Methylene blue is a synthetic chemical dye discovered in 1876 that has long been used in both medicine and laboratory science. In the medical field, it functions as an oxidizing and reducing agent, helping restore normal oxygen use inside cells. Doctors prescribe methylene blue for certain medical problems such as methemoglobinemia, urinary tract infections, ifosfamide-induced encephalopathy, and as a biological stain in diagnostics.
Although generally safe when used correctly, methylene blue can cause several side effects. Understanding these helps prevent complications and ensures responsible use.
Common Side Effects of Methylene Blue
Methylene blue has a distinctive deep blue color, and because of that, many of its mild side effects are easily recognizable. Below are the most frequently reported reactions.
- Change in Urine and Skin Color
Blue or green urine is one of the most common harmless effects.
Sometimes the skin or sclera (white of the eye) may temporarily appear bluish.
This discoloration usually fades within 24–48 hours after the medicine is cleared from the body.
- Mild Headache or Dizziness
Because methylene blue can alter the balance between oxygen and blood flow, some people experience mild dizziness, light-headedness, or headaches, especially after injection.
- Stomach Upset or Nausea
When taken orally or intravenously, it may irritate the stomach lining, leading to mild nausea, vomiting, or abdominal discomfort. Taking the medication after food or under medical supervision usually reduces this problem.
- Sweating and Feverish Feeling
A temporary rise in body temperature or mild sweating sometimes occurs as the body reacts to the drug. This is generally short-lived and disappears within a few hours.
Moderate Side Effects
Some individuals may face more noticeable side effects requiring medical attention, although not typically life-threatening.
- Chest Tightness or Rapid Heartbeat
Methylene blue can influence blood pressure and heart rhythm. Sensitive patients may feel palpitations, mild chest discomfort, or a racing heartbeat. Immediate medical consultation is advised if these symptoms persist.
- Confusion or Restlessness
Because methylene blue affects brain chemistry, especially serotonin levels, it may cause confusion, agitation, or restlessness in some cases. This risk increases when combined with antidepressants or other serotonergic drugs.
- Shortness of Breath
A rare side effect may include mild respiratory difficulty due to changes in hemoglobin and oxygen transport. Anyone experiencing breathing problems should stop the medication and seek emergency care.
Serious Side Effects (Require Immediate Medical Help)
Although uncommon, certain reactions are considered serious and demand urgent evaluation by a healthcare professional.
- Serotonin Syndrome
This is a dangerous condition caused by excessive serotonin buildup in the brain. It can happen when methylene blue is taken along with SSRIs, SNRIs, MAOIs, or other antidepressants.
Symptoms include:
High fever
Muscle stiffness or tremors
Confusion or agitation
Rapid heartbeat
Seizures
Serotonin syndrome can be fatal if not treated promptly, so patients using antidepressants should never take methylene blue without strict medical supervision.
- Severe Allergic Reaction (Anaphylaxis)
A very small number of patients may develop allergic responses such as:
Swelling of the face, lips, or throat
Severe rash or itching
Difficulty breathing
If these symptoms occur, emergency medical treatment is essential.
- High Blood Pressure Crisis
Because methylene blue can constrict blood vessels, high doses may trigger hypertensive reactions — a sudden rise in blood pressure accompanied by headache, blurred vision, or chest pain.
Long-Term and Rare Side Effects
- Hemolytic Anemia
People with G6PD deficiency (a genetic enzyme disorder) are at particular risk. In such cases, methylene blue can destroy red blood cells, leading to fatigue, yellowing of the eyes, and anemia.
Testing for G6PD deficiency is crucial before treatment.
- Kidney and Liver Stress
Prolonged use or overdose may put strain on the kidneys or liver, causing abnormal test results or jaundice. This is why blood tests are often recommended during long treatments.
- Interference with Lab Tests
Because of its strong color and chemical nature, methylene blue may interfere with certain laboratory assays, giving false readings for substances such as glucose or bilirubin.
Drug Interactions
Methylene blue interacts with several medicines. Major interactions include:
Antidepressants: (Fluoxetine, Sertraline, Paroxetine, Duloxetine) → Risk of serotonin syndrome
Adrenergic drugs: (Epinephrine, Phenylephrine) → High blood pressure spikes
Other oxidizing agents: May intensify oxidative stress
Anesthetic agents: Could alter brain oxygen levels
Always provide your doctor with a full list of medications before starting methylene blue therapy.
Precautions Before Using Methylene Blue
Pregnancy and Breastfeeding:
The safety of methylene blue during pregnancy has not been fully established; it should only be used if the potential benefit outweighs the risk. It may also pass into breast milk.
Children and Elderly:
Dosages must be adjusted carefully; younger and older patients are more sensitive to its effects.
Existing Health Conditions:
Avoid or use with caution in patients with:
Severe kidney or liver disease
G6PD deficiency
Heart rhythm disorders
History of mental illness or serotonin imbalance
Driving and Operating Machinery:
Because it can cause dizziness or blurred vision, avoid driving until the effect is known.
Overdose Symptoms
Taking excessive methylene blue can cause:
Severe nausea or vomiting
Abdominal cramps
Chest pain
Confusion, tremors, or seizures
Bluish discoloration of the skin (cyanosis)
Immediate hospital care is necessary. Treatment generally includes stopping the medication and providing oxygen and supportive therapy.
Safety Tips for Use
Use only under medical prescription; never self-medicate.
Follow dosage instructions strictly; more is not better.
Report any unusual symptoms immediately.
Store the medication away from light and out of children’s reach.
Do not mix with herbal or over-the-counter antidepressants.
When to Seek Emergency Help
Call emergency services or visit a hospital if you experience:
Severe shortness of breath
Persistent chest pain
Confusion, fever, or muscle rigidity
Swelling of the face or throat
Continuous vomiting or severe abdominal pain
Conclusion
Methylene blue is an important and versatile medical compound that can save lives in conditions like methemoglobinemia and drug-induced brain toxicity. However, like every potent medication, it must be used with respect and medical supervision.
Its side effects range from harmless discoloration of urine to life-threatening conditions such as serotonin syndrome or hemolytic anemia in sensitive individuals. Understanding its risks, drug interactions, and precautions is the key to safe use.
Before starting methylene blue, always discuss your medical history, current medications, and possible allergies with a qualified doctor. Proper monitoring ensures that the benefits far outweigh any potential side effects.
