Metoprolol: Succinate vs. Tartrate Explained, Avoiding Sleep Disturbances & When Bisoprolol Is Better

After bisoprolol, metoprolol is the second most commonly prescribed beta-blocker in Germany — with over 800 million daily doses of therapy per year. It slows the heartbeat, lowers blood pressure and protects the heart from numerous diseases. But metoprolol has a peculiarity that is often confusing: There are two different forms of salt — tartrate and succinate — with different properties. Metoprolol is also lipophilic (fat-soluble) and penetrates the brain, which explains sleep disorders and nightmares. This guide clarifies the most important differences.

See more detail

Table of contents

  1. At a glance: technical data sheet
  2. How it works
  3. Succinate vs. tartrate: the decisive difference
  4. Areas of use & dosage
  5. Side effects: why metoprolol causes sleep disturbances
  6. Stopping metoprolol: never suddenly!
  7. Interactions
  8. Metoprolol vs. bisoprolol: the big comparison
  9. The CYP2D6 trap: why some patients overreact
  10. Pregnancy & special groups
  11. Real-world data
  12. How brite supports you
  13. Metoprolol experiences: what patients really ask
  14. FAQ: common questions about metoprolol
  15. Sources
Note Never stop metoprolol suddenly! Abrupt stopping can trigger a racing heart, blood pressure rises, and a heart attack. Always taper off over 1–2 weeks.

1. At a glance: technical data sheet

Metoprolol is one of the most prescribed beta blockers in Germany – and at the same time one of the most common triggers of pharmacological confusion in the pharmacy. The reason: there are two different salt forms (tartrate and succinate) with different release profiles, intake intervals, and approvals. On top of that, there is a marked genetic variability in the breakdown via CYP2D6. Anyone who understands the basics can handle metoprolol safely and effectively.

PropertyDetails
Active substanceMetoprolol (as tartrate or succinate)
ATC codeC07AB02
Substance classSelective beta-1 blocker
Available formsTablets, modified-release tablets (ZOK/ZOT/NK), injection solution
Half-life3–7 hours (tartrate); succinate-ZOK: 24 h effect through modified release
LipophilicityHigh (penetrates the CNS → sleep disturbances!)
MetabolismCYP2D6 (caution: poor metabolisers!)
IntakeTartrate: 2×/day; succinate-ZOK: 1×/day
Prescription statusYes
Special feature100 mg tartrate ≈ 95 mg succinate – not interchangeable 1:1!
Table scrolls to the right

2. How it works

Metoprolol selectively blocks the beta-1 receptors at the heart. This lowers the heart rate, blood pressure, and the heart's oxygen consumption. This effect protects the heart in heart failure, coronary heart disease, and after a heart attack – and also explains the blood-pressure-lowering effect. The beta-1 selectivity is not absolute: at higher doses (over 100 mg tartrate or 95 mg succinate daily), beta-2 receptors in the bronchi and vessels are increasingly blocked too, which can cause respiratory complaints and cold extremities.

Why does metoprolol cause more sleep disturbances than other beta blockers?

This is due to the lipophilicity (fat solubility) of metoprolol. Fat-soluble substances cross the blood-brain barrier more easily than water-soluble ones. In the brain, metoprolol affects the sleep-wake rhythm and dream activity – which can lead to sleep disturbances, vivid dreams, and morning fatigue. Bisoprolol is less lipophilic and therefore penetrates the central nervous system less well – hence fewer CNS side effects.

3. Succinate vs. tartrate: the decisive difference

This is the most important and at the same time most frequently misunderstood topic with metoprolol. Many patients notice at a pharmacy switch that the pack is suddenly labelled differently – "metoprolol tartrate" instead of "metoprolol succinate ZOK" – and wonder whether it is the same medicine. The answer: it is the same active substance, but in a different salt form, with a completely different release profile, a different intake frequency, and – decisively – a different clinical approval.

