lines on the skin
increased hair growth
redness of the skin, skin rashes
itching
acne
excessive sweating
bone fragility (osteoporosis), bone tissue death and loss
muscle and joint pain, muscle diseases, reduced muscle mass
muscle weakness
joint rupture (especially of the foot) causing pain and/or swelling
irregular menstruation
reaction at the injection site
fatigue, malaise
abnormal liver function laboratory tests
possible liver damage, hepatitis, increased liver enzymes
decreased potassium levels in the blood
increased calcium levels in the urine
reduced response to skin tests
vertebral fractures (traumatic or spontaneous), tendon rupture, particularly of the Achilles tendon
blurred vision

Additional side effects in children
Frequency not known (frequency cannot be estimated from the available data):

growth retardation

Reporting of side effects
If you or your child experience any side effect, including those not listed in this leaflet, talk to your doctor or pharmacist. You can also report side effects directly via the national reporting system at http://www.aifa.gov.it/content/segnalazioni-reazioni-avverse. By reporting side effects, you can help provide more information on the safety of this medicine.

5. How to store LISAMETHYLE

Keep this medicine out of the sight and reach of children.
Do not use this medicine after the expiry date stated on the carton and vial after "Exp.". The expiry date refers to the last day of that month. The stated expiry date applies to the product stored in its original intact packaging and properly stored.
Store this medicine below 25 °C. Period of validity after reconstitution: use within 4 hours.
Do not dispose of any medicine via wastewater or household waste. Ask your pharmacist how to dispose of medicines you no longer use. This will help protect the environment.

6. Package contents and other information

What LISAMETHYLE contains
The active substance is methylprednisolone (as methylprednisolone sodium succinate).
LISAMETHYLE 20 mg/2 ml powder and solvent for injectable solution
Each vial of powder contains 20 mg of methylprednisolone (equivalent to 26.5 mg of methylprednisolone
sodium succinate).
The other component is: water for injections.
LISAMETHYLE 40 mg/2 ml powder and solvent for injectable solution
Each vial of powder contains 40 mg of methylprednisolone (equivalent to 53.0 mg of methylprednisolone
sodium succinate).
The other component is: water for injections.
LISAMETHYLE 120 mg/2 ml powder and solvent for injectable solution
Each vial of powder contains 120 mg of methylprednisolone (equivalent to 159.0 mg of
methylprednisolone sodium succinate).
The other component is: water for injections.
LISAMETHYLE 500 mg powder for injectable solution
Each vial of powder contains 500 mg of methylprednisolone (equivalent to 663.0 mg of
methylprednisolone sodium succinate).

Description of the appearance of LISAMETHYLE and contents of the pack
LISAMETHYLE 20 mg/2 ml powder and solvent for injectable solution is available in packs containing 1 vial of powder + 1 ampoule of solvent (2 ml).
LISAMETHYLE 40 mg/2 ml powder and solvent for injectable solution is available in packs containing 1 vial of powder + 1 ampoule of solvent (2 ml).
LISAMETHYLE 120 mg/2 ml powder and solvent for injectable solution is available in packs containing 1 vial of powder + 1 ampoule of solvent (2 ml).
LISAMETHYLE 500 mg powder for injectable solution is available in packs containing 1 vial.

Marketing Authorization Holder and Manufacturer
Lab. It. Biochim. Farm.co LISAPHARMA S.p.A. - Via Licinio 11 - 22036 Erba (CO)
February 2025

The following information is intended exclusively for physicians and healthcare professionals:
INCOMPATIBILITIES
To avoid compatibility and stability issues, methylprednisolone sodium succinate should be administered separately from other substances administered intravenously. Drugs that are physically incompatible in solution with methylprednisolone sodium succinate include, but are not limited to: allopurinol sodium, doxapram hydrochloride, tigecycline, diltiazem hydrochloride, as well as calcium gluconate, vecuronium bromide, rocuronium bromide, cisatracurium besylate, glycopyrronium, and propofol.

