Dexamethasone Kalceks 4 mg/ml solution for injection and infusion EFG

Package leaflet: Information for the user

Introduction

Package leaflet: information for the user

Dexamethasone Kalceks 4 mg/ml solution for injection and infusion EFG

dexamethasone phosphate

Read the entire leaflet carefully before you start using this medicine, as it contains important information for you.

• Keep this leaflet, as you may need to read it again.
• If you have any questions, consult your doctor or pharmacist.
• This medicine has been prescribed for you only, and you should not give it to other people, even if they have the same symptoms as you, because it may harm them.
• If you experience any adverse effects, consult your doctor or pharmacist, even if they are adverse effects not listed in this leaflet. See section 4.

Leaflet contents

1. What Dexamethasone Kalceks is and what it is used for
2. What you need to know before being given Dexamethasone Kalceks
3. How Dexamethasone Kalceks is administered
4. Possible side effects
5. How to store Dexamethasone Kalceks
6. Contents of the pack and other information

1. What Dexamethasone Kalceks is and what it is used for

This medicine contains the active substance dexamethasone phosphate (also known as dexamethasone). Dexamethasone is a synthetic glucocorticoid (adrenocortical hormone). It reduces symptoms of inflammation and plays a role in essential metabolic processes.

Systemic route (affects the whole body)

This medicine is often used following initial high-dose emergency treatment:

• Treatment and prophylaxis of cerebral oedema (brain swelling) in brain tumours (after surgery and X-ray radiation) and after spinal cord trauma.
• Shock state due to an allergic reaction called "anaphylactic shock" (e.g., in reaction to a contrast medium).
• Shock states following severe injuries, prevention of acute respiratory distress syndrome.
• Severe persistent symptoms of an asthma attack.
• Initial treatment of certain extensive, acute and severe skin disorders, such as pemphigus vulgaris or erythroderma.
• Severe blood disorders (e.g., acute thrombocytopenic purpura or haemolytic anaemia, as part of medication for leukaemia treatment).
• As second-line treatment in patients with reduced or absent adrenocortical activity (adrenocortical insufficiency, Addisonian crisis).

This medicine is used for the treatment of coronavirus disease 2019 (COVID-19) in adult and adolescent patients (from 12 years of age, with a body weight of at least 40 kg) who have difficulty breathing and require oxygen therapy.

Local route (affects a limited part of the body)

• Periarticular injection and infiltrative treatment (penetrating into the tissue), for example, for inflammation of the shoulder joint (scapulohumeral periarthritis), elbow joint (epicondylitis), joint cushioning sacs (bursitis), tendon sheath (tendovaginitis), and wrist (styloïditis).
• Intra-articular injection, for example, in rheumatoid arthritis, when individual joints are affected or do not respond adequately to systemic treatment, and accompanying inflammatory reactions in degenerative joint disease (osteoarthritis).

2. What you need to know before Dexametasona Kalceks is administered to you

Do not administer Dexametasona Kalceks

• If you are allergic to dexamethasone or to any of the other components of this medicine (listed in section 6).
• If you have an infection affecting your entire body, including one that could have been caused by a fungus (e.g., candidiasis) that is not being treated with antibiotics.
• Joint injection must not be administered in the following cases: infections within or near the joint to be treated; joint inflammation caused by bacteria (bacterial arthritis); instability of the joint to be treated; tendency to bleeding (spontaneous or due to anticoagulants); calcium deposits near the joint (periarticular calcification); localized death of bone tissue, especially in the head of the humerus and femur (avascular necrosis of the bone); tendon rupture; joint disease due to syphilis (Charcot joint).
• Infiltration without additional treatment of the underlying cause is contraindicated in the presence of infections within the area of administration.

Warnings and precautions

Talk to your doctor, pharmacist, or nurse before you start receiving this medicine, as special care is required if:

