How long does a short course of oral methylprednisolone (Medrol dose pack) raise the white‑blood‑cell count?

Duration of WBC Elevation After Medrol Dose Pack

A short course of oral methylprednisolone (Medrol dose pack) typically raises the white blood cell count for 48 hours after administration, with the peak effect occurring at this time point, followed by a gradual decline that may persist for several days to weeks depending on the dose and duration of therapy. 1

Time Course of WBC Elevation

Acute Phase (First 48 Hours)

• The peak WBC increase occurs at 48 hours after methylprednisolone administration, with mean elevations ranging from 0.3 × 10⁹/L for low doses to 4.84 × 10⁹/L for high doses. 1
• The WBC count can surge as early as the first day of treatment, particularly with higher doses, and this initial rise may be dramatic. 2
• For a standard Medrol dose pack (starting at 24 mg and tapering over 6 days), expect a moderate WBC increase peaking around day 2-3 of therapy. 1

Sustained Elevation During Treatment

• Leukocytosis reaches maximal values within two weeks in most patients, after which the WBC count begins to decrease but does not immediately return to baseline. 2
• Even small doses of prednisone (and by extension methylprednisolone) administered over a prolonged period can induce extreme and persistent leukocytosis that lasts for the entire duration of therapy. 2
• The degree of leukocytosis is dose-dependent, with higher doses producing earlier and more pronounced elevations. 2

Post-Treatment Resolution

• After discontinuation of a short course (such as a Medrol dose pack), the WBC count gradually returns toward baseline over several days, though the exact timeline varies by individual. 1, 2
• In patients receiving chronic methylprednisolone therapy, morning lymphocyte counts remain elevated and persist over time, with increases detected as early as 13 days after initiation. 3

Cellular Composition of the Leukocytosis

Predominant Cell Types

• The leukocytosis is attributed predominantly to a rise in polymorphonuclear neutrophils (PMNs), which accounts for the majority of the WBC increase. 2
• Monocytosis accompanies the neutrophilia, while eosinopenia and variable lymphopenia are also observed. 2
• For lymphocytes specifically, chronic methylprednisolone causes a paradoxical increase in morning counts (before the next dose), with the most marked elevation in CD4 T cells. 3

Distinguishing Steroid-Induced Leukocytosis from Infection

• A left shift (>6% band forms) and toxic granulation are rare in corticosteroid-induced leukocytosis but common in infection, making these features useful for differential diagnosis. 2
• Any WBC increase after low-dose steroids, or increases exceeding 4.84 × 10⁹/L after high-dose steroids, should prompt evaluation for alternative causes such as infection. 1

Dose-Specific Expectations for Medrol Dose Pack

Standard Medrol Dose Pack Dosing

• A typical Medrol dose pack contains 21 tablets of 4 mg methylprednisolone, tapered from 24 mg on day 1 (6 tablets) down to 4 mg on day 6 (1 tablet), representing a medium-dose regimen. 4
• For this medium-dose range, expect a mean WBC increase of approximately 1.7 × 10⁹/L at the 48-hour peak, with the elevation persisting throughout the 6-day course and gradually resolving over the subsequent week. 1

Clinical Context

• The absolute bioavailability of oral methylprednisolone tablets is 82%, ensuring reliable systemic exposure and predictable WBC effects. 5
• Volunteers receiving 100 mg oral methylprednisolone displayed the expected rise in peripheral blood neutrophil count, confirming that even single high doses produce measurable leukocytosis. 5

Key Clinical Pitfalls

Misinterpreting Persistent Elevation

• Do not assume that leukocytosis resolving within 48 hours rules out steroid effect; the WBC count may remain elevated for the entire treatment duration and beyond. 2
• Do not overlook infection simply because the patient is on steroids; use clinical context, left shift, and toxic granulation to guide your assessment. 2

Timing of Laboratory Monitoring

• Morning lymphocyte counts (before the next methylprednisolone dose) may show paradoxical lymphocytosis, while counts drawn 8 hours after administration show a 49% decrease. 3
• Heightened awareness that the timing of blood sampling affects lymphocyte counts should help avoid unnecessary investigations when hyperlymphocytosis is observed before the next dose. 3