Consumer medicine information

Celestone Chronodose

Betamethasone acetate; Betamethasone sodium phosphate

BRAND INFORMATION

Brand name

Celestone Chronodose

Active ingredient

Betamethasone acetate; Betamethasone sodium phosphate

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Celestone Chronodose.

What is in this leaflet?

This leaflet answers some common questions about Celestone Chronodose. It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you using Celestone Chronodose against the benefits they expect it will have for you.

If you have any concerns about being given this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine or in a safe place. You may want to read it again.

What Celestone Chronodose is used for

Celestone Chronodose contains betamethasone as the active ingredient. Betamethasone is a glucocorticoid and belongs to a group of medicines called corticosteroids.

Celestone Chronodose is used to treat symptoms associated with inflammatory processes and/or allergic reactions, which may include:

  • swelling
  • redness
  • itching.

It may be used as part of the treatment for a number of different diseases such as severe allergies, skin problems, asthma or arthritis.

Although Celestone Chronodose may relieve the symptoms of these diseases, it will not cure them.

Celestone Chronodose can also be used to prevent respiratory distress syndrome in premature infants.

Your doctor may have prescribed Celestone Chronodose for another reason.

Ask your doctor if you have any questions about why Celestone Chronodose has been prescribed for you.

Before you start Celestone Chronodose

When you must not receive it:

Celestone Chronodose should not be used if:

  1. you have an allergy to:
  • Celestone Chronodose, or betamethasone
  • any of the ingredients listed at the end of this leaflet
  • any other cortisone-like medicines.
Some of the symptoms of an allergic reaction may include:
- shortness of breath, wheezing, difficulty breathing or a tight feeling in your chest
- swelling of the face, lips, tongue or other parts of the body
- rash, itching, hives or flushed, red skin.
  1. you have a fungal infection within your body or any other serious or long-term infections
Cortisone-like medicines such as Celestone Chronodose may decrease your resistance and make infections spread.
  1. you have recently been vaccinated against smallpox.
Cortisone-like medicines such as Celestone Chronodose must not be injected into unstable joints, infected areas, intervertebral spaces or by the epidural route.

Celestone Chronodose must not be used if the packaging is torn or shows signs of tampering.

Celestone Chronodose must not be used after the expiry date (EXP) has passed.

If you are not sure whether you should start Celestone Chronodose, talk to your doctor.

Before you start to receive it

Tell your doctor if:

  • you are allergic to:
    - any other medicines including other cortisone-like medicines
    - any other substances such as foods, dyes or preservatives.
  • you are pregnant or intend to become pregnant
    If it is necessary for you to start Celestone Chronodose, your doctor will discuss the benefits and risks of using it during pregnancy.
  • you are breast-feeding or plan to breast-feed
    The active ingredients in Celestone Chronodose pass into breast milk and may affect your baby. If there is a need to use Celestone Chronodose, your doctor will discuss the benefits and risks of using it while breast-feeding.
  • you need any type of vaccination
    Cortisone-like medicines such as Celestone Chronodose may lower your body's immune response and result in nervous system complications if used with a vaccine.
  • you have any of the following:
    - osteoporosis
    - emotional or mental health problems
    - stomach or intestinal problems, including ulcers
    - tuberculosis
    - Herpes infection of the eye
    - any other infections, including recent measles or chicken pox
    - kidney or liver problems
    - high blood pressure or heart problems
    - diabetes
    - myasthenia gravis
    - glaucoma
    - Cushing's syndrome
    - thyroid problems
    - seizures
    - bruising or bleeding problems
    - Pheochromocytoma (tumour in the adrenal gland)

Children

Cortisone-like medicines such as Celestone Chronodose can cause infections such as chicken pox or measles to be more serious in children. These medicines can also slow or stop growth in children or growing teenagers if used for a long time.

After Celestone Chronodose has been given this can cause low blood sugar levels in newborns.

Taking other medicines

Tell your doctor if you are taking any other medicines, including medicines that you buy without a prescription from a pharmacy, supermarket or health food shop.

