Vamorolone - Indications, Pharmacology, Warnings, and Precautions

Overview:

Vamorolone is a novel medicine that has gained wide acceptance and popularity for tackling the manifestations associated with Duchenne muscular dystrophy, which is an inborn condition primarily targeting muscular and nervous functions. Being an investigational medicine, Vamorolone is formulated to subjugate the side effects associated with conventional medicines that are being advised for Duchenne muscular dystrophy. However, the minimal side effect is achieved without compromising the drug’s therapeutic values. Vamorolone possesses enhanced therapeutic properties when compared with other conventional medicines for Duchenne muscular dystrophy. Vamorolone received authorization from the drug regulatory body of the United States (US), the Food and Drug Administration (FDA), on October 26th, 2023. The investigational drug thus got licensed for Duchenne muscular dystrophy and is widely marketed.

Drug Group:

Vamorolone falls under the dissociative steroid drug class, and it is identified to be a first-in-class synthetic steroid. It is the single medication under this drug class that has gained FDA compliance. The therapeutic properties of the dissociative steroid drug class are similar to conventional corticosteroids with potent anti-inflammatory aspects.

Available Doses and Dosage Forms:

Vamorolone is available for oral intake as an oral suspension. No other dosage forms are marketed. The oral suspension is formulated so that each milliliter of the solution contributes to 40 milligrams of Vamorolone. The concerned doctor will determine the dosage for each individual and, accordingly, prescribe the exact milliliters of the medicine that must be taken.

For Patients:

What Is Duchenne Muscular Dystrophy?

Duchenne muscular dystrophy is an alarming medical condition that develops by birth. It is precipitated due to an alteration in the genetic pattern (mutation). In this condition, the gene that encodes for a specific muscle protein, dystrophin, will be structurally altered. The structural alteration or reorganization of the gene can flag errors in the corresponding proteins. Dystrophin protein is concerned with muscular strength and integrity. Impairment of the dystrophin precipitates deterioration and regression of the muscle fibers, potentially weakening the muscles.

The affected individuals start exhibiting manifestations at around two years of age. In the initial stages, the child starts exhibiting weakness in the legs and hip region, challenges in motor skills, and frequent trips. The compromised muscle strength makes it difficult for the child to walk, run, and do other activities like a normal kid. Besides muscle fatigue, the child flags learning ability and cognitive skills challenges. As age advances, the condition also worsens to the extent that it collapses one’s ability to move with legs and necessitates assistance from a third person or equipment like a wheelchair. It can wreck one’s quality of life. Furthermore, the breathing muscles also become incapacitated such that the person elicits challenges in breathing in and out, which can be potentially grave. Heart diseases are also reported in the later stages of the condition.

How Does Vamorolone Work?

Being a modified version of corticosteroid, Vamorolone works to tackle inflammation differently. Besides anti-inflammatory properties, Vamorolone mitigates the muscular deterioration triggered by Duchenne muscular dystrophy. Unlike conventional corticosteroid drug groups, Vamorolone exerts its effect only on specific receptors, thereby restricting the unintended interaction of the steroid with other receptors, potentially precipitating alarming complications that follow every corticosteroid therapy.

What Is the Dosage of Vamorolone?

Six milligrams of Vamorolone per kilogram (mg/kg) of body weight is the preferred daily dosage that is advised for patients detected with Duchenne muscular dystrophy. However, desirable outcomes are obtained in certain patients even with a dosage less than the daily recommended. Considering the patient's tolerance, the dose can be down-regulated in such cases. Three hundred milligrams is the safest maximum dose for an individual weighing over 110.23 pounds.

How Effective Is Vamorolone?

Vamorolone is a highly productive medicine for Duchenne muscular dystrophy. Various studies have demonstrated the effectiveness and potency of the drug. It effectively curbs inflammation, and in addition, it preserves the functional status of the muscles. Most importantly, it holds a higher safety profile than traditional steroid-based drugs. It selectively acts on the specific receptors while sparing other receptors so that many of the alarming adverse reactions associated with steroid therapy can be checked. It dramatically gears down the pace of muscle weakness and disease progression in Duchenne muscular dystrophy patients. Its potency and safety aspects enable the application of Vamorolone even in pediatric patients over two years of age.