• You have an acute or chronic bacterial infection.
• You have had tuberculosis.
• You have a fungal disease affecting internal organs.
• You have a parasitic disease (e.g., amoebic infection, worm infection).
• You have an acute viral infection (hepatitis B, herpes infection, chickenpox).
• You (or your child) have been or need to be vaccinated (see “Other medicines and Dexametasona Kalceks”). Especially inform your doctor if you have never had measles or chickenpox or if your child’s immune system is weakened.
• You have stomach or intestinal ulcers.
• You have osteoporosis (breakdown of bone tissue). Your doctor may wish to determine your bone density before starting long-term treatment. Your doctor may prescribe calcium, vitamin D supplements, and/or medications to reduce bone loss, if necessary. In patients with advanced osteoporosis, this medicine will only be used in life-threatening situations or for short periods.
• You have high blood pressure that is difficult to control.
• You have diabetes.
• You have a history of psychiatric illness, including suicide risk.
• You have increased pressure inside the eye (closed- and open-angle glaucoma), corneal lesions, or eye ulcers (as close monitoring and treatment by an ophthalmologist are required).
• You have heart or kidney disorders.
• You have myasthenia gravis (a muscle disease), as symptoms may initially worsen after dexamethasone administration; the initial dose should be selected with caution.
• You have a tumor of the adrenal glands (pheochromocytoma).

If you are unsure whether any of the above apply to you, consult your doctor or pharmacist.

Inform your doctor if you experience any of the following symptoms while being treated with this medicine:

• Muscle cramps, muscle weakness, confusion, worsening or loss of vision, and difficulty breathing, if you have blood cancer. These may be symptoms of tumor lysis syndrome.
• Blurred vision or other visual disturbances.

Concomitant use of corticosteroids

Do not stop taking any other corticosteroid medication unless instructed by your doctor.

General precautions regarding the use of corticosteroids in specific diseases, masking of infections, concomitant medications, etc., should follow current recommendations.

Severe allergic reactions

Severe allergic reactions, including anaphylaxis (a potentially life-threatening reaction), may occur, with symptoms such as irregular heartbeat, constriction of respiratory muscles, decreased or increased blood pressure, circulatory failure, or cardiac arrest.

Adrenocortical insufficiency

Abrupt discontinuation of treatment lasting more than 10 days may lead to acute adrenocortical insufficiency. Therefore, the dose should be gradually reduced if discontinuation is anticipated. Depending on the dose and duration of treatment, adrenocortical insufficiency caused by glucocorticoid therapy may persist for several months and, in individual cases, for more than one year after treatment has ended.

If specific physical stress situations occur during treatment, such as a febrile illness, an accident, or a surgical procedure, inform your doctor or emergency physician immediately about ongoing dexamethasone treatment. A temporary increase in the daily dose of dexamethasone may be necessary. Administration of glucocorticoids may also be required during physical stress if adrenocortical insufficiency persists after treatment ends.

Risk of infection

Dexamethasone doses higher than those required for maintenance therapy are associated with an increased risk of infection, possible worsening of a pre-existing infection, and possible activation of a latent infection. The anti-inflammatory effect may mask signs of infection until the infection has progressed significantly.

Gastrointestinal disorders

Due to the risk of intestinal wall perforation with peritonitis (inflammation of the peritoneum), this medicine should only be used if there are strong medical reasons, and under appropriate monitoring, in the following cases:

• Severe inflammation of the colon (ulcerative colitis) with imminent perforation;
• Abscesses or purulent infections (pus-filled);
• Diverticulitis (inflammation of pouches [diverticula] in the colon wall);
• After certain types of intestinal surgery (intestinal anastomosis) immediately following the procedure.

Patients receiving high doses of glucocorticoids may not show signs of peritoneal irritation after perforation of a stomach or intestinal ulcer.

Long-term treatment

During long-term treatment, periodic medical check-ups (including ophthalmological examinations every three months) are recommended. At relatively high doses, care should be taken to ensure adequate potassium intake (e.g., through vegetables or bananas) and restriction of sodium (salt) intake, and blood potassium levels should be monitored. Careful monitoring is also advised in patients with severe heart failure (inability of the heart to pump sufficient blood for metabolism, even at rest or during exertion).

Warnings related to specific administration methods

• The medicine will be injected slowly (over 2–3 minutes) into a vein, as too rapid injection may cause temporary unpleasant tingling or abnormal skin sensations lasting up to 3 minutes. These effects are harmless in themselves.
• Administration of glucocorticoids into a joint increases the risk of joint infections. Prolonged and repeated use of glucocorticoids in weight-bearing joints may lead to worsening of degenerative changes within the joint. One possible reason is overloading of the affected joint after pain or other symptoms subside.