Some medicines and Celestone Chronodose may interfere with each other. These include:

  • aspirin, salicylates, anti-inflammatory medicines
  • barbiturate sedatives
  • phenytoin, a medicine used to treat epilepsy
  • certain antibiotics such as rifampicin, clarithromycin and amphotericin b (amphotericin)
  • some cough and cold medicines
  • tablets or injections used to treat diabetes
  • hormone-type medicines including hormone replacement therapy and oral contraceptives
  • certain diuretics, also called fluid or water tablets
  • certain medicines used to treat heart failure
  • medicines used to stop blood clots
  • growth hormone
  • vaccines
  • certain antifungals such as ketoconazole and itraconazole
  • some medicines used to treat HIV infection such as ritonavir and cobicistat-containing products

You may need to take different amounts of your medicines or you may need to take different medicines.

How Celestone Chronodose is used

How it is given

Celestone Chronodose is usually given by a doctor or nurse. How it is given and the amount depends on the condition being treated.

Into a muscle (e.g. allergic, skin and rheumatic conditions, bursitis)

  • 1 mL, repeated weekly or more often if necessary
  • 2 mL if the illness is severe

Into soft tissue (e.g. bursitis, fibrositis)

  • 1 mL at intervals of 1 to 2 weeks

Into joints (e.g., rheumatoid arthritis, osteoarthritis, pain relief)

  • 0.25 to 2 mL

Into the skin (eg skin lesions, psoriasis)

  • not more than 1 mL at weekly intervals

How long it is given

Your doctor will decide how long you need to have this medicine. If you have been receiving it for some time, the dose will be reduced gradually before stopping.

If too much is given (overdose)

A single overdose of Celestone Chronodose is unlikely to cause serious side effects.

Repeated use of high doses may result in more severe side effects, as listed under Side Effects below.

Contact the Poisons Information Centre on 131126 if you think you or someone else may have been given too much Celestone Chronodose.

While you are using Celestone Chronodose

Things you must do

If you become pregnant while being treated with Celestone Chronodose, tell your doctor immediately.

If you are having emotional or physical stress such as serious infection, surgery or injury, tell your doctor. This may affect the dose of Celestone Chronodose you need.

Check with your doctor about drinking alcohol. If you drink alcohol while receiving Celestone Chronodose, the risk of ulcers is increased.

Tell all doctors, dentists and pharmacists who are treating you that you are being treated with Celestone Chronodose.

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are being treated with Celestone Chronodose.

Things you must not do

While you are being treated with Celestone Chronodose, and even after you stop it, do not have any vaccinations without your doctor's approval.

Things to be careful of

If Celestone Chronodose is injected into one of your joints, you should be careful not to put too much stress or strain on that joint for a while, even if it begins to feel better. Make sure your doctor has told you how much you are allowed to move this joint while it is healing.

If redness or swelling occurs at the place of injection, and continues or gets worse, check with your doctor.

Always check with your doctor as soon as possible if you notice any signs of a possible infection, such as sore throat, fever, sneezing or coughing. Celestone Chronodose may lower your resistance and make any infection you do get harder to treat.

If you are having any laboratory tests, tell your doctor. Celestone Chronodose may give false results in skin tests.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are using Celestone Chronodose.

All medicines have side effects. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

When this medicine is used for short periods of time, side effects are usually rare.

Ask your doctor or pharmacist any questions you may have.

Older patients are more likely to develop high blood pressure or bone disease from cortisone-like medicines. Women are especially at risk of developing bone disease.

Tell your doctor immediately if any of the following occur:

  • swelling of the face, lips or tongue that may cause difficulty in swallowing or breathing
  • asthma, wheezing, shortness of breath
  • sudden or severe itching, skin rash, hives
  • fainting, seizures or fits
  • vomiting blood or material that looks like coffee grounds
  • bleeding from the back passage (rectum), black sticky bowel motions (stools) or bloody diarrhoea
  • severe pain in the food pipe (oesophagus) or stomach
  • irregular heart rhythm.

These are serious reactions. You may need urgent medical attention.

Tell your doctor if you notice any of the following:

  • unusual weight gain, puffiness, swelling of the ankles or legs
  • muscle weakness with chronic fatigue, muscle loss, pain or cramps
  • tendon pain
  • joint pain
  • slow wound healing, thinning and breakdown of skin, bruising or reddish or purplish spots under the skin, red face, increased sweating
  • headache or dizziness
  • menstrual irregularities
  • swelling of the face (moon face), acne
  • thirst or passing large amounts of urine
  • feeling 'high', mood swings, depression and strange thoughts, personality changes, difficulty sleeping
  • visual disturbances or blurred vision
  • changes to your vision or pain in the eyes.

