Dosing & Uses
Dosage Forms & Strengths
oral suspension
- 40mg/mL
Duchenne Muscular Dystrophy
Indicated for treatment of Duchenne muscular dystrophy (DMD) in patients aged ≥2 years
6 mg/kg PO qDay, preferably with a meal
Weight >50 kg: Not to exceed 300 mg/day
Some patients may respond to 2 mg/kg PO qDay; may titrate doses down to 2 mg/kg/day as needed, according to individual tolerance
Dosage Modifications
Coadministration of a strong CYP3A4 inhibitor
- Decrease dose to 4 mg/kg PO qDay; not to exceed 200 mg/day if weight >50 kg
Renal impairment
- Use with caution
Hepatic impairment
- Mild-to-moderate (Child-Pugh A or B): 2 mg/kg qDay; not to exceed 100 mg/day if weight >50 kg
- Severe (Child-Pugh C): Not studied
- Titrate dose according to individual tolerance
Dosing Considerations
Immunizations
- Administer all immunizations according to immunization guidelines before initiating
- Administer live-attenuated or live vaccines at least 4-6 weeks before initiating
Switching from oral corticosteroid treatment to vamorolone
- Can switch from oral corticosteroid treatment (eg, prednisone, deflazacort) to vamorolone without treatment interruption or period of prior corticosteroid dosage reduction to minimize risk for adrenal insufficiency
- Long-term treatment with oral corticosteroids: Start vamorolone at 6 mg/kg/day
Discontinuance
- Decrease dose gradually if drug has been administered for >1 week
Dosage Forms & Strengths
oral suspension
- 40mg/mL
Duchenne Muscular Dystrophy
Indicated for treatment of Duchenne muscular dystrophy (DMD) in patients aged ≥2 years
6 mg/kg PO qDay, preferably with a meal
Weight >50 kg: Not to exceed 300 mg/day
Some patients may respond to 2 mg/kg PO qDay; may titrate doses down to 2 mg/kg/day as needed, according to individual tolerance
Dosage Modifications
Coadministration of a strong CYP3A4 inhibitor
- Decrease dose to 4 mg/kg PO qDay; not to exceed 200 mg/day if weight >50 kg
Renal impairment
- Use with caution
Hepatic impairment
- Mild-to-moderate (Child-Pugh A or B): 2 mg/kg qDay; not to exceed 100 mg/day if weight >50 kg
- Severe (Child-Pugh C): Not studied
- Titrate dose according to individual tolerance
Dosing Considerations
Immunizations
- Administer all immunizations according to immunization guidelines before initiating
- Administer live-attenuated or live vaccines at least 4-6 weeks before initiating
Switching from oral corticosteroid treatment to vamorolone
- Can switch from oral corticosteroid treatment (eg, prednisone, deflazacort) to vamorolone without treatment interruption or period of prior corticosteroid dosage reduction to minimize risk for adrenal insufficiency
- Long-term treatment with oral corticosteroids: Start vamorolone at 6 mg/kg/day
Discontinuance
- Decrease dose gradually if drug has been administered for >1 week
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
Contraindicated (0)
Serious - Use Alternative (0)
Monitor Closely (25)
- atazanavir
atazanavir will increase the level or effect of vamorolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce vamorolone starting dose to 4 mg/kg/day; not to exceed 200 mg/day if weight >50 kg.
- chloramphenicol
chloramphenicol will increase the level or effect of vamorolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce vamorolone starting dose to 4 mg/kg/day; not to exceed 200 mg/day if weight >50 kg.
- clarithromycin
clarithromycin will increase the level or effect of vamorolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce vamorolone starting dose to 4 mg/kg/day; not to exceed 200 mg/day if weight >50 kg.
- cobicistat
cobicistat will increase the level or effect of vamorolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce vamorolone starting dose to 4 mg/kg/day; not to exceed 200 mg/day if weight >50 kg.
- conivaptan
conivaptan will increase the level or effect of vamorolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce vamorolone starting dose to 4 mg/kg/day; not to exceed 200 mg/day if weight >50 kg.
- darunavir
darunavir will increase the level or effect of vamorolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce vamorolone starting dose to 4 mg/kg/day; not to exceed 200 mg/day if weight >50 kg.
- elvitegravir/cobicistat/emtricitabine/tenofovir DF
elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of vamorolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce vamorolone starting dose to 4 mg/kg/day; not to exceed 200 mg/day if weight >50 kg.
- grapefruit
grapefruit will increase the level or effect of vamorolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce vamorolone starting dose to 4 mg/kg/day; not to exceed 200 mg/day if weight >50 kg.
- idelalisib
idelalisib will increase the level or effect of vamorolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce vamorolone starting dose to 4 mg/kg/day; not to exceed 200 mg/day if weight >50 kg.
