Vamorolone 

Vamorolone – Description

• Vamorolone is a novel, oral corticosteroid indicated for the treatment of Duchenne muscular dystrophy (DMD) in persons 2 years of age and older.⁶⁹⁷⁰² 
• Vamorolone selectively targets the glucocorticoid receptor with a different pharmacologic profile compared to classic oral corticosteroids, such as prednisone and prednisolone.
• The pharmacological profile of vamorolone provides antiinflammatory efficacy and a potentially improved safety profile compared to classic corticosteroids, including a possible reduction in bone morbidities.^6970269810 
• The efficacy of vamorolone was assessed during a multicenter, randomized, double-blind study, during which male participants ages 4 to 7 years received vamorolone 6 mg/kg/day (n = 30), vamorolone 2 mg/kg/day (n = 30), prednisone 0.75 mg/kg/day (n = 31), or placebo (n = 30) for 24 weeks. The change from baseline to week 24 in Time to Stand Test (TTSTAND) velocity (rises/second) was significantly greater in participants treated with vamorolone 6 mg/kg/day compared to participants treated with placebo, with a difference from placebo of 0.06 (95% CI 0.023 to 0.098; p = 0.002). TTSTAND velocity is a measure of muscle function that measures the time required for the participant to stand to an erect position from a supine position (floor).
• The change from baseline to week 24 in TTSTAND velocity was also significantly greater in participants treated with vamorolone 2 mg/kg/day compared to participants treated with placebo, with a difference from placebo of 0.045 (95% CI 0.008 to 0.082; p = 0.017).⁶⁹⁷⁰² 
• Treatment with vamorolone did not produce significant linear growth delays and height percentile reductions that were associated with prednisone treatment. Vamorolone was also not associated with declines in bone turnover markers.⁶⁹⁸¹⁰ 
• Common adverse reactions reported during clinical trials of vamorolone include Cushingoid features, psychiatric disorders, weight gain, and vomiting.⁶⁹⁷⁰²

Indications & Dosage

•  Duchenne muscular dystrophy

General dosage information:

• Vaccinate persons according to immunization guidelines prior to vamorolone initiation. Administer live-attenuated or live vaccines at least 4 to 6 weeks prior to vamorolone initiation.
• Persons may be switched from oral corticosteroid treatment to vamorolone without treatment interruption or a period of prior corticosteroid dosage reduction to minimize the risk of adrenal insufficiency.⁶⁹⁷⁰²

For the treatment of Duchenne muscular dystrophy (DMD)

The FDA has designated vamorolone as an orphan drug for this indication.

Oral dosage

Adults weighing more than 50 kg:

6 mg/kg PO once daily. The maximum daily dose is 300 mg. The dose may be decreased to a minimum of 2 mg/kg/day PO if needed, based on individual tolerability. Use an initial dose of 6 mg/kg PO once daily when switching from long term treatment with oral corticosteroids. When discontinuing vamorolone, gradually decrease the dosage if it has been administered for more than 1 week. Coadministration of certain medications may need to be avoided or dosage adjustments may be necessary; review drug interactions.⁶⁹⁷⁰²

Adults weighing 50 kg or less:

6 mg/kg PO once daily. The dose may be decreased to a minimum of 2 mg/kg/day PO if needed, based on individual tolerability. Use an initial dose of 6 mg/kg PO once daily when switching from long term treatment with oral corticosteroids. When discontinuing vamorolone, gradually decrease the dosage if it has been administered for more than 1 week. Coadministration of certain medications may need to be avoided or dosage adjustments may be necessary; review drug interactions.⁶⁹⁷⁰²

Children and Adolescents 2 to 17 years weighing more than 50 kg:

6 mg/kg PO once daily. The maximum daily dose is 300 mg. The dose may be decreased to a minimum of 2 mg/kg/day PO if needed, based on individual tolerability. Use an initial dose of 6 mg/kg PO once daily when switching from long term treatment with oral corticosteroids. When discontinuing vamorolone, gradually decrease the dosage if it has been administered for more than 1 week. Coadministration of certain medications may need to be avoided or dosage adjustments may be necessary; review drug interactions.⁶⁹⁷⁰²

Children and Adolescents 2 to 17 years weighing 50 kg or less:

6 mg/kg PO once daily. The dose may be decreased to a minimum of 2 mg/kg/day PO if needed, based on individual tolerability. Use an initial dose of 6 mg/kg PO once daily when switching from long term treatment with oral corticosteroids. When discontinuing vamorolone, gradually decrease the dosage if it has been administered for more than 1 week. Coadministration of certain medications may need to be avoided or dosage adjustments may be necessary; review drug interactions.⁶⁹⁷⁰²

Maximum Dosage Limits:

•Adults

weighing more than 50 kg: 300 mg/day PO.

weighing 50 kg or less: 6 mg/kg/day PO.

•Geriatric

weighing more than 50 kg: 300 mg/day PO.

weighing 50 kg or less: 6 mg/kg/day PO.

•Adolescents

weighing more than 50 kg: 300 mg/day PO.

weighing 50 kg or less: 6 mg/kg/day PO.

•Children

2 years and older weighing more than 50 kg: 300 mg/day PO.

2 years and older weighing 50 kg or less: 6 mg/kg/day PO.

1 year: Safety and efficacy have not been established.

•Infants

Safety and efficacy have not been established.

•Neonates

Safety and efficacy have not been established.