Very rarely, cortisone-like medicines given by injection may cause blindness if given around the head and neck. Skin darkening or loss of pigment, skin breakdown, abscess or redness, and joint damage caused by the injection, may also rarely occur.

Other side effects not listed above may also occur in some patients. If you notice any other side effects, check with your doctor.

After using Celestone Chronodose

Storage

Celestone Chronodose is usually stored in the doctor's surgery or clinic, or at the pharmacy.

It should be protected from light and kept at temperatures below 25°C.

Product description

What it looks like

Celestone Chronodose is a clear, colourless, suspension. It is available in 1mL glass ampoules in packs of 2 and 5.

Ingredients

Active ingredient:

  • betamethasone sodium phosphate
  • betamethasone acetate

Inactive ingredients:

  • Benzalkonium chloride
  • Disodium edetate
  • Dibasic sodium phosphate
  • Monobasic sodium phosphate
  • Nitrogen
  • Water for Injections.

Sponsor

Organon Pharma Pty Ltd
Building A, 26 Talavera Road,
Macquarie Park, NSW 2113
Australia

Australian Registration Number

AUST R 18777

Date of Preparation

February 2022

RCN100000544-AU

Published by MIMS April 2022

BRAND INFORMATION

Brand name

Celestone Chronodose

Active ingredient

Betamethasone acetate; Betamethasone sodium phosphate

Schedule

S4

 

1 Name of Medicine

Betamethasone acetate and betamethasone sodium phosphate.

2 Qualitative and Quantitative Composition

Celestone Chronodose Injection is a sterile aqueous suspension containing the combination of betamethasone sodium phosphate and betamethasone acetate. Each mL of Celestone Chronodose Injection contains betamethasone 5.7 mg, as betamethasone sodium phosphate 3.9 mg (in solution) and betamethasone acetate 3 mg (in suspension) in an aqueous vehicle.

Excipients with known effect.

Celestone Chronodose contains benzalkonium chloride.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Suspension for injection.

4 Clinical Particulars

4.1 Therapeutic Indications

Celestone Chronodose is indicated in the treatment of both severe and moderate conditions, in acute and chronic self limiting diseases responsive to systemic corticosteroid therapy, especially in patients for whom treatment with oral corticosteroid medication is not feasible.

Representative conditions.

Rheumatic disorders.

Rheumatoid arthritis, acute and subacute bursitis, epicondylitis, acute nonspecific tenosynovitis, myositis, fibrositis, tendinitis, psoriatic arthritis.

Collagen diseases.

Systemic lupus erythematosus, scleroderma, dermatomyositis.

Allergic states.

Status asthmaticus, chronic bronchial asthma, seasonal or perennial allergic rhinitis, severe allergic bronchitis, contact dermatitis, atopic dermatitis, hypersensitivity reactions to drug and insect bites.

Dermatological conditions.

Localised, hypertrophic infiltrated lesions of lichen planus, psoriatic plaques, granuloma annulare and lichen simplex chronicus (neurodermatitis), keloids, discoid lupus erythematosus, necrobiosis lipoidica diabeticorum, alopecia areata.

Antepartum use in the prevention of respiratory distress syndrome in premature infants.

When it is deemed necessary to induce labour prior to the thirty-second week of gestation or when premature birth before the thirty-second week of gestation becomes inevitable because of obstetric complication.
Celestone Chronodose Injection should also be considered for prophylactic treatment if the fetus is known to have a low lecithin/ sphingomyelin ratio (or decreased foam stability test on amniotic fluid).

4.2 Dose and Method of Administration

Dosage must be adjusted to the specific requirements of the patient according to the severity of the condition, the response obtained and the patient's tolerance to the corticosteroid.
Recommended routes of administration are:
1. Intramuscular injection in allergic, dermatological, rheumatic and other conditions responsive to systemic corticosteroids, including bursitis.
2. Injection directly into the affected soft tissues in bursitis and associated inflammatory disorders of muscle such as fibrositis and myositis.
3. Intra-articular and periarticular injection in rheumatoid arthritis and osteoarthritis.
4. Intralesional injections in various dermatological conditions.

