Vamorolone

Vamorolone
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Rafael Garcia

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Overview

Vamorolone is {{{aOrAn}}} {{{drugClass}}} that is FDA approved for the treatment of AGAMREE (Vamorolone) is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients 2 years of age and older.. Common adverse reactions include The most common adverse reactions (>10% for AGAMREE and greater than placebo) are cushingoid features, psychiatric disorders, vomiting, weight increased, and vitamin D deficiency..

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

AGAMREE (Vamorolone) is indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients 2 years of age and older.

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

The recommended dosage is 6 mg/kg taken orally once daily preferably with a meal, up to a maximum daily dosage of 300 mg for patients weighing more than 50 kg. In patients with mild to moderate hepatic impairment, the recommended dosage is 2 mg/kg taken orally once daily preferably with a meal, up to a maximum daily dosage of 100 mg for patients weighing more than 50 kg. Decrease dosage gradually when administered for more than one week.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

The recommended dosage is 6 mg/kg taken orally once daily preferably with a meal.

Off-Label Use and Dosage (Pediatric)

Contraindications

Hypersensitivity to vamorolone or any of the inactive ingredients in AGAMREE.

Warnings

Alterations in Endocrine Function: Hypothalamic-pituitary-adrenal axis suppression, cushingoid features, and hyperglycemia can occur. Monitor patients for these conditions with chronic use of AGAMREE.

   Immunosuppression and Increased Risk of Infection: Increased risk of new infections, exacerbation, dissemination, or reactivation of latent infections, which can be severe and at times fatal; signs and symptoms of infections may be masked. 
   Alterations in Cardiovascular/Renal Function: Monitor for elevated blood pressure and monitor sodium and potassium levels in patients chronically treated with AGAMREE.
   Gastrointestinal Perforation: Increased risk in patients with certain GI disorders; signs and symptoms may be masked. 
   Behavioral and Mood Disturbances: May include euphoria, insomnia, mood swings, personality changes, severe depression, and psychosis. 
   Effects on Bones: Monitor for decreases in bone mineral density with chronic use of AGAMREE. 
   Ophthalmic Effects: May include cataracts, infections, and glaucoma; monitor intraocular pressure in patients chronically treated with AGAMREE. 
   Vaccination: Do not administer live or live attenuated vaccines to patients receiving immunosuppressive doses of corticosteroids. Administer live-attenuated or live vaccines at least 4 to 6 weeks prior to starting AGAMREE.

Adverse Reactions

Clinical Trials Experience

The following serious adverse reactions are discussed in more detail in other sections:

   Alterations in Endocrine Function
   Immunosuppression and Increased Risk of Infection
   Alterations in Cardiovascular/Renal Function
   Gastrointestinal Perforation
   Behavioral and Mood Disturbances
   Effects on Bones
   Ophthalmic Effects
   Immunizations
   Effects on Growth and Development
   Myopathy
   Kaposi's Sarcoma
   Thromboembolic Events
   Anaphylaxis

Postmarketing Experience

There is limited information regarding Vamorolone Postmarketing Experience in the drug label.

Drug Interactions

Strong CYP3A4 inhibitors: The maximum recommended daily dose is 4 mg/kg up to a maximum daily dosage of 200 mg for patients weighing more than 50 kg.

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Vamorolone in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Vamorolone in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Vamorolone during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Vamorolone in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Vamorolone in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Vamorolone in geriatric settings.

Gender

There is no FDA guidance on the use of Vamorolone with respect to specific gender populations.

Race

There is no FDA guidance on the use of Vamorolone with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Vamorolone in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Vamorolone in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Vamorolone in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Vamorolone in patients who are immunocompromised.

Administration and Monitoring

Administration

The recommended dosage is 6 mg/kg taken orally once daily preferably with a meal, up to a maximum daily dosage of 300 mg for patients weighing more than 50 kg. In patients with mild to moderate hepatic impairment, the recommended dosage is 2 mg/kg taken orally once daily preferably with a meal, up to a maximum daily dosage of 100 mg for patients weighing more than 50 kg. Decrease dosage gradually when administered for more than one week.