What Are the Things to Inform the Doctor Before Taking Vamorolone?

Before initiating pharmacological therapy, the doctors should be informed about certain critical patient information.

• The doctors should be informed about the patient's prior allergic encounters with Vamorolone or other conventional corticosteroids. Similarly, hyperreactivity with any components mentioned in the ingredient listing of Vamorolone oral suspension should be informed beforehand.

• Keep the doctors updated about the patient’s pregnancy and nursing status. Certain drugs can precipitate complications for the baby in the womb or breastfed baby. Therefore, it should be brought to the doctor's attention.

• A detailed medical history is another important thing that the doctor should be provided with. It should encompass all the information about the patient's medical history, including past illness, underlying disease conditions, and surgeries undergone or planned to undertake.

• Besides medical history, it is imperative to keep the doctors informed about the patient's drug history. It should be elaborate and comprehensive such that all the medicines, be they over-the-counter, dietary supplements, ayurvedic, or herbal, should be mentioned. Simultaneous intake of certain medicines can bring unwanted effects on the body, and at times, it may impair the working principle and potency of either or both medicines. Therefore, to check such unpleasant events, the doctors should thoroughly know the patient’s drug history.

How Is Vamorolone Administered?

Vamorolone is marketed in oral suspension formulations intended to be taken by mouth. Before administration, to ensure homogeneity in the composition, the oral formulation must be agitated by gentle shaking movements. A dispensing syringe is provided with the oral formulation that is employed to accurately extract the required amount of formulation for oral ingestion. After breaking the seal of the suspension bottle, it can be used for three months, after which it should be discarded and is not fit for use. The medicine is best advised to be ingested following a healthy meal.

What Are the Side Effects of Vamorolone?

Vamorolone is designed with minimal negative impacts on the body than conventional steroids. However, it does precipitate certain side effects. Some of the routinely reported side effects concerning Vamorolone include the following:

• Mood swings, depression (feeling lost and sad), anxiety (exaggerated fear), restlessness, and confusion are frequently encountered during Vamorolone therapy.

• Sleep disturbances and abnormal gathering of fat in the axial parts of the body, like the stomach and face, are also occasionally reported with Vamorolone therapy.

• Bone defects and enhanced susceptibility to bone fractures are other effects that necessitate immediate medical guidance.

Dietary Considerations:

No specific dietary consideration is advised for Vamorolone therapy. Reports demonstrated that the consumption of fatty meals can deplete the utmost concentration of the drug by 15 percent. However, considering patients' health status and concomitant ailments, the concerned doctors may advise certain dietary regulations to which patients must adhere.

Missed Dose:

Being a daily dose medicine, there are possibilities for the patient to miss medicine intake. In such cases, the missed dose can be ingested once the person becomes aware of the missing dose. However, if the person recalls the missed dose the next day when it is time for the subsequent dose, the forgotten dose can be disregarded, and the person can proceed with the upcoming dose. Attempting to balance out the missed one by simply doubling the subsequent dose can potentially bring in toxicity issues.

Overdose:

Consuming more than the intended dose of Vamorolone can bring in overdose problems. Overdosing enhances the toxicity potential of the medicine, and once atypical manifestations are flagged, immediate medical attention needs to be sought.

Storage:

Vamorolone oral formulation is marketed in glass bottles. 20 to 25 degrees Celsius (68 to 77 degrees Fahrenheit) is the ideal storage temperature for Vamorolone. However, keeping the medicine within the temperature range of 15 to 30 degrees Celsius (59 to 86 degrees Fahrenheit) is safe. Keep the medicine bottles inaccessible to small kids to check accidental medicine ingestion.

For Doctors:

Indication:

Duchenne muscular dystrophy is the medical condition for which Vamorolone is indicated. It can be prescribed for elderly and pediatric patients over two years of age.