Systemic administration.

Treatment of conditions requiring systemic corticoid effects can be carefully controlled by intramuscular injection of Celestone Chronodose Injection. Its rapid and prolonged action make it suitable for initiation of therapy in acute conditions in which control of inflammation must be achieved quickly and then maintained. The repository action of the drug assists in the prevention of recrudescence from irregular maintenance of corticoid effects.
Treatment is initiated with an intramuscular injection of 1 mL in most conditions and repeated weekly, or more often, if necessary. In severe illness, such as status asthmaticus or disseminated lupus erythematosus, 2 mL might be required initially.
In the antepartum use in the prevention of respiratory distress syndrome in premature infants and in the prophylactic treatment of the fetus known to have a low lecithin/ sphingomyelin ratio (or decreased foam stability tests on amniotic fluid), it is recommended that 2 mL be injected intramuscularly at least 24 hours before the expected time of delivery. A second dose (2 mL) should be given 24 hours later unless delivery has occurred.

Local administration.

If coadministration is desired, Celestone Chronodose Injection may be mixed (in the syringe not the ampoule) with 1% or 2% lidocaine (lignocaine) hydrochloride, procaine hydrochloride, or similar local anaesthetics, using formulations which do not contain hydroxybenzoates (parabens). Anaesthetics containing methyl hydroxybenzoate, propyl hydroxybenzoate, phenol, etc. should be avoided. The required dose is first withdrawn from the ampoule into the syringe. The local anaesthetic is then drawn into the syringe and then should be shaken briefly.
In bursitis (subdeltoid, subacromial and prepatellar) an intrabursal injection of 1 mL may relieve pain and may restore the full range of movement in a few hours. Several intrabursal injections at intervals of 1 to 2 weeks are usually required in recurrent acute bursitis and in acute exacerbations of chronic bursitis.
In tendinitis, myositis, fibrositis, tenosynovitis, peritendinitis and periarticular inflammatory conditions, three or four local injections of 1 mL each at intervals of one to two weeks are recommended in most cases. Injection should be made into the affected tendon sheaths rather than into the tendons themselves. In periarticular inflammatory conditions, the painful area should be infiltrated. In ganglions of joint capsules, 0.5 mL is injected directly into the ganglion cysts.
In rheumatoid arthritis and osteoarthritis, relief of pain, soreness and stiffness may be experienced in 2 to 4 hours after intra-articular injection. Dosages range from 0.25 to 2 mL, according to the size of the joint to be injected: very large joints (hip), 1 to 2 mL; large joints (knee, ankle and shoulder) 1 mL; medium joints (elbow and wrist), 0.5 to 1 mL; and small joints (hand and chest), 0.25 to 0.5 mL. Relief lasts usually from 1 to 4 or more weeks. Using a sterile technique, a 29 to 24 gauge needle, on an empty syringe for aspiration is inserted into the synovial cavity and a few drops of synovial fluid are withdrawn to confirm that the needle is in the joint. The aspirating syringe is replaced by the syringe containing Celestone Chronodose Injection and the injection is then made into the joint.
A portion of the administered dose of Celestone Chronodose Injection is absorbed systemically following intra-articular injection. Therefore, in patients being treated concomitantly with oral or parenteral corticosteroids, especially those receiving large doses, the systemic absorption of the drug administered intra-articularly should be considered.
In intralesional treatment, 0.2 mL/cm2 of Celestone Chronodose Injection is injected intradermally (not subcutaneously) using a tuberculin syringe with a 25 gauge, 1.27 cm needle. Care should be taken to deposit a uniform depot of medication intradermally. A total of not more than 1 mL at weekly intervals is recommended.

4.3 Contraindications

As with other corticosteroids, Celestone Chronodose Injection is contraindicated in systemic fungal infections and in patients hypersensitive to betamethasone sodium phosphate, betamethasone acetate, other corticosteroids or to any component of this product. Corticosteroids should not be injected into unstable joints, infected areas or intervertebral spaces. Celestone Chronodose Injection is not recommended for epidural administration.
Relative contraindications are osteoporosis, marked emotional instability, peptic ulcer, tuberculosis, acute or chronic infections, ocular herpes simplex, primary glaucoma, diverticulitis, recent intestinal anastomosis, Cushing's syndrome, renal insufficiency, hypertension, thromboembolic tendencies, diabetes mellitus and myasthenia gravis.
Corticosteroids are not indicated in the management of hyaline membrane disease after birth.

