Vamorolone (Monograph)
Brand name: Agamree
Drug class: Adrenals
Introduction
Synthetic corticosteroid.
Uses for Vamorolone
Duchenne Muscular Dystrophy
Treatment of Duchenne muscular dystrophy (DMD) in patients ≥2 years of age. Designated an orphan drug by FDA for this use.
Current standard of care for patients with DMD is the use of corticosteroids for improving muscle strength and function. The American Academy of Neurology (AAN) guidelines recommend prednisone or deflazacort to improve muscle strength, pulmonary function, and possibly also slow the development of scoliosis and need for surgery. Vamorolone was approved after the guidelines were published.
Vamorolone Dosage and Administration
General
Pretreatment Screening
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Administer all immunizations according to current guidelines prior to initiating vamorolone therapy.
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Screen for hepatitis B infection before initiating immunosuppressive treatment with vamorolone.
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For patients who have spent time in the tropics or who have unexplained diarrhea, rule out latent amebiasis or active amebiasis prior to initiating vamorolone.
Patient Monitoring
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Monitor cortisol levels after withdrawing vamorolone therapy.
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Monitor blood glucose at regular intervals during treatment.
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Monitor blood pressure and signs and symptoms of volume overload.
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Monitor serum potassium levels.
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Monitor bone mineral density in patients on long-term treatment with vamorolone.
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Monitor for infections.
Administration
Oral Administration
Administer orally once daily, preferably with a meal.
Commercially available as an oral suspension.
Administer using oral syringe provided by manufacturer. Shake oral suspension well for about 30 seconds before administration. After withdrawing appropriate dose into syringe, dispense directly into the mouth.
Dosage
Pediatric Patients
Duchenne Muscular Dystrophy
Oral
Pediatric patients ≥2 years of age: recommended dosage is 6 mg/kg once daily, up to a maximum of 300 mg for patients weighing >50 kg.
Some patients may respond to a dosage of 2 mg/kg daily; may titrate dosage down to 2 mg/kg per day as needed, based on patient tolerability.
Adults
Duchenne Muscular Dystrophy
Oral
Recommended dosage is 6 mg/kg once daily, up to a maximum of 300 mg for patients weighing >50 kg.
Some patients may respond to a dosage of 2 mg/kg daily; may titrate dosage down to 2 mg/kg per day as needed, based on patient tolerability.
Dosage Modification for Concomitant Use with CYP3A4 Inhibitors
If administered concomitantly with a strong CYP3A4 inhibitor, recommended dosage of vamorolone is 4 mg/kg once daily up to a maximum daily dosage of 200 mg for patients >50 kg. May titrate dosage down based on individual tolerability.
Transitioning From Another Corticosteroid to Vamorolone Therapy
Patients can be switched from oral corticosteroid treatment (such as prednisone or deflazacort) to vamorolone without treatment interruption or period of prior corticosteroid dosage reduction.
Patients switching after long-term treatment with oral corticosteroids should start vamorolone at a dosage of 6 mg/kg/day. When discontinuing therapy, decrease dosage gradually when administered for more than 1 week.
Special Populations
Hepatic Impairment
Mild (Child-Pugh A) to moderate (Child-Pugh B) hepatic impairment: recommended dosage is 2 mg/kg once daily up to a maximum daily dosage of 100 mg for patients >50 kg. May titrate dosage down based on individual tolerability.
Renal Impairment
No specific dosage recommendations.
Geriatric Patients
No specific dosage recommendations.
Cautions for Vamorolone
Contraindications
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Hypersensitivity to vamorolone or any of the inactive ingredients in the formulation.
Warnings/Precautions
Endocrine and Metabolic Effects
Corticosteroids can cause serious and life-threatening alterations in endocrine function, especially with chronic use. Monitor patients for Cushing's syndrome, hyperglycemia, and adrenal insufficiency after vamorolone withdrawal.
Patients with hypopituitarism, primary adrenal insufficiency or congenital adrenal hyperplasia, altered thyroid function, or pheochromocytoma may be at increased risk for adverse endocrine events.
May cause reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with potential for developing secondary adrenal insufficiency after withdrawal.
Risk of adrenal insufficiency is reduced by gradually tapering the dose when withdrawing treatment. May persist for months after discontinuation of prolonged therapy; therefore, supplementation with a systemic corticosteroid is recommended in any situation of stress during the period of discontinuation. For patients already taking corticosteroids, dosage increase may be necessary.
A steroid “withdrawal syndrome” seemingly unrelated to adrenocortical insufficiency may also occur following abrupt discontinuance of corticosteroids. Symptoms include anorexia, nausea, vomiting, lethargy, headache, fever, joint pain, desquamation, myalgia, and/or weight loss.
