Prednisone Side Effects: What to Expect and When to Call Your Doctor

Why does prednisone cause so many side effects?

Prednisone is converted in the liver into its active form (prednisolone) and binds to receptors found throughout the body — in the gut, liver, kidneys, bones, muscles, brain, eyes, and skin. It dials down inflammation by suppressing the immune and inflammatory response, which is exactly what you want when inflammation is causing harm. But because those receptors are everywhere, prednisone affects all of these systems, not just the inflamed tissue. That broad reach is why the side-effect list is long even though the drug works well.

What are the common short-term side effects?

On courses under two weeks, the following are common:

• Increased appetite and hunger — often significant
• Trouble sleeping — especially if you take prednisone late in the day; taking it in the morning can reduce this
• Mild mood shifts — feeling wired, irritable, or unusually energetic
• Fluid retention and mild puffiness
• Flushing of the face
• Blood sugar elevation — prednisone raises blood sugar in nearly everyone at moderate and higher doses; this can tip into steroid-induced diabetes in those already at risk (prediabetes, family history, obesity, or older age) 1Ref 1American Diabetes Association Professional Practice Committee (2024).Standards of Care in Diabetes—2024.Blood sugar monitoring recommendations for steroid-induced hyperglycemia, particularly in people with diabetes or prediabetes on corticosteroids

Most of these ease once the course ends or the dose is lowered.

What changes with longer courses?

Courses lasting weeks to months carry additional, more serious risks on top of the short-term effects:

• Bone thinning (osteoporosis): Prednisone reduces calcium absorption and bone density with prolonged use. The 2022 American College of Rheumatology (ACR) guideline on glucocorticoid-induced osteoporosis recommends risk assessment and preventive treatment for patients receiving glucocorticoids for more than three months 3Ref 3Humphrey MB, Russell L, Danila MI, et al. (American College of Rheumatology) (2022).2022 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis.ACR 2022 guideline: risk assessment and preventive treatment recommended for patients on glucocorticoids >3 months at ≥2.5 mg/day; highlights undertreatment of glucocorticoid-induced osteoporosis leading to preventable fractures. Your prescriber may recommend a DEXA bone density scan 2Ref 2US Preventive Services Task Force (2018).Screening for Osteoporosis to Prevent Fractures: US Preventive Services Task Force Recommendation Statement.DEXA bone density scanning as a tool to detect bone loss, relevant for patients on prolonged corticosteroid therapy and supplemental calcium and vitamin D.
• Muscle weakening: Particularly in the thighs and hips; you may notice difficulty climbing stairs.
• Weight gain: Especially in the face ("moon face") and abdomen.
• Skin thinning and easy bruising.
• Cataracts and glaucoma: Prolonged use increases the risk of both; an ophthalmology check is often recommended.
• Immune suppression: Higher doses suppress the immune system noticeably. Existing infections — including latent tuberculosis — can reactivate, and new infections may progress with fewer obvious symptoms.
• Adrenal suppression (see below).

Why can't you just stop prednisone when you feel better?

After more than a week or two, your adrenal glands have partially slowed their own cortisol production because prednisone was doing that job. If you stop suddenly, your body can be temporarily short on cortisol — causing fatigue, nausea, dizziness, and in severe cases, an adrenal crisis. Your prescriber will give you a tapering schedule (gradually reducing the dose) to let the adrenals restart. Never stop prednisone abruptly without guidance, especially after a course of more than a week or two.

How can you reduce day-to-day discomfort?

Several practical steps can help:

• Take prednisone in the morning with food to limit stomach upset and reduce sleep disruption.
• Limit salty foods to counter fluid retention.
• Track your blood sugar if your prescriber recommends it — especially if you have diabetes or prediabetes 1Ref 1American Diabetes Association Professional Practice Committee (2024).Standards of Care in Diabetes—2024.Blood sugar monitoring recommendations for steroid-induced hyperglycemia, particularly in people with diabetes or prediabetes on corticosteroids.
• Stay physically active to preserve muscle and bone where possible.
• Avoid contact with sick people during higher-dose periods, since your immune defense is reduced.

Talk to your prescriber before formalizing any of these changes into a plan.

Which conditions change the risk picture?

• Diabetes or prediabetes: Prednisone can cause significant blood sugar swings; more frequent glucose monitoring and possible medication adjustments are often needed 1Ref 1American Diabetes Association Professional Practice Committee (2024).Standards of Care in Diabetes—2024.Blood sugar monitoring recommendations for steroid-induced hyperglycemia, particularly in people with diabetes or prediabetes on corticosteroids.
• High blood pressure: Fluid retention can worsen hypertension.
• Older age: Greater risk of bone loss, fractures, cataracts, and falls.
• Concurrent NSAIDs (ibuprofen, naproxen, aspirin): Combining prednisone with NSAIDs substantially increases the risk of stomach ulcers and GI bleeding.
• History of psychiatric illness: Mood effects — including mania and depression — can be more pronounced.
• Pregnancy: Prednisone can be used in pregnancy when medically necessary, but requires careful risk-benefit discussion with your OB or specialist.