Bioequivalence & Safety

Pivotal Bioequivalence Study: Pharmacokinetics and Safety2

In a single-center, open-label, randomized, three-way crossover comparative study, 36 healthy volunteers received at least one dose of either a single 20 mg dexamethasone tablet, under fasting or fed conditions, or five 4 mg dexamethasone tablets (total 20 mg).

Study Objectives2

Primary Objectives:
  • Compare the rate and extent of absorption of a single dexamethasone 20 mg tablet to five 4 mg tablets of the originator Unites States Pharmacopeia reference formulation (total dose, 20 mg) under fasting conditions.
  • Evaluate the effect of food on the pharmacokinetic properties of the single dexamethasone 20 mg tablet following the administration of a single dose of 20 mg under fasting and fed conditions.
Secondary Objective:
  • Evaluate the safety and tolerability of dexamethasone 20 mg when administered as a single 20 mg dose in healthy subjects.

Pivotal Bioequivalence Study Design2

Number of Subjects3:

  • Withdrew consent from at least one period: 2
  • Withdrawal from at least one period: 1
  • Completed all study periods: 33
  • Safety population: 36
  • Pharmacokinectic population: 34 for A/B and 33 for C/A

Blood Sampling3:

  • Prior to drug administration, blood sampling occurred 0.167, 0.333, 0.500, 0.750, 1.00, 1.25, 1.50, 1.75, 2.00, 2.50, 3.00, 4.00, 5.00, 6.00, 8.00, 10.0, 12.0, 16.0, 20.0, 24.0, and 36.0 hours post-dose in each period

Bioequivalence2:

According to FDA guidelines criteria, dexamethasone 20 mg (Test), a single Hemady® tablet, is bioequivalent to dexamethasone USP 5 x 4 mg (Reference) following 1 x 20 mg dose under fasting conditions. Both the test and reference doses of dexamethasone demonstrated similar pharmacokinetic properties.

Dexamethasone 20 mg tablet demonstrates comparable total exposure (area under the curve up to the last measurable concentration [AUC0-t] and AUC to infinite time [AUC0-inf]) and mean plasma elimination half-lives (t1/2) under fed and fasted conditions.

Safety2:

No clinically meaningful differences in safety were observed between the test and reference formulations administered under fasting conditions and between the test formulation given under fasting and fed conditions. There were no deaths or serious adverse events reported during the study. The most commonly reported treatment-emergent adverse events were headache 22.2% (n=8/36), dizziness 16.7% (n=6/36), and upper respiratory tract infection 11.1% (n=4/36).

Please see full prescribing information to determine if Hemady® is right for your patient. Hemady® should not be used in patients with hypersensitivity to dexamethasone, or any of its excipients. Hemady® should not be used in patients with systemic fungal infections.1

Indications and Usage

Hemady® (dexamethasone) tablets, 20 mg, is a corticosteroid indicated in combination with other anti-myeloma products for the treatment of adults with multiple myeloma.

Select Important Safety Information for Healthcare Providers

Contraindications

Hypersensitivity: Hemady® is contraindicated in patients with hypersensitivity to dexamethasone, or to any components of this product. Rare instances of anaphylactic reactions have been reported.

Fungal Infections: Hemady® is contraindicated in patients with systemic fungal infections. Corticosteroids may exacerbate systemic fungal infections.

Warnings and Precautions

Alterations in Endocrine Function: Hemady® can cause serious and life-threatening alterations in endocrine function, especially with chronic use. Monitor patients for Cushing’s syndrome and hyperglycemia while receiving corticosteroids and adrenal insufficiency and steroid “withdrawal syndrome” after corticosteroid withdrawal.

Increased Risk of Infection: Corticosteroids, including Hemady®, suppress the immune system and increase the risk of infection with any pathogen including viral, bacterial, fungal, protozoan, or helminthic. Monitor for the development of infection and consider withdrawal of Hemady® or reduction of the dose of corticosteroids as needed.