Other warnings

• At high doses, a decrease in heart rate may occur.
• The risk of tendon disorders, inflammation, and rupture increases when fluoroquinolones (antibiotics) are used simultaneously with dexamethasone.
• In principle, vaccination with inactivated (killed) vaccines is possible. However, it should be remembered that higher doses may impair the immune response and thus the success of vaccination.
• In elderly patients, the doctor will carefully weigh the benefits and risks and pay attention to side effects such as osteoporosis (bone breakdown).
• If dexamethasone is administered to a premature infant, heart function and structure must be monitored.

Children and adolescents

Dexamethasone should not be routinely used in premature neonates with respiratory problems.

In children and adolescents, treatment should only be administered if there are strong medical reasons, due to the risk of growth retardation. For long-term treatment, intermittent therapy should be aimed for whenever possible.

Other medicines and Dexametasona Kalceks

Inform your doctor or pharmacist if you are taking, have recently taken, or might need to take any other medicines.

Some medicines may increase the effects of dexamethasone, and your doctor may wish to monitor you closely if you are taking these (including HIV medications: ritonavir, cobicistat).

Inform your doctor or pharmacist if you are taking any of the following medicines:

• Medicines for heart failure or asthma (cardiac glycosides);
• Medicines used to increase urine production (diuretics);
• Medicines to lower blood sugar levels (antidiabetics);
• Medicines to prevent blood clots/anticoagulants (coumarin derivatives);
• Ephedrine (used for asthma and poor circulation);
• Rifampicin (used to treat tuberculosis);
• Medicines for seizures and epilepsy (phenytoin, carbamazepine, primidone);
• Barbiturates (medicines to help you sleep);
• Ketoconazole, itraconazole (used to treat fungal infections);
• Medicines to treat infections (macrolide antibiotics such as erythromycin, or fluoroquinolones such as ciprofloxacin);
• Painkillers and anti-inflammatory/antirheumatic drugs (e.g., salicylates and indomethacin);
• Contraceptives containing estrogens;
• A medicine for treating intestinal parasite infestation (praziquantel);
• Medicines for treating high blood pressure and certain heart conditions (ACE inhibitors or angiotensin-converting enzyme inhibitors);
• Antimalarials (chloroquine, hydroxychloroquine, mefloquine);
• Somatropin (a growth hormone);
• Laxatives;
• Atropine and other anticholinergics (medicines that block the action of a certain brain neurotransmitter);
• Muscle relaxants;
• Medicines that suppress the immune system (cyclosporine);
• Bupropion (a smoking cessation aid).

Effect on diagnostic tests: Skin reactions to allergy tests may be suppressed. Interactions may occur with a medicine used in thyroid testing (protirelin: the increase in TSH caused by protirelin may be reduced).

If dexamethasone treatment is given 8 weeks before and up to 2 weeks after active preventive vaccination, a reduction or complete loss of vaccine efficacy may be expected.

Pregnancy, breastfeeding, and fertility

Pregnancy

If you are pregnant or breastfeeding, think you may be pregnant, or plan to become pregnant, consult your doctor or pharmacist before using this medicine.

Dexamethasone crosses the placental barrier. During pregnancy, especially in the first three months, it should only be used after careful assessment of benefit versus risk. Therefore, women should inform their doctor if they are or become pregnant. During long-term treatment in pregnancy, fetal growth disorders cannot be excluded. If glucocorticoids are administered at the end of pregnancy, there is a risk of adrenal insufficiency in the newborn, which may require gradual replacement therapy in the neonate, slowly tapered off. Newborns of mothers who received Dexametasona Kalceks near the end of pregnancy may have low blood sugar levels after birth.

Breastfeeding

Glucocorticoids are excreted in human milk. No harm to infants has been reported to date. However, they should only be used when strictly indicated during breastfeeding. If higher doses are required, breastfeeding should be discontinued.

Fertility

No fertility studies have been conducted.

Driving and using machines

No studies on the effects on the ability to drive and use machines have been performed.

Dexametasona Kalceks contains sodium

This medicine contains approximately 3 mg of sodium (main component of table/cooking salt) per ml of solution. This corresponds to 0.15% of the maximum daily recommended sodium intake for an adult.

3. How Dexamethasone Kalceks will be administered to you

This medicine should be used only as prescribed by your doctor. Your doctor will decide how long you should use dexamethasone. If in doubt, please consult your doctor or pharmacist again.

This medicine may be administered into a vein, into a muscle, into a joint, or as an infiltration into soft tissues.

The dose depends on the indication, the severity of symptoms, the individual patient's response, and, in the case of intra-articular injection, on the size of the joint.

