A-Methapred injection

Name: A-Methapred injection

What should I avoid while using A-Methapred (methylprednisolone injection)?

Do not receive a "live" vaccine while using methylprednisolone. Live vaccines include measles, mumps, rubella (MMR), rotavirus, typhoid, yellow fever, varicella (chickenpox), zoster (shingles), and nasal flu (influenza) vaccine.

Avoid being near people who are sick or have infections. Call your doctor for preventive treatment if you are exposed to chicken pox or measles. These conditions can be serious or even fatal in people who are using steroid medication.

A-Methapred Injection Description

A-METHAPRED™ Sterile Powder is an anti-inflammatory glucocorticoid, which contains methylprednisolone sodium succinate as the active ingredient. A-METHAPRED™ is available in several strengths and packages for intravenous or intramuscular administration.

40 mg Single-Dose Vial – Each mL (when mixed) contains methylprednisolone sodium succinate equivalent to 40 mg methylprednisolone; also 1.6 mg monobasic sodium phosphate anhydrous; 17.46 mg dibasic sodium phosphate anhydrous; 25 mg lactose anhydrous; 8.8 mg benzyl alcohol added as preservative.

125 mg Single-Dose Vial – Each 2 mL (when mixed) contains methylprednisolone sodium succinate equivalent to 125 mg methylprednisolone; also 1.6 mg monobasic sodium phosphate anhydrous; 17.4 mg dibasic sodium phosphate anhydrous; 17.6 mg benzyl alcohol added as preservative.

When necessary, the pH of each formula was adjusted with sodium hydroxide so that the pH of the reconstituted solution is within the USP specified range of 7 to 8 and the tonicities are, for the 40 mg per mL solution, 0.50 osmolar; for the 125 mg per 2 mL, 0.40 osmolar; (Isotonic saline = 0.28 osmolar).

The chemical name for methylprednisolone sodium succinate is pregna-1,4-diene-3,20-dione,21-(3-carboxy-1-oxo-propoxy)-11,17-dihydroxy-6-methyl-monosodium salt, (6α, 11β), and the molecular weight is 496.53.

The structural formula is represented below:

                                                     

A-METHAPRED™ (methylprednisolone sodium succinate for injection, USP) sterile powder contains methylprednisolone sodium succinate as the active ingredient. Methylprednisolone sodium succinate, USP, is the sodium succinate ester of methylprednisolone. Methylprednisolone sodium succinate, USP, occurs as a white, or nearly white, odorless hygroscopic, amorphous solid. It is very soluble in water and in alcohol; it is insoluble in chloroform and is very slightly soluble in acetone.

Methylprednisolone sodium succinate is so extremely soluble in water that it may be administered in a small volume of diluent and is especially well suited for intravenous use in situations in which high blood levels of methylprednisolone are required rapidly.

IMPORTANT – Use only Bacteriostatic Water For Injection with Benzyl Alcohol when reconstituting A-METHAPRED™.

Use within 48 hours after mixing.

Interactions

Drug interactions may change how your medications work or increase your risk for serious side effects. This document does not contain all possible drug interactions. Keep a list of all the products you use (including prescription/nonprescription drugs and herbal products) and share it with your doctor and pharmacist. Do not start, stop, or change the dosage of any medicines without your doctor's approval.

Some products that may interact with this drug include: aldesleukin, mifepristone, other drugs that can also cause bleeding/bruising (including antiplatelet drugs such as clopidogrel, "blood thinners" such as warfarin/dabigatran, NSAIDs such as ibuprofen, celecoxib, aspirin, salicylates).

If your doctor has directed you to take low-dose aspirin for heart attack or stroke prevention (usually at dosages of 81-325 milligrams a day), you should continue taking it unless your doctor instructs you otherwise. Ask your doctor or pharmacist for more details.

Other medications can affect the removal of methylprednisolone from your body, which may affect how methylprednisolone works. Examples include azole antifungals (such as ketoconazole), boceprevir, cyclosporine, estrogens, HIV protease inhibitors (such as ritonavir), macrolide antibiotics (such as erythromycin), rifamycins (such as rifampin), St. John's wort, some drugs used to treat seizures (such as phenytoin, phenobarbital), telaprevir, among others.