Monitoring

There is limited information regarding Vamorolone Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Vamorolone and IV administrations.

Overdosage

Treatment of acute overdosage of vamorolone is by immediate supportive and symptomatic therapy. Gastric lavage or emesis can be considered.

Pharmacology

There is limited information regarding Vamorolone Pharmacology in the drug label.

Mechanism of Action

Vamorolone is a corticosteroid that acts through the glucocorticoid receptor to exert anti-inflammatory and immunosuppressive effects. The precise mechanism by which vamorolone exerts its effect in patients with DMD is unknown.

Structure

AGAMREE (vamorolone) oral suspension contains vamorolone, a corticosteroid. Vamorolone [17α,21-dihydroxy-16α-methyl-pregna-1,4,9(11)-triene-3,20-dione] is a white to off-white powder with a molecular formula of C22H28O4 and a molecular weight of 356.46 g/mol

Pharmacodynamics

Vamorolone produced a dose-dependent decrease in morning cortisol levels in the clinical studies. Treatment with corticosteroids is associated with a suppression of endogenous cortisol concentrations and an impairment of the hypothalamus-pituitary-adrenal (HPA) axis function. A dose-dependent increase in leukocyte counts and lymphocyte counts was observed in clinical studies with vamorolone.

Pharmacokinetics

The major route of elimination is by metabolism with subsequent excretion of metabolites into urine. The pharmacokinetics (PK) are linear and vamorolone exposure increases proportionally with either single (0.1 to 20 mg/kg) or multiple (0.25 to 20 mg/kg) doses. Vamorolone does not accumulate with repeated administration after once daily dosing.

Nonclinical Toxicology

Carcinogenesis

Carcinogenicity studies have not been conducted with vamorolone.

Mutagenesis

Vamorolone was negative for genotoxicity in in vitro (bacterial reverse mutation and cultured mouse lymphocyte chromosomal aberration) and in vivo (mouse micronucleus) assays.

Impairment of Fertility

Fertility studies in animals were not conducted with vamorolone. Oral administration of vamorolone (0, 2, 10, or 50 mg/kg/day) for 39 weeks to dogs resulted in spermatocyte and spermatid degeneration in the testes and oligospermia and germ cell debris in the epididymis in males at the high dose and absence of corpora lutea in the ovaries in females at all doses. Plasma exposures (AUC) in males at the no-effect dose for testicular toxicity (10 mg/kg) was lower than that at the maximum recommended human dose of AGAMREE (300 mg/day).

Clinical Studies

The effectiveness of AGAMREE for the treatment of Duchenne muscular dystrophy (DMD) was evaluated in a multicenter, randomized, double-blind, parallel-group, placebo- and active-controlled, multinational 24-week study (Study 1; NCT03439670). The study randomized 121 male patients with DMD to one of the following treatment groups: AGAMREE 6 mg/kg/day (n=30), AGAMREE 2 mg/kg/day (n=30), prednisone 0.75 mg/kg/day (n=31), or placebo (n=30) for 24 weeks. After 24 weeks, patients on prednisone and placebo received either AGAMREE 6 mg/kg/day (n=29) or AGAMREE 2 mg/kg/day (n=29) for an additional 20 weeks. The study included patients 4 to less than 7 years of age at time of enrollment in the study who were corticosteroid naïve and ambulatory, with a confirmed diagnosis of DMD. At baseline, patients had a mean age of 5.4 years, 83% were Caucasian, 10% were Asian, and 96% were not Hispanic or Latino.

