Depo-Medrone with Lidocaine

1. Name Of The Medicinal Product

Depo-Medrone with Lidocaine

2. Qualitative And Quantitative Composition

Methylprednisolone BP 4%, Lidocaine Hydrochloride BP 1%

3. Pharmaceutical Form

White, sterile aqueous suspension for injection

4. Clinical Particulars

4.1 Therapeutic Indications

Corticosteroid (glucocorticoid). Depo-Medrone with Lidocaine is indicated in conditions requiring a glucocorticoid effect: e.g. anti-inflammatory or anti-rheumatic. It is recommended for local use where the added anaesthetic effect would be considered advantageous.

Depo

Intra

Rheumatoid arthritis

Osteo-arthritis with an inflammatory component

Periarticular administration

Epicondylitis

Intrabursal administration

Subacromial bursitis

Prepatellar bursitis

Olecranon bursitis

Tendon sheath administration

Tendinitis

Tenosynovitis

Epicondylitis

Therapy with Depo-Medrone with Lidocaine does not obviate the need for the conventional measures usually employed. Although this method of treatment will ameliorate symptoms, it is in no sense a cure and the hormone has no effect on the cause of the inflammation.

4.2 Posology And Method Of Administration

Depomust not be used by the intrathecal or intravenous routes (see Contra

Adults

Intra Rheumatoid arthritis, osteo-arthritis. The dose of Depo

Periarticular: Epicondylitis. Infiltrate 0.1 - 0.75 ml (4 - 30 mg of steroid) into the affected area.

Intrabursal: Subdeltoid bursitis, prepatellar bursitis, olecranon bursitis. For administration directly into bursae, 0.1 - 0.75 ml (4 - 30 mg of steroid). In most acute cases, repeat injections are not needed.

Into the tendon sheath: Tendinitis, tenosynovitis, epicondylitis. For administration directly into the tendon sheath, 0.1

Children:

For infants and children, the recommended dosage should be reduced, but dosage should be governed by the severity of the condition rather than by strict adherence to the ratio indicated by age or body weight.

Elderly:

When used according to instructions, there is no information to suggest that a change in dosage is warranted in the elderly. However, treatment of elderly patients, particularly if long-term, should be planned bearing in mind the more serious consequences of the common side-effects of corticosteroids in old age and close clinical supervision is required (see Other special warnings and precautions).

Special precautions should be observed when administering Depo

Intra

After injection the joint is moved slightly to aid mixing of the synovial fluid and the suspension. Subsequent to therapy care should be taken for the patient not to overuse the joint in which benefit has been obtained. Negligence in this matter may permit an increase in joint deterioration that will more than offset the beneficial effects of the steroid.

Intrabursal injections should be made as follows: the area around the injection site is prepared in a sterile way and a wheal at the site made with 1 percent procaine hydrochloride solution. A 20 to 24 gauge needle attached to a dry syringe is inserted into the bursa and the fluid aspirated. The needle is left in place and the aspirating syringe changed for a small syringe containing the desired dose. After injection, the needle is withdrawn and a small dressing applied. In the treatment of tenosynovitis and tendinitis, care should be taken to inject Depo

4.3 Contraindications

Depo-Medrone with Lidocaine is contra-indicated where there is known hypersensitivity to components or to any local anaesthetics of the amide type and in systemic infection unless anti-infective therapy is employed.

Due to its potential for neurotoxicity, Depomust not be given by the intrathecal route. In addition, as the product is a suspension it must not be given by the intravenous route (see Side-effects).

4.4 Special Warnings And Precautions For Use

1. Undesirable effects may be minimised by using the lowest effective dose for the minimum period. Frequent patient review is required to appropriately titrate the dose against disease activity (see Dosage and administration).

2. Patients should carry 'Steroid Treatment' cards which give clear guidance on the precautions to be taken to minimise risk and which provide details of prescriber, drug, dosage and the duration of treatment.

