L-glutamine is an oral amino acid used for the treatment of short bowel syndrome (SBS) and to reduce the acute complications of sickle cell disease (SCD). It is considered to be a 'conditionally essential' amino acid because under normal conditions dietary intake and synthesis from glutamate maintain adequate amounts. However, during times of catabolic stress, trauma, or infection, L-glutamine needs are greater due to decreased concentrations and increased tissue glutamine metabolism. In the intestine, L-glutamine functions in the regulation of gastrointestinal cell growth, function, and regeneration. L-glutamine, human growth hormone, and dietary modifications have been studied to promote the adaptation of the shortened bowel in patients with SBS. This combination has been beneficial in the reduction of parenteral nutrition volume, caloric energy requirements, and frequency of infusion in patients with SBS dependent on parenteral nutrition. Although the mechanism of L-glutamine in the treatment of SCD is not fully understood, it may play a role in the regulation and prevention of oxidative damage in red blood cells. In a clinical trial in 230 patients (age 5 to 58 years) with sickle cell anemia or sickle beta thalassemia, the efficacy of L-glutamine was demonstrated by a reduction in the number of sickle cell crises through week 48 compared with placebo. This clinical benefit was observed irrespective of hydroxyurea use. Patients treated with L-glutamine also experienced fewer hospitalizations for sickle cell pain at week 48, fewer cumulative days in the hospital, and had a lower incidence of acute chest syndrome compared to those who received placebo. Routine monitoring of hepatic and renal function is recommended in patients receiving parenteral nutrition and L-glutamine.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
NutreStore
-Reconstitute each dose in 8 ounces (240 mL) of water prior to consumption. However, the volume of water may be varied according to the patient's preference.
-Administer with meals or snacks at 2 to 3 hour intervals while awake. Doses may be delayed up to 2 hours if the patient experiences a transient intolerance to oral intake.
Endari
-Reconstitute each dose with 8 ounces (240 mL) of cold or room temperature beverage (e.g., water, milk, apple juice) or 4 to 6 ounces of soft food (e.g. applesauce, yogurt) immediately prior to consumption. Complete dissolution is not required prior to administration.
Constipation (21% vs. 18%), nausea (19% vs. 14%), headache (18% vs. 15%), abdominal pain (17% vs. 16%), cough (16% vs. 14%), extremity pain (13% vs. 7%), back pain (12% vs. 5%), and chest pain (unspecified) (12% vs. 8%) were the most commonly reported adverse reactions in patients receiving L-glutamine (n = 187) compared to placebo (n = 111), respectively, during clinical trials for sickle cell disease. In these trials, treatment discontinuation due to adverse reactions was reported in 2.7% of patients receiving L-glutamine; these reactions included one case each of hypersplenism, abdominal pain, dyspepsia, burning sensation, and hot flashes. Abdominal pain, nausea, constipation, headache, and back pain have also been commonly reported during clinical trials of L-glutamine for short bowel syndrome.
During an 18-week randomized, controlled, 3-arm, double-blind, parallel-group clinical trial of oral L-glutamine in conjunction with recombinant human growth hormone (rh-GH) in patients with short bowel syndrome (SBS) who were dependent on parenteral nutrition, the adverse reaction profile in patients receiving oral glutamine with rh-GH was similar to that of patients receiving rh-GH without glutamine. The most common adverse reactions (more than 10%) associated with L-glutamine during the first 4 weeks of treatment were flatulence, abdominal pain, nausea, tenesmus, vomiting, hemorrhoids, and xerostomia. In weeks 5 to 18, nausea, vomiting, tenesmus, pancreatitis, constipation, aggravated Crohn's disease, gastric ulcer, and gastrointestinal fistula were reported most commonly. Other adverse reactions reported by patients receiving oral L-glutamine plus rh-GH during the initial 4 weeks included peripheral edema, facial edema, arthralgia, musculoskeletal pain, fever, influenza-like symptoms, unspecified infections, viral infection, dizziness, headache, hypoesthesia, rash (unspecified), pruritus, rhinitis, unspecified ear/hearing symptoms, unspecified musculoskeletal disorders, unspecified respiratory system disorders, unspecified metabolic/nutritional disorders, unspecified urinary system disorders, and unspecified skin/appendage disorders. Adverse reactions experienced by subjects during weeks 5 through 18 were similar to those reported in weeks 1 through 4; additional reactions reported during weeks 5 to 18 included bacterial infection, sepsis, unspecified female reproductive disorders, and unspecified psychiatric disorders.
L-glutamine is metabolized to glutamate and ammonia. Routine monitoring of patients with hepatic disease/hepatic impairment or renal impairment who are receiving parenteral nutrition and L-glutamine is recommended. Ammonia liberated from the use of the product could exacerbate hepatic encephalopathy.