This medication may interfere with certain laboratory tests (including skin tests), possibly causing false test results. Make sure laboratory personnel and all your doctors know you use this drug.

Overdose

If someone has overdosed and has serious symptoms such as passing out or trouble breathing, call 911. Otherwise, call a poison control center right away. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

Notes

Do not share this medication with others.

Laboratory and/or medical tests (such as blood sugar/mineral levels, blood pressure, eye exams, bone density tests, height/weight measurements) should be performed periodically to monitor your progress or check for side effects during long-term treatment. Consult your doctor for more details.

Lifestyle changes that help reduce the risk of bone loss (osteoporosis) during long-term treatment include doing weight-bearing exercise, getting adequate calcium and vitamin D, stopping smoking, and limiting alcohol. Consult your doctor for specific advice.

Missed Dose

For the best possible benefit, it is important to receive each scheduled dose of this medication as directed. If you miss a dose, contact your doctor or pharmacist right away to establish a new dosing schedule. Do not double the dose to catch up.

Storage

Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company.Information last revised July 2017. Copyright(c) 2017 First Databank, Inc.

For the Consumer

Applies to methylprednisolone: oral tablet

Other dosage forms:

  • injection powder for solution, injection suspension

Along with its needed effects, methylprednisolone (the active ingredient contained in A-Methapred) may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking methylprednisolone:

More common
  • Aggression
  • agitation
  • anxiety
  • blurred vision
  • decrease in the amount of urine
  • dizziness
  • fast, slow, pounding, or irregular heartbeat or pulse
  • headache
  • irritability
  • mental depression
  • mood changes
  • nervousness
  • noisy, rattling breathing
  • numbness or tingling in the arms or legs
  • pounding in the ears
  • shortness of breath
  • swelling of the fingers, hands, feet, or lower legs
  • trouble thinking, speaking, or walking
  • troubled breathing at rest
  • weight gain
Incidence not known
  • Abdominal cramping and/or burning (severe)
  • abdominal pain
  • backache
  • bloody, black, or tarry stools
  • cough or hoarseness
  • darkening of skin
  • decrease in height
  • decreased vision
  • diarrhea
  • dry mouth
  • eye pain
  • eye tearing
  • facial hair growth in females
  • fainting
  • fatigue
  • fever or chills
  • flushed, dry skin
  • fractures
  • fruit-like breath odor
  • full or round face, neck, or trunk
  • heartburn and/or indigestion (severe and continuous)
  • increased hunger
  • increased thirst
  • increased urination
  • loss of appetite
  • loss of sexual desire or ability
  • lower back or side pain
  • menstrual irregularities
  • muscle pain or tenderness
  • muscle wasting or weakness
  • nausea
  • pain in back, ribs, arms, or legs
  • painful or difficult urination
  • skin rash
  • sleeplessness
  • sweating
  • trouble healing
  • trouble sleeping
  • unexplained weight loss
  • unusual tiredness or weakness
  • vision changes
  • vomiting
  • vomiting of material that looks like coffee grounds

Some side effects of methylprednisolone may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Increased appetite
Incidence not known
  • Abnormal fat deposits on the face, neck, and trunk
  • acne
  • dry scalp
  • lightening of normal skin color
  • red face
  • reddish purple lines on the arms, face, legs, trunk, or groin
  • swelling of the stomach area
  • thinning of the scalp hair

For Healthcare Professionals

Applies to methylprednisolone: compounding powder, injectable powder for injection, injectable suspension, oral tablet

General

The most commonly occurring side effects have included fluid retention, alteration in glucose tolerance, increased blood pressure, behavioral and mood changes, increased appetite, and weight gain; the incidence generally correlates with dosage, timing of administration, and duration of treatment.[Ref]

Hypersensitivity

Frequency not reported: Allergic or hypersensitivity reactions; anaphylactoid reaction, anaphylaxis, angioedema[Ref]

