FDA Approvals: Solodyn and Dacogen
News Author: Yael Waknine
CME Author: Yael Waknine
The US Food and Drug Administration (FDA) has approved minocycline HCl extended-release tablets for the once-daily treatment of inflammatory lesions of nonnodular moderate to severe acne vulgaris in patients aged 12 years and older; and decitabine injection for the treatment of patients with myelodysplastic syndromes.
Minocycline Extended-Release Tablets (Solodyn) for Acne in Adolescents and Adults
On May 8, the FDA approved an extended-release formulation of minocycline HCl tablets (Solodyn, made by Medicis Pharmaceutical Corp) for the treatment of inflammatory lesions of nonnodular moderate to severe acne vulgaris in patients aged 12 years and older.
According to a company news release, the lipid-soluble formulation exerts its action in the skin and sebum. It is not bioequivalent to any other previously approved minocycline products and is in no way interchangeable with other forms of the drug. Minocycline extended-release tablets have not been evaluated in the treatment of infections.
The approval was based on data from two 12-week multicenter, randomized, double-blind, clinical trials in 924 patients. Result showed that extended-release minocycline was associated with a greater mean percent change in inflammatory lesion counts from baseline, relative to placebo (study 1, 43.1% vs 31.7%; study 2, 45.8% vs 30.8%).
Moreover, a greater number of patients receiving minocycline therapy were clear or almost clear at 12 weeks, as rated using the Evaluator's Global Severity Assessment scale (study 1, 17.3% vs 7.9%; study 2, 15.9% vs 9.5%).
The most commonly reported adverse events related to use of the study drug included headache, fatigue, dizziness, and pruritus. Although central nervous system adverse effects, such as light-headedness, dizziness, and vertigo, have been reported with other minocycline therapies, these were not significant in patients receiving extended-release tablets. Photosensitivity was reported rarely.
The recommended dosage for minocycline extended-release tablets is 1 mg/kg daily for 12 weeks; no loading dose is required. According to FDA-approved labeling, higher doses have not conferred additional benefit in the treatment of inflammatory acne lesions and may be linked with more acute vestibular adverse effects. The tablets are supplied in 45-, 90-, and 135-mg strengths.
Minocycline extended-release tablets should not be used by individuals attempting to conceive a child nor should they be taken during pregnancy; concurrent use of minocycline may reduce the efficacy of oral contraceptives.
Decitabine Injection (Dacogen) for Patients With Precancerous Myelodysplastic Syndromes
On May 2, the FDA approved decitabine injection (Dacogen, made by MGI Pharma, Inc) for the treatment of patients with myelodysplastic syndromes (MDS). It is intended for use in previously treated and untreated, de novo, and secondary MDS of all French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia), and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups.
According to a company news release, the agent is thought to exert its antineoplastic effects via incorporation into DNA and inhibition of DNA methyltransferase. Decitabine-induced hypomethylation in neoplastic cells may restore normal function to genes previously silenced by abnormal methylation, thereby reestablishing control of cellular differentiation and proliferation.
The approval was based in part on data from an open-label, multicenter, phase 3 controlled clinical trial of 170 MDS patients at medium to high risk of developing acute myeloid leukemia.
Results showed that the addition of decitabine to supportive therapy yielded a significant increase in overall response rate compared with supportive therapy alone (17% vs 0%; P < .001; complete response, 9%; partial response, 8%). The median time to response was 93 days (range, 55 - 272 days), with a median duration of 288 days (range, 116 - 388 days).
Among decitabine-treated patients who had undergone 2 or more treatment cycles, the overall response rate was 21%. Benefit in the form of hematologic improvement was observed in an additional 13% of patients compared with 7% in the supportive care group. Treatment with decitabine did not significantly delay the median time to acute myeloid leukemia or death.
These findings were supported by results from 2 open-label, single-group, multicenter phase 2 studies, showing that decitabine induced overall response rates of 26% (n = 66) and 24% (n = 98), respectively.
Decitabine-related adverse events in the studies most commonly included neutropenia (90%), thrombocytopenia (89%), anemia (82%), pyrexia (53%), fatigue (48%), nausea (42%), cough (40%), petechiae (39%), constipation (35%), and diarrhea (34%).
The recommended dose of decitabine for the initial treatment cycle is 15 mg/m2 administered by continuous intravenous infusion for 3 hours and repeated every 8 hours for 3 days. Premedication with standard antiemetic therapy may be considered.
The cycle should be repeated every 6 weeks for a minimum of 4 cycles. The FDA notes that a complete or partial response may take longer than 4 cycles and that treatment may be continued as long as the patient continues to benefit.
If hematologic recovery (elevated neutrophil and platelet counts) from a previous treatment cycle requires longer than 6 weeks but less than 8 weeks, the next decitabine cycle should be delayed for up to 2 weeks. On resumption of therapy, the dose should be temporarily reduced to 11 mg/m2 every 8 hours (33 mg/m2/day, 99-mg/m2/cycle).
If recovery requires more than 8 but less than 10 weeks, the patient should be assessed for disease progression (bone marrow aspirates). In the absence of progression, the next decitabine cycle should be delayed for up to 2 more weeks, and the dose temporarily reduced as above.