Cushing's syndrome (hypercortisolism) may occur with prolonged use of corticosteroids; manifestations include hypertension, truncal obesity and thinning of the limbs, purple striae, facial rounding, facial plethora, muscle weakness, easy and frequent bruising with thin fragile skin, posterior neck fat deposition, osteopenia, acne, amenorrhea, hirsutism, and psychiatric abnormalities.
Corticosteroids can increase blood glucose, worsen pre-existing diabetes, predispose those on long-term therapy to diabetes mellitus, and may reduce the effect of anti-diabetic drugs. Monitor blood glucose at regular intervals. For patients with hyperglycemia, initiate or adjust anti-diabetic treatment accordingly.
Metabolic clearance of corticosteroids is decreased in hypothyroid patients and increased in hyperthyroid patients.
Changes in thyroid status may necessitate a dose adjustment of vamorolone. When concomitant administration of levothyroxine is required, administration of vamorolone should precede the initiation of levothyroxine therapy to reduce risk of adrenal crisis.
Pheochromocytoma crisis, which can be fatal, has occurred after administration of systemic corticosteroids. In patients with suspected or identified pheochromocytoma, consider risk of pheochromocytoma crisis prior to administering corticosteroids.
Immunosuppresson and Increased Risk of Infection
Corticosteroids suppress the immune system and can mask signs and symptoms of infection. Immunosuppressive effects can reduce resistance to new infections, exacerbate existing infections, increase risk of disseminated infections, or reactivate latent infections (e.g., HBV infection, amebiasis). Risk of infections with any pathogen (e.g., viral, bacterial, fungal, protozoan, helminthic) is increased.
Monitor patients for infections. Consider withdrawal of therapy or dosage reduction as needed.
Some infections (e.g., varicella [chickenpox], measles) can have a more serious or even fatal outcome, particularly in children. Avoid exposure to these infections in children and adults who have not been previously exposed. If exposure to varicella or measles occurs in susceptible patients, treat appropriately (e.g., with varicella zoster immune globulin [VZIG], immune globulin, or antiviral agent).
Use with great care in patients with known or suspected Strongyloides (threadworm) infection. Immunosuppression may lead to Strongyloides hyperinfection and dissemination with widespread larval migration, often accompanied by severe enterocolitis and potentially fatal gram-negative septicemia.
Do not use in patients with systemic fungal infections due to potential for exacerbation of infection.
Can reactivate latent amebiasis. Exclude possible amebiasis in any patient who has been in the tropics or who has unexplained diarrhea prior to initiating therapy.
Avoid use in patients with cerebral malaria.
Reactivation of tuberculosis may occur in patients with latent tuberculosis or tuberculin reactivity. Administer chemoprophylaxis during prolonged vamorolone therapy.
Alterations in Cardiovascular/Renal Function
Corticosteroids, including vamorolone, can cause elevation of blood pressure, salt and water retention, and increased excretion of potassium and calcium.
Sodium and water retention, increased blood pressure, and increased potassium and calcium excretion may occur. Use with caution in patients with heart failure, hypertension, recent MI, or renal insufficiency.
Monitor blood pressure, serum potassium, and assess for signs and symptoms of volume overload.
GI Perforation
Patients with certain GI disorders (e.g., active or latent peptic ulcers, diverticulitis, recent intestinal anastomoses, nonspecific ulcerative colitis) are at increased risk of GI perforation with corticosteroid use. Corticosteroids may mask signs of GI perforation (e.g., peritoneal irritation).
Avoid vamorolone if there is a probability of impending perforation, abscess, or other pyogenic infections; diverticulitis; fresh intestinal anastomoses; or active or latent peptic ulcer.
Behavioral and Mood Disturbances
Systemic corticosteroid therapy may precipitate potentially severe psychiatric effects, including hypomanic, manic, or depressive symptoms. Psychiatric adverse reactions in children usually involve hyperactivity symptoms (e.g., irritability, aggressive behavior, increased frequency of tantrums, and mood swings) and sleep disorders.
Symptoms typically emerge within a few days or weeks of starting treatment and may be dose-related.
Such effects may improve after dose reduction or withdrawal, although pharmacologic treatment may be necessary.
Inform patients of potential for behavioral and mood changes and to closely monitor for these effects.
Effects on Bones
Corticosteroids decrease bone formation and increase bone resorption, potentially leading to inhibited bone growth in pediatric patients and bone loss in patients of all ages.
Monitor BMD in patients on long-term treatment with vamorolone.
Corticosteroids may cause avascular necrosis.