Clinical trials of L-glutamine did not contain sufficient numbers of patients 65 years or older to determine whether they respond differently from younger patients. Reported clinical experience has not identified differences. In general, doses in the geriatric population should be cautious and individualized taking into account the greater frequency of decreased renal, hepatic, or cardiac function, and of concomitant disease in this population.
There are no data available on L-glutamine use in human pregnancy to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Animal reproduction studies have not been conducted with L-glutamine.
Endogenous glutamine is present in human milk. There are no data available on the effect of L-glutamine on the breastfed infant or the effect on milk production. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for L-glutamine and any potential adverse effects on the breastfed child from L-glutamine or the underlying maternal condition.
For the treatment of short bowel syndrome in patients receiving specialized nutritional support in conjunction with recombinant human growth hormone:
NOTE: Glutamine and rh-GH therapy should be used in conjunction with optimal management of short bowel syndrome which may include a specialized oral diet, enteral feedings, parenteral nutrition, fluid, and micronutrient supplements.
Oral dosage:
Adults: 5 g PO 6 times daily for up to 16 weeks given in conjunction with a specialized diet adjusted for individual patient requirements and preferences. Recombinant human growth hormone (rh-GH) should be given during the first 4 weeks of therapy. Safety and efficacy have not been studied beyond 16 weeks of treatment.
To reduce the acute complications of sickle cell disease:
NOTE: L-glutamine is designated as an orphan drug by the FDA for this indication.
Oral dosage:
Adults weighing more than 65 kg: 15 g PO twice daily.
Adults weighing 30 to 65 kg: 10 g PO twice daily.
Children and Adolescents 5 to 17 years weighing more than 65 kg: 15 g PO twice daily.
Children and Adolescents 5 to 17 years weighing 30 to 65 kg: 10 g PO twice daily.
Children and Adolescents 5 to 17 years weighing less than 30 kg: 5 g PO twice daily.
Maximum Dosage Limits:
-Adults
Maximum dosage information is not available.
-Geriatric
Maximum dosage information is not available.
-Adolescents
Maximum dosage information is not available; safety and efficacy have not been established for the treatment of short bowel syndrome.
-Children
5 to 12 years: Maximum dosage information is not available; safety and efficacy have not been established for the treatment of short bowel syndrome.
1 to 4 years: Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
There are no drug interactions associated with L-Glutamine products.
Glutamine is an amino acid used in the biosynthesis of proteins.
Short bowel syndrome
The role of L-glutamine in intestinal adaptation in patients with short bowel syndrome (SBS) remains largely unclear. Research has alluded to its role in gastrointestinal cell growth, function, and regeneration. Patients who have undergone bowel resection develop intestinal failure from the short-bowel resulting in malabsorption of fluids, electrolytes, and other nutrients; dependence on long-term parenteral nutrition may result. Over a period of time a resected bowel undergoes intestinal adaptation where the bowel dilates and lengthens and there is an increase in villus height, crypt depth, cell proliferation, and enzyme activity. This adaptation results in enhanced fluid, electrolyte, and nutrient absorption and an increase in transit time. Intestinal mucosa has the capability of extracting glutamine from arterial circulation where it takes part in the replication of cells located in the intestinal mucosa. Furthermore, glutamine has been shown to be involved in the maintenance of proliferative and secretory functions, mucosal structure, and the passive barrier to bacterial infiltration of intestinal cells.
Sickle cell disease
The mechanism of L-glutamine in treating sickle cell disease is not fully understood. Sickle red blood cells (RBC) are more vulnerable to oxidative damage compared to normal RBC, which may contribute to the chronic hemolysis and vaso-occlusive events associated with sickle cell disease. The pyridine nucleotides, NAD+ and its reduced form NADH, partially regulate and prevent oxidative damage in RBC. L-glutamine may improve the NAD redox potential in sickle RBC by increasing the availability of reduced glutathione.
L-glutamine is administered orally. After an IV bolus dose, Vd was estimated to be approximately 200 mL/kg with a terminal half-life of approximately 1 hour. Endogenous L-glutamine takes part in various metabolic activities, including formation of glutamate and synthesis of proteins, nucleotides, and amino sugars; exogenous L-glutamine is expected to undergo similar metabolism. L-glutamine is eliminated by glomerular filtration but is almost completely reabsorbed by the renal tubules.
-Route-Specific Pharmacokinetics
Oral Route
Mean peak L-glutamine concentrations of 150 mcg/mL occurred approximately 30 minutes after oral administration of L-glutamine 0.1 g/kg in healthy subjects. Multiple dose pharmacokinetics have not been adequately described. Plasma concentrations of L-glutamine after oral administration may be highly variable in patients with short bowel syndrome. Extent of absorption is dependent largely on the length, segment, and the presence or absence of ileal-cecal valve in the bowel remnant of these patients.