Glutamine (Endari) Side Effects: What to Expect and When to Call Your Doctor

If you're starting Glutamine (Endari or generic L-glutamine oral powder) for sickle cell disease, you want to know what to expect. While Glutamine is generally considered well-tolerated compared to some other SCD medications, it does have side effects — and knowing which ones are normal versus which ones need medical attention can make a real difference.

This guide covers everything from the most common mild effects to serious reactions you should report to your doctor immediately. All information is based on the FDA-approved prescribing information and data from the Phase 3 clinical trial.

Common Side Effects of Glutamine (Endari)

In clinical trials, the following side effects occurred in more than 10% of patients treated with Endari. These are generally manageable and may improve as your body adjusts to the medication:

Constipation — The most frequently reported side effect. Staying hydrated and increasing dietary fiber can help.

Nausea — Can often be reduced by mixing the powder in a thicker food like yogurt or applesauce rather than a thin liquid.

Headache — Reported in over 10% of trial participants. Usually mild and temporary.

Abdominal pain — Stomach discomfort is common, especially early in treatment.

Cough — More common in patients also experiencing sickle cell-related respiratory issues.

Pain in extremities (hands and feet) — Can overlap with SCD-related pain symptoms. It's important to tell your doctor if this pain seems different from your usual SCD pain.

Back pain — Another side effect that may overlap with SCD disease activity.

Non-cardiac chest pain — Always discuss any chest pain with your doctor to rule out serious causes including acute chest syndrome.

Serious Side Effects: When to Call Your Doctor Immediately

While Glutamine is generally well-tolerated, some side effects are serious and require immediate medical attention:

Severe allergic reaction (anaphylaxis): Signs include rash, hives, difficulty breathing, swelling of the face/lips/tongue/throat, rapid heartbeat, or dizziness. Stop taking Glutamine and seek emergency care immediately.

Hypersplenism: One case in the clinical trial led to discontinuation. Symptoms include fatigue, anemia, and feeling of fullness in the upper left abdomen. Report any new or worsening symptoms to your doctor.

Severe or new chest pain: While non-cardiac chest pain is listed as a side effect, any severe or new chest pain in an SCD patient should be evaluated promptly to rule out acute chest syndrome.

How Do Glutamine Side Effects Compare to the Overall Trial Safety Data?

In the Phase 3 clinical trial (230 patients, 48 weeks), only 2.7% of patients (5 patients) stopped taking Glutamine due to adverse reactions. This is relatively low, suggesting most side effects are tolerable. The side effects included one case each of hypersplenism, abdominal pain, dyspepsia, burning sensation, and hot flash.

Overall, the Phase 3 trial concluded that Glutamine had a "favorable safety profile" with low adverse event rates — which is one reason it's considered a viable option for long-term SCD management.

Side Effects vs. SCD Symptoms: How to Tell the Difference

One of the challenges with Glutamine side effects is that several of them — pain in extremities, back pain, chest pain — can overlap with the symptoms of sickle cell disease itself. Here's a practical approach:

If pain is worse than your usual SCD pain or located differently, contact your doctor

Keep a symptom diary in the first few weeks of treatment to track what's new vs. baseline

Tell your doctor if you notice the same symptom consistently after taking Glutamine doses

Tips for Managing Common Side Effects

Nausea: Try mixing with yogurt or applesauce instead of a liquid. Take with food.

Constipation: Increase fluid and fiber intake. Talk to your pharmacist about over-the-counter stool softeners if needed.

Headache: Stay well-hydrated. If persistent, discuss with your doctor.

Special Populations: Pregnancy, Breastfeeding, and Elderly Patients

There is no available safety data on Glutamine use during pregnancy. If you become pregnant while taking Glutamine, contact your doctor immediately. During clinical trials, women who became pregnant were taken off the study. The FDA assigns Glutamine a Category C pregnancy classification — meaning risk cannot be ruled out.

For breastfeeding: endogenous glutamine is present in human breast milk. The impact of supplemental glutamine on a breastfed infant is not known. Discuss the risks and benefits with your healthcare provider.

Related reading: Glutamine drug interactions | What is Glutamine? Uses, dosage, and what to know