Glucocorticoids should only be used for as short a time and at doses as low as absolutely necessary to achieve and maintain the desired effect. The duration of use is determined by the indication. Prolonged use of dexamethasone should not be stopped abruptly, but the dose should be gradually reduced according to the doctor's instructions.

For the treatment of COVID‑19

In adult patients, a dose of 6 mg administered intravenously once daily for up to 10 days is recommended.

Use in adolescents: It is recommended that pediatric patients (adolescents aged 12 years and older with a body weight of at least 40 kg) receive 6 mg intravenously once daily for up to 10 days.

Renal impairment

Dose adjustment is not necessary.

Hepatic impairment

In patients with severe liver disease, a dose adjustment may be necessary.

Children and adolescents

In children up to 14 years of age, during long-term treatment, a 4-day treatment-free interval should be introduced after each 3-day treatment period due to the risk of growth disturbances.

If you have been given more Dexamethasone Kalceks than you should have

Acute intoxication with dexamethasone is not known. In case of overdose, an increase in adverse effects may be expected. If you think you have been given an excessive amount of this medicine, inform your doctor immediately.

If you stop treatment with Dexamethasone Kalceks

Treatment should not be interrupted or stopped abruptly, unless directed by a doctor. If you nevertheless decide to discontinue treatment on your own, for example due to side effects or because you feel better, you not only risk compromising the success of your treatment, but also expose yourself to significant risks. In particular, after a prolonged period of treatment, you must never stop taking this medicine on your own. Always consult your doctor first.

If you have any further questions about 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 everyone will experience them.

In short-term treatment with dexamethasone, the risk of side effects is low. The following adverse effects may occur:

• gastric or duodenal ulcers;
• reduced body defences against infections;
• increased blood sugar levels (reduced glucose tolerance).

The following adverse effects may also occur. These depend largely on the dose and duration of treatment, and their frequency is therefore unknown (cannot be estimated from the available data):

Infections and infestations

Masking of infections, fungal, viral and other infections (opportunistic infections) which may promote the development or worsening of disease, activation of worms (see section 2, "Warnings and precautions").

Blood and lymphatic system disorders

Changes in blood count (moderate leucocytosis, lymphopenia, eosinopenia, polycythaemia).

Immune system disorders

Hypersensitivity reactions (e.g. rash), weakening of the immune system, allergic reactions and even anaphylaxis (acute allergic reaction that may be life-threatening), with symptoms such as irregular heartbeat, constriction of respiratory muscles, decreased or increased blood pressure, circulatory failure or cardiac arrest.

Endocrine system disorders

Cushing's syndrome (e.g. moon face, upper body obesity), adrenal inactivity or suppression (atrophy).

Metabolism and nutrition disorders

Sodium retention in the body with accumulation of water in tissues, increased potassium excretion (caution: possible disturbances in heart rhythm), weight gain, increased blood sugar levels (reduced glucose tolerance), diabetes, increased blood fat levels (cholesterol and triglycerides), increased appetite.

Psychiatric disorders

Psychosis, depression, irritability, euphoria (excessive happiness), sleep disturbances, emotional lability, anxiety, mania, hallucinations, suicidal thoughts.

Nervous system disorders

Pseudotumour cerebri ("false" brain tumour), new onset of epilepsy triggered in patients with latent epilepsy (previously "inactive"), and increased susceptibility to seizures in pre-existing epilepsy (attacks).

Eye disorders

Glaucoma, cataracts, worsening of corneal ulcer symptoms, promotion of eye inflammation due to viruses, fungi and bacteria; worsening of bacterial corneal inflammation, drooping eyelid (ptosis), dilated pupils, conjunctival eye oedema, iatrogenic scleral perforation (scleral [white part of the eye] injury induced by the physician), visual disturbance or loss, blurred vision. In rare cases, reversible protrusion of the eyeball (exophthalmos).

Cardiac disorders

Thickening of the heart muscle (hypertrophic cardiomyopathy) in premature infants, which usually resolves after treatment is stopped.

Vascular disorders

High blood pressure, increased risk of atherosclerosis (damage to blood vessel walls) and thrombosis (blockage of blood vessels by a clot), inflammation of blood and lymphatic vessels (vasculitis, also as withdrawal syndrome after prolonged treatment), fragility of blood vessel walls (capillary fragility).

Gastrointestinal disorders

Stomach discomfort, gastrointestinal ulcer, gastrointestinal bleeding, inflamed pancreas, risk of intestinal perforation in ulcerative colitis (severe inflammation of the large intestine).

