Betamethasone Sodium Phosphate/ Betamethasone Acetate

Registered South African indications:

• Rheumatic, dermatologic and allergic conditions - acute or severe
  Representative conditions include:
  - Collagen diseases
  - Musculoskeletal conditions 
  - Dermatologic conditions
  - Allergic conditions 
  - Disorders of the foot

Registered South African contraindications

• Hypersensitivity to the active ingredients or any of the excipients in this combination product
• Hypersensitivity to other corticosteroids
• Pregnancy
• Breastfeeding
• Systemic fungal infections
• Conditions ordinarily considered contraindicated to corticosteroid therapy (the anticipated clinical improvement must be weighed against the possibility of undesirable corticosteroid effects)
  - Osteoporosis
  - Marked emotional instability
  - Peptic ulcer
  - Tuberculosis
  - Acute ocular herpes simplex
  - Thromboembolic tendencies
  - Diverticulitis
  - Recent intestinal anastomosis
  - Acute and chronic infections

South African recommendations

• Males of reproductive potential
• Renal impairment
• Hepatic impairment
  - Cirrhosis
• Elderly
• Infants and children
• Latent tuberculosis or tuberculin reactivity 
• Epidural administration of corticosteroids
• History of allergic reactions to corticosteroids
• Management of hyaline membrane disease after birth
• Idiopathic thrombocytopenic purpura
• Local injection into a previously infected joint
• Unstable joints, infected areas or intervertebral spaces
• Repeated injections into joints of osteoarthritis
• Injecting corticosteroids directly into the substance of tendons
• Overuse of the joint in which symptomatic benefit has been obtained (following intra-articular corticosteroid therapy)
• Prolonged use
• High dosages 
• Vaccination against smallpox (while on corticosteroid therapy)
• Other immunisation procedures (See additional prescribing points)
• Exposure to chickenpox or measles
• Rapid withdrawal 
• Hypothyroidism 
• Pre-existing psychotic tendencies
• Non-specific ulcerative colitis
• Possibility of impending perforation, abscess or other pyogenic infection
• Hypertension
• Myasthenia gravis  
• Salt restricted diet

Forms avail. in South Africa and covered in this monograph: inj

South African registered indications and dosages

Rheumatic, dermatologic and allergic conditions - acute or severe
Collagen diseases
- Rheumatoid arthritis
- Disseminated lupus erythematosus
- Scleroderma
- Dermatomyositis
- Osteoarthritis

Rheumatoid arthritis and osteoarthritis

• Intra-articular (inj): 0.25-2ml according to the size of the joint to be injected; Very large joints (hip): 1-2ml; Large joints (knee, ankle and shoulder): 1ml; Medium joints (elbow and wrist): 0.5-1ml; Small joints (hand and chest): 0.25-0.5ml

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In rheumatoid arthritis and osteoarthritis, relief of pain, soreness and stiffness may be experienced in 2-4 hours after intra-articular injection of 1-2ml. Relief lasts usually 1-4 weeks or more

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Dermatologic conditions
- Neurodermatitis
- Hypertrophic lichen planus
- Circumscribed lichen simplex
- Nummular eczema
- Alopecia areata
- Discoid lupus erythematosus
- Psoriasis
- Keloids
- Contact dermatitis
- Drug reactions
- Insect bites

Localised neurodermatitis, hypertrophic infiltrated lesions of lichen planus, nummular eczema, alopecia areata, chronic discoid lupus erythematosus, circumscribed lichen simplex, psoriasis and keloids

• Intralesional, intradermal (inj): 0.2ml/cm², as a single dose; Max total dose (at all sites): 1ml/week

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In intralesional treatment betamethasone sodium phosphate/ betamethasone acetate is injected intradermally (not subcutaneously) using a tuberculin syringe with a 25 gauge, 12.7mm (0.5 inch) needle. Care should be taken to deposit a uniform depot of medication intradermally. Total amount injected at all sites weekly should not exceed 1ml. Should a local anaesthetic be desired it should be given prior to the administration of betamethasone sodium phosphate/ betamethasone acetate as a separate injection

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Allergic conditions 
- Status asthmaticus
- Chronic bronchial asthma
- Hay fever - severe
- Allergic bronchitis - severe
- Perennial allergic rhinitis - severe

Bronchial asthma, hay fever, allergic bronchitis and perennial allergic rhinitis

• IM: 1-2ml, once weekly 

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Treatment is initiated with an intramuscular injection of 1ml of betamethasone sodium phosphate/ betamethasone acetate in most conditions and repeated weekly or more often if necessary. In less severe disease, lower doses generally will suffice. In severe illness, such as status asthmaticus or disseminated lupus erythematosus, 2ml might be required initially