3. Depo

4. Depo-Medrone with Lidocaine is not recommended for epidural, intranasal, intra-ocular, or any other unapproved route of administration. See Side-effects section for details of side-effects reported from some non-recommended routes of administration.

5. Due to the absence of a true tendon sheath, the Achilles tendon should not be injected with Depo-Medrone with Lidocaine.

6. While crystals of adrenal steroids in the dermis suppress inflammatory reactions, their presence may cause disintegration of the cellular elements and physiochemical changes in the ground substance of the connective tissue. The resultant infrequently occurring dermal and/or subdermal changes may form depressions in the skin at the injection site and the possibility of depigmentation. The degree to which this reaction occurs will vary with the amount of adrenal steroid injected. Regeneration is usually complete within a few months or after all crystals of the adrenal steroid have been absorbed. In order to minimize the incidence of dermal and subdermal atrophy, care must be exercised not to exceed recommended doses in injections. Multiple small injections into the area of the lesion should be made whenever possible. The technique of intra-articular injection should include precautions against injection or leakage into the dermis.

7. Systemic absorption of methylprednisolone occurs following intra-articular injection of Depo-Medrone with Lidocaine. Systemic as well as local effects can therefore be expected.

8. Intra-articular corticosteroids are associated with a substantially increased risk of inflammatory response in the joint, particularly bacterial infection introduced with the injection. Charcot-like arthropathies have been reported particularly after repeated injections. Appropriate examination of any joint fluid present is necessary to exclude any bacterial infection, prior to injection.

9 Following a single dose of Depo-Medrone with Lidocaine, plasma cortisol levels are reduced and there is evidence of hypothalamic-pituitary-adrenal axis (HPA) suppression. This suppression lasts for a variable period of up to 4 weeks. The usual dynamic tests of HPA axis function can be used to diagnose evidence of impaired activity (e.g. Synacthen test).

10. Adrenal cortical atrophy develops during prolonged therapy 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. How dose reduction should be carried out depends largely on whether the disease is likely to relapse as the dose of systemic corticosteroids is reduced. Clinical assessment of disease activity may be needed during withdrawal. If the disease is unlikely to relapse on withdrawal of systemic corticosteroids, 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 to allow the HPA-axis to recover.

Abrupt withdrawal of systemic corticosteroid treatment, which has continued up to 3 weeks is appropriate if it considered that the disease is unlikely to relapse. 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 majority of patients. In the following patient groups, gradual withdrawal of systemic corticosteroid therapy should be considered even after courses lasting 3 weeks or less:

• Patients who have had 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 may have reasons for 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.

11. Since mineralocorticoid secretion may be impaired, salt and/or a mineralocorticoid should be administered concurrently.

12. Because rare instances of anaphylactic 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 drug allergy.

13. Corticosteroids may mask some signs of infection, and new infections may appear during their use. Suppression of the inflammatory response and immune function increases the susceptibility to fungal, viral and bacterial infections and their severity. The clinical presentation may often be atypical and may reach an advanced stage before being recognised.

14. Chickenpox is of serious concern since this normally minor illness may be fatal in immunosuppressed patients. Patients (or parents of children) without a definite history of chickenpox should be advised to avoid close personal contact with chickenpox or herpes zoster and if exposed they should seek urgent medical attention. 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. If a diagnosis of chickenpox is confirmed, the illness warrants specialist care and urgent treatment. Corticosteroids should not be stopped and the dose may need to be increased.

15. Live vaccines should not be given to individuals with impaired immune responsiveness. The antibody response to other vaccines may be diminished.

16. If corticosteroids are indicated in patients with latent tuberculosis or tuberculin reactivity, close observation is necessary as reactivation of the disease may occur. During prolonged corticosteroid therapy, these patients should receive chemoprophylaxis.

17. This product contains benzyl alcohol. Benzyl alcohol has been reported to be associated with a fatal "Gasping Syndrome" in premature infants.

18. Care should be taken for patients receiving cardioactive drugs such as digoxin because of steroid induced electrolyte disturbance/potassium loss (see Side-effects).