Metoprolol tartrateMetoprolol succinate (ZOK)
Salt formSalt of tartaric acidSalt of succinic acid
ReleaseFast (or first-order modified release)Zero-order modified release (ZOK = Zero Order Kinetics)
Intake2× daily (also the modified-release form!)1× daily
Active levelFluctuating (peaks and troughs)Even over 24 hours
Approved for heart failureNo (no study data)Yes (MERIT-HF study!)
Recognisable by"Retard", without an additionZOK, ZOT, NK, O.K., ZK, ZNT, NT
Dose equivalence100 mg95 mg
Interchangeable?NO – tartrate ≠ succinate! Not interchangeable 1:1!
Table scrolls to the right

Why succinate (ZOK) is mandatory in heart failure

The MERIT-HF study from 1999 is the reason. In this large randomised study, a reduction in overall mortality of 34% was demonstrated in patients with stable heart failure (NYHA II–IV) on metoprolol succinate-ZOK. These data exist exclusively for succinate-ZOK – tartrate was never investigated in a comparable heart failure study. That is why the guideline rule is: in heart failure always metoprolol succinate (ZOK) – not tartrate, even if it is cheaper or currently available. Record the exact salt form in your digital medication plan.

ZOK, ZOT, NK, O.K. – what is the difference? All of these abbreviations denote the same modified-release technology with an even 24-hour release (Zero Order Kinetics). They are from different manufacturers, but all contain metoprolol succinate and can be interchanged 1:1 with one another. What must NOT be exchanged: succinate for tartrate.

4. Areas of use & dosage

The correct salt form is just as important in the dosing as the dose itself. For heart failure, succinate-ZOK with slow building up is mandatory – too fast a start can destabilise the heart function.

IndicationStarting doseTarget doseSalt form
High blood pressure47.5–95 mg 1×/day190 mgSuccinate-ZOK preferred
Heart failure23.75 mg 1×/day190 mg (target dose!)ONLY succinate-ZOK!
CHD / angina pectoris47.5–95 mg190 mgSuccinate or modified-release tartrate
Heart rhythm disturbances50 mg tartrate 2–3×/dayIndividualTartrate (fast onset of action)
After a heart attack50 mg tartrate 2×/day100 mg 2×/dayTartrate
Migraine prophylaxis50 mg tartrate 2×/day100–200 mg/dayTartrate (approved)
Table scrolls to the right
Build up the dose slowly in heart failure! Start with 23.75 mg succinate-ZOK. Double the dose every 2 weeks. Target dose: 190 mg. Not all patients tolerate the full dose – aim for the highest tolerated dose. In older patients, start with particular care.

5. Side effects: why metoprolol causes sleep disturbances

Most beta blocker side effects are direct consequences of the pharmacological effect – not a sign of intolerance. Bradycardia is a therapeutic effect, dizziness arises from the blood pressure lowering, cold feet from peripheral vasoconstriction. Knowing the mechanism helps to choose the right reaction.

Side effectFrequencyCauseWhat to do
Bradycardia (slow pulse)CommonTherapeutic effectPulse <50: reduce the dose
Fatigue / lack of driveCommonBeta blockade + CNS effectOften improves after 2–4 weeks
Sleep disturbances / nightmaresCommonLipophilic → brain penetration!Take in the morning! Or switch to bisoprolol
Cold hands/feetCommonPeripheral vasoconstrictionWith PAD: dose the beta blocker low
Dizziness / hypotensionCommonBlood pressure loweringStand up slowly, adjust the dose
Weight gainOccasionalReduced basal metabolic rateDiet, exercise
Erectile dysfunctionOccasionalBeta-2 effect at a higher doseSwitch to nebivolol (vasodilating)
BronchospasmRareBeta-2 blockade at a high doseCaution with asthma! Bisoprolol is more selective
Table scrolls to the right

The diabetes issue deserves particular attention: metoprolol – like all beta blockers – can mask the typical warning symptoms of low blood sugar: a racing heart and trembling are suppressed. Patients with diabetes on metoprolol must therefore check their blood sugar closely and not rely on physical warning signs. Only sweating is not suppressed by beta blockers – it remains as a warning sign.