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Respiratory tract disorders: Effective control of symptoms of bronchial asthma, hay fever, allergic bronchitis and perennial allergic rhinitis: The initial dose should be maintained or adjusted until a satisfactory response is observed. If a satisfactory clinical response does not occur after a reasonable period of time, treatment with betamethasone sodium phosphate/ betamethasone acetate should be discontinued and other appropriate therapy initiated

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Intramuscular administration: Treatment of conditions requiring systemic corticosteroid effects can be carefully controlled by intramuscular injections of betamethasone sodium phosphate/ betamethasone acetate. Its prompt and prolonged actions make it especially suited for initial 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 corticosteroid effects

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Representative conditions responsive to intramuscular administration of betamethasone sodium phosphate/ betamethasone acetate include: Collagen disease, dermatologic conditions and respiratory tract disorders (status asthmaticus, chronic bronchial asthma, hay fever, allergic bronchitis and perennial allergic rhinitis)

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Musculoskeletal conditions
- Acute gouty arthritis
- Bursitis
- Epicondylitis
- Fibrositis
- Myositis
- Tendinitis
- Tenosynovitis
- Coccygodynia
- Low back syndrome
- Torticollis
- Ganglion cyst

Tendinitis, myositis, fibrositis, tenosynovitis, peri-tendinitis and peri-articular inflammatory conditions

• Intra-articular/ Intrabursal/ Peri-articular (inj): 3-4ml, at intervals of 1-2 weeks; In ganglions of joint capsules: 0.5ml, directly into the ganglion cyst

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 Injection should be made into the affected tendon sheaths rather than into the tendons themselves. In peri-articular inflammatory conditions, the painful area should be infiltrated

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Using sterile technique, a 20-24 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 betamethasone sodium phosphate/ betamethasone acetate and the injection is then made into the joint

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There is virtually no pain on injection, and the “secondary flare” that sometimes occurs a few hours after intra-articular injection of corticosteroids, has not been reported with betamethasone sodium phosphate/ betamethasone acetate

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Disorders of the foot
- Bursitis under heloma durum
- Bursitis under heloma molle
- Bursitis under calcaneal spur
- Bursitis over hallus rigidus
- Bursitis over digiti quinti varus
- Synovial cyst
- Tenosynovitis
- Periostitis of cuboid
- Acute gouty arthritis
- Metatarsalgia

Most podiatric conditions 

• Intralesional, intradermal (inj): 0.25-0.5ml, at intervals of 3-7 days; In acute gouty arthritis, doses up to 1ml may be necessary

Bursitis under heloma durum (hard corn)

• Intralesional, intradermal (inj): Two 0.25ml, as successive injections   

Bursitis (subdeltoid, subacromial and prepatellar)

• Intrabursal (inj): 1ml, as a single dose; Recurrent acute bursitis and acute exacerbations of chronic bursitis: Several injections at intervals of 1-2 weeks

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Betamethasone sodium phosphate/ betamethasone acetate is also effective in the treatment of corticosteroid-responsive disorders of the foot. In conditions such as hallux rigidus (flexion deformity of the great toe), digiti quinti varus (inward deviation of the fifth toe) and acute gouty arthritis, onset of relief may be rapid. Pain and stiffness have been relieved in 5-15 minutes. A tuberculin syringe with a 25 gauge, 19mm (0.75 inch) needle is suitable for most injections into the foot

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Betamethasone sodium phosphate/ betamethasone acetate can be administered intramuscularly for systemic effect and intraarticularly, peri-articularly, intrabursally, intradermally and intralesionally for local effect. Betamethasone sodium phosphate/ betamethasone acetate is not for intravenous or subcutaneous use

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For all indications: Dosing requirements are variable and must be individualised on the basis of the specific disease, its severity and the response of the patient

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Intra-articular, intrabursal and peri-articular administration: In those rare instances where administration of a local anaesthetic is desirable, it should be given prior to the administration of betamethasone sodium phosphate/ betamethasone acetate

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Intradermal and intralesional administration: After a favourable response is obtained the proper maintenance dosage should be determined by decreasing the initial dose in small decrements at appropriate time intervals until the lowest dose, which will maintain an adequate clinical response is determined

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Intradermal and intralesional administration: Exposure of the patient to stressful situations unrelated to the existing disease may necessitate an increased dose of betamethasone sodium phosphate/ betamethasone acetate. If the drug is to be discontinued after long-term therapy, the dose should be decreased gradually

No information available

Pregnancy

South African recommendations

• Contraindicated
• The safety in pregnancy has not been established

Breastfeeding

South African recommendations

• Contraindicated 
• The safety in breastfeeding has not been established

South African recommendations

• Caution; no dose adjustment recommended

South African recommendations

• Caution; no information available

South African recommendations

• Caution; no information available

Central Nervous System Disorders

• Seizures
• Increased intracranial pressure with papilloedema (pseudotumor cerebri)
• Headache
• Euphoria
• Mood swings
• Severe depression
• Frank psychotic manifestations
• Personality changes
• Insomnia