Cardiovascular

Frequency not reported: Bradycardia, cardiac arrest, cardiac arrhythmias, cardiac enlargement, circulatory collapse, congestive heart failure, fat embolism, hypertension, hypertrophic cardiomyopathy in premature infants, myocardial rupture following recent myocardial infarction, syncope, tachycardia, thromboembolism, thrombophlebitis, vasculitis, edema, hypotension[Ref]

Endocrine

Frequency not reported: Cushingoid state, hirsutism, secondary adrenocortical and pituitary unresponsiveness (particularly in times of stress, as in trauma, surgery, or illness), moon face[Ref]

Gastrointestinal

Frequency not reported: Abdominal distention, nausea, pancreatitis, peptic ulcer, perforation of the small and large intestine, ulcerative esophagitis, gastric hemorrhage, vomiting, abdominal pain, diarrhea, dyspepsia, nausea[Ref]

Hepatic

Frequency not reported: Hepatomegaly, elevation in liver enzymes, toxic hepatitis[Ref]

Reversible transaminase elevations (AST, ALT) have been observed following corticosteroid therapy. These changes have generally been small and not associated with any clinical syndrome. Toxic hepatitis has been reported with high doses of cyclically pulsed IV therapy, onset has been several weeks or longer. Resolution has been reported with discontinuation; however, recurrence has been reported with rechallenge.[Ref]

Metabolic

Frequency not reported: Decreased carbohydrate and glucose tolerance, manifestations of latent diabetes, hypokalemic alkalosis, potassium loss, sodium retention, increased appetite, negative nitrogen balance due to protein catabolism, weight gain, metabolic acidosis, dyslipidemia, lipomatosis[Ref]

Musculoskeletal

Frequency not reported: Suppression of growth in pediatric patients, aseptic necrosis of femoral and humeral heads, calcinosis, Charcot-like atrophy, loss of muscle mass, muscle weakness, osteoporosis, pathologic fracture of long bones, postinjection flare, steroid myopathy, tendon rupture, particularly of the Achilles tendon, vertebral compression fractures, myalgia, muscle atrophy, osteonecrosis, neuropathic arthralgia, growth retardation[Ref]

Hematologic

Frequency not reported: Leucocytosis[Ref]

Immunologic

Frequency not reported: Opportunistic infection[Ref]

Ocular

Blindness has been reported with corticosteroid injection to scalp, tonsillar fauces, sphenopalatine ganglion.[Ref]

Frequency not reported: Exophthalmos, glaucoma, increased intraocular pressure, posterior subcapsular cataracts, blindness, chorioretinopathy[Ref]

Psychiatric

Frequency not reported: Depression, emotional instability, euphoria, insomnia, mood swings, personality changes, psychic disorders, confusional states, anxiety, abnormal behavior, irritability[Ref]

Dermatologic

Frequency not reported: Acne, allergic dermatitis, cutaneous and subcutaneous atrophy, dry scaly skin, ecchymosis, petechiae, erythema, hyperpigmentation, hypopigmentation, impaired wound healing, increased sweating, rash, sterile abscess, striae, suppressed reactions to skin tests, thin fragile skin, thinning scalp hair, urticaria, hypertrichosis, angioedema, skin atrophy, hyperhidrosis, pruritus[Ref]

Local

Frequency not reported: Injection site infections, injection site reactions[Ref]

Nervous system

Frequency not reported: Convulsions, headache, increased intracranial pressure with papilledema (pseudotumor cerebri) usually following discontinuation of treatment, neuritis, neuropathy, paresthesia, amnesia, dizziness[Ref]

Other

Frequency not reported: Vertigo, abnormal fat deposits, malaise, sterile abscess, impaired healing, fatigue[Ref]

Oncologic

Frequency not reported: Kaposi's sarcoma[Ref]

Respiratory

Frequency not reported: Pulmonary edema, pulmonary embolism, hiccups[Ref]