Ophthalmic Effects
Corticosteroids may produce posterior subcapsular cataracts and glaucoma (with possible damage to the optic nerves).
Intraocular pressure may become elevated in some patients taking corticosteroids. If treatment is continued for more than 6 weeks, monitor intraocular pressure.
May increase susceptibility to secondary ocular infections; do not use in patients with active ocular herpes infection.
Immunizations
Do not administer live or live attenuated vaccines to patients receiving immunosuppressive dosages of corticosteroids. Patients on vamorolone may receive concurrent vaccinations, except for live-attenuated or live vaccines.
Administer live-attenuated or live vaccines at least 4 to 6 weeks prior to starting vamorolone.
Effects on Growth and Development
Long-term use of corticosteroids can have negative effects on growth and development in children.
Myopathy
Acute myopathy observed with use of corticosteroids, particularly in patients with disorders of neuromuscular transmission (e.g., myasthenia gravis) or receiving concomitant therapy with neuromuscular blocking agents. Resolution or clinical improvement may occur weeks to years after discontinuance of corticosteroid therapy.
Kaposi's Sarcoma
Kaposi's sarcoma reported in patients receiving corticosteroid therapy, most often for chronic conditions. Discontinuation of treatment may result in clinical improvement.
Thromboembolic Events
Increased risk of thromboembolism, particularly with higher cumulative doses of corticosteroids, noted in observational studies. Use with caution in patients who have or may be predisposed to thromboembolic disorders.
Anaphylaxis
Rare instances of anaphylaxis reported in patients receiving corticosteroid therapy. Contraindicated in patients with hypersensitivity to vamorolone or any of the inactive ingredients in the formulation.
Specific Populations
Pregnancy
Use during pregnancy only if potential benefit justifies potential risk to the fetus.
Monitor infants born to women who received substantial doses of corticosteroids during pregnancy for symptoms of adrenal insufficiency.
Lactation
Not known whether vamorolone is distributed into human milk or affects milk production. Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects.
Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for vamorolone and any potential adverse effects on the breastfed infant.
Females and Males of Reproductive Potential
Fertility studies in animals not conducted with vamorolone.
Pediatric Use
Safety and efficacy in pediatric patients <2 years of age not established.
Adverse effects on growth and development reported in children, particularly after long-term use; monitor for such effects.
Geriatric Use
Duchenne muscular dystrophy is largely a disease of children and young adults; therefore, there is no geriatric experience with vamorolone.
Hepatic Impairment
Moderate (Child-Pugh B) hepatic impairment increases vamorolone exposure. No experience in patients with severe (Child-Pugh C) hepatic impairment.
Renal Impairment
The effects of renal impairment on vamorolone pharmacokinetics not evaluated; < 1% of the drug is excreted unchanged in the kidney.
Common Adverse Effects
Most common adverse reactions (>10%): cushingoid features, psychiatric disorders, vomiting, increased weight, vitamin D deficiency.
Drug Interactions
Metabolized by CYP3A4/5 and 2C8 and by UGT1A3, UGT2B7, and UGT2B17.
Induces CYP3A4 in vitro.
Does not inhibit P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP)1B1, OATBP1B3, organic cation transporter (OCT)2, organic anion transporter (OAT)1, OAT3, multidrug and toxin extrusion (MATE)1, MATE2-K, or bile salt export pump (BSEP) at clinically relevant concentrations. Not a substrate of P-gp, BCRP, OATP1B1, OATBP1B3, OCT2, OAT1, OAT3, MATE1, MATE2-K, or BSEP.
Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes
CYP3A4 substrates: concomitant use may decrease plasma concentrations of the substrate; however, no clinical drug interaction studies with CYP3A4 substrates conducted.
Strong CYP3A4 inhibitors: increased peak plasma concentrations and AUC of vamorolone. Reduce dosage of vamorolone if used concomitantly.
Moderate or weak CYP3A4 inhibitors: no experience with concomitant use.
Specific Drugs
Drug |
Interaction |
Comment |
---|---|---|
Antidiabetic agents |
Corticosteroids may reduce efficacy of antidiabetic agents |
|
Itraconazole |
Increased peak plasma concentrations and AUC of vamorolone by 8 and 44%, respectively |
Reduce dosage of vamorolone |
Levothyroxine |
Possible increased risk of adrenal crisis |
Initiate vamorolone prior to levothyroxine therapy |
Neuromuscular blocking agents (e.g., pancuronium) |
Possible increased risk of acute myopathy |
|
Vaccines |
May cause a diminished response to live or live-attenuated vaccines |
Live or live attenuated vaccines not recommended in individuals receiving immunosuppressive dosages of corticosteroids; administer 4-6 weeks before starting vamorolone |
Vamorolone Pharmacokinetics
Absorption
Plasma Concentrations
Exhibits linear pharmacokinetics following single and multiple-dose administration.