Cardiovascular Disorders

• Congestive heart failure (in susceptible patients)
• Hypertension

Gastrointestinal Disorders 

• Hiccups
• Peptic ulcer with possible subsequent perforation and haemorrhage
• Pancreatitis
• Abdominal distention
• Ulcerative oesophagitis

Endocrine and Metabolic Disorders  

• Sodium retention
• Potassium loss
• Hypokalaemic alkalosis
• Menstrual irregularities
• Cushingoid state
• Secondary adrenocortical and pituitary unresponsiveness (particularly in times of stress, as in trauma, surgery or illness)
• Decreased carbohydrate tolerance
• Latent diabetes mellitus
• Increased requirements of insulin or oral hypoglycaemic agents in diabetes
• Negative nitrogen balance 
• Childhood growth

Musculoskeletal Disorders 

• Muscle weakness
• Corticosteroid myopathy
• Muscle mass loss
• 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)
• Charcot-like arthropathy

Skin and Subcutaneous Tissue Disorders 

• Impaired wound healing
• Skin atrophy
• Thin fragile skin
• Petechiae
• Ecchymoses
• Facial erythema
• Increased sweating
• Suppressed reactions to skin tests
• Skin reactions
  - Allergic dermatitis
  - Urticaria
  - Angioneurotic oedema
• Hyperpigmentation
• Hypopigmentation
• Subcutaneous and cutaneous atrophy
• Sterile abscess
• Post-injection flare (following intra-articular use)

Immune, Blood and Lymphatic System Disorders 

• Fluid retention
• Anaphylactoid or hypersensitivity reactions
• Hypotensive or shock-like reactions

Sensory Disorders 

• Posterior subcapsular cataracts
• Increased intraocular pressure
• Glaucoma
• Exophthalmos
• Blurred vision
• Blindness (associated with intralesional therapy around the face and head)
• Vertigo

Others

• Suppression of foetal intrauterine growth

• Phenobarbitone
• Phenytoin
• Rifampin
• Ephedrine
• Oestrogen
• Potassium-depleting diuretics
• Cardiac glycosides
• Amphotericin B
• Coumarin-type anticoagulants
• Non-steroidal anti-inflammatory drugs (NSAIDs) 
• Acetylsalicylic acid
• Antidiabetic agent
• Somatotropin
• Ketoconazole
• Strong CYP3A4 inhibitors
• Itraconazole
• Clarithromycin
• Ritonavir
• Cobicistat-containing products

Other interactions

• Alcohol
• Nitro-blue tetrazolium test (See additional prescribing points)

None routine. Specific cases may require

• Growth (in children)

Additional observation

• Injection site reactions
• Risk of infection

Nitro-blue tetrazolium test

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

Immunisation procedures

• 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

Tuberculosis

• Betamethasone sodium phosphate/ betamethasone acetate 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 anti-tuberculosis regimen
• If betamethasone sodium phosphate/ betamethasone acetate is indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary since reactivation of the disease may occur. During prolonged betamethasone sodium phosphate/ betamethasone acetate therapy, patients should receive chemoprophylaxis. If rifampin is used in a chemoprophylactic programme, its enhancing effect on metabolic hepatic clearance of corticosteroids should be considered; adjustment in corticosteroid dosage may be required

Special warnings and precautions for use

• With long-term corticosteroid therapy, transfer from parenteral to oral administration should be considered after weighing the potential benefits and risks
• The lowest possible dose of corticosteroid should be used to control the condition under treatment; when dosage reduction is possible, it should be gradual
• Since complications of glucocorticosteroid treatment are dependent on dose, size and duration of treatment, a risk/benefit decision must be made with each patient
• 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 1 year following cessation of long-term or high-dose corticosteroid therapy

Betamethasone sodium phosphate/ betamethasone acetate is an injectable preparation of soluble and slightly soluble esters of betamethasone that produces enhanced anti-inflammatory, anti-rheumatic and anti-allergic effects. 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. Betamethasone sodium phosphate/ betamethasone acetate is recommended for intramuscular injection in various conditions requiring systemic corticosteroid therapy. Except in unusual circumstances, betamethasone sodium phosphate/ betamethasone acetate may be administered for systemic or local effect without restricting sodium intake or supplementing dietary potassium. Betamethasone sodium phosphate/ betamethasone acetate is well tolerated locally and is recommended for direct injection into joints and into bursae, muscle, tendon sheaths, skin and other soft tissues. Betamethasone has high glucocorticosteroid activity and slight mineralocorticosteroid activity.

COMBINATION PREPARATIONS

Betamethasone Sodium Phosphate/ Betamethasone Acetate

Injection (per ml) 3mg/3mg

• Celestone Soluspan Injection (Organon) originator
• Celestone Soluspan Injection (Schering-Plough) (Discontinued: 01/04/2018)