Methylprednisolone succinate and

Methylprednisolone Succinate and Acetate (Solu-Medrol, DepO Medrol) [Steroid] Uses Tx inflammation d/t anaphylaxis and asthma suspected SCI Action Adrenal corticost oid Dose Adul. Anaphylaxis/ status asthmaticus 125-250 mg IV/EM Suspected SCI Load w/ 30 mg/kg then inf... 

A previously healthy 35-year-old man with conjunctival irritation had fluorescein dye instilled using a fluorescein-treated ophthalmic strip and isotonic saline. Within 30 minutes he began to notice a pruritic rash around his eye and on his arms, chest, and legs. His joints felt swollen. He had a diffuse erythematous macular rash with evidence of moderate excoriation over his arms and legs. His wrists and ankles were swollen. There were no oral lesions, and all laboratory studies, including the white blood cell count, were normal. Methylprednisolone succinate 125 mg plus diphenhydramine 50 mg produced rapid improvement. 

The prodrug approach described above also can be used to alter the solubility characteristics, which, in turn, can increase the flexibility in formulating dosage forms. The solubility of methylprcdnisolonc can be altered from essentially water-insoluble methylpredni.solone acetate to slightly water-insoluble methylprednisolone to water-soluble meth-ylprednisolone. sodium succinate. The water-soluble sodium hemisuccinate salt is used in oral, intravenous, and intramuscular dosage forms. Methylprednisolone itself is normally found in tablels. The acetate ester is found in topical ointments and sterile aqueous suspensions for intramuscular injection. Both the succinate and acetate esters are hydrolyzed to the active methylprednisolone by the patient s own systemic hydrolytic enzymes (esterases). 

Figure 7 The effect of chamber pressure on the rate of primary drying, (a) 0.18 M methylprednisolone sodium succinate 2 mL in molded vials (2.54 cm2), shelf temperature +45°C. (Smoothed data from Ref. 6.) (b) Dobutamine hydrochloride and mannitol (4% w/w in water), 12 mL in tubing vials (5.7 cm2) and shelf surface temperature +10°C. (MJ Pikal. Unpublished data.) (Modified from Ref. 1.)... 

Monitor Monitor patients closely for the first few doses. Methylprednisolone sodium succinate 8 mg/kg IV given 1 to 4 hours prior to muromonab-CD3 administration is strongly recommended to decrease the incidence of reactions to the first dose. Acetaminophen and antihistamines, given concomitantly, may reduce early reactions. Patient temperature should not exceed 37.8°C (100°F) prior to first administration. 

The mineralocorticosteroid activity of methyl-prednisolone is even less than that of prednisone/ prednisolone. It has a comparable duration of action. It is less suitable for substitution therapy in patients with adrenal hypofunctional states. Methyl-prednisolone sodium succinate is formulated for parental administration while methylprednisolone acetate is used for intra-articularly or peri-articularly injections. It can also be administered IM and then has prolonged systemic effects, lasting 1 weeks as the acetate is absorbed slowly from the site of injection. Oral absorption is rapid with peak effects within 1-2 hours. The duration of action is then about 1.5 days. 

Synthetic glucocorticoids are prednisolone, prednisone, methylprednisolone, dexamethasone, betamethasone and triamcinolone (Table 13.2). Hydrocortisone is available as either succinate or phosphate salts for oral and intravenous administration. It is the drug of choice when a rapid effect is required, e.g. acute adrenal insufficiency, or as peri-operative replacement therapy. Prednisolone can also be given intravenously. It has about 0.8 of the mineralocorticoid activity of hydrocortisone. Prednisone is a prodrug that is converted to prednisolone in the body. For chronic therapy, synthetic steroids without mineralocorticoid activity are preferred, such as dexamethasone, betamethasone or triamcinalone. Beclo-metasone passes membranes poorly and is more active topically than when given orally. It is used as an aerosol for chronic rhinitis and asthma, and topically in severe eczema. Fludrocortisone is a synthetic halogenated derivate of cortisol that is used for its mineralocorticoid effect. 

Wth adipate esters at the 21-hydroxyl group of methylprednisolone, no intramolecular catalysis is observed. Decreasing the chain length to succinate or malonate resulted in rate enhancements of 100- and 7700-fold, respectively, in the catalyzed region near pH 5. 

