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Methylprednisolone acetate parenteral

Presentation

Suspension for injection containing methylprednisolone acetate

Drugs List

  • DEPO-MEDRONE 120mg/3ml injection
  • DEPO-MEDRONE 40mg/1ml injection
  • DEPO-MEDRONE 80mg/2ml injection
  • methylprednisolone acetate 120mg/3ml injection
  • methylprednisolone acetate 40mg/1ml injection
  • methylprednisolone acetate 80mg/2ml injection
  • Therapeutic Indications

    Uses

    Inflammatory or allergic conditions

    Dosage

    Undesirable effects may be minimised by using the lowest effective dose for the minimum period.

    Dosage should be individualised and depends on condition being treated and its severity. Frequent patient review is needed to titrate dose against disease activity.

    Adults

    Intramuscular administration - for sustained systemic effect:

    Frequency should be determined by duration of clinical response, on average an 80mg injection may be expected to last 2 weeks.

    Allergic conditions (severe seasonal and perennial allergic rhinitis, asthma, drug reactions): 80 to 120 mg.

    For seasonal allergic rhinitis a single injection is usually sufficient, a second may be used after 2-3 weeks.

    Dermatological conditions: 40 to 120 mg

    Rheumatic disorders and collagen diseases (rheumatoid arthritis, systemic lupus erythematosus): 40 to 120 mg per week.

    Intra-articular Administration:

    Rheumatoid arthritis, osteo-arthritis:

    Injections may be repeated at intervals of 1 to 5 weeks depending on the degree of relief obtained from the initial injection.

    Large joint: (knee, ankle, shoulder) 20 to 80 mg

    Medium joint: (elbow, wrist) 10 to 40 mg

    Small joint: (metacarpophalangeal, interphalangeal, sternoclavicular, acromioclavicular) 4 to 10 mg

    Intrabursal:

    Subdeltoid bursitis, prepatellar bursitis, olecranon bursitis:

    Administered directly into bursae 4 to 30 mg.
    In most cases repeated injection is not necessary.

    Tendon sheath:

    Tenosynovitis, epicondylitis:

    Administer directly in to the tendon sheath 4 to 30 mg. In chronic or recurrent conditions repeat injections may be necessary.

    Intralesional:

    Keloids, localised lichen planus, localised lichen simplex, granuloma annulare, alopecia areata, discoid lupus erythematosus:

    Administered directly into the lesion for local effect in dermatological conditions 20 to 60 mg.

    For large lesions, the dose may be distributed by repeated local injections of 20 to 40 mg. One to four injections are commonly used.

    Peri-articular:

    Epicondylitis:

    Infiltrate 4 to 30 mg in to the affected area.

    Elderly

    There is no information to warrant a change in dosage, however, the more serious consequences of the common side effects should be borne in mind, particularly for long term treatment.

    Close clinical supervision is required.

    Children

    Dosage may be reduced for infants and children but should be governed more by the severity of the condition and patient response rather than age or size.

    Administration

    May be used by any of the following routes: Intramuscular, intra-articular, periarticular, intrabursal, intralesional and in to the tendon sheath.

    The slower rate of absorption by the intramuscular route should be recognised. In conditions where a prompt response is desirable, an alternative route should be considered.

    Due to the absence of a true tendon sheath, the Achilles tendon should not be injected with methylprednisolone acetate.

    Injection into the deltoid muscle should be avoided because of a high incidence of subcutaneous atrophy.

    Contraindications

    Uncontrolled systemic infection

    Precautions and Warnings

    Abscess
    Children under 18 years
    Elderly
    Family history of diabetes mellitus
    Family history of glaucoma
    Predisposition to thromboembolic disease
    Predisposition to thrombophlebitis
    Breastfeeding
    Congestive cardiac failure
    Cushing's disease
    Diabetes mellitus
    Diverticulitis
    Glaucoma
    Hepatic cirrhosis
    History of severe affective disorders
    History of steroid myopathy
    History of steroid-induced psychosis
    History of tuberculosis
    Hypertension
    Hypothyroidism
    Joint infection
    Latent or healed tuberculosis
    Myasthenia gravis
    Ocular herpes simplex infection
    Peptic ulcer
    Phaeochromocytoma
    Pregnancy
    Recent gastrointestinal anastomosis
    Renal impairment
    Seizures
    Severe affective disorders
    Ulcerative colitis

