GLUTAMINE: 3,333 Adverse Event Reports & Safety Profile

L-glutamine is an amino acid. L-glutamine is designated chemically as (S)-2-aminoglutaramic acid, L-glutamic acid 5-amide, or (S)-2,5-diamino-5-oxopentanoic acid. The molecular formula is C 5 H 10 N 2 O 3 with the molecular weight of 146.15 g/mol and the following structural formula: L-glutamine Oral Powder is formulated as a white to off-white colored powder and is packaged as 5 grams in a foil-plastic laminate packet for oral administration. structure

1 INDICATIONS & USAGE L-glutamine is indicated to reduce the acute complications of sickle cell disease in adult and pediatric patients 5 years of age and older. L-glutamine 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. (1)

AND ADMINISTRATION 5 grams to 15 grams orally, twice daily based on body weight. ( 2 ) Each dose of Endari should be mixed in 8 oz. (240 mL) of cold or room temperature beverage or 4 oz. to 6 oz. of food before ingestion. ( 2 )

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.

Dosage and Administration Advise patient to take a missed dose as soon as they remember. Patient should not double the dose that they take . Instruct patient to mix each dose in 8 oz. (240 mL) of cold or room temperature beverage or 4 to 6 oz. of food. Advise patient that complete dissolution is not required prior to administration.

None None ( 4 )

REACTIONS Most common adverse reactions (incidence > 10%) are constipation, nausea, headache, abdominal pain, cough, pain in extremity, back pain, and chest pain. (6) To report SUSPECTED ADVERSE REACTIONS, contact Novitium Pharma LLC at 1-855-204-1431 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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 L-glutamine in 187 patients, including 136 exposed for 6 months and 109 exposed for ≥1 year. L-glutamine 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 L-glutamine (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 L-glutamine. 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 L-glutamine treatment group as compared to none in the placebo treatment group. None of the deaths were considered to be related to L-glutamine treatment. Adverse reactions occurring in greater than 10% of patients treated with L-glutamine are shown in Table 2 below.

Table

2.

Adverse Reactions

Occurring at an Incidence > 10% in Clinical Studies of L-glutamine Adverse reaction L-glutamine N = 187 (%) Placebo N = 111 (%)

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 *Abdominal pain = abdominal pain and abdominal pain, upper

WARNINGS In case of overdose, get medical help or contact a poison control center right away. Keep out of the reach of children. If pregnant or breastfeeding, ask a healthcare professional before use.

Drug Interactions No drug interaction studies have been conducted.

ACTIVE INGREDIENTS L-Glutamine 15X, 20X, 30X, 60X, 200X

INACTIVE INGREDIENTS 20% ethanol, purified water.