Dose:

Six milligrams (mg) per kilogram of body weight is the recommended daily dose for Vamorolone. Each patient's body weight modifies the dosage. 300 mg is the maximum daily dose of Vamorolone that is considered safe for an individual weighing a minimum of 110.23 pounds. However, individual tolerability is also considered. Certain patients, particularly younger patients, elicit desired outcomes even at a lower daily dosage of two milligrams per kilogram of body weight.

Dosing Considerations:

Certain dosing considerations are being advised for Vamorolone. The daily dose must be downregulated for individuals with compromised liver functions (mild to moderate). Two milligrams per kilogram of body weight is the recommended dosage of Vamorolone for such patients. Similarly, the daily dose is limited to 100 milligrams, not to overburden the liver.

When conventional corticosteroid therapy is switched with Vamorolone therapy, there is no need for an off-on interval. Vamorolone therapy is initiated as a continuation of conventional corticosteroids without a drug-free period to check the development of adrenal insufficiency with the standard daily dose of six milligrams per kilogram of body weight.

Abrupt withdrawal of Vamorolone can bring in certain unpredictable events. Hence, the withdrawal should be done by gradual dose reduction.

What Are the Pharmacological Aspects of Vamorolone?

• Mechanism of Action: Vamorolone elicits its effects by tempering the immune response. It brings down the inflammation triggered by Duchenne muscular dystrophy. The drug molecules communicate with the glucocorticoid receptors and establish bonds with them in a specific manner. This binding modulates the functioning of glucocorticoid receptors, making it favorable for enhancing muscle function and immune response. Its effects are more pronounced on the target sites, which aid in reducing the possibility of severe adverse reactions reported with corticosteroid therapy. Immunosuppressive and anti-inflammatory aspects contribute to the efficacy of Vamorolone therapy in dealing with Duchenne muscular dystrophy.

• Pharmacodynamics: Apart from the immunosuppressive effects, Vamorolone also depreciates the cortisol level, which is remarkably reflected in the morning hours. This dip in cortisol is directly proportional to the dose of Vamorolone being administered. In addition to cortisol levels, it also inflates the count of certain immune cells like lymphocytes and leukocytes.

• Pharmacokinetics: Vamorolone is taken up from the intestine into the bloodstream after oral intake. Vamorolone attains its utmost concentration within two hours post-oral intake. The Vamorolone drug molecules are distributed with plasma proteins' help and reach the target sites. The liver enzymes cleave Vamorolone molecules into simpler metabolites by various pathways, like reduction, glucuronidation, and hydroxylation. The therapeutic aspects of these metabolites are not known. The elimination of Vamorolone occurs through urinary and fecal routes. A smaller proportion is eliminated in the unchanged form, while the remaining is eliminated as metabolites.

Toxicity:

There is only limited information available about Vamorolone’s toxicity profile. Overdose consumption of Vamorolone can bring in toxicity issues, which are often tackled with supportive interventions. Gastric lavage is advised to flush out the ingested drug molecules, which aids in alleviating the toxicity symptoms. The carcinogenic profile of Vamorolone has not been explored much, and hence, it is not known. In vitro studies preclude the possibility of genotoxicity. However, they lack clinical evidence from human studies.

Clinical Studies:

Various studies on Vamorolone demonstrated its potential for tackling Duchenne muscular dystrophy. The randomized, multicentric, case-controlled, and double-blinded study was conducted for 24 weeks. The study was conducted in 121 subjects. Vamorolone’s effectiveness was compared to that of the conventional corticosteroid Prednisolone. Study results illustrated a remarkable decline in unwanted adverse reactions and enhanced therapeutic values associated with Vamorolone therapy.

What Are the Contraindications of Vamorolone?

There are specific conditions in which Vamorolone therapy should not be undertaken. Some potent contraindications include the following:

• Patients who have had prior allergic encounters with Vamorolone should refrain from Vamorolone therapy.

