Metoprolol is a prescription beta-blocker that mainly blocks β1-adrenergic receptors in the heart. It slows the heart rate, lowers the force of each beat and lowers blood pressure. In the US it comes in two salt forms that behave differently: immediate-release metoprolol tartrate (Lopressor and generics), usually taken two or more times a day, and extended-release metoprolol succinate (Toprol-XL and generics), taken once a day.
The two forms share hypertension and angina indications, but their other approvals differ. Only the tartrate is labeled for use right after a heart attack, and only the succinate is labeled for heart failure, based on the MERIT-HF trial. Both labels warn that stopping metoprolol suddenly can trigger worsening angina or a heart attack. Older Toprol-XL labels printed this as a boxed warning. Metoprolol is also named on the WADA Prohibited List as a beta-blocker banned in certain precision sports.
This page summarizes what the FDA labels, major clinical trials and the WADA list report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Beta-adrenergic blocker, β1-selective (cardioselective), without intrinsic sympathomimetic activity |
| Brands / approval | Lopressor (tartrate), NDA 017963, approved August 1978; Toprol-XL (succinate, extended release), NDA 019962, approved January 1992; generics of both |
| Route | Oral tablets (an intravenous form is used in hospitals after a heart attack) |
| Strengths | Lopressor 50 and 100 mg (plus a newer 12.5 mg tablet); Toprol-XL 25, 50, 100 and 200 mg (labeled as the equivalent tartrate dose) |
| Labeled dose ranges | Tartrate 100–450 mg/day for hypertension; succinate 25–100 mg once daily to start, studied up to 400 mg/day |
| Half-life (labels) | 3–4 h for immediate release, 7–9 h in CYP2D6 poor metabolizers; the Toprol-XL label gives about 3–7 h |
| Metabolism | Mainly by the liver enzyme CYP2D6; strong CYP2D6 inhibitors roughly double blood levels |
| US status | Prescription only |
| WADA status | P1 beta-blocker: banned in competition in specific sports (e.g. archery, shooting, golf, darts), and also out of competition in some |
What it is
Metoprolol is a racemic mixture of R- and S-enantiomers (mirror-image forms) with the formula C₁₅H₂₅NO₃ and a molecular weight of 267.4 g/mol for the free base (PubChem). Medicines use one of two salts. The salt does not change how metoprolol acts once absorbed; what differs is the tablet design and the release rate.
| Feature | Metoprolol tartrate (Lopressor) | Metoprolol succinate (Toprol-XL) |
|---|---|---|
| Release | Immediate release | Extended release: many small controlled-release pellets per tablet |
| Usual dosing | Single or divided doses; twice daily for angina, every 6 h early after a heart attack | Once daily |
| Strength convention | Labeled as mg of tartrate | 23.75, 47.5, 95 and 190 mg of succinate, labeled as 25, 50, 100 and 200 mg tartrate-equivalent |
| Salt molecular weight | 684.82 g/mol | 652.8 g/mol |
| Labeled indications | Hypertension, angina, myocardial infarction | Hypertension, angina, heart failure |
| Handling | Take with or right after meals | Tablets are scored and can be split, but must not be crushed or chewed |
Sources for the table: the Lopressor label and the Toprol-XL label. A newer 12.5 mg Lopressor tablet (label) is labeled only for stable patients after a heart attack. The Toprol-XL label says that when switching from immediate-release metoprolol, the same total daily dose of Toprol-XL should be used.
How it works
Both labels describe metoprolol as β1-selective, but not absolutely so. At higher blood levels it also blocks β2 receptors, which sit mainly in the airways and blood vessels. The labels put the point where β1-selectivity fades at plasma concentrations above 300 nmol/L. Evidence for its selectivity, per the labels:
- in healthy people, it cannot reverse the β2-mediated widening of blood vessels caused by epinephrine, unlike non-selective blockers;
- in people with asthma, it lowers lung function (FEV₁ and FVC) significantly less than propranolol at equal β1-blocking doses.