Genitourinary

Frequency not reported: Menstrual irregularities, increased or decreased motility and number of spermatozoa, increased urine calcium, glycosuria[Ref]

Some side effects of A-Methapred may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Methylprednisolone Pregnancy Warnings

This drug should only be used during pregnancy if the benefit outweighs the potential risk to the fetus AU TGA pregnancy category: A AU TGA pregnancy category: C (acetate suspension) US FDA pregnancy category: C Comments: -Observe for signs and symptoms of hypoadrenalism in infants exposed to this drug in utero. -Women who become pregnant while using this drug should be apprised of the potential fetal risks. -The short-term use of corticosteroids antepartum for the prevention of respiratory distress syndrome does not seem to pose a risk to the fetus or newborn infant.

Teratogenicity including increased incidence of cleft palate have occurred in animal studies. A number of cohort and case controlled studies in humans suggest maternal corticosteroid use in the first trimester produces a slight increased risk of cleft lip with or without cleft palate (increased from 1 out of 1000 to 3 to 5 out of 1000 infants). Reduced placental and birth weight have been recorded in animals and humans after long term treatment. There is the possibility of adrenal cortex suppression in the newborn with long term use in the mother; however the short term use of corticosteroids antepartum for the prevention of respiratory distress syndrome does not seem to pose a risk to the fetus or the newborn infant. Cataracts have been observed rarely in infants born to mothers receiving long-term corticosteroid therapy during pregnancy. Maternal pulmonary edema has been reported with inhibition of uterine contractions and fluid overload. There are no adequate and well controlled studies in pregnant women. AU TGA pregnancy category A: Drugs which have been taken by a large number of pregnant women and women of childbearing age without any proven increase in the frequency of malformations or other direct or indirect harmful effects on the fetus having been observed. AU TGA pregnancy category C: Drugs which, owing to their pharmacological effects, have caused or may be suspected of causing, harmful effects on the human fetus or neonate without causing malformations. These effects may be reversible. Accompanying texts should be consulted for further details. US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Methylprednisolone Levels and Effects while Breastfeeding

Summary of Use during Lactation

Amounts of methylprednisolone in breastmilk are very low after oral ingestion by the mother. No adverse effect have been reported in breastfed infants with maternal use of any corticosteroid during breastfeeding. With maternal intravenous doses of methylprednisolone 1 gram, fully breastfed infants would receive doses less than their daily cortisol output, and much less than a therapeutic dose on the day of infusion; accumulation of the drug does not occur in breastmilk with 3 consecutive daily doses. Avoiding breastfeeding during the infusion and for 2 to 4 hours after a 1 gram intravenous dose would further reduce infant exposure. Local injections, such as for tendinitis, would not be expected to cause any adverse effects in breastfed infants, but might occasionally cause temporary loss of milk supply.

Drug Levels

Maternal Levels. In one woman taking 6 mg daily of methylprednisolone by mouth, 2 peak milk levels occurred: one at 2 hours after the dose and another 8 hours after the dose. Peaks were about 7 mcg/L, while levels fell to about 2.5 mcg/L 6 hours after the dose and to about 1 mcg/L 10 hours after the dose.[1]

A woman with multiple sclerosis had a relapse in the first 3 months postpartum. She was given methylprednisolone 1 gram daily for 3 days. Milk samples were obtained after one of the doses. The breastmilk methylprednisolone was 3 mg/L immediately after the dose and 1.2 mg/L at 4 hours after the dose. The authors estimated that an infant who nurses at 4 hours after a dose will ingest 0.168 mg of methylprednisolone which is equivalent of 0.84 mg of cortisol or 42% of the daily output. An infant who nurses starting at 8 hours after a dose will ingest 0.048 mg of methylprednisolone which is equivalent to 12% of daily cortisol production. The authors did not specify their method of calculating these values.[2]