19. The following precautions apply for parenteral corticosteroids: Following intra-articular injection, a marked increase in pain accompanied by local swelling, further restriction of joint motion, fever, and malaise are suggestive of septic arthritis. If this complication occurs and the diagnosis of sepsis is confirmed, appropriate antimicrobial therapy should be instituted.

No additional benefit derives from the intramuscular administration of Depo-Medrone with Lidocaine. Where parenteral corticosteroid therapy for sustained systemic effect is desired, plain Depo-Medrone should be used.

Local injection of a steroid into a previously infected joint is to be avoided.

Corticosteroids should not be injected into unstable joints.

Sterile technique is necessary to prevent infections or contamination.

Special precautions:

Particular care is required when considering the use of systemic corticosteroids in patients with the following conditions and frequent patient monitoring is necessary.

1. Osteoporosis (post-menopausal females are particularly at risk).

2. Hypertension or congestive heart failure.

3. Existing or previous history of severe affective disorders (especially previous steroid psychosis).

4. Diabetes mellitus (or a family history of diabetes).

5. History of tuberculosis.

6. Glaucoma (or a family history of glaucoma).

7. Previous corticosteroid-induced myopathy.

8. Liver failure or cirrhosis.

9. Renal insufficiency.

10. Epilepsy.

11. Peptic ulceration.

12. Fresh intestinal anastomoses.

13. Predisposition to thrombophlebitis.

14. Abscess or other pyogenic infections.

15. Ulcerative colitis.

16. Diverticulitis.

17. Myasthenia gravis.

18. Ocular herpes simplex, for fear of corneal perforation.

19. Hypothyroidism.

20. Patients and/or carers should be warned that potentially severe psychiatric adverse reactions may occur with systemic steroids (see section 4.8). Symptoms typically emerge within a few days or weeks of starting treatment. Risks may be higher with high doses/systemic exposure (see also section 4.5 Interaction with Other Medicaments and Other Forms of Interaction that can increase the risk of side effects), although dose levels do not allow prediction of the onset, type, severity or duration of reactions. Most reactions recover after either dose reduction or withdrawal, although specific treatment may be necessary. Patients/carers should be encouraged to seek medical advice if worrying psychological symptoms develop, especially if depressed mood or suicidal ideation is suspected. Patients/carers should be alert to possible psychiatric disturbances that may occur either during or immediately after dose tapering/withdrawal of systemic steroids, although such reactions have been reported infrequently.

Particular care is required when considering the use of systemic corticosteroids in patients with existing or previous history of severe affective disorders in themselves or in their first degree relatives. These would include depressive or manic-depressive illness and previous steroid psychosis.

Use in children: Corticosteroids cause growth retardation in infancy, childhood and adolescence which may be irreversible. Treatment should be limited to the minimum dosage for the shortest possible time.

Use in the elderly: The common adverse effects of systemic corticosteroids may be associated with more serious consequences in old age, especially osteoporosis, hypertension, hypokalaemia, diabetes, susceptibility to infection and thinning of the skin. Close clinical supervision is required to avoid life-threatening reactions.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

1. Convulsions have been reported with concurrent use of methylprednisolone and cyclosporin. Since concurrent administration of these agents results in a mutual inhibition of metabolism, it is possible that convulsions and other adverse effects associated with the individual use of either drug may be more apt to occur.

2. Drugs that induce hepatic enzymes, such as rifampicin, rifabutin, carbamazepine, phenobarbitone, phenytoin, primidone, and aminoglutethimide enhance the metabolism of corticosteroids and its therapeutic effects may be reduced.

3. Drugs such as erythromycin and ketoconazole may inhibit the metabolism of corticosteroids and thus decrease their clearance.

4. Steroids may reduce the effects of anticholinesterases in myasthenia gravis. The desired effects of hypoglycaemic agents (including insulin), anti-hypertensives and diuretics are antagonised by corticosteroids, and the hypokalaemic effects of acetazolamide, loop diuretics, thiazide diuretics and carbenoxolone are enhanced.