The labels say the exact way beta-blockers lower blood pressure is not fully known. Proposed mechanisms include lower cardiac output from blocking catecholamines at the heart, reduced sympathetic outflow from the brain and suppressed renin release. In angina, slowing the heart and reducing its contraction lowers the heart’s oxygen demand at a given level of effort.
Pharmacokinetics
| Parameter | Immediate release (tartrate) | Extended release (succinate) |
|---|---|---|
| Oral bioavailability | About 50%, due to saturable first-pass metabolism in the liver | At steady state, 77% of the same dose of immediate-release metoprolol |
| Peak level | Reference | About one-quarter to one-half of the immediate-release peak |
| Food | Take with or right after meals | Absorption not significantly affected |
| Plasma protein binding | About 10% | About 12% |
| Half-life | 3–4 h; 7–9 h in CYP2D6 poor metabolizers | About 3–7 h (plasma) |
| Excretion | About 95% recovered in urine, mostly as inactive metabolites | Under 5% of an oral dose excreted unchanged |
Sources: Lopressor label; Toprol-XL label.
Other label points:
- Metoprolol crosses into the brain. The Toprol-XL label reports cerebrospinal fluid levels at 78% of plasma levels.
- It crosses the placenta and appears in breast milk.
- Kidney failure does not change its availability or half-life to a clinically important degree, so no dose cut is needed. Poor liver function is likely to raise levels substantially, so the labels advise starting low.
- Hemodialysis is unlikely to help remove it in an overdose.
CYP2D6 and genetics
CYP2D6, the main enzyme that breaks metoprolol down, is absent in about 8% of white people and about 2% of most other populations (“poor metabolizers”). These people have several-fold higher blood levels, and metoprolol becomes less β1-selective at those levels. The same happens in normal metabolizers who take a CYP2D6-inhibiting drug (see Interactions).
The extended-release form changes the shape of the blood-level curve, not the total effect. In five studies in healthy people, once-daily succinate and immediate-release metoprolol taken one to four times a day gave comparable total β1-blockade over 24 hours at 100–400 mg. At 50 mg once daily, the succinate gave more total blockade (Toprol-XL label).
Approved medical use
| Indication | Tartrate (Lopressor) labeled dosing | Succinate (Toprol-XL) labeled dosing |
|---|---|---|
| Hypertension (adults) | 100 mg/day in single or divided doses to start; effective range 100–450 mg/day | 25–100 mg once daily to start; doses above 400 mg/day not studied |
| Hypertension (children ≥ 6 years) | Not labeled | 1 mg/kg once daily, no more than 50 mg to start; above 2 mg/kg (or 200 mg) not studied |
| Angina pectoris | 100 mg/day in two divided doses to start; effective range 100–400 mg/day | 100 mg once daily to start; up to 400 mg/day studied |
| Acute myocardial infarction | After intravenous metoprolol: 50 mg every 6 h for 48 h, then 100 mg twice daily for at least 3 months | Not labeled |
| Heart failure | Not labeled | 25 mg once daily (NYHA class II) or 12.5 mg (more severe), doubled every 2 weeks as tolerated up to 200 mg |
Sources: Lopressor label; Toprol-XL label. Both labels say dose changes should be made at weekly or longer intervals. NYHA class is the New York Heart Association scale of heart failure symptoms, from I (no limits on activity) to IV (symptoms at rest).
The Lopressor label adds that lower once-daily doses (especially 100 mg) may not keep blood pressure down for the full 24 hours, so blood pressure should be checked near the end of the dosing interval.