    Administration of live vaccines is not recommended
    Disease reactivation may occur in patients with latent TB
    May mask symptoms of peptic ulcer
    May mask symptoms or signs of infections
    Exclude joint infection before injection
    Passive immunisation of chicken pox / herpes zoster may be required
    Aseptic technique should be used throughout
    Aspirate prior to injection to avoid intravascular administration
    Do not inject into unstable joints
    Do not mix with other drugs or substances
    For intralesional administration, if possible use multiple injection sites
    For single use only
    Resuscitation facilities must be immediately available
    Avoid injection into deltoid muscle-high incidence of subcutaneous atrophy
    Avoid local injection into previously infected joints
    Frequent review needed to titrate dose to disease activity
    Monitor and discontinue if appropriate if psychiatric or CNS problems occur
    Possible mineralocorticoid secretion suppression & need for supplementation
    Advise patients/carers to seek medical advice if changes in behaviour/mood
    Antibody response to non-live vaccines may be diminished
    Breastfeeding: Risk of adrenal suppression in breastfed infant
    Consider septic arthritis post joint inj if pain,fever,swelling occur
    Corticosteroids may cause growth retardation in children under 18 years
    May exacerbate diabetes mellitus
    May precipitate diabetes mellitus
    Patient should report worrying psychological changes esp. suicidal thoughts
    Potassium supplements may be required
    Reduces response of pituitary-adrenal axis to stress
    Sudden withdrawal may be inadvisable -see product information/SPC
    Advise patient not to take NSAIDs unless advised by clinician
    Advise patient not to take St John's wort concurrently
    Advise patient to avoid grapefruit products
    Dietary salt restriction may be necessary
    Advise patient to rest treated joint after intra-articular injection
    Advise those on systemic corticosteroids to avoid chickenpox/H zoster
    Ensure patient receives Steroid Treatment/Steroid Emergency Card
    If exposed to chickenpox or Herpes zoster seek urgent medical attention

    Undesirable effects may be minimised by using the lowest effective dose for the minimum period.

    The presence of crystals of adrenal steroids in the dermis may cause disintegration of the cellular elements and physiochemical changes in the connective tissue. These changes may result in depressions in the skin at the injection site. The degree to which this reaction occurs will vary with the amount of adrenal steroid administered. It usually takes a few months to complete the regeneration process (until all of the crystals of the adrenal steroid have been absorbed). Multiple smaller injections into the area of the lesion should be made if possible. The technique of intra-articular and intramuscular injection should include precautions against injection or leakage into the dermis.
    Intralesional doses should be injected deeply, particularly in visible sites in patients with pigmented skins, as there have been reports of subcutaneous depigmentation and atrophy. Systemic as well as local effects should be expected as systemic absorption of methylprednisolone occurs following intra-articular injections.
    There is an increased risk of inflammatory response in the joint when corticosteroids are injected intra-articularly, particularly bacterial infection introduced with the injection. Charcot-like arthropathies have been reported particularly after repeated injections. To exclude any bacterial infection prior to injection, examination of any joint fluid present is recommended.

    Chickenpox and measles can have a more serious (or fatal) course in non-immune children or adults on corticosteroids. Passive immunization with varicella/zoster immunoglobin (VZIG) is needed by exposed non-immune patients who are receiving systemic corticosteroids or who have used them within the previous 3 months. This should be given within 10 days of exposure to chickenpox. The illness warrants specialist care and urgent treatment if a diagnosis of chickenpox is confirmed. It is important to note that corticosteroids should not be stopped and the dose may need to be increased.