Decitabine should be discontinued permanently pending resolution of certain nonhematologic toxicities, such as serum creatinine levels of 2 mg/dL or greater; serum glutamic pyruvic transaminase or total bilirubin levels 2 or more times the upper limit of normal; and active or uncontrolled infection.
Because of the risk for fetal harm, women of childbearing potential should take measures to avoid becoming pregnant during decitabine therapy. Also, men should not father children during treatment and for 2 months after receiving their last dose of decitabine.
Decitabine is supplied in vials containing 50 mg of the lyophilized product for reconstitution to a 0.1- to 1.0-mg/mL solution. If possible, it should be administered within 15 minutes of reconstitution. Alternatively, the injection can be reconstituted using cold fluid and stored for up to 7 hours at 2 to 8°C.
The product previously was granted orphan drug status by the FDA for this indication and the treatment of chronic myelogous leukemia and by the European Commission as an orphan drug for MDS. Its use for acute myeloid leukemia is currently being investigated in a phase 3 trial.
Learning Objectives for This Educational Activity
Upon completion of this activity, participants will be able to:
Identify a new formulation of minocycline for the treatment of acne.
Describe the appropriate use of minocycline extended-release tablets.
Evaluate the benefits of decitabine therapy for the treatment of MDS.
Pearls for Practice
The FDA has approved an extended-release formulation of minocycline tablets for the treatment of inflammatory lesions of nonnodular moderate to severe acne vulgaris in patients aged 12 years and older. The product is not bioequivalent to any other minocycline products nor is it interchangeable with any other forms of the drug.
The recommended dosage for minocycline extended-release tablets is 1 mg/kg daily for 12 weeks; no loading dose is required. The tablets are supplied in 45-, 90-, and 135-mg strengths. Adverse events may include headache, fatigue, dizziness, and pruritus. Pregnant patients and those of both sexes attempting to conceive a child should not receive minocycline therapy; treatment may also reduce the efficacy of oral contraceptives.
The FDA has approved decitabine injection for the treatment of myelodysplastic syndromes. In clinical trials, decitabine induced overall response rates ranging from 17% to 26% vs 0% for supportive therapy alone. Decitabine is administered by continuous infusion (15 mg/m2 for 3 hours), repeated every 8 hours for 3 days. The cycle should be repeated every 6 weeks for a minimum of 4 cycles. Pretreatment with standard antiemetic therapy should be considered.
Saludos Cordiales
Dr. José Manuel Ferrer Guerra
CME Author: Yael Waknine
The US Food and Drug Administration (FDA) has approved minocycline HCl extended-release tablets for the once-daily treatment of inflammatory lesions of nonnodular moderate to severe acne vulgaris in patients aged 12 years and older; and decitabine injection for the treatment of patients with myelodysplastic syndromes.
Minocycline Extended-Release Tablets (Solodyn) for Acne in Adolescents and Adults
On May 8, the FDA approved an extended-release formulation of minocycline HCl tablets (Solodyn, made by Medicis Pharmaceutical Corp) for the treatment of inflammatory lesions of nonnodular moderate to severe acne vulgaris in patients aged 12 years and older.
According to a company news release, the lipid-soluble formulation exerts its action in the skin and sebum. It is not bioequivalent to any other previously approved minocycline products and is in no way interchangeable with other forms of the drug. Minocycline extended-release tablets have not been evaluated in the treatment of infections.
The approval was based on data from two 12-week multicenter, randomized, double-blind, clinical trials in 924 patients. Result showed that extended-release minocycline was associated with a greater mean percent change in inflammatory lesion counts from baseline, relative to placebo (study 1, 43.1% vs 31.7%; study 2, 45.8% vs 30.8%).
Moreover, a greater number of patients receiving minocycline therapy were clear or almost clear at 12 weeks, as rated using the Evaluator's Global Severity Assessment scale (study 1, 17.3% vs 7.9%; study 2, 15.9% vs 9.5%).
The most commonly reported adverse events related to use of the study drug included headache, fatigue, dizziness, and pruritus. Although central nervous system adverse effects, such as light-headedness, dizziness, and vertigo, have been reported with other minocycline therapies, these were not significant in patients receiving extended-release tablets. Photosensitivity was reported rarely.
The recommended dosage for minocycline extended-release tablets is 1 mg/kg daily for 12 weeks; no loading dose is required. According to FDA-approved labeling, higher doses have not conferred additional benefit in the treatment of inflammatory acne lesions and may be linked with more acute vestibular adverse effects. The tablets are supplied in 45-, 90-, and 135-mg strengths.
Minocycline extended-release tablets should not be used by individuals attempting to conceive a child nor should they be taken during pregnancy; concurrent use of minocycline may reduce the efficacy of oral contraceptives.
Decitabine Injection (Dacogen) for Patients With Precancerous Myelodysplastic Syndromes
On May 2, the FDA approved decitabine injection (Dacogen, made by MGI Pharma, Inc) for the treatment of patients with myelodysplastic syndromes (MDS). It is intended for use in previously treated and untreated, de novo, and secondary MDS of all French-American-British subtypes (refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia), and intermediate-1, intermediate-2, and high-risk International Prognostic Scoring System groups.