Skin and subcutaneous tissue disorders

Stretch marks, thinning of the skin, small localized haemorrhages under the skin, bruising, steroid acne, perioral skin inflammation, dilation of superficial blood vessels, excessive body hair growth, changes in skin pigmentation.

Musculoskeletal and connective tissue disorders

Muscle weakness, muscle atrophy, inflammatory muscle disease, disorders, inflammation or rupture of tendons, breakdown of bone tissue (osteoporosis), growth retardation in children, aseptic bone necrosis (death of bone tissue without presence of microbes), increased fatty tissue in the spinal canal.

Reproductive system and breast disorders

Disorders of sex hormone secretion, such as absence of menstruation, excessive growth of male-pattern body hair in women, impotence.

General disorders and administration site conditions

Delayed wound healing.

Local use

Local irritation and signs of intolerance (sensations of heat, prolonged pain) are possible, especially with ocular use. Tissue atrophy cannot be ruled out if dexamethasone is not carefully injected into the joint cavity.

Reporting of adverse effects

If you experience any type of adverse effect, consult your doctor or pharmacist, even if they are possible adverse effects not listed in this leaflet. You may also report them directly via the Spanish Pharmacovigilance System for Human Medicines: www.notificaRAM.es. By reporting adverse effects, you can help provide more information on the safety of this medicine.

5. Storage of Dexamethasone Kalceks

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

Do not store above 30 °C.

Store the ampoules in the outer packaging to protect from light.

After opening the ampoule: Once opened, the medicine should be used immediately.

Period of validity after dilution

Chemical and physical in-use stability has been demonstrated for 48 hours at 25 °C (protected from light) and at 2–8 °C.

From a microbiological standpoint, the diluted solution should be used immediately. If not used immediately, the in-use storage times and preceding conditions prior to use are the responsibility of the user and normally should not exceed 24 hours at a temperature of 2 to 8 °C, unless the dilution was carried out under controlled and validated aseptic conditions.

Do not use this medicine after the expiry date stated on the carton and on the ampoule after EXP. The expiry date refers to the last day of the month indicated.

Medicines should not be disposed of via wastewater or household waste. Unused containers and medicines should be returned to the SIGRE point at your pharmacy. If in doubt, ask your pharmacist how to dispose of unused containers and medicines. This will help protect the environment.

6. Contents of the pack and other information

Composition of Dexamethasone Kalceks

• The active substance is dexamethasone phosphate.

Each 1 ml ampoule contains sodium dexamethasone phosphate equivalent to 4 mg of dexamethasone phosphate.

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

Appearance of Dexamethasone Kalceks and contents of the pack

Clear, colourless solution, free from visible particles.

Type I colourless transparent glass ampoules of 1 ml with a score mark.

The ampoules are marked with a ring code of a specific colour.

The ampoules are placed in trays. The trays are packaged in cardboard boxes.

Pack sizes:

3, 10, 25, 50 or 100 ampoules of 1 ml.

Only certain pack sizes may be marketed.

Marketing Authorisation Holder and Manufacturer

AS KALCEKS

Krustpils iela 71E,

Riga, LV‑1057,

Latvia

Tel.: +371 67083320

E‑mail: [email protected]

Further information on this medicine can be requested from the local representative of the Marketing Authorisation Holder

EVER Pharma Therapeutics Spain SL

c/ Toledo 170

28005 Madrid

Spain

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

Estonia Dexamethasone Kalceks

Austria, Germany Dexamethasone Kalceks 4 mg/ml Injektions-/Infusionslösung

Croatia Deksametazon Kalceks 4 mg/ml otopina za injekciju/infuziju

Czech Republic, Poland Dexamethasone Kalceks

Denmark, Norway Dexamethasone phosphate Kalceks

Finland Dexalcex 4 mg/ml injektio-/infuusioneste, liuos

France DEXAMETHASONE KALCEKS 4 mg/1 mL, solution injectable/pour perfusion

Hungary Dexamethasone Kalceks 4 mg/ml oldatos injekció vagy infúzió

Ireland Dexamethasone phosphate 4 mg/ml solution for injection/infusion

Italy Desametasone Kalceks

Latvia Dexamethasone Kalceks 4 mg/ml škidums injekcijam/infuzijam

Lithuania Dexamethasone Kalceks 4 mg/ml injekcinis ar infuzinis tirpalas

Netherlands Dexamethasonfosfaat Kalceks 4 mg/ml oplossing voor injectie/infusie

Portugal Dexametasona Kalceks

Slovenia Deksametazon Kalceks 4 mg/ml raztopina za injiciranje/infundiranje

Spain Dexametasona Kalceks 4 mg/ml soluci?n inyectable y para perfusi?n EFG

Sweden Dexalcex

Date of the most recent revision of this leaflet: January 2022.