4.4 Special Warnings and Precautions for Use

Celestone Chronodose Injection should not be administered intravenously. Strict aseptic technique is mandatory. Subcutaneous injection should be avoided.
Serious neurologic events, some resulting in death, have been reported with epidural injection of corticosteroids. Specific events reported include, but are not limited to, spinal cord infarction, paraplegia, quadriplegia, cortical blindness, and stroke. These serious neurologic events have been reported with and without use of fluoroscopy. The safety and effectiveness of epidural administration of corticosteroids have not been established, and corticosteroids are not approved for this use. (See Section 4.3 Contraindications).
Rare instances of anaphylactoid/anaphylactic reactions with a possibility of shock have occurred in patients receiving parenteral corticosteroid therapy. Appropriate precautionary measures should be taken with patients who have a history of allergic reactions to corticosteroids.
Pheochromocytoma crisis, which may be fatal, has been reported after administration of systemic corticosteroids. Corticosteroids should only be administered to patients with suspected or identified pheochromocytoma after an appropriate risk/benefit evaluation.
Intramuscular injections of corticosteroids should be given deep into large muscle masses to avoid local tissue atrophy.
Soft tissue, intralesional and intra-articular administration of a corticosteroid may produce systemic as well as local effects.
Celestone Chronodose Injection contains two betamethasone esters, one of which, betamethasone sodium phosphate, disappears rapidly from the injection site. The potential for systemic effect produced by this soluble portion of Celestone Chronodose Injection should, therefore, be taken into account by the physician when using this preparation.
The lowest possible dose of corticosteroid should be used to control the condition under treatment; when dosage reduction is possible, it should be gradual.
Drug induced secondary adrenocortical insufficiency may result from too rapid corticosteroid withdrawal and may be minimised by gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy; therefore, if stress occurs during that period, corticotherapy should be reinstituted. If the patient is receiving corticosteroids already, the dosage may have to be increased.
Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticosteroid should be administered concurrently.
In certain conditions ordinarily considered contraindications to corticosteroid therapy, the physician must weigh anticipated clinical improvement against the possibility of undesirable corticosteroid effects.
Corticosteroids may mask the signs of infection and enhance the dissemination of an infecting organism. Hence, patients receiving corticosteroids should be watched for evidence of intercurrent infection. Should infection occur, vigorous, appropriate anti-infective therapy should be initiated. Abrupt withdrawal of corticosteroids should be avoided.
Celestone Chronodose Injection should not be administered to patients with an acute or chronic infection unless the condition is severe and unless appropriate anti-infective agents are administered concurrently. When corticosteroids are used, decreased resistance and inability to localise infection may occur.
Examination of any joint fluid present is necessary to exclude a septic process. Local injection into a previously infected joint is to be avoided. A marked increase in pain and local swelling, further restriction of joint motion, fever and malaise are suggestive of septic arthritis. If the diagnosis of sepsis is confirmed, appropriate antimicrobial therapy should be instituted.
While on corticosteroid therapy patients should not be vaccinated against smallpox. Other immunisation procedures should not be undertaken in patients receiving corticosteroids, especially high doses, because of possible hazards of neurological complications and lack of antibody response. However, immunisation procedures may be undertaken in patients who are receiving corticosteroids as replacement therapy, e.g. for Addison's disease.
Patients who are on immunosuppressant doses of corticosteroids should be warned to avoid exposure to chickenpox or measles and, if exposed, to obtain medical advice. This is of particular importance in children.
Corticosteroid therapy in active tuberculosis should be restricted to those cases of fulminating or disseminated tuberculosis in which the corticosteroid is used for management in conjunction with an appropriate antituberculous regimen.
If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary since reactivation of the disease may occur. During prolonged corticosteroid therapy, patients should receive chemoprophylaxis. If rifampicin is used in a chemoprophylactic program, its enhancing effect on metabolic hepatic clearance of corticosteroids should be considered; adjustment in corticosteroid dosage may be required.
Prolonged corticosteroid use may produce posterior subcapsular cataracts (especially in children), glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infections due to fungi or viruses. Because rare instances of anaphylactoid reactions have occurred in patients receiving parenteral corticosteroid therapy, appropriate precautionary measures should be taken prior to administration, especially when the patient has a history of allergy to any drug.
Following intra-articular steroid therapy, care should be taken by the patient to avoid overuse of the joint in which symptomatic benefit has been obtained.
Repeated injections into joints of osteoarthritis may increase joint destruction. Avoid injecting corticosteroids directly into the substance of tendons, because delayed appearance of tendon rupture has resulted.
Celestone Chronodose Injection should be administered intramuscularly with caution to patients with idiopathic thrombocytopenic purpura.
With long-term corticosteroid therapy, transfer from parenteral to oral administration should be considered after weighing the potential benefits and risk.
Dosage adjustments may be required with remission or exacerbation of the disease process, the patient's individual response to therapy and exposure of the patient to emotional or physical stress such as serious infection, surgery or injury. Monitoring may be necessary for up to one year following cessation of long-term or high dose corticosteroid therapy.
Corticosteroid effect is enhanced in patients with hypothyroidism or in those with cirrhosis.
Cautious use of corticosteroids is advised in patients with ocular herpes simplex because of possible corneal perforation.
Psychic derangements may appear with corticosteroid therapy. Existing emotional instability or psychotic tendencies may be aggravated by corticosteroids.
Average and large doses of corticosteroids can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium. These effects are less likely to occur with the synthetic derivatives except when used in large doses. Dietary salt restriction and potassium supplementation may be considered. All corticosteroids increase calcium excretion.
Corticosteroids should be used with caution in: nonspecific ulcerative colitis, if there is a probability of impending perforation, abscess, or other pyogenic infection; diverticulitis; fresh intestinal anastomoses; active or latent peptic ulcer; renal insufficiency; hypertension; osteoporosis; and myasthenia gravis.
Since complications of glucocorticosteroid treatment are dependent on dose, size and duration of treatment, a risk/ benefit decision must be made with each patient.
Corticosteroids may alter the motility and number of spermatozoa in some patients.
Results from a single, multicentre, randomised, controlled study with another corticosteroid, methylprednisolone hydrogen succinate, showed an increase of early mortality (at 2 weeks) and late mortality (at 6 months) in patients with cranial trauma who had received methylprednisolone, compared to placebo. The causes of mortality in the methylprednisolone group have not been established. Of note, this study excluded patients who were felt to have a clear indication for corticosteroids.
Visual disturbance may be reported with systemic and topical (including, intranasal, inhaled and intraocular) corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes of visual disturbances which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.

