|
Depo-Medrol
METHYLPREDNISOLONE ACETATE
Sterile aqueous suspension
Composition
DEPO-MEDROL Sterile aqueous suspension 40 mg per ml
Each ml contains:
Methylprednisolone acetate 40 mg.
Forms, ways of administration and packages
FORM: sterile aqueous suspension for single use.
WAYS OF ADMINISTRATION
- Intramuscular
- Intra-articular, periarticular, intrabursal or soft tissues
- Intralesional
- Intrarectal instillation
DEPO-MEDROL is contra-indicated for I.V. administration. DEPO-MEDROL is not
recommended for intrathecal, epidural, intranasal, intra-ocular or any other
unapproved route of administration (see ADVERSE REACTIONS reported from non
recommended routes of administration).
Packages
DEPO-MEDROL Sterile aqueous suspension 40 mg per ml is available In the
following presentations
(not all presentations may be marketed):
1 ml vial
5 ml vial
Properties
DEPO-MEDROL is a sterile aqueous suspension of the synthetic glucocorticoid
methylprednisolone acetate. It has a strong and prolonged anti-inflammatory,
immunosuppressive and anti-allergic activity. DEPO-MEDROL can be
administered I.M. for a prolonged systemic activity as well as in situ for a
local treatment. The prolonged activity of DEPO-MEDROL is explained by the
slow release of the active substance.
PHARMACODYNAMICS
Methylprednisolone acetate has the general properties of the glucocorticoid
methylprednisolone but is less soluble and less readily metabolised, which
explains its prolonged activity.
Glucocorticoids diffuse across cell membranes and complex with specific
cytoplasmic receptors. These complexes then enter the cell nucleus, bind to
DNA (chromatin), and stimulate transcription of mRNA and subsequent protein
synthesis of various enzymes thought to be ultimately responsible for the
numerous effects after systemic use. Glucocorticoids not only have an
important influence on inflammatory and immune processes, but also affect
the carbohydrate, protein and fat metabolism. They also act on the
cardiovascular system, the skeletal muscles and the central nervous system.
- Effect on the inflammatory and immune process:
The anti-inflammatory, immunosuppressive and anti-allergic properties of
glucocorticoids are responsible for most of the therapeutic applications.
These properties lead to the following results:
- reduction of the immunoactive cells near the inflammation focus;
- reduced vasodilation;
- stabilization of the lysosomal membranes;
- inhibition of phagocytosis;
- reduced production of prostaglandins and related substances.
A dose of 4.4 mg methylprednisolone acetate (4 mg methylprednisolone) has
the same glucocorticosteroid (anti-inflammatory) effect as 20 mg
hydrocortisone. Methylprednisolone has only a minimal mineralocorticoid
effect (200 mg methylprednisolone are equivalent to 1 mg
desoxycorticosterone).
- Effect on carbohydrate and protein metabolism:
Glucocorticoids have a protein catabolic action. The liberated amino acids
are converted into glucose and glycogen in the liver by means of the
gluconeogenesis process. Glucose absorption in peripheral tissues decreases,
which can lead to hyperglycemia and glucosuremia, especially in patients who
are prone to diabetes.
- Effect on fat metabolism:
Glucocorticoids have a lipolytic action. This lipolytic activity mainly
affects the limbs. They also have a lipogenetic effect which is most evident
on chest, neck and head. All this leads to a redistribution of the fat
deposits.
Maximum pharmacologic activity of glucocorticoids lays behind peak blood
levels, suggesting that most effects of the drugs result from modification
of enzyme activity rather than from direct actions by the drug.
PHARMACOKINETICS
Methylprednisolone acetate is hydrolised to its active form by serum
cholinesterases. In man, methylprednisolone forms a weak dissociable bond
with albumin and transcortin. Approximately 40 to 90% of the drug is bound.
The intracellular activity of glucocorticoids results in a clear difference
between plasma half-life and pharmacological half-life. Pharmacological
activity persists after measurable plasma levels have disappeared.
The duration of anti-inflammatory activity of glucocorticoids approximately
equals the duration of hypothalamic-pituitary-adrenal (HPA) axis
suppression.
I.M. injections of 40 mg/ml give after approximately 7.3 ± 1 hour (Tmax)
methylprednisolone serum peaks of 1.48 ± 0.86 µg/100 ml (Cmax). The
half-life is in this case 69.3 hours. After a single I.M. injection of 40 to
80 mg methylprednisolone acetate, duration of HPA axis suppression ranged
from 4 to 8 days.
An intra-articular injection of 40 mg in both knees (total dose: 80 mg)
gives after 4 to 8 hours methylprednisolone peaks of approximately 21.5 µg/100
ml. After intra-articular administration methylprednisolone acetate diffuses
from the joint into systemic circulation over approximately 7 days, as
demonstrated by the duration of the HPA axis suppression and by the serum
methylprednisolone values.
Metabolism of methylprednisolone occurs via hepatic routes qualitatively
similar to that of cortisol. The major metabolites are 20 beta-hydroxymethyl-prednisolone
and 20 beta-hydroxy-6 alpha-methylprednisone. The metabolites are mainly
excreted in the urine as glucuronides, sulfates and unconjugated compounds.
These conjugation reactions occur principally in the liver and to some
extent in the kidney.
1
2
3
4
5 |