Figure 12 Rate of appearance of methylprednisolone, the hydrolysis product of methylprednisolone sodium succinate during stress testing at 40° C control using 250 mg drug per vial with no excipient (closed circles), 40 mg of drug in 210 mg lactose (open circles), 125 mg drug in 125 mg mannitol (open triangles), and 40 mg drug in 210 mg mannitol (closed triangles).

Figure 13 X-ray powder diffractograms of methylprednisolone sodium succinate in mannitol during stress testing at 40°C, showing crystallization of mannitol during storage (A) initial freeze-dried powder (B) two months and (C) six months.

Amsacrine Amsacrine is incompatible with sodium chloride mixtures and glucose-containing injections with acyclovir sodium, ganciclovir sodium, aztreonam, amphotericin, cimetidine hydrochloride, ceftazidime, frusemide, ceftriaxone sodium, heparin sodium, methylprednisolone sodium succinate, metoclopramide hydrochloride, and some antineoplastics.204 Asparaginase is incompatible with many drugs and rubber, and should be stored at 2° to 8 °C for stability. 

Hall, E.D., Wolf, D.L. and Braughler, J.M. (1984) Effects of a single large dose of methylprednisolone sodium succinate on experimental post-traumatic spinal cord ischemia dose-response and time-action analysis, J. Neurosurg. 61, 124-130. 

Braughler, J.M., Hall, E.D., Means, E.D., Waters, T. and Anderson, D.K. (1987) Evaluation of an intensive methylprednisolone sodium succinate dosing regimen in experimental spinal cord injury, J. Neurosurg. 67, 102-105. 

A 17-year-old boy took amfebutamone (dose unstated) for attention deficit disorder and 1 week later developed a generalized pruritic rash, but continued to take amfebutamone (27). After a further week he presented as an emergency with large joint tenderness and joint swelling. A punch biopsy of a skin lesion showed urticaria with vasculitis. Amfebutamone was withdrawn and a single dose of methylprednisolone sodium succinate was given. His symptoms resolved completely within 36 hours. 

Inflammations of the posterior segment, optic nerve, or orbit usually require systemic administration of steroids. Selection of the particular steroid preparation and the dosage remains largely an individual choice, but the tendency is to use compoimds with minimal mineralocor-ticoid activity. Table 12-2 compares various systemic steroids to hydrocortisone in terms of equivalent dose (20 mg) and relative anti-inflammatory and sodium-retaining activities when giving a value of 1.0 for hydrocortisone. Prednisone is a popular agent of choice for oral administration. For intravenous administration, methylprednisolone sodiiun succinate has proven useful. 

B. D. Herman, B. D. Sinclair, N. Milton, and S. L. Nail, The effect of bulking agent on the solid-state stability of freeze-dried methylprednisolone sodium succinate. Pharm. Res. //. 1467-1473 (1994). 

Spaced single enormous doses (pulse treatment), e.g. methylprednisolone (as sodium succinate) up to 1 g i.v. on 3 consecutive days, are sometimes used to suppress highly active inflammatory disease and buy time to change the DMARD or dose. 

Anaphylactic shock has been described after intranasal hydrocortisone acetate, intramuscular methylprednisolone (SEDA-21, 419) (251), intravenous methylprednisolone (SEDA-22, 448) (252), intramuscular dexamethasone (SEDA-22, 448) (253), and intra-articular methylprednisolone (SEDA-22, 449) (254). A life-threatening anaphylac-tic-like reaction to intravenous hydrocortisone has been described in patients with asthma (255). Acute laryngeal obstruction has been described for the first time after the intravenous administration of hydrocortisone (SEDA-22, 449) (256). There is some reason to believe that sodium succinate esters are more likely to cause hypersensitivity reactions (SEDA-17, 449), but unconjugated glucocorticoids can definitely produce allergy in some cases (SEDA-16, 452). 

Infusion-related adverse effects of gemtuzumab ozogamicin can be treated with a brief course of an intravenous glucocorticoid. Of 143 patients with refractory myeloid leukemia treated with gemtuzumab ozogamicin, 110 received paracetamol 650 mg orally with diphenhydramine 50 mg intravenously and 33 received the same premeditations plus methylprednisolone sodium succinate 50 mg intravenously before the infusion and repeated 1 hour later (1). There were grade 2 or worse infusion-related adverse events in 32 (29%) of the former, but in only one of the latter (3%). 

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