Use in the elderly.

No data available.

Paediatric use.

Since corticosteroid administration can disturb growth rates and inhibit endogenous corticosteroid production in infants and children, the growth and development of these patients receiving prolonged therapy should be followed carefully.

Effects on laboratory tests.

Corticosteroids may affect the nitro-blue tetrazolium test for bacterial infection and produce false negative results.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Concurrent use of corticosteroids with potassium-depleting diuretics may enhance hypokalaemia. Concurrent use of corticosteroids with cardiac glycosides may enhance the possibility of arrhythmias or digitalis toxicity associated with hypokalaemia. Corticosteroids may enhance the potassium depletion caused by amphotericin B (amphotericin). In all patients taking any of these drug therapy combinations, serum electrolyte determinations, particularly potassium levels, should be monitored closely.

Anticoagulants, oral.

Concurrent use of corticosteroids with coumarin-type anti-coagulants may increase or decrease the anti-coagulant effects, possibly requiring adjustment in dosage.

Antidiabetics.

The hyperglycaemic effect of betamethasone may offset the hypoglycaemic effect of oral antidiabetic drugs. Dosage adjustments of an anti-diabetic drug may be necessary when corticosteroids are given to diabetics.

Estrogens, including oral contraceptives.

Patients receiving both a corticosteroid and an estrogen should be observed for excessive corticosteroid effects.

Hepatic enzyme inducers.

Concurrent use of phenobarbital (phenobarbitone), phenytoin, rifampicin or ephedrine may enhance the metabolism of corticosteroids, reducing their therapeutic effects.

Interactions with strong CYP3A4 inhibitors.

