Is tiredness a side effect of azathioprine?

Tiredness as a Side Effect of Azathioprine

Yes, tiredness can be a side effect of azathioprine, though it is not among the most commonly reported adverse effects in clinical guidelines. While nausea, bone marrow suppression, and hypersensitivity reactions are more frequently documented, fatigue may occur as part of the overall side effect profile.

Common Side Effects of Azathioprine

• Nausea and anorexia are the most frequently observed adverse effects, occurring in approximately 10-20% of patients 1
• Early, mild nausea is common and often self-limiting, usually resolving after a few weeks without dose alteration 1
• About 25% of patients with autoimmune hepatitis develop side effects on azathioprine, requiring withdrawal in about 10% of cases 1
• Side effects are more common in patients with cirrhosis 1

Serious Side Effects to Monitor

• Bone marrow suppression (neutropenia) is a potentially serious and not uncommon dose-dependent side effect, with rates ranging from 5-30% across studies 1
• About 5% of patients develop a severe early hypersensitivity reaction with fever, arthralgia, skin rash, and influenza-like symptoms 1, 2
• The risk of marrow toxicity can sometimes be predicted by measuring thiopurine methyltransferase (TPMT) activity 1
• Severe muscular weakness has been reported as an unusual adverse effect in some cases 3

Fatigue and Tiredness

While tiredness is not specifically highlighted in the major guidelines as a primary side effect, it may occur:

• Fatigue may be associated with mild bone marrow suppression, which is quite common in patients receiving azathioprine 1
• Tiredness could be a component of the general malaise that some patients experience, particularly those with mild lymphopenia 1
• Fatigue might be related to other side effects such as nausea or anorexia that affect overall well-being 1

Management of Side Effects

• For nausea: taking azathioprine with food, splitting the daily dose, temporary dose reduction, or antiemetics may help 1
• Gradual dose escalation when starting azathioprine may minimize initial side effects 1
• Regular monitoring of blood counts is essential regardless of TPMT status 1
• If tiredness is severe or persistent, consider checking complete blood count to rule out bone marrow suppression 1, 4

Important Considerations

• TPMT testing should be performed before starting therapy to identify patients at high risk for toxicity 1, 5
• About one in 300 people is homozygous for a low-activity TPMT allele and has very low enzyme activity, putting them at high risk for serious toxicity 1
• Side effects requiring drug withdrawal occur in approximately 10% of patients 1
• Patients should be monitored with regular blood tests, particularly during the first few months of treatment 1

If a patient reports significant tiredness while on azathioprine, it should be taken seriously and evaluated with appropriate laboratory testing to rule out bone marrow suppression or other complications that may require dose adjustment or medication change.