Alterations in Cardiovascular/Renal Function: Alterations in cardiovascular and renal function can occur. Monitor for elevated blood pressure and sodium, and decreased potassium levels. Use with caution in patients with congestive heart failure and recent myocardial infarction.

Venous and Arterial Thromboembolism: Thromboembolism is a known adverse reaction of dexamethasone, including Hemady®. When administered with anti-myeloma products (e.g., thalidomide, lenalidomide, pomalidomide, and carfilzomib) the risk for venous and arterial thromboembolism increases significantly. Refer to the prescribing information of these anti-myeloma products. Consider using anticoagulant prophylaxis and monitor for evidence of thromboembolism.

Vaccination: Avoid administration of live or live attenuated vaccines in patients receiving immunosuppressive doses of corticosteroids.

Ophthalmic Effects: Use of corticosteroids including Hemady® may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infections. If steroid therapy is continued for more than 6 weeks, intraocular pressure should be monitored.

Gastrointestinal Perforation: There is an increased risk of gastrointestinal perforation during corticosteroid use in patients with certain gastrointestinal disorders. Avoid corticosteroids such as Hemady® if there is a possibility of impending perforation, abscess, or other pyrogenic infections; diverticulitis; fresh intestinal anastomoses; or active or latent peptic ulcer.

Osteoporosis: Corticosteroids decrease bone formation and increase bone resorption. Special consideration should be given to patients at increased risk of osteoporosis (e.g., postmenopausal women) before initiating Hemady®therapy.

Myopathy: An acute myopathy has been observed with the use of high doses of corticosteroids.

Behavioral and Mood Disturbances: Potentially severe psychiatric adverse reactions may occur with systemic corticosteroids, including Hemady®. Inform patients and caregivers of the potential for behavioral and mood changes and encourage them to seek medical attention if symptoms develop.

Kaposi’s Sarcoma: Kaposi’s sarcoma has been reported to occur in patients receiving corticosteroid therapy, most often for chronic conditions. Discontinuation of corticosteroids may result in clinical improvement.

Embryo-Fetal Toxicity: Hemady® can cause fetal harm when administered to pregnant women. Advise females of reproductive potential to use effective contraception during treatment and for one month after treatment with Hemady®. Refer to the prescribing information of the combination anti-myeloma product for additional Contraindications, Warnings and Precautions.

Adverse Reactions

The most common adverse reactions are cardiovascular, dermatologic, endocrine, fluid and electrolyte disturbances, gastrointestinal, metabolic, musculoskeletal, neurological/psychiatric, ophthalmic, abnormal fat deposits, decreased resistance to infection, hiccups, increased or decreased motility and number of spermatozoa, malaise, moon face, and weight gain.

Please see Full Prescribing Information for Hemady®.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088 (1-800-332-1088). You also may contact Edenbridge Pharmaceuticals, LLC at 1-877-381-3336.

Hemady® [Prescribing Information]. Edenbridge Pharmaceuticals, LLC. June 2023.

References
  1. Hemady® [Prescribing Information]. Edenbridge Pharmaceuticals, LLC. June 2023.
  2. Bashir Q, et al. Clin Lymphoma Myeloma Leuk. 2020;20:768-7735.
  3. Data on file (Pivotal bioequivalence study). Edenbridge Pharmaceuticals, LLC. February 2020.

Select Important Safety Information

Indications and Usage

Hemady® (dexamethasone) tablets, 20 mg, is a corticosteroid indicated in combination with other anti-myeloma products for the treatment of adults with multiple myeloma.

Select Important Safety Information for Healthcare Providers

Contraindications

Hypersensitivity: Hemady® is contraindicated in patients with hypersensitivity to dexamethasone, or to any components of this product. Rare instances of anaphylactic reactions have been reported.

Fungal Infections: Hemady® is contraindicated in patients with systemic fungal infections. Corticosteroids may exacerbate systemic fungal infections.