Corticosteroids (including betamethasone) are metabolized by CYP3A4.
Coadministration with strong CYP3A4 inhibitors, (e.g. ketoconazole, itraconazole, clarithromycin, ritonavir, cobicistat-containing products) may lead to increased exposures of corticosteroids and therefore the potential for increased risk of systemic corticosteroid side effects.
Consider the benefit of coadministration versus the potential risk of systemic corticosteroid effects, in which case patients should be monitored for systemic corticosteroid side-effects.

Nonsteroidal anti-inflammatory agents (NSAIDs).

Plasma levels of salicylates may be reduced. Aspirin should be used cautiously in conjunction with corticosteroids in hypoprothrombinaemia.
Combined effects of nonsteroidal anti-inflammatory drugs or alcohol with glucocorticosteroids may result in an increased occurrence or increased severity of gastrointestinal ulceration.

Somatotropin.

Concomitant glucocorticosteroid therapy may inhibit the response to somatotropin. Doses of betamethasone in excess of 0.3 to 0.45 mg per m2 of body surface per day should be avoided during the administration of somatotropin.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C)
The use of corticosteroids in pregnancy or in women of childbearing potential requires that the possible benefits of the drug be weighed against the potential hazards to the mother and fetus.
In the prophylactic treatment of hyaline membrane disease in premature infants, corticosteroids should not be administered to pregnant women with pre-eclampsia, eclampsia or evidence of placental damage.
Since use of prophylactic corticosteroids beyond the 32nd week of gestation is still controversial, the physician should weigh the benefits against the potential hazards to the mother and the fetus when using corticosteroids beyond this period of gestation.
In animal experiments, corticosteroids have been found to cause malformations of various kinds (cleft palate, skeletal malformations) and abortion. These findings do not seem to be relevant to humans. Reduced placental and birthweight have been recorded in animals and humans after long-term treatment. Since the possibility of suppression of the adrenal cortex in the newborn baby after long-term treatment must be considered, the needs of the mother must be carefully weighed against the risk to the fetus when prescribing these drugs. The short-term use of corticosteroids antepartum for the prevention of respiratory distress syndrome does not seem to pose a risk to the fetus or the newborn infant.
Maternal pulmonary oedema has been reported with tocolysis and fluid overload.
Infants born of mothers who received substantial doses of corticosteroids during pregnancy should be observed carefully for signs of hypoadrenalism. When mothers were given betamethasone injections prenatally, the infants had transient suppression of fetal growth hormone and presumably of those pituitary hormones which regulate corticosteroid production by both the definitive and fetal zones of the fetal adrenal glands. However, the suppression of fetal hydrocortisone did not interfere with the pituitary adrenocortical responses to stress after birth.
Since transplacental passage of corticosteroids occurs, newborn and young infants born of mothers who were dosed with corticosteroids throughout most or some portion of their pregnancy should be examined carefully for the possible very rare occurrence of congenital cataracts.
Women who have been on corticosteroids during pregnancy should be monitored during and after labour and delivery for any indication of adrenal insufficiency because of the stresses associated with childbirth.
The drug is excreted in breast milk and may be harmful to young children because it could suppress growth or cause other adverse effects such as hypoadrenalism. Potential benefits to the mother should outweigh these possible hazards to the infant.

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.8 Adverse Effects (Undesirable Effects)

Adverse reactions to Celestone Chronodose injection relate both to dose and to duration of therapy. These reactions can usually be reversed or minimised by a reduction in dosage; this is generally preferable to withdrawal of drug treatment.
Adverse reactions have been the same as those reported to other corticosteroids: fluid and electrolyte, musculoskeletal, gastrointestinal, dermatological, neurological, endocrine, ophthalmic, metabolic and psychiatric disturbances.

Cardiovascular.

Congestive heart failure in susceptible patients; hypertension.

Fluid and electrolyte disturbances.

Sodium retention, potassium loss, hypokalaemic alkalosis; fluid retention.

Musculoskeletal.

Muscle weakness, corticosteroid myopathy, loss of muscle mass; aggravation of myasthenic symptoms in myasthenia gravis; osteoporosis; vertebral compression fractures; aseptic necrosis of femoral and humeral heads, pathologic fracture of long bones; tendon rupture; joint instability (from repeated intra-articular injections).