What the research shows
Heart failure: MERIT-HF (succinate)
MERIT-HF was a double-blind trial in 3,991 patients with heart failure (NYHA class II–IV, ejection fraction of 40% or less) who were already on standard treatment. They were randomized to metoprolol succinate, titrated over 8 weeks toward 200 mg once daily, or placebo (MERIT-HF, Lancet 1999). At randomization, 89% were taking ACE inhibitors and 90% diuretics. The trial was stopped early after a mean follow-up of about 1 year because of a clear survival benefit. The mean final dose was 159 mg/day (Toprol-XL label).
| Outcome | Placebo (n = 2,001) | Metoprolol succinate (n = 1,990) | Relative risk (95% CI) |
|---|---|---|---|
| All-cause death | 217 | 145 | 0.66 (0.53–0.81) |
| Cardiovascular death | 203 | 128 | 0.62 (0.50–0.78) |
| Sudden death | 132 | 79 | 0.59 (0.45–0.78) |
| Death from worsening heart failure | 58 | 30 | 0.51 (0.33–0.79) |
| Death or any hospitalization | 767 | 641 | 0.81 (0.73–0.90) |
| Death or heart failure hospitalization | 439 | 311 | 0.69 (0.60–0.80) |
Fewer patients stopped metoprolol for adverse reactions than stopped placebo (10.3% vs 12.2%).
Heart failure: tartrate vs carvedilol (COMET)
COMET was a double-blind trial in 3,029 patients with heart failure and an ejection fraction under 35%. It compared carvedilol (target 25 mg twice daily) with metoprolol tartrate (target 50 mg twice daily) over a mean of 58 months (Poole-Wilson et al., Lancet 2003). All-cause mortality was 34% with carvedilol and 40% with metoprolol tartrate (hazard ratio 0.83, 95% CI 0.74–0.93). The combined outcome of death or any hospital admission did not differ significantly.
COMET did not test the succinate form or the dose used in MERIT-HF. The FDA heart failure indication applies only to metoprolol succinate.
After a heart attack
The trial behind Lopressor’s heart attack indication was a double-blind study in 1,395 patients with definite or suspected heart attack, done before modern reperfusion treatment (Hjalmarson et al., Lancet 1981). Patients got 15 mg of metoprolol intravenously, then 100 mg by mouth twice daily for 90 days, or placebo. Deaths fell from 62 (8.9%) with placebo to 40 (5.7%) with metoprolol, a 36% relative reduction.
Later trials qualified this result:
| Trial | Design | Main result |
|---|---|---|
| COMMIT (Chen et al., Lancet 2005) | 45,852 patients within 24 h of a suspected heart attack; up to 15 mg IV, then 200 mg/day oral metoprolol or placebo, for up to 4 weeks in hospital | No reduction in death (7.7% vs 7.8%; OR 0.99, 95% CI 0.92–1.05). Fewer reinfarctions (2.0% vs 2.5%) and less ventricular fibrillation (2.5% vs 3.0%), but more cardiogenic shock (5.0% vs 3.9%; OR 1.30, 95% CI 1.19–1.41), mostly on days 0–1 |
| REDUCE-AMI (Yndigegn et al., NEJM 2024) | 5,020 patients after a heart attack with ejection fraction ≥ 50%, open-label; long-term metoprolol or bisoprolol vs no beta-blocker; median 3.5 years | Death or new heart attack 7.9% vs 8.3% (HR 0.96, 95% CI 0.79–1.16): no significant benefit |
The COMMIT authors concluded that it may be prudent to start beta-blockers in hospital only once the patient’s circulation has stabilized. This matches the label’s restriction to “hemodynamically stable” patients.
Hypertension
In a 9-week double-blind trial in 1,092 people with mild to moderate hypertension, metoprolol succinate 25, 100 or 400 mg once daily lowered sitting blood pressure by 6–8/4–7 mmHg more than placebo at 24 hours after the dose (Toprol-XL label). In older comparative trials, immediate-release metoprolol lowered blood pressure about as much as propranolol, methyldopa and thiazide diuretics (Lopressor label).