Patients with Hepatic Impairment Dosing

Mild hepatic impairment (Child-Pugh class A): 2 mg/kg PO once daily, up to a maximum of 100 mg/day in persons weighing more than 50 kg. Dose may be titrated down based on individual tolerability.

Moderate hepatic impairment (Child-Pugh class B): 2 mg/kg PO once daily, up to a maximum of 100 mg/day in persons weighing more than 50 kg. Dose may be titrated down based on individual tolerability.

Severe hepatic impairment (Child-Pugh class C): No dosage recommendations are available. There is no clinical experience with vamorolone in persons with severe hepatic impairment.

Patients with Renal Impairment Dosing

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Interactions

•  Adagrasib
•  Amoxicillin; Clarithromycin; Omeprazole
•  Anthrax Vaccine
•  Atazanavir
•  Atazanavir; Cobicistat
•  Bacillus Calmette-Guerin Vaccine, BCG
•  Ceritinib
•  Chikungunya Vaccine, Live
•  Chikungunya Vaccine, Recombinant
•  Chloramphenicol
•  Cholera Vaccine
•  Clarithromycin
•  Cobicistat
•  Darunavir
•  Darunavir; Cobicistat
•  Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
•  Dengue Tetravalent Vaccine, Live
•  Diphtheria Toxoid, Tetanus Toxoid, Acellular Pertussis Vaccine, DTaP; Haemophilus influenzae type b Conjugate Vaccine; Hepatitis B Vaccine, Recombinant; Inactivated Poliovirus Vaccine, IPV
•  Diphtheria Toxoid, Tetanus Toxoid, Acellular Pertussis Vaccine, DTaP; Haemophilus influenzae type b Conjugate Vaccine; Inactivated Poliovirus Vaccine, IPV
•  Diphtheria Toxoid, Tetanus Toxoid, Acellular Pertussis Vaccine, DTaP; Hepatitis B Vaccine, Recombinant; Inactivated Poliovirus Vaccine, IPV
•  Diphtheria Toxoid, Tetanus Toxoid, Acellular Pertussis Vaccine, DTaP; Inactivated Poliovirus Vaccine, IPV
•  Diphtheria Toxoid; Tetanus Toxoid Adsorbed, DT, Td
•  Diphtheria/Tetanus Toxoids; Pertussis Vaccine
•  Ebola Zaire Vaccine, Live
•  Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide
•  Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate
•  Gallium Ga 68 Dotatate
•  grapefruit juice
•  Haemophilus influenzae type b Conjugate Vaccine
•  Hepatitis A Vaccine, Inactivated
•  Hepatitis A Vaccine, Inactivated; Hepatitis B Vaccine, Recombinant
•  Hepatitis B Vaccine, Recombinant
•  Human Papillomavirus 9-Valent Vaccine
•  Idelalisib
•  Influenza Virus Vaccine
•  Intranasal Influenza Vaccine
•  Itraconazole
•  Japanese Encephalitis Virus Vaccine
•  Ketoconazole
•  Lansoprazole; Amoxicillin; Clarithromycin
•  Levoketoconazole
•  Live Vaccines
•  Lonafarnib
•  Lopinavir; Ritonavir
•  Lutetium Lu 177 dotatate
•  Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live
•  Measles/Mumps/Rubella Vaccines, MMR
•  Meningococcal Group B (MenB-4C) Vaccine
•  Meningococcal Group B (MenB-FHbp) Vaccine
•  Meningococcal Groups A, B, C, W, and Y Vaccine (5 valent)
•  Meningococcal Groups A, C, W, and Y Vaccine (4 valent)
•  Mifepristone
•  Nefazodone
•  Nelfinavir
•  Nirmatrelvir; Ritonavir
•  Non-Live Vaccines
•  Pneumococcal Vaccine, Polyvalent
•  Ponesimod
•  Posaconazole
•  Rabies Vaccine
•  Respiratory Syncytial Virus Vaccine
•  Ribociclib
•  Ribociclib; Letrozole
•  Ritonavir
•  Rotavirus Vaccine
•  Saquinavir
•  SARS-CoV-2 (COVID-19) vaccines
•  SARS-CoV-2 Virus (COVID-19) mRNA Vaccine
•  SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine
•  Smallpox and Monkeypox Vaccine, Live, Nonreplicating
•  Smallpox and Mpox (Vaccinia) Vaccine, Live
•  Tick-Borne Encephalitis Vaccine
•  Tipranavir
•  Tucatinib
•  Typhoid Vaccine
•  Varicella-Zoster Virus Vaccine, Live
•  Vonoprazan; Amoxicillin; Clarithromycin
•  Voriconazole
•  Yellow Fever Vaccine, Live

Adverse Reactions

Adverse Reactions

•  adrenocortical insufficiency
•  agitation
•  anaphylactoid reactions
•  anxiety
•  appetite stimulation
•  avascular necrosis
•  bone fractures
•  cataracts
•  cough
•  Cushing syndrome
•  Cushingoid features
•  diabetes mellitus
•  diarrhea
•  euphoria
•  fluid retention
•  GI perforation
•  growth inhibition
•  headache
•  hepatitis
•  hyperglycemia
•  hypertension
•  hypothalamic-pituitary-adrenal (HPA) suppression
•  immunosuppression
•  infection
•  insomnia
•  irritability
•  leukocytosis
•  mania
•  myopathy
•  ocular infection
•  rhinitis
•  sepsis
•  sodium retention
•  thromboembolism
•  vitamin D deficiency
•  vomiting
•  weight gain
•  withdrawal

References

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