Gastrointestinal.

Hiccups, peptic ulcer with possible subsequent perforation and haemorrhage; pancreatitis; abdominal distension; ulcerative oesophagitis.

Dermatologic.

Impaired wound healing; skin atrophy; thin fragile skin; petechiae and ecchymoses; facial erythema; increased sweating; suppressed reactions to skin tests; reactions such as allergic dermatitis, urticaria, angioedema.

Neurologic.

Convulsions, increased intracranial pressure with papilloedema (pseudotumour cerebri) usually after treatment; vertigo; headache.

Endocrine.

Menstrual irregularities; development of cushingoid state; suppression of fetal intrauterine and childhood growth; secondary adrenocortical and pituitary unresponsiveness, particularly in times of stress, as in trauma, surgery or illness; decreased carbohydrate tolerance, manifestations of latent diabetes mellitus, increased requirements of insulin or oral hypoglycaemic agents in diabetics.

Ophthalmic.

Posterior subcapsular cataracts; increased intraocular pressure, glaucoma; exophthalmos, vision blurred.

Metabolic.

Negative nitrogen balance due to protein catabolism.

Psychiatric.

Euphoria, mood swings; severe depression to frank psychotic manifestations; personality changes; insomnia.

Other.

Anaphylactoid or hypersensitivity and hypotensive or shock-like reactions.
Neonatal hypoglycemia has been reported after antenatal administration.
Additional adverse reactions related to parenteral corticosteroid therapy include rare instances of blindness associated with intralesional therapy around the face and head; hyperpigmentation or hypopigmentation; subcutaneous and cutaneous atrophy; sterile abscess; postinjection flare (following intra-articular use); Charcot-like arthropathy.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at http://www.tga.gov.au/reporting-problems.

4.9 Overdose

A single overdose of a corticosteroid would not be expected to produce acute symptoms. Hypercorticoid effects are not anticipated unless there has been repeated administration of high doses.

Symptoms.

Systemic effects of chronic overdosage with steroids include effects on sodium and water retention, increased appetite, mobilisation of calcium and phosphorus with osteoporosis, nitrogen depletion, hyperglycaemia, effects on tissue repair, increased susceptibility to infection, adrenal insufficiency, adrenal cortex hyperactivity, mental and neurological disturbances and muscular weakness.

Treatment.

In case of an acute overdose, maintain adequate fluid intake and monitor electrolytes in serum and urine, with particular attention to sodium and potassium balance. In case of chronic toxicity, slowly withdraw drug. Treat electrolyte imbalance if necessary.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Celestone Chronodose is an injectable preparation containing both soluble and slightly soluble esters of betamethasone that provides anti-inflammatory, antirheumatic and antiallergic effects in the treatment of corticosteroid responsive disorders.

Mechanism of action.

No data available.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Prompt therapeutic activity in conditions responsive to corticosteroids is initiated by betamethasone sodium phosphate, a soluble ester that is absorbed quickly into tissues after injection.
Sustained activity is provided by betamethasone acetate, which is only slightly soluble and affords a repository for slow absorption.
The combined rapid and depot actions of these forms of betamethasone facilitate rapid control as well as steady maintenance of corticosteroid effects.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Benzalkonium chloride, disodium edetate, dibasic sodium phosphate, monobasic sodium phosphate, water for injections.

Inactive ingredients.

Nitrogen.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

The expiry date can be found on the packaging. In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG).

6.4 Special Precautions for Storage

Protect ampoules from light.
Store below 25°C.

6.5 Nature and Contents of Container

Injection, suspension in flint glass (Type I) ampoule with rubber stopper. Ampoules, 1 mL: 5s, 2s.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.


Betamethasone acetate.

9-fluoro-11β,17-dihydroxy-16β-methyl-3,20-dioxopregna-1,4diene-21-yl acetate. Molecular formula: C24H31FO6. MW: 434.5.

CAS number.

987-24-6.

Chemical structure.


Betamethasone sodium phosphate.

9-fluoro-11β,17-dihydroxy-16β-methyl-3,20-dioxopregna-1,4diene-21-yl disodium phosphate. Molecular formula: C22H28FNa2O8P. MW: 516.4.

CAS number.

151-73-5.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes