CELESTONE CRONODOSE INJECTABLE SUSPENSION

Introduction

Package Leaflet: Information for the User

Celestone Cronodose Injectable Suspension

Betamethasone, sodium phosphate/betamethasone acetate

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

• Keep this leaflet, you may need to read it again.
• 1. If you have any further questions, ask your doctor, pharmacist, or nurse.

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

Contents of the pack and other information

1. What is Celestone Cronodose and what is it used for
2. What you need to know before you use Celestone Cronodose
3. How to use Celestone Cronodose
4. Possible side effects

5 Conservation of Celestone Cronodose

1. Contents of the pack and other information

1. What is Celestone Cronodose and what is it used for

Celestone Cronodose contains betamethasone. It is a corticosteroid (glucocorticoid) with anti-inflammatory properties. It is recommended for conditions that respond to injectable corticosteroid treatment when a sustained effect is required (if necessary, as a complement to the main treatment), and it is especially useful in patients who cannot be treated with oral or local corticosteroids.

Celestone Cronodose is used for the treatment of:

Via intramuscular:

• Allergic conditions, skin conditions, rheumatic conditions, and other conditions that respond to corticosteroids.

Via local infiltration:

• Bursitis and inflammatory disorders associated with tendons (such as tenosynovitis); and inflammatory disorders of the muscle (such as fibrosis and myositis).

Via intra-articular:

• Rheumatoid arthritis and osteoarthritis.

Via intradermal/intralesional:

• Various skin conditions, in certain inflammatory and cystic disorders of the foot.

Do not administer via intravenous or subcutaneous route.

2. What you need to know before you use Celestone Cronodose

Do not use Celestone Cronodose:

• if you are allergic to betamethasone or any of the other ingredients of this medicine (listed in section 6).
• if you have an infection (except if you are being treated for that infection).

Warnings and precautions

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

You must inform all your doctors if you are taking or have recently taken glucocorticoids.

Your doctor will use the lowest possible dose of this medicine to control the condition to be treated and, whenever possible, will apply a gradual dose reduction.

Avoid sudden withdrawal of treatment as it may cause a corticosteroid withdrawal syndrome that can persist for months after withdrawal of this medicine. Therefore, in situations of stress during this period, treatment should be reinstated along with the necessary supply of salts and/or with a mineralocorticosteroid.

If the medicine is administered locally (via intra-articular route), systemic unwanted effects may occur.

Intramuscular administration of the medicine should be performed with special caution in patients with idiopathic thrombocytopenic purpura.

Repeated intra-articular injections can cause cartilage destruction and instability in the joint. Therefore, excessive use of a previously treated joint should be avoided.

Corticosteroids can mask the signs of an infection as well as increase the risk of contracting infections and/or make their diagnosis difficult. Latent infections may reactivate during the use of this medicine.

This medicine should not be injected into a previously infected joint. If septic arthritis (i.e., a significant increase in pain along with local swelling, restriction of joint mobility, fever, and general malaise) occurs and the diagnosis of sepsis is confirmed, appropriate antimicrobial treatment should be initiated.

Inform your doctor as precautions will be necessary, such as closer monitoring of your condition, or additional therapeutic measures:

• if you have a history of tuberculosis or amoebiasis, as reactivation of the disease may occur; or if you have active tuberculosis or amoebiasis.
• immediately, in case of contact or exposure to chickenpox or measles.
• if you have fungal or parasitic infections.
• if you are to be vaccinated.
• if you are allergic to any medicine.
• if you have diabetes.
• if you have osteoporosis (calcium loss in bones), especially in postmenopausal women.
• if you have any psychiatric disorder or history (in yourself or in your close relatives).
• if you have pheochromocytoma (a tumor of the adrenal gland).
• if you have cataracts, glaucoma (increased intraocular pressure), infections, or simple herpes in the eye.
• if you have hypothyroidism or liver cirrhosis.
• if you have ulcerative colitis, inflammatory diseases of the digestive system, or digestive ulcers, esophagitis, renal failure, heart failure, arterial hypertension, myasthenia gravis (severe muscle weakness).

Contact your doctor if you experience blurred vision or other visual disturbances.

Especially with medium and high doses of corticosteroids, sufficient potassium intake and salt restriction in the diet should be considered, as well as monitoring blood pressure and potassium levels in the blood.

This medicine should not be administered via the epidural route. The safety and efficacy of epidural administration of corticosteroids have not been established.

This medicine may produce a positive result in doping control tests.

Administration of corticosteroids may alter the value of some laboratory tests. Similarly, skin reactions in allergy tests may be masked.

Children and adolescents

In infants, children, and adolescents, the doctor should assess the benefits of treatment, especially in prolonged treatment with corticosteroids, as it may affect their growth and development. Therefore, in prolonged treatment with this medicine, your doctor will closely monitor the development and growth of children and adolescents.

Using Celestone Cronodose with other medicines

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

It may be necessary to adjust the dose of one of your medicines and monitor the appearance of adverse reactions. This is especially important if you are taking the following medicines:

• Amphotericin B, as the risk of decreased potassium levels (hypokalemia) may increase.
• Antibiotics, as the elimination of corticosteroids is significantly reduced.
• Oral anticoagulants, as the desired effect of the anticoagulant may be altered.
• Antidiabetics, as the dose may need to be adjusted.
• Antitubercular medicines, as their level in the blood may decrease.
• Medicines used to treat heart diseases, such as cardiac glycosides, as the risk of arrhythmias due to decreased potassium levels (hypokalemia) may increase.
• Estrogens (including oral contraceptives), as they may alter the action of this medicine.
• Enzyme-inducing medicines (e.g., barbiturates, phenytoin, carbamazepine, rifampicin), as the dose of this medicine may need to be increased.
• Medicines against fungal diseases (ketoconazole), as they may increase the possible adverse effects of this medicine.
• Certain medicines may increase the effects of Celestone Cronodose, so your doctor will perform thorough checks if you are taking these medicines (including some for HIV: ritonavir, cobicistat).
• Non-steroidal anti-inflammatory drugs (NSAIDs), as they may increase the risk of gastrointestinal adverse effects.
• Aminoglutethimide (a medicine for the treatment of certain tumors), as it may decrease the action of this medicine induced by adrenal suppression.
• Anticholinesterase, as it may produce severe weakness in patients with myasthenia gravis, which may require its withdrawal at least 24 hours before starting treatment with this medicine.
• Somatropin (human growth hormone), as it may inhibit its response.

Interference with laboratory tests

If you are going to have any laboratory tests (including blood tests, urine tests, skin tests using allergens, etc.), inform your doctor that you are taking this medicine, as it may alter the results.

Using Celestone Cronodose with alcohol

Using this medicine with alcohol may increase the cases or severity of digestive ulcers.

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 taking this medicine.

Pregnancy

Betamethasone crosses the placenta. During pregnancy, treatment should only be administered after weighing the risk/benefit ratio for both the mother and the fetus, even when used prophylactically beyond the 32nd week of gestation.

With long-term treatment with corticosteroids during pregnancy, close monitoring of the child will be necessary to identify signs of hypoadrenalism.

Corticosteroids are not indicated in the management of the disease of the hyaline membrane after birth and should not be administered to pregnant women with preeclampsia, eclampsia, or evidence of placental damage.

Newborns of mothers who received Celestone Cronodose near the end of pregnancy may have low blood sugar levels after birth.

Breastfeeding

Corticosteroids, including this medicine, pass into breast milk and may delay growth, interfere with the production of their own corticosteroid, or cause other adverse effects. Therefore, caution is recommended when administering this medicine during breastfeeding.

Fertility

In some patients, steroids may increase or decrease sperm motility and number.

Driving and using machines

The influence of this medicine on the ability to drive and use machines is negligible. Some adverse effects of this medicine (such as muscle weakness or muscle mass loss, psychiatric disorders (such as euphoria or depression), decreased visual acuity, increased intraocular pressure, or vertigo) may affect these activities, so try not to perform these tasks until you verify how you tolerate the medicine.

Use in athletes

This medicine contains betamethasone, which may produce a positive result in doping control tests.

Celestone Cronodose contains sodium and benzalkonium chloride

This medicine contains less than 23 mg of sodium (1 mmol) per ml; i.e., it is essentially "sodium-free".

This medicine contains 0.4 mg of benzalkonium chloride in each 2 ml vial, equivalent to 0.2 mg/ml.

3. How to use Celestone Cronodose

Follow exactly the administration instructions of this medicine indicated by your doctor or pharmacist. In case of doubt, consult your doctor or pharmacist again.

The initial dose varies depending on the specific disease being treated.

During treatment, your doctor may adjust the dose of this medicine. In certain situations of stress, a temporary increase in the dose of this medicine may be necessary. When possible, the dose reduction will be gradual.

The recommended dose is:

Intramuscular administration:

In most cases, treatment with Celestone Cronodose is initiated with an intramuscular administration of 1 ml, and the injection is repeated once a week, or more frequently depending on the patient's needs.

In severe conditions, it may be necessary to administer 2 ml initially.

Intra-articular administration:

Doses range from 0.25 ml to 2 ml, according to the size of the joint treated. The usual dose is as follows: very large joints (hip), 1 to 2 ml; large joints (knee, ankle, and shoulder), 1 ml; medium-sized joints (elbow and wrist), 0.5 to 1 ml; small joints (hand and thorax), 0.25 to 0.5 ml.

Pain and stiffness relief are observed 2 to 4 hours after intra-articular injection.

Administration by local infiltration:

In bursitis, in inflammatory disorders associated with tendons, and in inflammatory disorders around the joint, the usual dose is 1 ml, and the injection is repeated at intervals of one week. In bursitis, pain relief and complete recovery are observed a few hours after injection.

In cysts of the joint capsules, the usual dose is 0.5 ml in the cystic cavity.

In acute gouty arthritis, the usual dose is 0.25 to 1 ml, and the injection is repeated at intervals of 3 days to 1 week.

Intralesional/intradermal administration:

In foot diseases, the usual dose is 0.25 to 0.50 ml, and the injection is repeated at intervals of 3 days to 1 week.

In dermatological conditions, it is administered by intradermal injection (not subcutaneous) of 0.2 ml/cm2, as required, but not more than 1 ml per week.

Hypothyroidism and liver cirrhosis

In patients with hypothyroidism or liver cirrhosis, it may be necessary to adjust the dose.

Elderly patients

In elderly patients, it may be necessary to closely monitor the treatment by your doctor.

Use in children

In general, the recommended initial dose in children is 0.02 to 0.3 mg/kg per day, in three or four divided doses (0.6 to 9 mg/m2 body surface area/day). The initial dose may vary depending on the type of disease.

If you use more Celestone Cronodose than you should

In case of overdose or accidental ingestion, consult your doctor, pharmacist, or call the Toxicology Information Service, phone 91.562.04.20, indicating the medicine and the amount used.

Treatment of acute overdose is supportive and symptomatic. To manage chronic overdose with a severe disease that requires continuous treatment with steroids, the dose of the corticosteroid may be temporarily reduced, or treated on alternate days.

If you stop using Celestone Cronodose

Do not stop treatment before your doctor indicates or abruptly, as it may worsen your disease.

Dose reduction should be performed progressively. Similarly, treatment suspension should be done progressively, whenever possible.

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

4. Possible Adverse Effects

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

The following adverse effects have been described with the use of corticosteroids:

Disorders of the immune system: Anaphylactic reactions, hypersensitivity reactions.

Endocrine disorders: Menstrual irregularities, development of Cushingoid state (moon face, adiposity in the trunk), lack of adrenal cortical and hypophyseal response (particularly in periods of stress such as trauma, surgery, or illness), manifestations of latent diabetes mellitus, and increased requirements for insulin or oral hypoglycemics in diabetics.

Metabolic and nutritional disorders: Sodium retention, potassium loss, hypokalemic alkalosis, fluid retention.

Psychiatric disorders: Euphoria, mood changes, depression, personality changes, insomnia.

Nervous system disorders: Seizures, increased intracranial pressure with papilledema (pseudotumor cerebri) usually after treatment, headache.

Ocular disorders: Posterior subcapsular cataract, glaucoma (increased intraocular pressure), exophthalmos (abnormal protrusion of one or both eyes), blurred vision with unknown frequency (frequency cannot be estimated from available data).

Ear and labyrinth disorders: Vertigo.

Cardiac disorders: Heart failure.

Vascular disorders: Hypertension.

Gastrointestinal disorders: Gastrointestinal ulcer with possible perforation and hemorrhage, pancreatitis (inflammation of the pancreas), abdominal distension, ulcerative esophagitis (inflammation of the tissue lining the inner wall of the esophagus), hiccups.

Skin and subcutaneous tissue disorders: Allergic dermatitis, edema, thin and fragile skin, petechiae and ecchymoses (red spots on the skin), erythema (redness of the skin), increased sweating, urticaria, angioedema.