5. The efficacy of coumarin anticoagulants may be enhanced by concurrent corticosteroid therapy and close monitoring of the INR or prothrombin time is required to avoid spontaneous bleeding.

6. The renal clearance of salicylates is increased by corticosteroids and steroid withdrawal may result in salicylate intoxication. Salicylates and non-steroidal anti-inflammatory agents should be used cautiously in conjunction with corticosteroids in hypothrombinaemia.

7. Steroids have been reported to interact with neuromuscular blocking agents such as pancuronium with partial reversal of the neuromuscular block.

4.6 Pregnancy And Lactation

Pregnancy

The ability of corticosteroids to cross the placenta varies between individual drugs, however, methylprednisolone does cross the placenta.

Administration of corticosteroids to pregnant animals can cause abnormalities of foetal development including cleft palate, intra-uterine growth retardation and affects on brain growth and development. There is no evidence that corticosteroids result in an increased incidence of congenital abnormalities, such as cleft palate in man, however, when administered for long periods or repeatedly during pregnancy, corticosteroids may increase the risk of intra-uterine growth retardation. Hypoadrenalism may, in theory, occur in the neonate following prenatal exposure to corticosteroids but usually resolves spontaneously following birth and is rarely clinically important. As with all drugs, corticosteroids should only be prescribed when the benefits to the mother and child outweigh the risks. When corticosteroids are essential, however, patients with normal pregnancies may be treated as though they were in the non-gravid state.

The use of local anaesthetics such as lidocaine during labour and delivery may be associated with adverse effects on mother and foetus. Lidocaine readily crosses the placenta.

Lactation

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

It is not known whether lidocaine is excreted in human breast milk.

4.7 Effects On Ability To Drive And Use Machines

None stated.

4.8 Undesirable Effects

The incidence of predictable undesirable side-effects associated with the use of corticosteroids, including hypothalamic-pituitary-adrenal suppression correlates with the relative potency of the drug, dosage, timing of administration and duration of treatment (See other special warnings and precautions).

Side-effects for the Depo-Medrone component may be observed including:

PARENTERAL CORTICOSTEROID THERAPY - Anaphylactic reaction or allergic reactions, hypopigmentation or hyperpigmentation, subcutaneous and cutaneous atrophy, sterile abscess, post injection flare (following intra-articular use), charcot-like arthropathy.

GASTRO-INTESTINAL - Dyspepsia, peptic ulceration with perforation and haemorrhage, abdominal distension, oesophageal ulceration, oesophageal candidiasis, acute pancreatitis, perforation of bowel.

Increases in alanine transaminase (ALT, SGPT) aspartate transaminase (AST, SGOT) and alkaline phosphatase have been observed following corticosteroid treatment. These changes are usually small, not associated with any clinical syndrome and are reversible upon discontinuation.

ANTI-INFLAMMATORY AND IMMUNOSUPPRESSIVE EFFECTS - Increased susceptibility and severity of infections with suppression of clinical symptoms and signs, opportunistic infections, may suppress reactions to skin tests, recurrence of dormant tuberculosis (see Other special warnings and precautions).

MUSCULOSKELETAL - Proximal myopathy, osteoporosis, vertebral and long bone fractures, avascular osteonecrosis, tendon rupture, aseptic necrosis, muscle weakness.

FLUID AND ELECTROLYTE DISTURBANCE - Sodium and water retention, potassium loss, hypertension, hypokalaemic alkalosis, congestive heart failure in susceptible patients.

DERMATOLOGICAL - Impaired healing, petechiae and ecchymosis, thin fragile skin, skin atrophy, bruising, striae, telangiectasia, acne.

ENDOCRINE/METABOLIC - Suppression of the hypothalamo-pituitary-adrenal axis; growth suppression in infancy, childhood and adolescence; menstrual irregularity and amenorrhoea. Cushingoid facies, hirsutism, weight gain, impaired carbohydrate tolerance with increased requirement for antidiabetic therapy, negative nitrogen and calcium balance. Increased appetite.