Minimal to no accumulation observed with once-daily dosing.
Food
After oral administration with a high-fat/high-calorie meal, time to peak plasma concentration of vamorolone was delayed by 1 hour, peak plasma concentrations decreased by 18%, and AUC increased by 13%; co-administration with a low-fat/low-calorie meal also delayed time to peak plasma concentrations by 1 hour, but reduced peak plasma concentrations and increased AUC to a lesser extent than the high-fat/high-calorie meal.
Distribution
Extent
Corticosteroids are distributed into human milk.
Plasma Protein Binding
About 88%.
Elimination
Metabolism
Metabolized by multiple Phase I and Phase II pathways including glucuronidation, hydroxylation, and reduction.
Metabolism mediated by 3A4/5 and CYP2C8, and UGT1A3, UGT2B7, and UGT2B17.
Elimination Route
Approximately 30% of a dose is excreted in feces (15.4% as unchanged drug) and 48% of a dose is excreted in the urine as mainly glucuronide metabolites (<1% as unchanged drug).
Half-life
Terminal half-life approximately 2 hours.
Special Populations
Race and sex do not appear to have a clinically significant effect on the pharmacokinetics of vamorolone.
Stability
Storage
Oral
Suspension
Store bottle upright at room temperature between 20 to 25ºC. After opening, store upright in refrigerator (2 to 8ºC). Do not freeze.
Discard any unused vamorolone oral suspension remaining after 3 months of first opening the bottle.
Actions
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Synthetic corticosteroid that acts through the glucocorticoid receptor to exert anti-inflammatory and immunosuppressive effects.
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Belongs to class of synthetic steroidal drugs that include prednisone, methylprednisolone, and dexamethasone.
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Exact mechanism of action in Duchenne muscular dystrophy unknown.
Advice to Patients
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Advise patients and/or caregivers to read the FDA-approved patient labeling.
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Warn patients and/or caregivers to not stop taking vamorolone abruptly or without first checking with their healthcare providers as there may be a need for gradual dose reductions to decrease the risk of adrenal insufficiency crisis.
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Vamorolone oral suspension should be taken once daily, preferably with a meal.
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Vamorolone oral suspension must be shaken well for about 30 seconds prior to measuring out each dose with the enclosed oral syringe.
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Advise patients and/or caregivers to inform their healthcare provider if the patient has had recent or ongoing infections or if they have recently received a vaccine. Medical advice should be sought immediately if the patient develops fever or other signs of infection. Patients and/or caregivers should be made aware that some infections can potentially be severe and fatal.
-
Warn patients who are on corticosteroids to avoid exposure to chickenpox or measles and to alert their healthcare provider immediately if they are exposed.
-
Inform patients and/or caregivers that corticosteroids, including vamorolone, can cause an increase in blood pressure and water retention. If this occurs, dietary salt restriction and potassium supplementation may be needed.
-
Advise patients and/or caregivers about the potential for severe behavioral and mood changes with vamorolone and encourage them to seek medical attention if psychiatric symptoms develop.
-
Advise patients and/or caregivers about the risk of osteoporosis with prolonged use of vamorolone, which can predispose the patient to vertebral and long bone fractures.
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Inform patients and/or caregivers that vamorolone may cause cataracts or glaucoma and advise monitoring if administered for more than 6 weeks.
-
Advise patients and/or caregivers to bring immunizations up-to-date according to immunization guidelines prior to starting therapy with vamorolone. Live-attenuated or live vaccines should be administered at least 4 to 6 weeks prior to starting vamorolone. Inform patients and/or caregivers that they may receive concurrent vaccinations with use of vamorolone, except for live-attenuated or live vaccines.
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Certain medications can cause an interaction with vamorolone. Advise patients and/or caregivers to inform their healthcare provider of all the medicines the patient is taking, including over-the-counter medicines (such as insulin, aspirin or other NSAIAs), dietary supplements, and herbal products. Inform patients and/or caregivers that alternate therapy, dosage adjustment, and/or special test(s) may be needed during the treatment.
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Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.
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Advise women to inform their clinician if they are or plan to become pregnant or plan to breast-feed.
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Inform patients of other important precautionary information.
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Preparations
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Vamorolone is available only from designated specialty pharmacies. For additional information see [Web]
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Oral |
Suspension |
40 mg/mL |
Agamree |
Catalyst Pharmaceutical |
AHFS DI Essentials™. © Copyright 2025, Selected Revisions November 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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