Lowering blood pressure is not the same as preventing heart attacks and strokes. A Cochrane review of 13 randomized trials of beta-blockers as first-line treatment for hypertension found no effect on all-cause death compared with placebo (RR 0.99, 95% CI 0.88–1.11) and a modest drop in stroke (RR 0.80, 95% CI 0.66–0.96) (Wiysonge et al., Cochrane 2017). Stroke was more common with beta-blockers than with calcium channel blockers (RR 1.24) or renin-angiotensin system inhibitors (RR 1.30). About three-quarters of the beta-blocker patients in these trials took atenolol, not metoprolol, and most trials had a high risk of bias. For comparison, see the library pages on amlodipine, losartan and lisinopril.
Use with anabolic steroids
No controlled trial has tested metoprolol in people using anabolic steroids or other performance drugs. Raised blood pressure and heart rate in this group are covered on the library’s antihypertensive pages, including the related β1-selective blocker nebivolol, which also widens blood vessels through nitric oxide.
Side effects and risks
Abrupt cessation (formerly a boxed warning)
Both current labels list this as the first Warning and Precaution: after sudden withdrawal of some beta-blockers, angina has worsened and some patients have had heart attacks (Lopressor label; Toprol-XL label). The labels say:
- when stopping long-term metoprolol, the dose should be reduced gradually over 1–2 weeks with monitoring, especially in people with ischemic heart disease;
- if angina markedly worsens, metoprolol should be restarted promptly;
- because coronary artery disease is common and may be undiagnosed, sudden stopping should be avoided even in people treated only for hypertension.
Earlier Toprol-XL labels carried this text as a boxed warning headed “Warning: Ischemic heart disease” (Toprol-XL label, 2020 repackager version). The current Lopressor and Toprol-XL labels on DailyMed have no boxed section; the warning now sits in Warnings and Precautions. Abrupt withdrawal can also precipitate a thyroid storm in people with an overactive thyroid.
Common side effects
In hypertension and angina, the Lopressor label describes most adverse effects as mild and transient:
| Effect | Approximate rate (Lopressor label) |
|---|---|
| Tiredness and dizziness | About 10% |
| Depression | About 5% |
| Diarrhea | About 5% |
| Itching or rash | About 5% |
| Shortness of breath; slow heart rate | About 3% |
| Cold hands and feet, Raynaud-type circulation problems, palpitations, swelling, low blood pressure | About 1% |
| Wheezing (bronchospasm) | About 1% |
Confusion, short-term memory loss, headache, nightmares and insomnia have also been reported. In MERIT-HF, only dizziness/vertigo (1.8% vs 1.0%) and slow heart rate (1.5% vs 0.4%) were at least 0.5 percentage points more common than with placebo (Toprol-XL label).
In the original heart attack trial, the label reports these rates:
| Event | Metoprolol | Placebo |
|---|---|---|
| Low blood pressure (systolic under 90 mmHg) | 27.4% | 23.2% |
| Slow heart rate (under 40 beats/min) | 15.9% | 6.7% |
| First-degree heart block | 5.3% | 1.9% |
| Second- or third-degree heart block | 4.7% | 4.7% |
| Heart failure | 27.5% | 29.6% |
Heart rhythm, heart failure and surgery
- Slow heart rate and heart block. The Toprol-XL label reports sinus pauses, heart block and cardiac arrest. The risk is higher with existing conduction disease or other heart-slowing drugs.
- Worsening heart failure. This can occur while the dose is being raised. The labels advise adjusting diuretics and lowering or pausing metoprolol until stable.
- Starting high doses before surgery. In the POISE trial, 8,351 patients with or at risk of atherosclerotic disease got metoprolol succinate 100 mg 2–4 h before non-cardiac surgery, then 200 mg/day for 30 days, or placebo (POISE, Lancet 2008). Heart attacks fell (4.2% vs 5.7%; HR 0.73), but deaths (3.1% vs 2.3%; HR 1.33, 95% CI 1.03–1.74) and strokes (1.0% vs 0.5%; HR 2.17, 95% CI 1.26–3.74) rose. The labels now advise against starting high-dose metoprolol around non-cardiac surgery, while also saying long-term therapy should not be routinely stopped before surgery.
Other warnings
- Lung disease. People with bronchospastic disease such as asthma should generally not take beta-blockers. Metoprolol may be used at the lowest possible dose when alternatives fail, with bronchodilators at hand.
- Low blood sugar. Beta-blockers can hide warning signs such as a fast heartbeat, and raise the risk of severe or prolonged hypoglycemia, especially in diabetes, in children and during fasting or vomiting.
- Pheochromocytoma. Metoprolol should only be given after an alpha-blocker has been started; a beta-blocker alone can paradoxically raise blood pressure.
- Peripheral artery disease. Symptoms of poor blood flow to the limbs can worsen.
- Severe allergies. People with a history of anaphylaxis may react more strongly and may not respond to usual doses of epinephrine.
- Sexual function and fertility. Both labels say beta-blockers, including metoprolol, may cause erectile dysfunction and reduce sperm motility, based on published literature. The Toprol-XL label also lists decreased libido and Peyronie’s disease among post-marketing reports.
- Blood lipids and liver tests. Post-marketing reports include higher triglycerides, lower HDL cholesterol and raised liver enzymes (Lopressor label).
Who should not take it
The labels list these contraindications:
- severe bradycardia (slow heart rate);
- second- or third-degree heart block;
- sick sinus syndrome without a permanent pacemaker;
- cardiogenic shock or decompensated heart failure;
- hypersensitivity to any ingredient;
- for Lopressor, also a systolic blood pressure under 100 mmHg.
Overdose
Overdose can cause severe bradycardia, low blood pressure and cardiogenic shock, as well as heart block, bronchospasm and loss of consciousness. The labels note that beta-blocker overdose can resist treatment with adrenergic drugs. Glucagon is among the listed treatments.
Pregnancy and breastfeeding
Observational studies have not linked metoprolol to major birth defects, but reports of slowed fetal growth, preterm birth and perinatal death are inconsistent and methodologically limited. Metoprolol crosses the placenta, and newborns exposed before birth may have low blood pressure, low blood sugar, slow heart rate and breathing problems. The infant dose through breast milk is estimated at 0.5–2% of the mother’s weight-adjusted dose (Toprol-XL label).
Interactions
| Interacting drug or group | Effect reported in the labels |
|---|---|
| Strong CYP2D6 inhibitors (quinidine, fluoxetine, paroxetine, propafenone) | About double metoprolol levels; less β1-selectivity. Quinidine 100 mg tripled S-metoprolol levels and doubled the half-life; propafenone raised steady-state levels 2–5-fold in 4 patients |
| Moderate or weak CYP2D6 inhibitors | No data, but likely to raise levels |
| Digoxin and other digitalis glycosides, clonidine, diltiazem, verapamil | Added slowing of heart rate and AV conduction; higher bradycardia risk |
| Clonidine withdrawal | Beta-blockers can worsen rebound hypertension; the beta-blocker should be stopped several days before clonidine is tapered |
| Catecholamine-depleting drugs (reserpine, MAO inhibitors) | Additive effect; risk of low blood pressure, marked bradycardia, dizziness or fainting |
| Epinephrine | People with a history of severe allergic reactions may not respond to usual doses of epinephrine |
Sources: Lopressor label; Toprol-XL label.
Legal status and anti-doping
In the US, metoprolol tartrate and succinate are prescription-only drugs (Drugs@FDA, NDA 017963; Drugs@FDA, NDA 019962).
WADA lists metoprolol by name under P1, beta-blockers, a class banned only in particular sports (WADA 2026 Prohibited List). All beta-blockers are Specified Substances.
| Sport (federation) | When prohibited |
|---|---|
| Archery (WA) | In and out of competition |
| Shooting (ISSF, IPC) | In and out of competition |
| Underwater sports (CMAS): all freediving, spearfishing and target shooting subdisciplines | In and out of competition |
| Automobile (FIA) | In competition |
| Billiards, all disciplines (WCBS) | In competition |
| Darts (WDF) | In competition |
| Golf (IGF) | In competition |
| Mini-golf (WMF) | In competition |
The reason for the ban is shown by a double-blind crossover study in 33 pistol shooters (Kruse et al., J Appl Physiol 1986). Compared with placebo, metoprolol improved scores by an average of 13.4% of the possible improvement, with the clearest gains in the most skilled shooters. The improvement did not track changes in heart rate or blood pressure, and the authors attributed it to reduced hand tremor.
Key takeaways
- Two salts, two products. Tartrate (Lopressor) is immediate release and labeled for hypertension, angina and heart attack. Succinate (Toprol-XL) is once-daily extended release and labeled for hypertension, angina and heart failure.
- Heart failure evidence is for succinate. In MERIT-HF, metoprolol succinate cut all-cause death by 34% (RR 0.66). In COMET, metoprolol tartrate at 50 mg twice daily did worse than carvedilol.
- Do not stop suddenly. Abrupt withdrawal can worsen angina or cause a heart attack. The labels call for tapering over 1–2 weeks; older Toprol-XL labels boxed this warning.
- CYP2D6 matters. Poor metabolizers and people on strong CYP2D6 inhibitors such as fluoxetine or paroxetine can have several-fold higher levels and lose β1-selectivity.
- Banned in precision sports. WADA names metoprolol under P1. It is banned in competition in sports such as golf and darts, and at all times in archery and shooting.
Sources
- Validus Pharmaceuticals. Lopressor (metoprolol tartrate) tablets, prescribing information. DailyMed; 12.5 mg tablet label (2025) DailyMed; Drugs@FDA, NDA 017963.
- Melinta Therapeutics. Toprol-XL (metoprolol succinate) extended-release tablets, prescribing information (revised 2026). DailyMed; Drugs@FDA, NDA 019962.
- Aphena Pharma Solutions. Toprol-XL (metoprolol succinate) extended-release tablets, repackager label with boxed warning (2020). DailyMed.
- National Center for Biotechnology Information. Metoprolol, PubChem CID 4171. PubChem.
- MERIT-HF Study Group. Effect of metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF). Lancet. 1999;353(9169):2001–2007. PubMed.
- Poole-Wilson PA, Swedberg K, Cleland JG, et al. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial. Lancet. 2003;362(9377):7–13. PubMed.
- Hjalmarson A, Elmfeldt D, Herlitz J, et al. Effect on mortality of metoprolol in acute myocardial infarction. A double-blind randomised trial. Lancet. 1981;2(8251):823–827. PubMed.
- Chen ZM, Pan HC, Chen YP, et al. Early intravenous then oral metoprolol in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet. 2005;366(9497):1622–1632. PubMed.
- Yndigegn T, Lindahl B, Mars K, et al. Beta-blockers after myocardial infarction and preserved ejection fraction. N Engl J Med. 2024;390(15):1372–1381. PubMed.
- POISE Study Group, Devereaux PJ, Yang H, et al. Effects of extended-release metoprolol succinate in patients undergoing non-cardiac surgery (POISE trial): a randomised controlled trial. Lancet. 2008;371(9627):1839–1847. PubMed.
- Wiysonge CS, Bradley HA, Volmink J, et al. Beta-blockers for hypertension. Cochrane Database Syst Rev. 2017;1(1):CD002003. PubMed.
- Kruse P, Ladefoged J, Nielsen U, et al. beta-Blockade used in precision sports: effect on pistol shooting performance. J Appl Physiol. 1986;61(2):417–420. PubMed.
- World Anti-Doping Agency. The 2026 Prohibited List, P1 Beta-blockers. WADA 2026 Prohibited List.