Posology : מינונים

4.2      Posology and method of administration

Methylprednisolone sodium succinate may be administered by intravenous (IV) injection or infusion, or by intramuscular (IM) injection. The preferred method for initial emergency use is IV injection. See Table 1 for recommended dosages. Dosage may be reduced for infants and children but should be selected based on the severity of the condition and the response of the patient rather than on the age or weight of the patient. The paediatric dosage should not be less than 0.5 mg/kg every 24 hours.

Table 1. Recommended dosages for methylprednisolone sodium succinate.

Indication                                          Dosage
Adjunctive therapy in       Administer 30 mg/kg IV over a period of at least 30 life-threatening            minutes. Dose may be repeated every 4 to 6 hours for up to conditions                  48 hours.

Rheumatic disorders         Administer either regimen as IV pulse dosing over at least unresponsive to             30 minutes. The regimen may be repeated if improvement standard therapy (or        has not occurred within a week after therapy, or as the during exacerbation         patient's condition dictates.
episodes)
1 g/day for 1 to 4 days, or

1 g/month for 6 months.
Systemic lupus              Administer 1 g/day for 3 days as IV pulse dosing over at erythematosus               least 30 minutes. The regimen may be repeated if unresponsive to             improvement has not occurred within a week after therapy, standard therapy (or        or as the patient's condition dictates.
during exacerbation episodes)
Multiple sclerosis          Administer 1 g/day for 3 or 5 days as IV pulse dosing over at unresponsive to             least 30 minutes. The regimen may be repeated if standard therapy (or        improvement has not occurred within a week after therapy, during exacerbation         or as the patient's condition dictates.
episodes)
Edematous states, such      Administer either regimen as IV pulse dosing over at least as glomerulonephritis       30 minutes. The regimen may be repeated if improvement or lupus nephritis,         has not occurred within 1 week after therapy, or as the unresponsive to             patient's condition dictates.
standard therapy (or during exacerbation         30 mg/kg every other day for 4 days, or episodes)
1 g/day for 3, 5 or 7 days.
Terminal cancer (to         Administer 125 mg /day IV for up to 8 weeks.
Page 4 of 27                                2024-0091167 ; 2024-00935426 Table 1. Recommended dosages for methylprednisolone sodium succinate.

Indication                                      Dosage improve quality of life)
Prevention of nausea       For mild to moderately emetogenic chemotherapy: and vomiting associated    Administer 250 mg IV over at least 5 minutes 1 hour before with cancer                start of chemotherapy. Repeat dose of methylprednisolone chemotherapy               at the initiation of chemotherapy and at the time of discharge. A chlorinated phenothiazine may also be used with the first dose of methylprednisolone for increased effect.

For severely emetogenic chemotherapy:
Administer 250 mg IV over at least 5 minutes with appropriate doses of metoclopramide or a butyrophenone 1 hour before start of chemotherapy. Repeat dose of methylprednisolone at the initiation of chemotherapy and at the time of discharge.
Acute spinal cord          Treatment should begin within 8 hours of injury.
injury
For patients initiated on treatment within 3 hours of injury:
Administer 30 mg/kg as an IV bolus over a 15-minute period, followed by a 45-minute pause, and then a continuous IV infusion of 5.4 mg/kg/h for 23 hours.

For patients initiated on treatment within 3 to 8 hours of injury: Administer 30 mg/kg as an IV bolus over a 15- minute period, followed by a 45-minute pause, and then a continuous IV infusion of 5.4 mg/kg/h for 47 hours.
There should be a separate intravenous site for the infusion pump.
Pneumocystis jiroveci      Therapy should begin within 72 hours of initial anti- pneumonia in patients      pneumocystis treatment.
with AIDS
One possible regimen is to administer 40 mg IV every 6 to
12 hours with gradual tapering over a maximum of 21 days or until the end of pneumocystis therapy.

Due to the increased rate of reactivation of tuberculosis in
AIDS patients, consideration should be given to the administration of antimycobacteria therapy if corticosteroids are used in this high risk group. The patient should also be observed for activation of other latent infections.
Exacerbation of chronic Two dose regimens have been studied: obstructive pulmonary disease (COPD)          0.5 mg/kg IV every 6 hours for 72 hours, or

Page 5 of 27                              2024-0091167 ; 2024-00935426 Table 1. Recommended dosages for methylprednisolone sodium succinate.

