Prospect: information for the user

Celestone Cronodose injectable suspension

Betametasona, sodium phosphate/betametasona, acetate

Read this prospect carefully before starting to use this medication,because it contains important information for you.

• Keep this prospect, as you may need to read it again.
• 1. If you have any doubts, consult your doctor,pharmacistor nurse.

-This medication has been prescribedonlyto you, and you must not give it to other people even iftheyhave the same symptomsas you,as it may harm them.

• If you experience any adverse effects,consult your doctor, pharmacist or nurse, evenifthey are not listed in this prospect. See section 4.

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

2.What you need to know beforestartingto use Celestone Cronodose

3.How to use Celestone Cronodose

4.Possible adverse effects

5Storage of Celestone Cronodose

6.Contents of the package and additional information

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

Celestone Cronodose is used for the treatment of:

By intramuscular route:

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

By local infiltration:

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

By intra-articular route:

• Rheumatoid arthritis andosteoarthritis.

By intradermal/intralesional route:

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

It should not be administered by intravenous or subcutaneous route.

Do not use Celestone Cronodose:

• If you are allergic to betamethasone or any of the other components of this medication (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 medication.

Inform all your doctors if you are taking or have recently taken glucocorticoids.

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

Avoid abrupt discontinuation of treatment as it may cause a corticosteroid withdrawal syndrome that can persist for months after stopping this medication. Therefore, in situations of stress during this period, treatment should be re-established along with the necessary supply of salts and/or a mineralocorticosteroid.

If administered locally (intraarticularly), systemic unwanted effects may occur.

Administration of the medication by intramuscular injection should be carried out with special caution in patients with idiopathic thrombocytopenic purpura.

Repeated intraarticular injections may cause cartilage destruction and joint instability. Therefore, excessive use of a previously treated joint should be avoided.

Corticosteroids may mask the signs of an infection as well as increase the risk of contracting infections and/or make their diagnosis more difficult. Latent infections may be reactivated during the use of this medication.

This medication should not be injected into an infected joint previously. 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 it will be necessary to adopt precautions, such as closer monitoring of your condition, or additional therapeutic measures:

• If you have a history of tuberculosis or amebiasis, as it could cause reactivation of the disease; or if you have active tuberculosis or amebiasis.
• Immediately, in case of potential 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 medication.
• If you have diabetes.
• If you have osteoporosis (bone calcium loss), especially in postmenopausal women.
• If you have any psychiatric illness 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 herpes simplex in the eye.
• If you have hypothyroidism or liver cirrhosis.
• If you have ulcerative colitis, inflammatory bowel disease, or peptic ulcers, esophagitis, renal insufficiency, heart failure, hypertension, myasthenia gravis (severe muscle weakness).

Contact your doctorif you experience blurred vision or other visual disturbances.

Especially with medium and high doses of corticosteroids, consider sufficient potassium supplementation and salt restriction in the diet; also monitor blood pressure and potassium levels.

This medication should not be administered epidurally.The safety and efficacy of epidural administration of corticosteroids have not been established.

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

The administration of corticosteroids may alter the value of some laboratory tests. Additionally, skin reactions in allergy tests may be masked.

Children and adolescents

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

Use of Celestone Cronodose with other medications

Inform your doctor or pharmacist if you aretaking, havetakenrecentlyor may need to take any other medication, including those purchased without a prescription.

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

• Anfotericina B, as it may increase the risk of hypokalemia (low potassium levels).
• Antibiotics, as they significantly reduce the elimination of corticosteroids.
• Oral anticoagulants, as it may alter the desired effect of the anticoagulant.
• Antidiabetic medications, as you may need to adjust the dose.
• Tuberculosis medications, as it may decrease their blood levels.
• Medications used to treat heart disease, such as cardiac glycosides, as it may increase the risk of arrhythmias due to hypokalemia.
• Estrógenos (including oral contraceptives), as they may alter the action of this medication.
• Medications that induce liver enzymes (e.g., barbiturates, phenytoin, carbamazepine, rifampicin), as you may need to increase the dose of this medication.
• Medications against fungal diseases (ketoconazole), as they may increase the possible adverse effects of this medication.
• Some medications may increase the effects of Celestone Cronodose, so your doctor will perform close monitoring if you are taking these medications (including some for HIV: ritonavir, cobicistat).
• Nonsteroidal anti-inflammatory drugs (NSAIDs), as they may increase the risk of gastrointestinal adverse effects.
• Aminoglutetimida (medication for the treatment of certain tumors), as it may decrease the adrenal suppression effect induced by this medication.
• Anticholinesterase, as they may cause severe muscle weakness in patients with myasthenia gravis, which may require their withdrawal at least 24 hours before starting treatment with this medication.
• Somatropina (human growth hormone), as it may inhibit its response.

Interference with laboratory tests

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

Use of Celestone Cronodose with alcohol

The use of this medication with alcohol may increase the cases or severity of peptic ulcers.

Pregnancy,lactationand fertility

If you are pregnant or breastfeeding, or if you think you may be pregnant, consult your doctor or pharmacist before using this medication.

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 prolonged treatment with corticosteroids during pregnancy, your doctor will closely monitor the child to identify signs of hypoadrenalism.

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

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

Lactation

Corticosteroids, including this medication, pass into breast milk and may delay growth, interfere with the production of the body's own corticosteroid, or cause other adverse effects. Therefore, caution should be exercised when administering this medication during lactation.

Fertility

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

Driving and operating machinery

The influence of this medication on the ability to drive and operate machinery is negligible or insignificant. Some adverse effects of this medication (such as muscle weakness or loss of muscle mass, psychiatric disorders (such as euphoria or depression), visual acuity decrease, increased intraocular pressure, or vertigo) may affect these activities, so be sure to check how you tolerate the medication before performing these tasks.

Use in athletes

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

Celestone Cronodose contains sodium and benzalkonium chloride

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

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

Follow exactly the administration instructions of this medication as 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 medication. In certain situations of stress, a temporary increase in the dose of this medication may be necessary. When possible, the dose reduction will be gradual.

The recommended dose is:

Intramuscular administration:

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

In severe conditions, an initial dose of 2ml may be necessary.

Intraarticular administration:

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

Pain relief and stiffness relief are observed 2 to 4 hours after intraarticular injection.

Local infiltration administration:

In bursitis, in inflammatory disorders associated with tendons, and in inflammatory disorders around the joint, the usual dose is 1ml 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 capsular joint cysts, the usual dose is 0.5ml in the cystic cavity.

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

Intradermal/intralesional administration:

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

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

Hypothyroidism and liver cirrhosis

In patients with hypothyroidism or liver cirrhosis, the dose may need to be adjusted.

Older patients

In older patients, it may be necessary for your doctor to closely monitor the treatment.

Use in children

Generally, the recommended initial dose in children is 0.02to 0.3mg/kg per day, in three or four divided doses (0.6to 9mg/m2body surface area per 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 Toxicological Information Service, phone 91.562.04.20, indicating the medication and the amount used.

The treatment of acute overdose is supportive and symptomatic. To manage chronic overdose with a serious disease that requires continued treatment with steroids, the dose of the corticosteroid can be temporarily reduced, or treated on alternate days.

If you interrupt treatment with Celestone Cronodose

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

The dose reduction should be done progressively. Similarly, the suspension of treatment should be done progressively, whenever possible.

If you have any other doubts about the use of thismedication, ask your doctor,pharmacistor nurse.

Like all medicines, this medicine can cause side effects, although not everyone will experience them.

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

Immune system disorders: Anaphylactic reactions, hypersensitivity reactions.

Endocrine disorders: Irregular menstrual cycles, development of Cushing's syndrome (moon face, truncal obesity), secondary and hypophyseal adrenocortical insufficiency (particularly in periods of stress such as trauma, surgery, or disease), manifestations of latent diabetes mellitus, and increased requirements for insulin or oral hypoglycemic agents in diabetics.

Metabolism and nutrition disorders: Sodium retention, potassium loss, hypokalemic alkalosis, fluid retention.

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

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

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

Vestibular disorders: Vertigo.

Cardiac disorders: Heart failure.

Vascular disorders: Hypertension.

Gastrointestinal disorders: Gastrointestinal ulcer with possible perforation and hemorrhage, pancreatitis (pancreas inflammation), abdominal distension, ulcerative esophagitis (inflammation of the esophageal mucosa), hiccups.

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

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

General disorders and administration site conditions: Wound healing alteration.

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

Reporting of side effects:

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

Do not store at a temperature above 25°C.

Keepthis medicationout of the sight and reach of children.

Do not usethis medicationafter the expiration date that appears on the packaging after CAD. The expiration date is the last day of the month indicated.

Do not usethis medicationif you observea possible agglomeration or precipitation (although it could be due to exposure to freezing).

Medications should not be disposed of through drains or in the trash. Dispose of the containers and medications you no longer need at the SIGRE collection pointat the pharmacy. If in doubt, ask your pharmacist how to dispose of the containers and medications you no longer need. In this way, you will help protect the environment.

Celestone Cronodose Composition

• The active principles aresodium phosphate of betamethasone and betamethasone acetate.

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

• The other components(excipients)are:sodium monobasic phosphate, sodium dibasic phosphate, disodium edetate, benzalkonium chlorideandwater for injection preparations.

Product Appearance and Packaging Contents

Celestone Cronodose is asterile, transparent, and colorless aqueous suspension for injection, with white particles in suspension, without visible agglomerates or foreign particles.

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

Marketing Authorization Holder and Responsible Manufacturer

Marketing Authorization Holder

Organon Salud, S.L.

Paseo de la Castellana, 77

28046 Madrid

Spain

Tel.: 915911279

Responsible Manufacturer

Organon Heist bv

Industriepark30

2220 Heist-op-den-Berg

Belgium

Last Review Date of thisLeaflet:12/2021.

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

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

This information is intended solely for healthcare professionals:

ADMINISTRATION INSTRUCTIONS

For intramuscular, intraarticular, intrasinovial, intralesional, or intradermal administration. Do not administer by intravenous or subcutaneous route.

This medicineshould 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 in the gluteal muscle to avoid local tissue atrophy.

• Intraarticular Administration:

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

Intraarticular injection should be performed under aseptic conditions and with 22to24gaugeneedles.

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

Intraarticular injection of this medicine does not cause appreciable pain, nor has secondary exacerbation been reported, which sometimes occurs a few hours after intraarticular application of other corticosteroids.

• Intralesional and Intradermal Administration:

Intralesional treatment is performed by intradermal injection (not subcutaneously). A tuberculin syringe and a 1.5cm long, 25gaugeneedle will be used.

The medicine should be applied in such a way that it forms a uniform intradermal deposit.

Foot Diseases:In most cases, the medicine can be administered with a tuberculin syringe and a 2cm long, 25gaugeneedle.

Use with Local Anesthetics

Administration of the medicine by local route is well tolerated. However, if it is considered necessary to use local anesthetics, the suspension can be mixed in the same syringe with an equal amount of hydrochloride of procaine or lidocaine at 1or2% 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, shaking the syringe briefly. The anesthetic should not be introduced into the Celestone Cronodose vial. Formulations of anesthetics containing parabens should not be used.