Can metoprolol succinate (extended-release) be split to obtain a half dose?

Metoprolol Succinate Extended-Release Tablets Should Not Be Split

Do not split metoprolol succinate (extended-release) tablets, as splitting destroys the controlled-release mechanism and causes unpredictable drug delivery with significant dose variation.

Why Splitting Is Contraindicated

Destruction of Extended-Release Technology

• Metoprolol succinate tablets contain multiple controlled-release pellets embedded within the tablet, each designed to deliver drug continuously over approximately 20 hours at a near-constant rate. 1
• Splitting the tablet disrupts these pellets and destroys the extended-release mechanism, converting the formulation into an immediate-release product with unpredictable absorption. 2
• The controlled-release pellets are not homogeneously distributed throughout the tablet, leading to significant dose variation when split. 3

Evidence of Dose Inaccuracy

• A rigorous study using high-performance liquid chromatography found that 33.3% of metoprolol succinate half-tablets (10 of 30) fell outside acceptable drug content specifications, with a relative standard deviation of 8.98%—exceeding the USP specification of <6%. 4
• Weight variation was similarly problematic, with 20% of half-tablets (6 of 30) falling outside acceptable weight specifications and a relative standard deviation of 7.70%. 4
• Dissolution studies demonstrated that crushed metoprolol succinate tablets had significantly different dissolution profiles compared to whole tablets at pH 4.5 (f2=45.43) and pH 6.8 (f2=31.47), indicating non-bioequivalence. 2

Clinical Implications

• The altered dissolution profile means that split tablets release drug according to different kinetic models (Higuchi, Weibull, or Korsmeyer-Peppas) compared to whole tablets (Hopfenberg, logistic, or first-order models), resulting in unpredictable plasma concentrations. 2
• This unpredictability is particularly dangerous for patients requiring precise beta-blockade, such as those with heart failure, post-myocardial infarction, or atrial fibrillation requiring rate control.

Recommended Alternatives

Use Lower-Strength Whole Tablets

• Metoprolol succinate is available in multiple strengths: 25 mg, 50 mg, 100 mg, and 200 mg tablets. 5
• If a patient requires 50 mg daily, prescribe a 50 mg tablet rather than splitting a 100 mg tablet. 5
• For doses between available strengths, work with the prescriber to adjust to the nearest available whole-tablet dose.

Consider Metoprolol Tartrate for Flexible Dosing

• If precise dose titration in small increments is required, switch to metoprolol tartrate (immediate-release), which can be split more reliably because it does not contain controlled-release technology. 6
• The conversion ratio is 1:1 for total daily dose: metoprolol tartrate 50 mg twice daily equals metoprolol succinate 100 mg once daily. 6
• Metoprolol tartrate is typically dosed twice daily at 25-100 mg per dose, allowing for more granular dose adjustments. 7, 5

Gradual Transition Protocol

• When converting from succinate to tartrate, the American College of Cardiology recommends a gradual transition over 2-3 days to ensure stable blood levels. 6
• Start metoprolol tartrate 15 minutes after the last dose of metoprolol succinate. 5

Common Clinical Scenarios

Patient Requiring 100 mg Daily

• Prescribe metoprolol succinate 100 mg once daily as a whole tablet, not a split 200 mg tablet. 5

Patient Requiring 75 mg Daily

• This dose is not achievable with whole metoprolol succinate tablets.
• Convert to metoprolol tartrate 37.5 mg twice daily (split a 75 mg tablet or use 25 mg + 12.5 mg). 6
• Alternatively, use metoprolol succinate 50 mg or 100 mg once daily and titrate based on clinical response (heart rate, blood pressure). 5

Patient with Swallowing Difficulties

• Do not crush or split metoprolol succinate tablets for administration via feeding tube, as this significantly alters drug release and plasma concentrations. 2
• Switch to metoprolol tartrate, which can be crushed if necessary, or consider intravenous metoprolol in acute settings. 5

Critical Monitoring If Splitting Has Already Occurred

• If a patient has been splitting metoprolol succinate tablets, assess for signs of inadequate beta-blockade (tachycardia, uncontrolled hypertension, breakthrough angina) or excessive beta-blockade (symptomatic bradycardia, hypotension). 5
• Measure heart rate and blood pressure at each visit, targeting a resting heart rate of 50-60 bpm unless limiting side effects occur. 5
• Transition to an appropriate whole-tablet dose or switch to metoprolol tartrate. 6