Vamorolone

Vamorolone is a prescription medication indicated for the treatment of Duchenne muscular dystrophy (DMD) in patients aged 2 years and older.

• Vamorolone is available under the following different brand names: Agamree

Common side effects of Vamorolone include:

• cushingoid features
• psychiatric disorders
• weight gain, vomiting, and vitamin D deficiency

Serious side effects of Vamorolone include:

• change in cardiovascular and kidney function - increase in blood pressure and water retention
• changes in behavior and mood disturbances - seek medical attention if psychiatric symptoms develop
• lower bone mineral density - the risk of osteoporosis
• eye effects - may cause cataracts or glaucoma
• muscle weakness when used with neuromuscular blocking agents (e.g., pancuronium) or patients with disorders of neuromuscular transmission (e.g., myasthenia gravis)

Rare side effects of Vamorolone include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Oral suspension

• 40 mg/mL

Duchenne muscular dystrophy

Adult dosage

• 6 mg/kg orally once a day, preferably with a meal
• Weighing more than 50 kg: Not to exceed 300 mg/day
• Some patients may respond to 2 mg/kg orally once a day; may titrate doses down to 2 mg/kg/day as needed, according to individual tolerance

Dosage Considerations – Should be Given as Follows:

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, healthcare provider, or pharmacist first.

• Vamorolone has severe interactions with no other drugs
• Vamorolone has serious interactions with no other drugs
• Vamorolone has moderate interactions with at least 25 other drugs
• Vamorolone has minor interactions with no other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Hypersensitivity to vamorolone or any of the inactive ingredients in drug product

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Vamorolone?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Vamorolone?”

Cautions

• Long-term use of corticosteroids may have negative effects on growth and development in children
• Coadministration with neuromuscular blocking agents (e.g., pancuronium) or patients with disorders of neuromuscular transmission (e.g., myasthenia gravis) may increase the risk of developing acute myopathy
• Kaposi sarcoma is associated with corticosteroid use, most often for chronic conditions; discontinuing treatment may result in clinical improvement of Kaposi sarcoma
• May increase the 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 were 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 the 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 above 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, 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; in any situation of stress occurring during that period of discontinuance, supplementation with a systemic corticosteroid recommended
  • Consider increasing the dose for patients already taking corticosteroids during times of stress
  • Acute adrenal insufficiency can occur if therapy is 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 the 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 hyperthyroid patients
  • 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 the 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 the risk of a 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 the risk of disseminated infections
    • Increase the 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, advised to avoid exposure to varicella and measles
  • If the treated patient is exposed to varicella, prophylaxis with varicella zoster immunoglobulin may be indicated
  • If varicella develops, consider treating it with antiviral agents
  • If the 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 the use of corticosteroids in patients with certain GI disorders (e.g., active or latent peptic ulcers, diverticulitis, fresh intestinal anastomoses, and nonspecific ulcerative colitis)
  • Signs of GI perforation (e.g., 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 (e.g., euphoria, insomnia, mood swings) during treatment and depressive episodes after discontinuation of treatment
  • Psychiatric adverse reactions with corticosteroids usually involve hypomanic or manic symptoms (e.g., 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 (i.e., decreasing absorption and increasing excretion) and through inhibition of osteoblast function
  • Bone loss can predispose patients to vertebral and long-bone fractures
  • Consider the 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 and Lactation

• Vamorolone is indicated for the treatment of DMD, which is a disease of young men’s
• However, corticosteroids in general should be used during pregnancy only if the potential benefit justifies the potential risk to the 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
• Lactation
  • There are no data on the presence of vamorolone in human milk or its effects on milk production