- indinavir
indinavir will increase the level or effect of vamorolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce vamorolone starting dose to 4 mg/kg/day; not to exceed 200 mg/day if weight >50 kg.
- itraconazole
itraconazole will increase the level or effect of vamorolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce vamorolone starting dose to 4 mg/kg/day; not to exceed 200 mg/day if weight >50 kg.
- ketoconazole
ketoconazole will increase the level or effect of vamorolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce vamorolone starting dose to 4 mg/kg/day; not to exceed 200 mg/day if weight >50 kg.
- levoketoconazole
levoketoconazole will increase the level or effect of vamorolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce vamorolone starting dose to 4 mg/kg/day; not to exceed 200 mg/day if weight >50 kg.
- lonafarnib
lonafarnib will increase the level or effect of vamorolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce vamorolone starting dose to 4 mg/kg/day; not to exceed 200 mg/day if weight >50 kg.
- mifepristone
mifepristone will increase the level or effect of vamorolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce vamorolone starting dose to 4 mg/kg/day; not to exceed 200 mg/day if weight >50 kg.
- nefazodone
nefazodone will increase the level or effect of vamorolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce vamorolone starting dose to 4 mg/kg/day; not to exceed 200 mg/day if weight >50 kg.
- nelfinavir
nelfinavir will increase the level or effect of vamorolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce vamorolone starting dose to 4 mg/kg/day; not to exceed 200 mg/day if weight >50 kg.
- nirmatrelvir/ritonavir
nirmatrelvir/ritonavir will increase the level or effect of vamorolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce vamorolone starting dose to 4 mg/kg/day; not to exceed 200 mg/day if weight >50 kg.
- posaconazole
posaconazole will increase the level or effect of vamorolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce vamorolone starting dose to 4 mg/kg/day; not to exceed 200 mg/day if weight >50 kg.
- ritonavir
ritonavir will increase the level or effect of vamorolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce vamorolone starting dose to 4 mg/kg/day; not to exceed 200 mg/day if weight >50 kg.
- rucaparib
rucaparib will increase the level or effect of vamorolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce vamorolone starting dose to 4 mg/kg/day; not to exceed 200 mg/day if weight >50 kg.
- saquinavir
saquinavir will increase the level or effect of vamorolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce vamorolone starting dose to 4 mg/kg/day; not to exceed 200 mg/day if weight >50 kg.
- stiripentol
stiripentol will increase the level or effect of vamorolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce vamorolone starting dose to 4 mg/kg/day; not to exceed 200 mg/day if weight >50 kg.
- tucatinib
tucatinib will increase the level or effect of vamorolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce vamorolone starting dose to 4 mg/kg/day; not to exceed 200 mg/day if weight >50 kg.
- voriconazole
voriconazole will increase the level or effect of vamorolone by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Reduce vamorolone starting dose to 4 mg/kg/day; not to exceed 200 mg/day if weight >50 kg.
Minor (0)
Adverse Effects
>10%
2 mg/kg/day
- Vomiting (17%)
6 mg/kg/day
- Cushingoid features (29%)
- Psychiatric disorders (21%)
- Vomiting (14%)
- Increased weight (11%)
- Vitamin D deficiency (11%)
1-10%
2 mg/kg/day
- Cough (10%)
- Cushingoid features (7%)
- Psychiatric disorders (7%)
- Vitamin D deficiency (7%)
- Headache (7%)
- Diarrhea (3%)
- Increased appetite (3%)
- Rhinitis (3%)
6 mg/kg/day
- Cough (7%)
- Headache (7%)
- Diarrhea (7%)
- Increased appetite (7%)
- Rhinitis (7%)
Warnings
Contraindications
Hypersensitivity to vamorolone or any of inactive ingredients in drug product
Cautions
Long-term use of corticosteroids may have negative effects on growth and development in children
Coadministration with neuromuscular blocking agents (eg, pancuronium) or patients with disorders of neuromuscular transmission (eg, myasthenia gravis) may increase risk of developing acute myopathy
Kaposi sarcoma associated with corticosteroid use, most often for chronic conditions; discontinuing treatment may result in clinical improvement of Kaposi sarcoma
May increase risk of thromboembolism (including venous thromboembolism), particularly with higher cumulative corticosteroid doses; caution in patients who have or may be predisposed to thromboembolic disorders
Rare cases of anaphylaxis reported in patients with corticosteroid therapy
May cause avascular necrosis
Ophthalmic effects
- Corticosteroids may produce posterior subcapsular cataracts; may also cause glaucoma with possible damage to the optic nerves and may increase risk of secondary ocular infections caused by bacteria, fungi, or viruses
- Not recommended for patients with active ocular herpes simplex
- Monitor intraocular pressure if treatment continued for >6 weeks
Alterations in endocrine function
