Endari

L-glutamine is used to is used to reduce the frequency of painful episodes (crises) in adults and children 5 years of age and older with sickle cell anemia (an inherited blood disorder in which the red blood cells are abnormally shaped [shaped like a sickle] and cannot bring enough oxygen to all parts of the body). L-glutamine is in a class of medications called amino acids. It works by helping to prevent damage to red blood cells.

L-Glutamine is an amino acid.1

Contraindications

None.1

Warnings/Precautions

Specific Populations

There are no available data on L-glutamine use in pregnant women to inform a drug-associated risk of major birth defects and miscarriage. Animal reproduction studies were not conducted with L-glutamine.1

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 US 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.1

There are no data on the presence of L-glutamine 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 L-glutamine and any potential adverse effects on the breastfed child from L-glutamine or from the underlying maternal condition.1

The safety and effectiveness of L-glutamine have been established in pediatric patients 5 years and older. Use of L-glutamine 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).1

The safety and effectiveness of L-glutamine in pediatric patients with sickle cell disease younger than 5 years old has not been established.1

Clinical studies of L-glutamine 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.1

Common Adverse Effects

Most common adverse reactions (incidence >10%) are constipation, nausea, headache, abdominal pain, cough, pain in extremity, back pain, and chest pain.1

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

Please see product labeling for drug interaction information.

AHFS First Release. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

Dosage

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

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.

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.

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.

Manufactured for:
Emmaus Medical, Inc
Torrance, CA 90503

Glutamine has been assigned to pregnancy category C by the FDA. Animal reproduction studies have not been reported. There are no controlled data in human pregnancy. Glutamine should only be given during pregnancy when benefit outweighs risk.

Use Endari as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• To gain the most benefit, do not miss doses.
• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.
• Mix with 8 ounces (240 mL) of liquid like water, milk, or apple juice. Do not mix with hot liquids. You can also mix with 4 to 6 ounces (120 to 180 mL) of food like applesauce or yogurt. This medicine may not dissolve all the way.
• After mixing, take your dose right away. Do not store for future use.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

Mechanism of Action

Sickle cell disease

• The mechanism of action of the amino acid L-glutamine in treating sickle cell disease (SCD) is not fully understood
• Oxidative stress phenomena are involved in the pathophysiology of SCD; sickle RBCs are more susceptible to oxidative damage than normal RBCs, which may contribute to the chronic hemolysis and vaso-occlusive events associated with SCD
• Pyridine nucleotides, NAD+ and its reduced form NADH, play roles in regulating and preventing oxidative damage in RBCs L-glutamine may improve the NAD redox potential in sickle RBCs through increasing the availability of reduced glutathione

Short bowel syndrome

• L-glutamine has important functions in regulation of gastrointestinal cell growth, function, and regeneration
• When glutamine was administered in combination with growth hormone to rats, villous height, bowel growth, plasma insulin-like growth factor I, and body weight were significantly higher than in rats treated with either glutamine or rhGH alone

Absorption

Peak plasma time: 30 min

Peak plasma concentration: 150 mcg/mL

Distribution

Vd: ~200 mL/kg

Metabolism

Glutamine participates in various metabolic activities, including the formation of glutamate, and synthesis of proteins, nucleotides, and amino sugars

Elimination

Half-life: ~1 hr

Metabolism is the major route of elimination for glutamine

Although glutamine is eliminated by glomerular filtration, it is almost completely reabsorbed by the renal tubules

Oral Administration

Endari

• Mix immediately before ingestion with 8 oz of cold or room temperature beverage (eg, water, milk, apple juice) or 4-6 oz of soft food (eg, applesauce, yogurt)
• Complete dissolution is not required prior to administration

NutreStore

• Dissolve each 5 g packet in 8 oz water prior to drinking; volume of water may be varied according to the patient’s preference
• Take with meals or snacks at 2-3 hr intervals while awake
• If transiently intolerant to oral intake, a dose may be delayed for up to 2 hr

Storage

Store at 20-25°C (68-77°F) away from direct sunlight