A woman with multiple sclerosis who was 5 months postpartum received 1 gram of methylprednisolone infused intravenously over 2 hours on 3 successive days. She provided milk samples at 0, 1, 2, 4, 8 and 12 hours after each dose. Breastmilk levels at 0 and 12 hours were not quantifiable (<0.06 mg/L). Peak levels occurred at 1 hour after the end of the infusion and averaged 5.3 mg/L (range 5.1 to 5.6 mg/L). By 4 hours, after the dose, milk levels averaged 1.1 mg/L (range 1.0 to 1.6 mg/L) and by 8 hours, milk levels averaged 0.27 mg/L (range 0.2 to 0.37 mg/L). The authors calculated that a fully breastfed infant would have received an average of 0.19 mg/kg daily (range 0.16 to 0.21 mg/kg daily) of methylprednisolone, which is less than the lowest recommended therapeutic dose for infants. Withholding nursing for 2 to 4 hours after a dose would reduce the dose substantially.[3]

A woman who was nursing a 9-month-old infant was given 1 gram of methylprednisolone daily for 3 days to treat multiple sclerosis. Cortisol milk levels were measured in breastmilk because of a lack of a methylprednisolone assay. By the fourth hour after the last dose, the cortisol concentration in breastmilk was approximately equal to the endogenous production of cortisol in an infant. The authors considered that waiting 4 hours after a 1 gram dose of methylprednisolone before resuming breastfeeding to be adequate.[4]

Sixteen nursing mothers with multiple sclerosis received 1 gram of methylprednisolone intravenously over 1 hour, either monthly (n = 7) or over 3 consecutive days (n = 9).[5] Breastmilk samples were taken at 1, 2 4, 8 and 12 hours after the each dose of their therapy, and 2 women receiving 3 doses also provided milk samples prior to their doses. Peak methylprednisolone concentrations occurred at 1 hour after the end of the infusion in all women and averaged 1.24 mg/L (range 0.55 to 2.1 mg/L). Subsequent average milk levels were 0.76 mg/L, 0.29 mg/L, 0.04 mg/L and 0.01 mg/L at 2, 4, 8 and 12 hours after the infusion, respectively. The average daily dosage over the 13 hours from the start of the infusion to 12 hours after the infusion was 0.047 mg/kg, which is much lower than the methylprednisolone dosages of 1.6 to 30 mg/kg daily given to neonates safely.[6][7] The daily dosage that a fully breastfed infant would receive in breastmilk is lower than the average production of cortisol in infants and no accumulation of the drug occurred in breastmilk in the mothers receiving 3 consecutive days of therapy.[5] Infant Levels. Relevant published information was not found as of the revision date.

Effects in Breastfed Infants

None reported with methylprednisolone or any other corticosteroid. None reported with methylprednisolone or any other corticosteroid. Three infants were breastfed from birth during maternal use of methylprednisolone 6 to 8 mg daily with no reported adverse effects up to 3 months.[1][8] In one of the papers, 2 infants had normal blood cell counts, no increase in infections and above average growth rates.[8]

Sixteen nursing mothers with multiple sclerosis received 1 gram of methylprednisolone intravenously over 1 hour, either monthly (n = 7) or over 3 consecutive days (n = 9). Infants did not breastfeed for 4 hours after the dose. No adverse effects were observed in infants during 3 to 12 months of follow-up.[5]

Effects on Lactation and Breastmilk

A patient who was 6 weeks postpartum and predominantly breastfeeding her infant received 24 mg of depot methylprednisolone plus 15 mg of lidocaine intralesionally for tenosynovitis of the wrist. Thirty hours after the injection, lactation ceased. Her breasts were soft and not engorged at that time. Thirty-six hours later, lactation resumed slowly, reaching normal milk production 24 hours later. The author hypothesized that the suppression might have occurred because the injection was in a highly mobile joint, which might have caused rapid release of the corticosteroid.[9] Large doses of triamcinolone injected into the shoulder and into the wrist have also been reported to cause temporary drop or cessation of lactation.[10][11]

A study of 46 women who delivered an infant before 34 weeks of gestation found that a course of another corticosteroid (betamethasone, 2 intramuscular injections of 11.4 mg of betamethasone 24 hours apart) given between 3 and 9 days before delivery resulted in delayed lactogenesis II and lower average milk volumes during the 10 days after delivery. Milk volume was not affected if the infant was delivered less than 3 days or more than 10 days after the mother received the corticosteroid.[12] An equivalent dosage regimen of methylprednisolone might have the same effect.