6. Stopping metoprolol: never suddenly!

This is the clinically most important warning about beta blockers: sudden stopping is dangerous. The body has got used to the beta blockade – the beta receptors have upregulated, so more receptors are formed to compensate for the reduced signal. When metoprolol is stopped abruptly, the body's own adrenaline meets considerably more receptors than normal. The consequence: rebound tachycardia with a racing heart, blood pressure peaks, and in the worst case angina pectoris or a heart attack.

The solution is consistent tapering off over 1–2 weeks – the dose is halved each week:

Starting doseReduction stepDuration
190 mg → 95 mgHalve1 week
95 mg → 47.5 mgHalve1 week
47.5 mg → 23.75 mgHalve1 week
23.75 mg → stopStop or every 2nd day3–7 days
Table scrolls to the right
Never stop on your own and never abruptly! Always discuss it with the doctor. During the tapering, reduce physical exertion. With a racing heart or chest pain during the stopping process: see a doctor at once.

7. Interactions

Metoprolol has some clinically significant interactions. The most important absolute contraindication is the combination with verapamil or diltiazem. Check all combinations in the interaction check.

Substance / medicationInteractionRecommendation
Verapamil / diltiazemAdditive heart rate and conduction inhibition → AV block, bradycardiaCONTRAINDICATED as a combination!
fluoxetine / paroxetine (SSRIs)CYP2D6 inhibition → metoprolol level rises stronglyReduce the dose or bisoprolol (no CYP2D6)
Terbinafine (antifungal)CYP2D6 inhibition → metoprolol level risesAvoid the combination or bisoprolol
Ibuprofen / diclofenacBlood pressure lowering weakenedPrefer paracetamol
AmlodipineEnhanced blood pressure lowering (desired), caution in heart failureCombination possible, check blood pressure
ClonidineWhen stopping clonidine: rebound hypertension enhancedStop the beta blocker BEFORE clonidine!
Insulin / antidiabeticsHypoglycaemia symptoms (trembling, tachycardia) can be masked!Check blood sugar closely
AlcoholEnhanced blood pressure lowering, dizzinessRestrict
Table scrolls to the right

8. Metoprolol vs. bisoprolol: the big comparison

Both are cardioselective beta-1 blockers, both are in line with the guideline in heart failure, and both cost comparably little in the generic form. Nevertheless, there are pharmacological differences that are clinically decisive in certain situations.

PropertyMetoprololBisoprolol
LipophilicityHigh (penetrates the CNS!)Medium (fewer CNS side effects)
Sleep disturbancesMore commonLess common
MetabolismCYP2D6 (caution: interactions!)50% liver / 50% kidney (no CYP2D6!)
Intake (modified-release)1×/day (succinate-ZOK) or 2×/day (tartrate)1×/day
Heart failure studyMERIT-HF (succinate-ZOK)CIBIS-II
Mortality reduction in heart failureYes (succinate-ZOK)Yes
Beta-1 selectivityGood, lost from 100 mg upwardsVery high, retained longer
Asthma tolerabilityLimited (higher doses)Better (higher selectivity)
Price (30 days)€2–4€2–4
Table scrolls to the right
When bisoprolol instead of metoprolol? With sleep disturbances or nightmares on metoprolol. With CYP2D6 interactions (fluoxetine, paroxetine, terbinafine). In asthmatics (higher beta-1 selectivity). When a simple 1×-daily intake without ZOK technology is wanted. More on this in the bisoprolol article.

9. The CYP2D6 trap: why some patients overreact

Metoprolol is broken down mainly via the liver enzyme CYP2D6. That sounds technical – but it has practical consequences for every third to fifth patient. About 7–10% of the European population are so-called CYP2D6 poor metabolisers: their body breaks down metoprolol considerably more slowly than the average. The consequence: the metoprolol level in the blood rises to a multiple of the expected value – with correspondingly enhanced side effects. Extreme bradycardia, pronounced fatigue, and dizziness, which despite a "normal" dose feel like an overdose.