The primary endpoint was the change from baseline to Week 24 in Time to Stand Test (TTSTAND) velocity for AGAMREE 6 mg/kg/day compared to placebo. TTSTAND velocity is a measure of muscle function that measures the time required for the patient to stand to an erect position from a supine position (floor). The key secondary endpoints consisted of change from baseline to Week 24 in TTSTAND velocity (AGAMREE 2 mg/kg/day vs placebo), 6 Minute Walk Test (6MWT) distance (AGAMREE 6 mg/kg/day vs placebo and 2 mg/kg/day vs placebo) and Time to Run/Walk 10 meters (TTRW) velocity (AGAMREE 6 mg/kg/day vs placebo and 2 mg/kg/day vs placebo). The 6MWT measures the distance that a patient can walk on a flat, hard surface in a period of 6 minutes and TTRW measures the time that it takes a patient to run or walk 10 meters. The fixed sequential testing process was applied to the key secondary endpoints in the order listed above.

How Supplied

AGAMREE oral suspension is an orange flavored homogeneous white to off-white suspension, containing 40 mg/mL of vamorolone.

AGAMREE is supplied as 100 mL in 125 mL glass bottle packaged with one bottle adapter, two 5 mL oral syringes, and an Instructions for Use: NDC 69616-264-38.

Storage

Store the bottle upright at room temperature between 20°C to 25°C (68°F to 77°F). Excursions permitted between 15°C to 30°C (59°F to 86°F) in the original carton. See USP controlled room temperature.

After opening, store the bottle upright in a refrigerator 2°C to 8°C (36°F to 46°F). Do not freeze.

Discard any unused AGAMREE oral suspension remaining after 3 months of first opening the bottle.

Images

Drug Images

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Package and Label Display Panel

Principal Display Panel – 100 mL Carton Label

NDC 69616-264-38

100 mL

AGAMREE® (vamorolone)

Oral suspension

Rx only

40 mg/mL

For Oral Administration Only

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Patient Counseling Information

Administration

   Warn patients and/or caregivers to not stop taking AGAMREE 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 [see Dosage and Administration (2.7) and Warnings and Precautions (5.1)].
   AGAMREE oral suspension should be taken once daily, preferably with a meal.
   AGAMREE oral suspension must be shaken well for about 30 seconds prior to measuring out each dose with the enclosed oral syringe.
   Discard any unused AGAMREE oral suspension remaining after 3 months of first opening the bottle.

Immunosuppression and Increased Risk of Infection

Tell 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 [see Warnings and Precautions (5.2)].

Alterations in Cardiovascular/Renal Function

Inform patients and/or caregivers that corticosteroids, including AGAMREE, can cause an increase in blood pressure and water retention. If this occurs, dietary salt restriction and potassium supplementation may be needed [see Warnings and Precautions (5.3)].

Behavioral and Mood Disturbances

Advise patients and/or caregivers about the potential for severe behavioral and mood changes with AGAMREE and encourage them to seek medical attention if psychiatric symptoms develop [see Warnings and Precautions (5.5)].

Decreases in Bone Mineral Density

Advise patients and/or caregivers about the risk of osteoporosis with prolonged use of AGAMREE, which can predispose the patient to vertebral and long bone fractures [see Warnings and Precautions (5.6)].

Ophthalmic Effects

Inform patients and/or caregivers that AGAMREE may cause cataracts or glaucoma and advise monitoring if administered for more than 6 weeks [see Warnings and Precautions (5.7)].

Vaccination

Advise patients and/or caregivers to bring immunizations up-to-date according to immunization guidelines prior to starting therapy with AGAMREE. Live-attenuated or live vaccines should be administered at least 4 to 6 weeks prior to starting AGAMREE. Inform patients and/or caregivers that they may receive concurrent vaccinations with use of AGAMREE, except for live-attenuated or live vaccines [see Warnings and Precautions (5.8)].

Drug Interactions

Certain medications can cause an interaction with AGAMREE [see Drug Interactions (7.1)]. 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 NSAIDS), 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.

Precautions with Alcohol

Alcohol-Vamorolone interaction has not been established. Talk to your doctor regarding the effects of taking alcohol with this medication.

Brand Names

AGAMREE

Look-Alike Drug Names

There is limited information regarding Vamorolone Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.