NEUROPSYCHIATRIC

OPHTHALMIC - Increased intra-ocular pressure, glaucoma, papilloedema, cataracts with possible damage to the optic nerve, corneal or scleral thinning, exacerbation of ophthalmic viral or fungal disease, exophthalmos.

GENERAL - Leucocytosis, hypersensitivity including anaphylaxis, thrombo-embolism, nausea, vertigo.

WITHDRAWAL SYMPTOMS - Too rapid a reduction of corticosteroid dosage following prolonged treatment can lead to acute adrenal insufficiency, hypotension and death. However, this is more applicable to corticosteroids with an indication where continuous therapy is given (see Other special warnings and precautions).

A 'withdrawal syndrome' may also occur including, fever, myalgia, arthralgia, rhinitis, conjunctivitis, painful itchy skin nodules and loss of weight.

Side-effects for the Lidocaine component include:

CENTRAL NERVOUS SYSTEM - Lightheadedness, nervousness, apprehension, euphoria, confusion, dizziness, drowsiness, tinnitus, blurred or double vision, vomiting, sensation of heat, cold, numbness, twitching, tremors, convulsions, loss of consciousness, respiratory depression, respiratory arrest.

CARDIOVASCULAR SYSTEM - Bradycardia, hypotension, cardiovascular collapse, cardiac arrest.

ALLERGIC REACTIONS - Cutaneous lesions, urticaria, oedema, anaphylactic reactions.

CERTAIN SIDE-EFFECTS REPORTED WITH SOME NON RECOMMENDED ROUTES OF ADMINISTRATION:

Intrathecal: Usual systemic corticoid adverse reactions, headache, meningismus, meningitis, paraplegia, spinal fluid abnormalities, nausea, vomiting, sweating, arachnoiditis, convulsions.

Extradural: Wound dehiscence, loss of sphincter control.

Intranasal: Permanent/temporary blindness, allergic reactions, rhinitis.

Ophthalmic (Subconjunctival): Redness and itching, abscess, slough at injection site, residue at injection site, increased intra-ocular pressure, decreased vision - blindness, infection.

Miscellaneous: Scalp, tonsillar fauces, sphenopalatine ganglion: blindness.

4.9 Overdose

There is no clinical syndrome of acute overdosage with Depo

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Methylprednisolone acetate is a synthetic glucocorticoid with the actions and use of natural corticosteroids. However the slower metabolism of the synthetic corticosteroid with their lower protein-binding affinity may account for their increased potency compared with the natural corticosteroids.

Lidocaine has the actions of a local anaesthetic.

5.2 Pharmacokinetic Properties

Administration of methylprednisolone acetate 40 mg intramuscularly produced measurable plasma concentrations of methylprednisolone for 11-17 days. The average peak plasma concentration was 14.8 ng per ml and occurred after 6-8 hours.

Plasma concentrations of lidocaine decline rapidly after an intravenous dose with an initial half life of less than 30 minutes; the elimination half life is 1-2 hours.

5.3 Preclinical Safety Data

Due to the age and well established safety nature of this product, preclinical data has not been included.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Sodium chloride, myristyl-gamma-picolinium chloride, benzyl alcohol, macrogol, sodium hydroxide, hydrochloric acid and water for injection.

6.2 Incompatibilities

None

6.3 Shelf Life

24 months

6.4 Special Precautions For Storage

Store at room temperature. Protect from freezing.

6.5 Nature And Contents Of Container

Glass vials with rubber cap containing 1 or 2 ml of suspension.

6.6 Special Precautions For Disposal And Other Handling

None

Administrative Data

7. Marketing Authorisation Holder

Pharmacia Limited,

Ramsgate Road,

Sandwich,

Kent CT13 9NJ

U.K.

8. Marketing Authorisation Number(S)

PL 0032/0076

9. Date Of First Authorisation/Renewal Of The Authorisation

MA granted: 03 March 1981

MA renewed: 25 November 1991

10. Date Of Revision Of The Text

October 2009

11. Legal category

POM

Ref: DML5_0 UK