• Prior hyperreactivity issues to any of the components in Varomolorone oral formulation is another potent contraindication for Vamorolone therapy.

Warnings and Precautions:

• Impaired Hormonal Functions: Vamorolone therapy can potentially bring in irregularities in endocrine function, which can be even grave and life-threatening. Following long-term therapy using Vamorolone, the patient’s endocrine profile needs to be tracked to identify abnormalities. Adrenal insufficiency, hyperglycemia, hypercalcemia, and Cushing’s syndrome may develop post-therapy. The susceptibility to hormonal disruption is higher in patients with known endocrine diseases.

• Renal and Cardiovascular Irregularities: Prolonged therapy using Vamorolone can influence the electrolyte balance in the body and can potentially bring about renal insufficiency, hypertension, or congestive heart failure. Hence, regular kidney and heart function assessment is warranted to ensure safety.

• Risk of Infections: Since Vamorolone can dramatically gear down the body’s immune response, there are possibilities for developing other opportunistic infections against which the body is otherwise immune. In addition, it can even make the condition favorable for an existing infection to flourish and exacerbate. Therefore, the patient should be periodically assessed for any underlying infection.

• Intestinal Perforations: Vamorolone therapy in patients with known gastrointestinal conditions, particularly ulcerative colitis, peptic ulcers, intestinal anastomosis, and diverticulitis, is more vulnerable to gastrointestinal perforation. The corticosteroid therapy may even cover up the manifestations associated with gastrointestinal perforation. Therefore, caution needs to be exercised while advising Vamolorone in susceptible patients.

• Eye Disorders: Long-term Vamorolone therapy is reported to be associated with various eye issues. Certain studies reported an appreciable hike in intraocular pressure. Glaucoma, posterior subcapsular cataracts, and ocular infections are the frequent ophthalmic issues precipitated by Vamorolone therapy.

• Psychiatric Issues: Vamorolone therapy may precipitate psychiatric issues like mood disorders or behavioral problems. The associated manifestations are often flagged in the initial stages of the Vamorolone therapy, which subsides upon drug withdrawal.

• Impaired Bone Growth: Vamorolone can influence calcium regulation by enhancing the resorptive process while gearing down bone formation. Thus, it can grossly impact bone growth in younger patients and, at the same time, make one susceptible to bone fracture.

• Myopathy: Vamorolone therapy enhances the possibility of myopathy, particularly in patients with known neuromuscular ailments.

What Are the Drug Interactions of Vamorolone?

Simultaneous administration of Itraconazole and Vamorolone can potentiate the concentration of Vamorolone in the blood. Therefore, necessary down-regulation of the Vamorolone dosage is advised in such cases. Similarly, Vamorolone dose reduction is recommended during concomitant administration with other medicines that are strong inhibitors of CYP3A4 (cytochrome 3A4).

Specific Considerations:

• Vamorolone During Pregnancy: Expectant women are generally not advised to take Vamorolone, as it carries a potential threat to fetal health. However, the doctor may advise Vamorolone by considering the maternal needs and after analyzing the risks and benefits associated with Vamorolone therapy. Hypoadrenalism, growth restriction, orofacial clefts, and low birth weight of the baby are some of the routine complications concerning Vamorolone therapy in pregnant women.

• Vamorolone During Lactation: There is not much information available concerning the discharge of Vamorolone through breast milk following oral ingestion of the drug by the lactating mother. Considering the toxicity potentialities associated with systemic corticosteroids on breastfed babies, the possibility of adverse effects on the babies cannot be ruled out with oral Vamorolone therapy.

• Vamorolone in Pediatric Patients: Vamorolone is a safe and effective therapeutic choice for Duchenne muscular dystrophy in pediatric patients over two years of age. However, its application is limited to babies over two years of age as Vamorolone’s efficacy and safety aspects are not yet explored in patients younger than two.

• Vamorolone in Geriatric Patients: No relevant information is available concerning Vamorolone’s safety and efficacy profile in the geriatric population to establish a conclusive choice.