- Corticosteroids can cause serious and life-threatening alterations in endocrine function, especially with chronic use
- Monitor for Cushing 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
-
Risk of adrenal insufficiency
- Vamorolone produces reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, which may develop into secondary adrenal insufficiency after withdrawal
- Adrenal insufficiency may persist for months after discontinuance of prolonged therapy; any situation of stress occurring during that period of discontinuance, supplementation with a systemic corticosteroid recommended
- Consider increasing dose for patients already taking corticosteroids during times of stress
- Acute adrenal insufficiency can occur if therapy withdrawn abruptly and could be fatal
- Gradual taper dose when withdrawing treatment to reduce risk
- Steroid “withdrawal syndrome” may also occur following abrupt discontinuance; symptoms include anorexia, nausea, vomiting, lethargy, headache, fever, joint pain, desquamation, myalgia, and/or weight loss
-
Cushing syndrome
- Cushing syndrome (hypercortisolism) occurs with prolonged exposure to exogenous corticosteroids
- Symptoms 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
-
Hyperglycemia
- Corticosteroids can increase blood glucose, worsen preexisting diabetes, predispose those on long-term therapy to diabetes mellitus, and possibly reduce effect of antidiabetic drugs
- Monitor blood glucose at regular intervals
- For patients with hyperglycemia, initiate or adjust antidiabetic treatment
-
Patients with altered thyroid function
- Metabolic clearance of corticosteroids is decreased in patients who are hypothyroid and increased in patients who are hyperthyroid
- Consider adjustments of corticosteroid dosage with changes in thyroid status
- If coadministration with levothyroxine is required, administration of vamorolone should precede initiating levothyroxine therapy to reduce risk of adrenal crisis
-
Pheochromocytoma crisis
- Pheochromocytoma crisis, which can be fatal, reported after administration of systemic corticosteroids
- If pheochromocytoma is suspected or identified, consider risk of pheochromocytoma crisis before administering corticosteroids
Immunosuppression and increased risk of infection
- Corticosteroids suppress the immune system and increase the risk of infection with any pathogen, including viral, bacterial, fungal, protozoan, or helminthic pathogens
- Rate of infectious complications increases with increasing corticosteroid dosages
-
Corticosteroids can:
- Reduce resistance to new infections
- Exacerbate existing infections
- Increase risk of disseminated infections
- Increase risk of reactivation or exacerbation of latent infections
- Mask some signs of infection
- Corticosteroids cause a dose-dependent increase in lymphocyte and neutrophil counts
- Monitor for developing infection and consider withdrawal or dosage reduction of vamorolone as needed
-
Viral infections
- Varicella and measles can have a serious or even fatal course in nonimmune patients taking corticosteroids
- In corticosteroid-treated patients who have not had these diseases or are nonimmune, advise to avoid exposure to varicella and measles
- If treated patient is exposed to varicella, prophylaxis with varicella zoster immunoglobulin may be indicated
- If varicella develops, consider treating with antiviral agents
- If treated patient is exposed to measles, prophylaxis with immunoglobulin may be indicated
-
Hepatitis B virus reactivation
- Hepatitis B virus reactivation can occur in patients who are hepatitis B carriers treated with immunosuppressive dosages of corticosteroids
- Reactivation can also occur in corticosteroid-treated patients who appear to have resolved hepatitis B infection
- Screen for hepatitis B infection before initiating immunosuppressive treatment
- For patients who show evidence of hepatitis B infection, consult with physicians with expertise in managing hepatitis B regarding monitoring and consideration for hepatitis B antiviral therapy
-
Fungal infections
- Corticosteroids may exacerbate systemic fungal infections; therefore, avoid use in the presence of such infections
- For patients on long-term therapy who develop systemic fungal infections, withdrawal or dosage reduction is recommended
Amebiasis
- Corticosteroids may activate latent amebiasis
- Rule out latent amebiasis or active amebiasis before initiating in any patient who has spent time in the tropics or any patient with unexplained diarrhea
-
Strongyloides infestation
- Use with caution in patients with known or suspected Strongyloides (threadworm) infestation
- For patients on corticosteroids who develop Strongyloides infestation, reduce dosage or withdraw corticosteroid
Altered cardiovascular/renal function
- Corticosteroids can cause blood pressure elevation, salt and water retention, and increased potassium and calcium excretion
- Monitor blood pressure and assess for signs and symptoms of volume overload
- Monitor serum potassium levels
- Use caution in patients with congestive heart failure, hypertension, or renal insufficiency
- Use caution in patients who experienced a recent myocardial infarction