    Supplemental corticosteroids have been suggested to be beneficial in patients with septic shock who exhibit adrenal insufficiency. However, the routine use of corticosteroids in septic shock is not recommended. A systematic review of short course high dose corticosteroids did not support their use. Conversely, meta-analyses and a review suggest that longer courses (5 to 11 days) of low-dose corticosteroids might reduce mortality, especially in patients with vasopressor dependent septic shock.

    When corticosteroids are administered for prolonged periods at pharmacologic doses, hypothalamic-pituitary-adrenal (HPA) suppression may occur. The duration and degree of adrenocortical insufficiency produced is variable and depends on the dose, frequency, time of administration, and duration of glucocorticoid therapy. This effect may be minimized by use of alternate-day therapy. In addition, if glucocorticoids are withdrawn abruptly, acute adrenal insufficiency leading to a fatal outcome may occur. Drug-induced secondary adrenocortical insufficiency may be minimized by gradual reduction of dosage. This type of relative insufficiency may persist for months after discontinuation of therapy. Thus, in any situation of stress occurring during that period, hormone therapy should be reinstituted. Salt/mineralocorticoid should only required if mineralocorticoid secretion is impaired.
    Epidural lipomatosis has been reported in patients taking corticosteroids, typically with long-term use at high doses.

    Posterior subcapsular cataracts and nuclear cataracts (particularly in children), exophthalmos, or increased intraocular pressure, which may result in glaucoma with possible damage to the optic nerves, and enhanced establishment of secondary ocular infections due to fungi or viruses may occur with prolonged use of corticosteroids.

    Cyclical pulsed IV methylprednisolone (usually at initial doses of more than 1 g per day) may cause drug induced liver injury including acute hepatitis or liver enzyme increase. The time to onset of symptoms may be several weeks or longer. Resolution of the adverse events has been observed after treatment was discontinued in most cases. Appropriate monitoring is required.

    Pregnancy and Lactation

    Pregnancy

    Use methylprednisolone acetate with caution during pregnancy.

    Methylprednisolone acetate crosses the placenta. There have been reports of an increased incidence of low birth weights in infants born of mothers receiving corticosteroids.

    Corticosteroids may increase the risk of intrauterine growth retardation when administered for long periods or repeatedly during pregnancy. Hypoadrenalism may occur in the neonate following prenatal exposure to corticosteroids but usually resolves after birth. Infants should be evaluated for signs of adrenal insufficiency if they have been exposed to corticosteroids in utero, although neonatal adrenal insufficiency appears to be rare. Patients with normal pregnancies may be treated as though they were in the non-gravid state if corticosteroids are essential. Cataracts have been observed in infants born to mothers treated with long term corticosteroids during pregnancy.

    The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

    Lactation

    Use methylprednisolone acetate with caution during breastfeeding.

    Corticosteroids are excreted in small amounts in breast milk. 40 mg methylprednisolone daily are unlikely to cause systemic effects in the infant. Infants of mothers taking higher doses than this have a potential risk of adrenal suppression. However, the benefits of breastfeeding are likely to outweigh any possible risk.

    LactMed suggests that no adverse effect have been reported in breastfed infants whose mothers have used corticosteroids during breastfeeding. A temporary reduction in milk supply may occur after local injections, such as for tendinitis, have been administered. These local injections would not be expected to cause any adverse effects in breastfed infants.

    Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
    Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