A study of 87 pregnant women found that betamethasone given as above during pregnancy caused a premature stimulation of lactose secretion during pregnancy. Although the increase was statistically significant, the clinical importance appears to be minimal.[13] An equivalent dosage regimen of methylprednisolone might have the same effect.

Sixteen nursing mothers with multiple sclerosis received 1 gram of methylprednisolone intravenously over 1 hour, either monthly (n = 7) or over 3 consecutive days (n = 9). None of the mothers reported a decrease in their milk supply.[5]

Alternate Drugs to Consider

Prednisolone, Prednisone

References

1. Coulam CB, Moyer TP, Jiang NS et al. Breast-feeding after renal transplantation. Transplant Proc. 1982;13:605-9. PMID: 6817481

2. Strijbos E, Coenradie S, Touw D, Aerden L. High-dose methylprednisolone for multiple sclerosis during lactation: Concentrations in breast milk. Mult Scler. 2015;21:797-8. PMID: 25583837

3. Cooper SD, Felkins K, Baker TE, Hale TW. Transfer of methylprednisolone into breast milk in a mother with multiple sclerosis. J Hum Lact. 2015;31:237-9. PMID: 25691380

4. Gunduz S, Gencler OS, Celik HT. Four hours is enough for lactation interruption after high-dose methylprednisolone treatment in multiple sclerosis mothers by measuring milk cortisol levels. J Matern Fetal Neonatal Med. 2016;29:3495. PMID: 26755401

5. Boz C, Terzi M, Zengin Karahan S et al. Safety of IV pulse methylprednisolone therapy during breastfeeding in patients with multiple sclerosis. Mult Scler. 2017. PMID: 28649909

6. Drago BB, Kimura D, Rovnaghi CR et al. Double-blind, placebo-controlled pilot randomized trial of methylprednisolone infusion in pediatric acute respiratory distress syndrome. Pediatr Crit Care Med. 2015;16:e74-81. PMID: 25634565

7. Huang YY, Chen MJ, Chiu NT et al. Adjunctive oral methylprednisolone in pediatric acute pyelonephritis alleviates renal scarring. Pediatrics. 2011;128:e496-504. PMID: 21844061

8. Grekas DM, Vasiliou SS, Lazarides AN. Immunosuppresive therapy and breast-feeding after renal transplantation. Nephron. 1984;37:68. Letter. PMID: 6371564

9. Babwah TJ, Nunes P, Maharaj RG. An unexpected temporary suppression of lactation after a local corticosteroid injection for tenosynovitis. Eur J Gen Pract. 2013;19:248-50. PMID: 24261425

10. McGuire E. Sudden loss of milk supply following high-dose triamcinolone (Kenacort) injection. Breastfeed Rev. 2012;20:32-4. PMID: 22724311

11. Smuin DM, Seidenberg PH, Sirlin EA et al. Rare adverse events associated with corticosteroid injections: A case series and literature review. Curr Sports Med Rep. 2016;15:171-6. PMID: 27172081

12. Henderson JJ, Hartmann PE, Newnham JP, Simmer K. Effect of preterm birth and antenatal corticosteroid treatment on lactogenesis ii in women. Pediatrics. 2008;121:e92-100. PMID: 18166549

13. Henderson JJ, Newnham JP, Simmer K, Hartmann PE. Effects of antenatal corticosteroids on urinary markers of the initiation of lactation in pregnant women. Breastfeed Med. 2009;4:201-6. PMID: 19772378

Administrative Information

LactMed Record Number

180

Last Revision Date

20170706

Disclaimer

Information presented in this database is not meant as a substitute for professional judgment. You should consult your healthcare provider for breastfeeding advice related to your particular situation. The U.S. government does not warrant or assume any liability or responsibility for the accuracy or completeness of the information on this Site.

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