Medications as CYP2D6 inhibitors: the hidden interaction

Even more relevant than the genetic polymorphism is the medicinal inhibition of CYP2D6 by substances taken at the same time. Fluoxetine and paroxetine (SSRI antidepressants) are among the strongest CYP2D6 inhibitors of all. Anyone who takes fluoxetine or paroxetine together with metoprolol can considerably raise their metoprolol level – even if they are genetically a normal metaboliser. Terbinafine (an antifungal) and bupropion (an antidepressant / smoking-cessation aid) also strongly inhibit CYP2D6.

The elegant solution: bisoprolol. It is not broken down via CYP2D6 – this problem simply does not exist with bisoprolol. Anyone who has to combine an SSRI and a beta blocker is pharmacologically safer with bisoprolol. Check all combinations in the interaction check.

10. Pregnancy & special groups

Metoprolol can be used in pregnancy when the benefit outweighs the risk. It is among the preferred beta blockers in pregnancy (together with labetalol). The important restriction: metoprolol can cause bradycardia and hypoglycaemia in the newborn. Newborns of mothers who took metoprolol during the birth should therefore be monitored for 48–72 hours. Breastfeeding: metoprolol passes into breast milk – individual consultation with the doctor is recommended.

In older patients: build up the dose slowly, since this group reacts more sensitively to bradycardia and hypotension. With kidney impairment: no dose adjustment needed, since metoprolol is eliminated hepatically. With liver impairment: reduce the dose – with liver cirrhosis the first-pass effect is increased, which raises the bioavailability and thereby the metoprolol level.

11. Real-world data: what brite users report

The brite app shows a clear pattern with metoprolol: the tartrate/succinate mix-up and sleep disturbances are the most common topics.

Note Anonymised brite app user data; does not replace clinical studies.
ObservationFrequencyTypical comment
Sleep disturbances / nightmaresVery common"Since the beta blocker I sleep badly. The app explained to me that bisoprolol causes fewer sleep problems."
Mix-up of tartrate/succinateCommon"At the pharmacy the pack was suddenly labelled differently – I was unsettled."
CYP2D6 interaction with fluoxetine not recognisedOccasional"I felt extremely dizzy – the app recognised the combination as a risk."
Sudden stoppingOccasional"I simply left out the beta blocker. Then my heart raced."
Dose-splitting unnecessaryCommon"My doctor split the succinate-ZOK into morning and evening – that was not necessary at all."
Table scrolls to the right

The dose-splitting problem is more common than expected: succinate-ZOK is a modified-release formulation that releases the active substance evenly over 24 hours. It must be taken once daily – not split up. Anyone who takes succinate-ZOK twice daily disturbs the zero-order release and gets more uneven levels. When in doubt: read the package leaflet or consult the medication plan.

12. How brite supports you with metoprolol

Transparency notice brite is a health app. The following features refer to functionality within the app.
  • CYP2D6 interaction scan: Recognises fluoxetine, paroxetine, terbinafine and warns of a level increase. → Interaction check
  • Succinate/tartrate check: Explains the difference and warns against an uncritical exchange.
  • Verapamil warning: Recognises the contraindicated combination with verapamil/diltiazem.
  • Stopping warning: Warns against sudden stopping and accompanies the step-by-step tapering. → Pill reminder
  • Sleep disturbance monitoring: Recommends a switch to bisoprolol with persistent CNS side effects.
  • Digital medication plan: Documented with the salt form and intake time. → Create a medication plan
Register for free now

Metoprolol experiences: what patients really ask

Metoprolol succinate tartrate difference – how do I recognise which one I have? Metoprolol tartrate has no special additional designation – or simply says "Retard". Metoprolol succinate is always marked with one of the abbreviations ZOK, ZOT, NK, O.K., ZK, ZNT or NT. If one of these abbreviations is on your pack: succinate-ZOK. If not: tartrate. When in doubt, ask the pharmacist or look in the package leaflet – the salt form is always stated there explicitly.