    Side Effects

    Abscess (sterile)
    Acne
    Acute adrenal insufficiency
    Altered glucose tolerance
    Amenorrhoea
    Amnesia
    Anaphylaxis
    Angioedema
    Anxiety
    Arthralgia
    Blindness
    Blood pressure changes
    Cataracts
    Charcot-like arthropathy
    Chorioretinopathy
    Cognitive impairment
    Confusion
    Congestive cardiac failure
    Conjunctivitis
    Corneal thinning
    Cushingoid changes
    Depression
    Dizziness
    Dyslipidaemia
    Ecchymosis
    Electrolyte disturbances
    Epidural lipomatosis
    Exacerbation of ophthalmic fungal disease
    Exacerbation of ophthalmic viral disease
    Exophthalmos
    Fatigue
    Fever
    Fluid retention
    Gastro-intestinal symptoms
    Glaucoma
    Growth suppression in infancy, childhood and adolescence
    Headache
    Hepatitis
    Hyperpigmentation of skin
    Hypersensitivity reactions
    Hypertension
    Hypokalaemic alkalosis
    Hypopigmentation
    Impaired carbohydrate tolerance, increased need for anti-diabetic therapy
    Impaired healing
    Increased appetite
    Increased intra-ocular pressure
    Increased susceptibility and severity of infections
    Insomnia
    Lability of affect
    Leucocytosis
    Local infection at injection site
    Malaise
    Menstrual disturbances
    Mood changes
    Muscle weakness
    Myalgia
    Myopathy
    Oedema
    Opportunistic infections
    Osteonecrosis
    Osteoporosis
    Peritonitis
    Personality change
    Petechiae
    Psychological dependence
    Psychosis
    Pulmonary embolism
    Raised intracranial pressure
    Rare instances of blindness with intralesional therapy around face and head
    Recurrence of dormant tuberculosis
    Reversible elevations in liver enzymes
    Rhinitis
    Scleral thinning
    Seizures
    Skin disorder
    Skin nodules
    Sodium/water retention
    Striae
    Suicidal tendencies
    Suppression of clinical signs of infection
    Suppression of the hypothalamic-pituitary-adrenal axis
    Tendon rupture
    Thinning of skin
    Thromboembolism
    Vertebral and long bone fractures
    Vertebral compression fractures
    Vertigo
    Weight changes
    Withdrawal symptoms

    Withdrawal Symptoms and Signs

    Following abrupt discontinuance of glucocorticoids, a steroid “withdrawal syndrome� (seemingly unrelated to adrenocortical insufficiency) may also occur. This syndrome includes symptoms such as: anorexia, nausea, vomiting, lethargy, headache, fever, joint pain, desquamation, myalgia, weight loss, and/or hypotension. These adverse effects are thought to be related to the sudden change in glucocorticoid concentration.

    During prolonged therapy, adrenal cortical atrophy develops and may persist for months after stopping treatment. In patients who have received more than physiological doses of systemic corticosteroids (approximately 6 mg methylprednisolone) for greater than 3 weeks, withdrawal should not be abrupt. Dose reduction should be carried out with regards to whether the disease is likely to relapse as the dose of systemic corticosteroids is reduced. If the disease is unlikely to relapse on withdrawal, but there is uncertainty about HPA suppression, the dose of systemic corticosteroid may be reduced rapidly to physiological doses. Once a daily dose of 6 mg methylprednisolone is reached, dose reduction should be slower in order to allow the HPA-axis to recover. If it considered that the disease is unlikely to relapse, abrupt withdrawal of systemic corticosteroid treatment which has continued up to 3 weeks is considered appropriate. This is because abrupt withdrawal of doses up to 32 mg daily of methylprednisolone for 3 weeks is unlikely to lead to clinically relevant HPA axis suppression. In the following patient groups, gradual withdrawal of systemic corticosteroid therapy should be considered even if corticosteriod treatment has lasted for 3 weeks or less: • Individuals who have received repeated courses of systemic corticosteroids, particularly if taken for greater than 3 weeks. • When a short course has been prescribed within one year of cessation of long term therapy (months or years). • Patients who are predisposed to adrenocortical insufficiency other than exogenous corticosteroid therapy. • Patients receiving doses of systemic corticosteroid greater than 32 mg daily of methylprednisolone. • Patients repeatedly taking doses in the evening.

    Overdosage

    It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

    The following number will direct the caller to the relevant local centre (0844) 892 0111

    Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

    Further Information

    Last Full Review Date: May 2017

    Reference Sources

    Joint Formulary Committee. British National Formulary. 72nd ed. London: BMJ Group and Pharmaceutical Press; 2016.

    Summary of Product Characteristics: Depo-Medrone 40mg/ml. Pfizer Limited. Revised January 2017.

    US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
    Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
    Methylprednisolone. Last revised: 27 January 2017
    Last accessed: 22 March 2017

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