According to a company news release, the agent is thought to exert its antineoplastic effects via incorporation into DNA and inhibition of DNA methyltransferase. Decitabine-induced hypomethylation in neoplastic cells may restore normal function to genes previously silenced by abnormal methylation, thereby reestablishing control of cellular differentiation and proliferation.
The approval was based in part on data from an open-label, multicenter, phase 3 controlled clinical trial of 170 MDS patients at medium to high risk of developing acute myeloid leukemia.
Results showed that the addition of decitabine to supportive therapy yielded a significant increase in overall response rate compared with supportive therapy alone (17% vs 0%; P < .001; complete response, 9%; partial response, 8%). The median time to response was 93 days (range, 55 - 272 days), with a median duration of 288 days (range, 116 - 388 days).
Among decitabine-treated patients who had undergone 2 or more treatment cycles, the overall response rate was 21%. Benefit in the form of hematologic improvement was observed in an additional 13% of patients compared with 7% in the supportive care group. Treatment with decitabine did not significantly delay the median time to acute myeloid leukemia or death.
These findings were supported by results from 2 open-label, single-group, multicenter phase 2 studies, showing that decitabine induced overall response rates of 26% (n = 66) and 24% (n = 98), respectively.
Decitabine-related adverse events in the studies most commonly included neutropenia (90%), thrombocytopenia (89%), anemia (82%), pyrexia (53%), fatigue (48%), nausea (42%), cough (40%), petechiae (39%), constipation (35%), and diarrhea (34%).
The recommended dose of decitabine for the initial treatment cycle is 15 mg/m2 administered by continuous intravenous infusion for 3 hours and repeated every 8 hours for 3 days. Premedication with standard antiemetic therapy may be considered.
The cycle should be repeated every 6 weeks for a minimum of 4 cycles. The FDA notes that a complete or partial response may take longer than 4 cycles and that treatment may be continued as long as the patient continues to benefit.
If hematologic recovery (elevated neutrophil and platelet counts) from a previous treatment cycle requires longer than 6 weeks but less than 8 weeks, the next decitabine cycle should be delayed for up to 2 weeks. On resumption of therapy, the dose should be temporarily reduced to 11 mg/m2 every 8 hours (33 mg/m2/day, 99-mg/m2/cycle).
If recovery requires more than 8 but less than 10 weeks, the patient should be assessed for disease progression (bone marrow aspirates). In the absence of progression, the next decitabine cycle should be delayed for up to 2 more weeks, and the dose temporarily reduced as above.
Decitabine should be discontinued permanently pending resolution of certain nonhematologic toxicities, such as serum creatinine levels of 2 mg/dL or greater; serum glutamic pyruvic transaminase or total bilirubin levels 2 or more times the upper limit of normal; and active or uncontrolled infection.
Because of the risk for fetal harm, women of childbearing potential should take measures to avoid becoming pregnant during decitabine therapy. Also, men should not father children during treatment and for 2 months after receiving their last dose of decitabine.
Decitabine is supplied in vials containing 50 mg of the lyophilized product for reconstitution to a 0.1- to 1.0-mg/mL solution. If possible, it should be administered within 15 minutes of reconstitution. Alternatively, the injection can be reconstituted using cold fluid and stored for up to 7 hours at 2 to 8°C.
The product previously was granted orphan drug status by the FDA for this indication and the treatment of chronic myelogous leukemia and by the European Commission as an orphan drug for MDS. Its use for acute myeloid leukemia is currently being investigated in a phase 3 trial.
Learning Objectives for This Educational Activity
Upon completion of this activity, participants will be able to:
Identify a new formulation of minocycline for the treatment of acne.
Describe the appropriate use of minocycline extended-release tablets.
Evaluate the benefits of decitabine therapy for the treatment of MDS.
Pearls for Practice
The FDA has approved an extended-release formulation of minocycline tablets for the treatment of inflammatory lesions of nonnodular moderate to severe acne vulgaris in patients aged 12 years and older. The product is not bioequivalent to any other minocycline products nor is it interchangeable with any other forms of the drug.
The recommended dosage for minocycline extended-release tablets is 1 mg/kg daily for 12 weeks; no loading dose is required. The tablets are supplied in 45-, 90-, and 135-mg strengths. Adverse events may include headache, fatigue, dizziness, and pruritus. Pregnant patients and those of both sexes attempting to conceive a child should not receive minocycline therapy; treatment may also reduce the efficacy of oral contraceptives.
The FDA has approved decitabine injection for the treatment of myelodysplastic syndromes. In clinical trials, decitabine induced overall response rates ranging from 17% to 26% vs 0% for supportive therapy alone. Decitabine is administered by continuous infusion (15 mg/m2 for 3 hours), repeated every 8 hours for 3 days. The cycle should be repeated every 6 weeks for a minimum of 4 cycles. Pretreatment with standard antiemetic therapy should be considered.
Saludos Cordiales
Dr. José Manuel Ferrer Guerra
posted by Klip7 at
8:42 AM