Gastrointestinal (GI) perforation
- Increased risk of GI perforation with use of corticosteroids in patients with certain GI disorders (eg, active or latent peptic ulcers, diverticulitis, fresh intestinal anastomoses, and nonspecific ulcerative colitis)
- Signs of GI perforation (eg, peritoneal irritation) may be masked in patients receiving corticosteroids
- Avoid 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
- Potentially severe psychiatric adverse reactions may occur with systemic corticosteroids
- Symptoms typically emerge within a few days or weeks of starting treatment and may be dose-related
- Psychiatric adverse reactions with corticosteroids usually involve hypomanic or manic symptoms (eg, euphoria, insomnia, mood swings) during treatment and depressive episodes after discontinuation of treatment
- Psychiatric adverse reactions with corticosteroids usually involve hypomanic or manic symptoms (eg, euphoria, insomnia, mood swings) during treatment and depressive episodes after discontinuance of treatment
Decreased bone mineral density
- Corticosteroids decrease bone formation and increase bone resorption both through their effect on calcium regulation (ie, decreasing absorption and increasing excretion) and through inhibition of osteoblast function
- Bone loss can predispose patients to vertebral and long-bone fractures
- Consider risk of osteoporosis before initiating corticosteroid therapy
- Monitor bone mineral density in patients on long-term treatment
Drug interaction overview
- Substrate of CYP3A4
- Inducer of CYP3A4 in vitro (not studied)
-
Immunizations
- Administer all immunizations according to immunization guidelines before initiating
- Administer live-attenuated or live vaccines at least 4-6 weeks before initiating
- Currently treated patients may receive concurrent vaccinations, except for live-attenuated or live vaccines
-
Strong CYP3A4 inhibitors
- Reduce vamorolone dose
- Strong CYP3A4 inhibitors increase vamorolone exposure
Pregnancy & Lactation
Pregnancy
Vamorolone is indicated for treatment of DMD, which is a disease of young males
However, corticosteroids in general should be used during pregnancy only if the potential benefit justifies potential risk to fetus
Infants born to mothers who have received substantial doses of corticosteroids during pregnancy should be carefully observed for signs of hypoadrenalism
There are no data on use during pregnancy
Adverse developmental outcomes, including orofacial clefts (cleft lip with or without cleft palate), intrauterine growth restriction, and decreased birth weight, have been reported with maternal use of corticosteroids during pregnancy
Animal data
- Animal reproduction studies have not been conducted
- Animal reproduction studies conducted with corticosteroids in pregnant mice, rats, hamsters, and rabbits using clinically relevant doses have shown an increased incidence of cleft palate
- An increase in embryofetal death, intrauterine growth retardation, and constriction of the ductus arteriosus were observed in some animal species
Lactation
There are no data on presence of vamorolone in human milk or effects on milk production
Pregnancy Categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available.Pharmacology
Mechanism of Action
First-in-class steroidal anti-inflammatory drug that differs from conventional glucocorticoids in its lack of an 11β hydroxy-carbonyl group
Removal of this contact site with the glucocorticoid receptor significantly alters structure and activity associations
Additionally, unlike glucocorticoids, vamorolone is not a substrate for 11β-hydroxysteroid dehydrogenase regulatory enzymes and is a mineralocorticoid receptor antagonist
It retains subactivities associated with efficacy (transrepression, physicochemical membrane effects, synchronization of tissue remodeling), and dissociates efficacy from other subactivities associated with detrimental side effects
Absorption
Peak plasma time: 2 hr
Effect of food
- High-fat/high-calorie meal: Reduced Cmax by 18%, increased AUC by 13%, and delayed Tmax by 1 hr
Distribution
Vd: 162 L
Protein bound: 88.1%
Blood-to-plasma ratio: 0.87
Metabolism
Metabolized via multiple Phase I and Phase II metabolic pathways, such as glucuronidation, hydroxylation, and reduction
Main plasma and urine metabolites are formed through direct glucuronidation as well as hydrogenation with subsequent glucuronidation
Metabolism of vamorolone is mediated through CYP3A4/5, CYP2C8, UGT1A3, UGT2B7, and UGT2B17
Elimination
Clearance: 58 L/hr
Half-life: ~2 hr
Excretion: Feces (30%; 15.4% unchanged); urine (48% metabolites)
Administration
Oral Administrat
Shake oral suspension well ~30 seconds before administering
Use only oral syringe provided with product to measure dose
After withdrawing appropriate dose into oral syringe, dispense directly into mouth
Storage
Before opening: Store bottle upright at room temperature (20-25°C [68-77°F]); excursion permitted between 15º and 30ºC (59-86ºF) in original carton
After opening: Refrigerate at 2-8ºC (36-46ºF)
Do not freeze
Discard any unused oral suspension remaining after 3 months of first opening bottle
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