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Vamorolone (Monograph)

Brand name: Agamree
Drug class: Adrenals

Medically reviewed by Drugs.com on Nov 10, 2024. Written by ASHP.

[Web]

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

Patient Monitoring

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

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

Advice to Patients

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]

Vamorolone

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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