Metoprolol sleep disturbances, what to do? First step: move the intake time to the morning. The maximum metoprolol level is then during the day, not at night – this reduces the CNS effect during sleep. If that does not help: talk to the doctor about a switch to bisoprolol. Bisoprolol is less fat-soluble, penetrates the brain less well, and causes sleep disturbances considerably less often.

Metoprolol stopping schedule – how long do I need? With the typical dose of 95 mg or 190 mg succinate-ZOK: 3–4 weeks for safe tapering. The dose is halved each week (190 → 95 → 47.5 → 23.75 → stop). Important: during the stopping, reduce physical exertion and with a racing heart or chest pain see the doctor at once. Never taper off on your own and never faster than recommended.

ZOK ZOT NK difference – is that the same? Yes – all of these abbreviations denote the same principle (Zero Order Kinetics): an even 24-hour release of metoprolol succinate. The different abbreviations are manufacturer designations for the same technology. ZOK, ZOT, NK, O.K., ZK, ZNT and NT are interchangeable 1:1 with one another – all contain metoprolol succinate. What is not interchangeable: ZOK for tartrate.

Metoprolol tired – when does it get better? Fatigue and lack of drive at the start of therapy are common and improve in most patients after 2–4 weeks, once the body has got used to the beta blockade. Anyone who still suffers markedly from fatigue after a month should review the dose with the doctor or consider a switch to bisoprolol or nebivolol. The CYP2D6 situation should also be considered – anyone who at the same time takes fluoxetine, paroxetine or terbinafine can have excessively high metoprolol levels.

FAQ: common questions about metoprolol

Both contain the same active substance, but succinate-ZOK is released evenly over 24 hours (1×/day), tartrate has more fluctuating levels (usually 2×/day). In heart failure: ONLY succinate-ZOK (MERIT-HF study). Not interchangeable 1:1!
Yes – more often than other beta blockers. Metoprolol is strongly fat-soluble and penetrates the brain, where it affects the sleep-wake rhythm. Tip: take it in the morning. With persistent problems: switch to bisoprolol.
Not better across the board, but in many situations simpler: fewer CNS side effects, no CYP2D6 issue, higher beta-1 selectivity, always 1×/day. Both are equally well evidenced in heart failure.
NO! Sudden stopping can lead to a dangerous rebound: a racing heart, blood pressure peaks, angina pectoris. Always taper off over 1–2 weeks by halving each week.
Tolerable short-term, but ibuprofen/diclofenac weaken the blood pressure lowering. Better alternative: paracetamol.
All denote the same modified-release technology: an even 24-hour release (Zero Order Kinetics). ZOK, ZOT, NK, O.K., ZK, ZNT, NT – all contain metoprolol succinate and are interchangeable with one another. Not interchangeable: for tartrate!
Beta blockers suppress the typical hypoglycaemia warning signs (a racing heart, trembling). Diabetics then do not notice that their blood sugar is too low. Therefore: on beta blockers, check blood sugar closely.
Yes – especially in the first weeks. Often improves after 2–4 weeks. With persistent fatigue: consider a dose reduction or a switch to bisoprolol/nebivolol. With a CYP2D6-inhibitor combination (fluoxetine) the level can be excessively high.

Sources

  1. Gelbe Liste: Metoprolol (Germany) – gelbe-liste.de
  2. German Heart Foundation: Metoprolol succinate vs. tartrate (Germany) – herzstiftung.de
  3. MERIT-HF Study Group (1999): Lancet 353:2001-07
  4. CIBIS-II Investigators (1999): Lancet 353:9-13
  5. Metoprolol prescribing information (2024)
  6. ESC Guidelines on Heart Failure (2023 Focused Update)
  7. Embryotox: Metoprolol (Germany) – embryotox.de
  8. brite App: Anonymised user data, as of February 2026
Medical disclaimer: Never stop beta blockers on your own. Always discuss changes to metoprolol therapy with the doctor. Last updated: February 2026.