Endari

ENDARI- glutamine powder, for solution
Emmaus Medical, Inc.

1 INDICATIONS AND USAGE

Endari is indicated to reduce the acute complications of sickle cell disease in adult and pediatric patients 5 years of age and older.

2 DOSAGE AND ADMINISTRATION

2.1 Dosage

Administer Endari orally, twice per day at the dose based on body weight according to Table 1.

Table 1. Recommended Dosing
Weight in kilograms Weight in pounds Per dose in grams Per day in grams Packets per dose Packets per day
less than 30 less than 66 5 10 1 2
30 to 65 66 to 143 10 20 2 4
greater than 65 greater than 143 15 30 3 6

2.2 Preparation of Product

Mix Endari immediately before ingestion with 8 oz. (240 mL) of cold or room temperature beverage, such as water, milk or apple juice, or 4 oz. to 6 oz. of food such as applesauce or yogurt. Complete dissolution is not required prior to administration.

3 DOSAGE FORMS AND STRENGTHS

Oral powder: 5 grams of L–glutamine as a white crystalline powder in paper-foil-plastic laminate packets

4 CONTRAINDICATIONS

None

6 ADVERSE REACTIONS

6.1 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 β0 -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 EndariN = 187(%) PlaceboN = 111(%)
*
Abdominal pain = abdominal pain and abdominal pain, upper
Constipation 21 18
Nausea 19 14
Headache 18 15
Abdominal Pain * 17 16
Cough 16 14
Pain in extremity 13 7
Back pain 12 5
Chest pain 12 8

8 USE IN SPECIFIC POPULATIONS

8.1 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.

8.2 Lactation

Risk Summary

There are no data on the presence of Endari in human milk, the effect on the breastfed infant or the effect on milk production. The developmental and health benefits from breastfeeding should be considered along with the mother’s clinical need for Endari and any potential adverse effects on the breastfed child from Endari or from the underlying maternal condition.

8.4 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.

8.5 Geriatric Use

Clinical studies of Endari did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

10 OVERDOSAGE

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.

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