Prednisolone and Clarithromycin Interaction

Question 1

1. Interaction
   PK/metabolism

Answer 1

The interaction is pharmacokinetic, specifically affecting the metabolism of prednisolone in the liver.

Question 2

2. Clarithromycin IE COPD

Answer 2

clarithromycin affects the metabolism of prednisolone.
In COPD exacerbation. It’s the preferred antibiotic when patients are penicillin-allergic or unresponsive to doxycycline (NICE guidelines).

Question 3

3. CYP450 Enzyme Inhibition

Answer 3

Clarithromycin is a potent inhibitor of CYP3A4 activity, this reduces the metabolism of prednisolone, leading to higher plasma concentrations of the drug. Prednisolone’s biological half-life (~18–36 hours) means even minor changes in clearance due to CYP3A4 inhibition can lead to significant accumulation over time.

Question 4

4. increased plasma concentration, side effect.

Answer 4

One UK manufacturer of prednisolone predicts that clarithromycin might increase prednisolone concentrations by 113%. Increased prednisolone exposure may cause fluid retention, hyperglycemia, or mood changes, requiring frequent monitoring.

Question 5

Interaction management
dose change

Answer 5

Lowering the dose of clarithromycin to 250mg does not significantly change its inhibitory effect on CYP3A4 activity or its impact on prednisolone metabolism.

I would consider lowering the dose of prednisolone to 20mg daily, can help counteract the prolonged half-life and elevated levels. I would advise patients to take it early in the morning (to replicate the body’s natural cortisol peak), and with food to slow absorption.

Question 6

management and monitoring

Answer 6

The severe interaction is theoretical and is said to increase exposure to prednisolone. I would counsel the [patient to contact me with any symptoms of mood changes (e.g., anxiety, irritability).
Fluid retention
Signs of hyperglycemia
and explain the infection risks that prednisolone suppress the immune system and advice they contact me with any new or worsening infection symptoms.
I would advise diabetic patients to monitor blood sugar levels closely. If side effects occur, I can reduce the prednisolone dose further.

Safety netting would be discussed any issues discussed with the GP.
I would repeat blood tests (HbA1c, bone profile, urea/electrolytes, liver function) in one week.
I would advise the GP to consider prescribing bone protection to reduce the risk of osteoporosis for at risk patients (if FRAX score high).

Answer 7

Prednisolone interaction with clarithromycin is pharmacokinetic interaction as it affects the metabolism of prednisolone. During a COPD exacerbation, patients often may need treatment with both steroids and antibiotics. Clarithromycin is the drug of choice for patient who are penicillin allergic and do not respond to Doxycycline as per NICE guidelines. BNF- Severe (theoretical) interaction. Advises to avoid or monitor for adverse effects.

Clarithromycin is a potent inhibitor of liver enzyme CYP450 family and specifically CYP3A4, it decreases its production and activity by 75%. Clarithromycin binds to CYP3A4 and inhibits prednisolone from binding to the enzyme to be metabolised. This result will reduce prednisolone from being metabolised leading to increased drug plasma concentration causing increased side effects.

One UK manufacturer of prednisolone predicts that clarithromycin might increase prednisolone concentrations by 113%. Increased prednisolone exposure may cause fluid retention, hyperglycemia, or mood changes, requiring frequent monitoring.

I would consider lowering the dose of prednisolone to 20mg to be taken early in the morning as close to waking (to replicate body’s own natural cortisol peak) with food to slow the absorption.

By spacing the doses, prednisolone can be cleared from the body (half-life: 2.1–3.5 hours) before significant interaction occurs. Lowering the clarithromycin dose to 250 mg does not alter its inhibitory effects, half-life, or absorption, so adjusting timing is a more effective strategy to reduce interaction risks.

I will advise the patient to monitor for side effects such as raised blood sugars, blood pressure, oedema, sleep/mood disturbances. I will consider a further dose reduction in case the patient presents with side effects and will discuss the case with a doctor to safety net the patient.

I will consider repeating blood such as HBA1C, bone profile, urea and electrolytes and liver function in a week’s time. I will request GP to consider prescribing bone protection to avoid osteoporosis and fractures in at risk patients.