Musculoskeletal disorders: Muscle weakness, steroid myopathy (muscle pain), muscle mass loss, osteoporosis (calcium loss in bones), vertebral compression fractures, aseptic necrosis of the humeral and femoral heads, pathological fractures of long bones, tendon rupture, growth retardation in childhood.

General disorders and administration site conditions: Wound healing alteration.

Investigations: Decreased carbohydrate tolerance, negative nitrogen balance due to protein catabolism, increased intraocular pressure, suppression of skin test reactions.

Reporting of Adverse Effects:

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

5. Storage of Celestone Cronodose

Do not store at a temperature above 25°C.

Keep this medicine out of sight and reach of children.

Do not use this medicine after the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Do not use this medicine if you observe a possible agglomeration or precipitation (although it could be due to exposure to freezing).

Medicines should not be thrown away through drains or into the trash. Deposit the packaging and medicines you no longer need at the SIGRE Point in the pharmacy. In case of doubt, ask your pharmacist how to dispose of the packaging and medicines you no longer need. This way, you will help protect the environment.

6. Package Contents and Additional Information

Celestone Cronodose Composition

• The active ingredients are sodium betamethasone phosphate and betamethasone acetate.

Each vial (2 ml) contains 11.4 mg of betamethasone, 6 mg of betamethasone (as sodium phosphate) and 5.4 mg of betamethasone (as 6 mg of betamethasone acetate).

• The other components (excipients) are: monobasic sodium phosphate, dibasic sodium phosphate, disodium edetate, benzalkonium chloride, and water for injectable preparations.

Product Appearance and Package Contents

Celestone Cronodose is a sterile, injectable, transparent, and colorless aqueous suspension with white particles in suspension, without visible agglomerates or foreign particles.

It is presented in a glass vial with a rubber stopper and an aluminum and polypropylene cap. Each box contains 1 vial.

Marketing Authorization Holder and Manufacturer

Marketing Authorization Holder

Organon Salud, S.L.

Paseo de la Castellana, 77

28046 Madrid

Spain

Tel.: 915911279

Manufacturer

Organon Heist bv

Industriepark 30

2220 Heist-op-den-Berg

Belgium

Date of the Last Revision of this Prospectus:12/2021.

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

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This information is intended only for healthcare professionals:

INSTRUCTIONS FOR CORRECT ADMINISTRATION

For intramuscular, intra-articular, intra-synovial, intra-lesional, or intradermal administration. Do not administer by intravenous or subcutaneous route.

This medicine should not be injected into an unstable joint.

This medicine should be administered under aseptic conditions.

To restore the homogeneity of the suspension, shake the vial before opening it.

This medicine should not be used if a possible agglomeration or precipitation is observed (which could be due to exposure to freezing).

Once the necessary amount of the suspension has been loaded into the syringe, it should be injected immediately to avoid sedimentation.

• Intramuscular administration:

Corticosteroids should be administered by deep intramuscular injection into the gluteal muscle to avoid local tissue atrophy.

• Intra-articular administration:

Injections should be performed into the affected tendon sheaths and not into the tendons themselves. In periarticular inflammatory conditions, the injection should be performed in the painful area.

The intra-articular injection should be performed using aseptic conditions and with 22 to 24 gauge needles.

The technique is as follows: the needle, adapted to an empty syringe, is introduced into the synovial cavity, and aspirated. If synovial fluid is obtained, the puncture has been correct. Then, the first syringe is replaced by another loaded with the necessary amount of the suspension, and the injection is performed.

The intra-articular injection of this medicine does not cause appreciable pain, nor has secondary exacerbation been reported, which sometimes occurs a few hours after the intra-articular application of other corticosteroids.

• Intra-lesional and intradermal administration:

Intra-lesional treatment is performed by intradermal injection (not subcutaneously). A tuberculin syringe and a 1.5 cm long, 25 gauge needle will be used.

The medicine should be applied so that it forms a uniform intradermal deposit.

Diseases of the feet: In most cases, the medicine can be administered with a tuberculin syringe with a 2 cm long, 25 gauge needle.

Use with local anesthetics

Local administration of the medicine is well tolerated. However, if the use of local anesthetics is considered necessary, the suspension can be mixed in the same syringe with an equal amount of procaine hydrochloride or lidocaine at 1 or 2% before proceeding with the injection. The necessary amount of the suspension is first transferred from the vial to the syringe, and then the anesthetic is introduced, briefly shaking the syringe. The anesthetic should not be introduced into the Celestone Cronodose vial. Anesthetic formulations containing parabens should not be used.