Warnings and Precautions

Alterations in Endocrine Function: Hemady® can cause serious and life-threatening alterations in endocrine function, especially with chronic use. Monitor patients for Cushing’s syndrome and hyperglycemia while receiving corticosteroids and adrenal insufficiency and steroid “withdrawal syndrome” after corticosteroid withdrawal.

Increased Risk of Infection: Corticosteroids, including Hemady®, suppress the immune system and increase the risk of infection with any pathogen including viral, bacterial, fungal, protozoan, or helminthic. Monitor for the development of infection and consider withdrawal of Hemady® or reduction of the dose of corticosteroids as needed.

Alterations in Cardiovascular/Renal Function: Alterations in cardiovascular and renal function can occur. Monitor for elevated blood pressure and sodium, and decreased potassium levels. Use with caution in patients with congestive heart failure and recent myocardial infarction.

Venous and Arterial Thromboembolism: Thromboembolism is a known adverse reaction of dexamethasone, including Hemady®. When administered with anti-myeloma products (e.g., thalidomide, lenalidomide, pomalidomide, and carfilzomib) the risk for venous and arterial thromboembolism increases significantly. Refer to the prescribing information of these anti-myeloma products. Consider using anticoagulant prophylaxis and monitor for evidence of thromboembolism.

Vaccination: Avoid administration of live or live attenuated vaccines in patients receiving immunosuppressive doses of corticosteroids.

Ophthalmic Effects: Use of corticosteroids including Hemady® may produce posterior subcapsular cataracts, glaucoma with possible damage to the optic nerves, and may enhance the establishment of secondary ocular infections. If steroid therapy is continued for more than 6 weeks, intraocular pressure should be monitored.

Gastrointestinal Perforation: There is an increased risk of gastrointestinal perforation during corticosteroid use in patients with certain gastrointestinal disorders. Avoid corticosteroids such as Hemady® if there is a possibility of impending perforation, abscess, or other pyrogenic infections; diverticulitis; fresh intestinal anastomoses; or active or latent peptic ulcer.

Osteoporosis: Corticosteroids decrease bone formation and increase bone resorption. Special consideration should be given to patients at increased risk of osteoporosis (e.g., postmenopausal women) before initiating Hemady®therapy.

Myopathy: An acute myopathy has been observed with the use of high doses of corticosteroids.

Behavioral and Mood Disturbances: Potentially severe psychiatric adverse reactions may occur with systemic corticosteroids, including Hemady®. Inform patients and caregivers of the potential for behavioral and mood changes and encourage them to seek medical attention if symptoms develop.

Kaposi’s Sarcoma: Kaposi’s sarcoma has been reported to occur in patients receiving corticosteroid therapy, most often for chronic conditions. Discontinuation of corticosteroids may result in clinical improvement.

Embryo-Fetal Toxicity: Hemady® can cause fetal harm when administered to pregnant women. Advise females of reproductive potential to use effective contraception during treatment and for one month after treatment with Hemady®. Refer to the prescribing information of the combination anti-myeloma product for additional Contraindications, Warnings and Precautions.

Adverse Reactions

The most common adverse reactions are cardiovascular, dermatologic, endocrine, fluid and electrolyte disturbances, gastrointestinal, metabolic, musculoskeletal, neurological/psychiatric, ophthalmic, abnormal fat deposits, decreased resistance to infection, hiccups, increased or decreased motility and number of spermatozoa, malaise, moon face, and weight gain.

Please see Full Prescribing Information for Hemady®.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088 (1-800-332-1088). You also may contact Edenbridge Pharmaceuticals, LLC at 1-877-381-3336.

Hemady® [Prescribing Information]. Edenbridge Pharmaceuticals, LLC. June 2023.

References
  1. Hemady® [Prescribing Information]. Edenbridge Pharmaceuticals, LLC. June 2023.
  2. Bashir Q, et al. Clin Lymphoma Myeloma Leuk. 2020;20:768-7735.
  3. Data on file (Pivotal bioequivalence study). Edenbridge Pharmaceuticals, LLC. February 2020.