DOSAGE
The dose must be determined according to the clinical condition being treated and its severity.
It is recommended to use the lowest effective dose for the shortest possible duration.
Treatment should be adjusted based on the observed response, and maintenance therapy should be established through gradual titration to achieve an adequate clinical response.
In case of long-term treatment, the medicine should be discontinued gradually (see "Warnings and Precautions").
After completion of emergency treatment, consider using a longer-acting injectable formulation or an oral formulation.
For high-dose treatment, the recommended dose of LISAMETHYLE is 30 mg/kg administered intravenously over a period of at least 30 minutes. The dose may be repeated every 4–6 hours within 48 hours. High-dose treatment should continue until clinical stabilization; however, it should not extend beyond 48–72 hours. Short-term use of high doses may lead to the development of peptic ulcer; therefore, concomitant prophylactic treatment is recommended (see "Warnings and Precautions" and "Undesirable Effects").

Exacerbations of systemic lupus erythematosus and edematous states due to glomerulonephritis or lupus nephritis:
Pulsed intravenous administration of 250–1000 mg per day for 1–3 days is recommended.
In case of exacerbation of pathological conditions or lack of response to standard therapies, the following intravenous boluses are recommended:

Multiple sclerosis
1 g per day intravenously for 3–5 days

Acute spinal cord injury
Treatment should be initiated within 8 hours of trauma with a bolus of 30 mg/kg administered over 15 minutes, followed by a 45-minute interval and then a maintenance infusion of 5.4 mg/kg/hour for the next 23 hours.
Treatment choice must be made on a case-by-case basis, carefully weighing the risk-benefit ratio, and referring to official guidelines.
Strict monitoring of the patient is also required due to the high risk of toxicity associated with the high dose of methylprednisolone administered.

Palliative therapy in very advanced cancer
The recommended dose is 120 mg per day; short-term treatment should be carefully evaluated on a case-by-case basis.

Prevention of nausea and vomiting associated with mildly or moderately emetogenic chemotherapy:
120–240 mg of LISAMETHYLE, possibly in combination with a phenothiazine, one hour before chemotherapy.
A second dose of LISAMETHYLE is administered at the time of chemotherapy, followed by a final dose before discharge.

Prophylaxis of nausea and vomiting associated with highly emetogenic chemotherapy:
240 mg of LISAMETHYLE combined with 1–2.5 mg of droperidol or 1.5–2 mg/kg of metoclopramide, one hour before chemotherapy.
A second dose of LISAMETHYLE is administered at the time of chemotherapy, followed by a final dose before discharge.
In all cases, short duration of treatment is recommended.

Adjuvant therapy of severe Pneumocystis jirovecii pneumonia in AIDS patients
0.5 mg/kg every 6 hours for 10 days.
Administration must begin within 72 hours of starting antimicrobial therapy.

For other indications, the initial dose may range from 10 to 40 mg of methylprednisolone, depending on the clinical condition being treated.
Higher doses may be required in acute and severe conditions. In such cases, treatment should be kept as brief as possible.
The initial dose should be administered intravenously over several minutes.
Subsequent doses may be given intravenously or intramuscularly; the choice of route should depend on the condition being treated and the response achieved.
Corticosteroid therapy is an adjuvant therapy and does not replace conventional treatment.
If remission occurs during treatment of a chronic disease, the medicine should be discontinued (see "Warnings and Precautions").

Paediatric population
In children over 3 years of age, the dose should be guided more by the severity of the condition and the response achieved than by age or weight.
The daily dose should not be less than 0.5 mg/kg.
Dosage should be gradually reduced if treatment has been prolonged for several days.

METHOD OF ADMINISTRATION
Remove the protective cap from the vial and proceed as usual.
LISAMETHYLE may be administered via intravenous or intramuscular injection, by infusion (drip), or via infusion pump.
In emergencies, the intravenous route is preferred.
For intramuscular and intravenous injections, no further dilution is required. For infusions, dilute LISAMETHYLE in a volume of 100 to 1000 ml of 5% glucose solution or physiological saline.
After dilution or reconstitution, LISAMETHYLE must be used within 4 hours.

UNDESIRABLE EFFECTS
When administered via contraindicated routes (intrathecal/epidural), the following adverse reactions have been reported: arachnoiditis, gastrointestinal/bladder dysfunction, headache, meningitis, paraparesis/paraplegia, seizures, sensory disturbances. The frequency of these adverse reactions is unknown.

For further information, please consult the SmPC (Summary of Product Characteristics).

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