Endari Drug Information
Generic name: GLUTAMINE
Amino Acid [EPC]
Uses of Endari
Endari is indicated to reduce the acute complications of sickle cell disease in adult and pediatric patients 5 years of age and older. ENDARI is an amino acid indicated to reduce the acute complications of sickle cell disease in adult and pediatric patients 5 years of age and older.
Dosage & Administration of Endari
| less than 30 | less than 66 |
|---|---|
| 30 to 65 | 66 to 143 |
| greater than 65 | greater than 143 |
Side Effects of Endari
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The data described below reflect exposure to Endari in 187 patients, including 136 exposed for 6 months and 109 exposed for ≥1 year. Endari was studied in 2 placebo-controlled clinical trials (a phase 3 study, n=230 and a phase 2 study, n=70). In these trials, patients with sickle cell anemia or sickle β 0 -thalassemia were randomized to receive Endari (n=187) or placebo (n=111) orally twice daily for 48 weeks followed by 3 weeks of tapering.
Both studies included pediatric and adult patients (5-58 years of age) and 54% were female. The majority of patients were black (97.3%), had a diagnosis of sickle cell anemia (89.9%) and were receiving hydroxyurea at baseline (63.4%). Treatment discontinuation due to adverse reactions was reported in 2.7% (n=5) of patients receiving Endari. These adverse reactions included one case each of hypersplenism, abdominal pain, dyspepsia, burning sensation, and hot flash.
Serious adverse reactions were reported in both treatment groups, more frequently in the placebo group, and were consistent with the underlying disease. Three deaths (3/187=1.6%) occurred during the study in the Endari treatment group as compared to none in the placebo treatment group. None of the deaths were considered to be related to Endari treatment.
Adverse reactions occurring in greater than 10% of patients treated with Endari are shown in Table 2 below. Table 2. Adverse Reactions Occurring at an Incidence > 10% in Clinical Studies of Endari Adverse reaction Endari N = 187 (%) Placebo N = 111 (%) Constipation 21 18 Nausea 19 14 Headache 18 15 Abdominal Pain Abdominal pain = abdominal pain and abdominal pain, upper 17 16 Cough 16 14 Pain in extremity 13 7 Back pain 12 5 Chest pain 12 8
Drug Interactions with Endari
Drug Interactions No drug interaction studies have been conducted.
Pregnancy Safety for Endari
Pregnancy Risk Summary There are no available data on Endari use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. Animal reproduction studies were not conducted with Endari. Adverse outcomes in pregnancy occur regardless of the health of the mother or the use of medications.
The background risk of major birth defects and miscarriage for the indicated population are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Pediatric Use of Endari
Pediatric Use The safety and effectiveness of Endari have been established in pediatric patients 5 years and older. Use of Endari is supported by evidence from 2 placebo-controlled studies in adult and pediatric patients with sickle cell disease. The clinical studies enrolled 110 pediatric patients in the following age groups: 46 children (5 years up to less than 12 years) and 64 adolescents (12 years to less than 17 years). The safety and effectiveness of Endari in pediatric patients with sickle cell disease younger than 5 years old has not been established.
Overdosage Information for Endari
Single oral doses of L-glutamine at about 20 g/kg to 22 g/kg, 8 g/kg to 11 g/kg, and 19 g/kg were lethal in mice, rats, and rabbits, respectively. Supportive measures should be undertaken in the event of overdose of Endari.
Clinical Studies of Endari
Clinical Studies The efficacy of Endari in sickle cell disease was evaluated in a randomized, double-blind, placebo-controlled, multi-center clinical trial entitled "A Phase III Safety and Efficacy Study of L-Glutamine to Treat Sickle Cell Disease or Sickle β o -thalassemia" (see Table 3 ). The clinical trial evaluated the efficacy and safety of Endari in 230 patients (5 to 58 years of age) with sickle cell anemia or sickle β 0 -thalassemia who had 2 or more painful crises within 12 months prior to enrollment. Eligible patients stabilized on hydroxyurea for at least 3 months continued their therapy throughout the study. The trial excluded patients who had received blood products within 3 weeks, had renal insufficiency or uncontrolled liver disease, or were pregnant (or planning pregnancy) or lactating.
Study patients received Endari or placebo for a treatment duration of 48 weeks followed by 3 weeks of tapering. Efficacy was demonstrated by a reduction in the number of sickle cell crises through Week 48 and prior to the start of tapering among patients that received Endari compared to patients who received placebo. This clinical benefit was observed irrespective of hydroxyurea use.
A sickle cell crisis was defined as a visit to an emergency room/medical facility for sickle cell disease-related pain which was treated with a parenterally administered narcotic or parenterally administered ketorolac. In addition, the occurrence of chest syndrome, priapism, and splenic sequestration were considered sickle cell crises. Treatment with Endari also resulted in fewer hospitalizations due to sickle cell pain at Week 48, fewer cumulative days in hospital and a lower incidence of acute chest syndrome.
Table 3. Results from the Endari Clinical Trial in Sickle Cell Disease Event Endari (n = 152) Placebo (n = 78) Median number of sickle cell crises (min,max) Measured through 48 weeks of treatment 3 4 Median number of hospitalizations for sickle cell pain (min, max) 2 3 Median cumulative days hospitalized (min, max) 6.5 11 Median time (days) to first sickle cell crisis (95% CI), Hazard Ratio=0.69 (95% CI=0.52, 0.93), estimated based on unstratified Cox's proportional model. Median time and 95% CI were estimated based on the Kaplan Meier method. 84 54 Patients with occurrences of acute chest syndrome (%) 13 (8.6%) 18 (23.1%) The recurrent crisis event time analysis (Figure 1) yielded an intensity rate ratio (IRR) value of 0.75 with 95% CI= and based on unstratified models using the Andersen-Gill and Lin, Wei, Yang and Ying methods, respectively in favor of Endari, suggesting that over the entire 48-week period, the average cumulative crisis count was reduced by 25% from the Endari group over the placebo group. Figure 1. Recurrent Event Time for Sickle Cell Crises by Treatment Group *Andersen-Gill: 95% CI ; Lin-Wei-Yang-Ying: 95% CI Figure 1
Drug information sourced from the FDA. This content is for informational purposes only and does not constitute medical advice. Consult a healthcare professional before making any medication decisions.
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