Indication                                      Dosage
125 mg IV every 6 hours for 72 hours, switch to an oral corticosteroid and taper dose. Total treatment period should be at least 2 weeks.
As adjunctive therapy      Initial dose will vary from 10 to 500 mg IV, depending on in other indications       the clinical condition. Larger doses may be required for short-term management of severe, acute conditions. Initial doses up to 250 mg should be administered IV over a period of at least 5 minutes, while larger doses should be administered over at least 30 minutes. Subsequent doses may be administered IV or IM at intervals dictated by the patient's response and clinical condition.

To avoid compatibility and stability problems, it is recommended that methylprednisolone sodium succinate be administered separately from other drugs whenever possible, as either IV push, through an IV medication chamber, or as an IV "piggy-back" solution (see section 6.6).

NOTE: Some of the Methylprednisolone sodium succinate formulations contain benzyl alcohol (see section 4.4 Special warnings and precautions for use, paediatric population).

Undesirable effects may be minimised by using the lowest effective dose for the minimum period (see Other special warnings and precautions).

Parenteral drug products should wherever possible be visually inspected for particulate matter and discoloration prior to administration.

Paediatric population: In the treatment of high dose indications, such as haematological, rheumatic, renal and dermatological conditions, a dosage of 30 mg/kg/day to a maximum of 1 g/day is recommended. This dosage may be repeated for three pulses either daily or on alternate days. In the treatment of graft rejection reactions following transplantation, a dosage of 10 to 20 mg/kg/day for up to 3 days, to a maximum of 1 g/day, is recommended. In the treatment of status asthmaticus, a dosage of 1 to 4 mg/kg/day for 1-3 days is recommended.

Elderly patients: Solu-Medrol is primarily used in acute short-term conditions. There is no information to suggest that a change in dosage is warranted in the elderly. However, treatment of elderly patients 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 section 4.4).

Detailed recommendations for adult dosage are as follows:
In anaphylactic reactions adrenaline or noradrenaline should be administered first for an immediate haemodynamic effect, followed by intravenous injection of Solu-Medrol (methylprednisolone sodium succinate) with other accepted procedures. There is evidence that corticosteroids through their prolonged haemodynamic effect are of value in preventing recurrent attacks of acute anaphylactic reactions.


Page 6 of 27                              2024-0091167 ; 2024-00935426 In sensitivity reactions Solu-Medrol is capable of providing relief within one half to two hours.
In patients with status asthmaticus Solu-Medrol may be given at a dose of 40 mg intravenously, repeated as dictated by patient response. In some asthmatic patients it may be advantageous to administer by slow intravenous drip over a period of hours.

In graft rejection reactions following transplantation doses of up to 1 g per day have been used to suppress rejection crises, with doses of 500 mg to 1 g most commonly used for acute rejection. Treatment should be continued only until the patient's condition has stabilised; usually not beyond 48-72 hours.

In cerebral oedema corticosteroids are used to reduce or prevent the cerebral oedema associated with brain tumours (primary or metastatic).

In patients with oedema due to tumour, tapering the dose of corticosteroid appears to be important in order to avoid a rebound increase in intracranial pressure. If brain swelling does occur as the dose is reduced (intracranial bleeding having been ruled out), restart larger and more frequent doses parenterally. Patients with certain malignancies may need to remain on oral corticosteroid therapy for months or even life. Similar or higher doses may be helpful to control oedema during radiation therapy.

The following are suggested dosage schedules for oedemas due to brain tumour.

Schedule A (1)                 Dose (mg)         Route          Interval           Duration in hours

Pre-operative:                 20                IM             3-6
During Surgery:                20 to 40          IV             hourly Post operative:                20                IM              3                 24 hours 16                IM              3                 24 hours
12                IM              3                 24 hours
8                IM              3                 24 hours
4                IM              3                 24 hours
4                IM              6                 24 hours
4                IM             12                 24 hours

Schedule B (2)                 Dose (mg)         Route          Interval           Days in hours           Duration

Pre-operative:                 40                IM              6                 2-3 Post-operative:                40                IM              6                 3-5 20                Oral            6                  1
12                Oral            6                  1
8                Oral            8                  1
4                 Oral           12                  1
4                 Oral                               1

Aim to discontinue therapy after a total of 10 days.

REFERENCES

Page 7 of 27                             2024-0091167 ; 2024-00935426 1.      Fox JL, MD. "Use of Methylprednisolone in Intracranial Surgery" Medical Annals of the District of Columbia, 34:261-265,1965.

2.      Cantu RC, MD Harvard Neurological Service, Boston, Massachusetts. Letter on file, The Upjohn Company (February 1970).

Corticosteroid therapy is an adjunct to, and not replacement for, conventional therapy.