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

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This information is intended for healthcare professionals only:

Dosage and method of administration

If high doses are required for a particular treatment, consideration should be given to using medicines containing higher concentrations/volumes of dexamethasone.

1. Systemic route

For the treatment and prophylaxis of cerebral oedema associated with brain tumours (postoperatively and after X-ray radiation) and after spinal cord trauma

Depending on the cause and severity, the initial dose is 8–10 mg (up to 80 mg) administered intravenously, followed by 16–24 mg (up to 48 mg)/day divided into 3–4 (6) single intravenous doses over 4–8 days. During radiotherapy and conservative treatment of inoperable brain tumours, long-term administration of lower doses of dexamethasone phosphate may be required.

In anaphylactic shock, first administer intravenous adrenaline, then intravenous injection of 40–100 mg (children 40 mg), repeated as necessary.

Polytrauma shock/prophylaxis of post-traumatic pulmonary shock

Initially, 40–100 mg (children 40 mg) intravenously, repeated after 12 hours, or 16–40 mg every 6 hours for 2–3 days.

For severe exacerbations of asthma, 8–40 mg intravenously as soon as possible; if necessary, repeated injections of 8 mg every 4 hours.

For severe acute dermatoses and serious blood disorders, initial treatment with 20–40 mg of intravenous dexamethasone phosphate, followed by treatment according to the severity of the case, with the same daily dose or lower doses in the first days, switching to oral therapy.

For the treatment of acute adrenocortical insufficiency (Addisonian crisis), initiate treatment with 4–8 mg of dexamethasone phosphate intravenously.

For the treatment of COVID-19

Adult patients: 6 mg intravenously once daily for up to 10 days.

Elderly patients, renal impairment, hepatic impairment [treatment with low doses (6 mg daily) and short duration]: Dose adjustment is not necessary.

Paediatric population: Paediatric patients (adolescents aged 12 years and older with a body weight of at least 40 kg) should be given 6 mg intravenously once daily for up to 10 days.

The duration of treatment should be guided by clinical response and individual patient requirements.

1. Local route

For local infiltrative, periarticular and intra-articular treatment, under strictly aseptic conditions, inject 4 mg or 8 mg of dexamethasone phosphate. For injection into a small joint, 2 mg of dexamethasone phosphate is sufficient. Depending on the severity of the disease, no more than 3–4 infiltrations or injections should be performed per joint. The interval between injections should not be less than 3–4 weeks.

Method of administration

Intravenous, intramuscular, intra-articular or local (infiltration).

This medicine is generally administered by slow intravenous injection (2–3 minutes) in acute conditions, either as an injection or infusion. However, it may also be administered intramuscularly (only in exceptional cases), as a local infiltration or intra-articularly.

Instructions for use, disposal and other handling

For single use only.

After opening, the medicine should be used immediately. Any remaining contents should be discarded.

Visually inspect the ampoule before use. Only use if the solution is clear and free from particles.

pH of the solution between 7.0–8.5

This medicine must not be mixed with others except those mentioned below.

This medicine should preferably be administered by direct intravenous injection or injected into the infusion line. However, the injectable solutions are compatible with the following infusion solutions (250 ml and 500 ml):

• Sodium chloride solution 9 mg/ml (0.9%)
• Glucose solution 50 mg/ml (5%)
• Ringer's solution.

When combining with infusion solutions, the information provided by the respective manufacturers regarding their infusion solutions, including compatibility data, contraindications, adverse effects and interactions, must be taken into account.

Instructions for opening the ampoule:

1. Hold the ampoule with the coloured dot facing upwards. If any solution remains in the upper part of the ampoule, gently tap with the finger to allow all the solution to flow down to the lower part.
2. Use both hands to open it: while holding the lower part of the ampoule with one hand, use the other hand to snap off the top of the ampoule in the direction opposite to the coloured dot (see images below).

Disposal of unused medicine and of all materials that have been in contact with it must be carried out in accordance with local regulations.