Metoprolol Succinate
Extended release beta 1 blocker for hypertension, coronary disease and heart failure
Metoprolol succinate is the succinate salt of metoprolol, a selective β1 receptor blocker. In Germany it is marketed under the brand names Beloc Zok, Beloc Zok mite and Beloc Zok forte, as well as in numerous generic formulations. The difference from the more commonly prescribed metoprolol tartrate lies in the release profile: the succinate is formulated as an extended release preparation (CR/XL, controlled release), which provides stable plasma concentrations over 24 hours and allows once daily dosing.
Metoprolol succinate is established in chronic heart failure therapy through the MERIT-HF trial, which significantly reduced mortality in patients with reduced ejection fraction. In arterial hypertension, coronary artery disease, supraventricular tachyarrhythmias and as secondary prevention after myocardial infarction, the substance is a standard option. Once daily administration improves adherence and plasma level stability compared with immediate release metoprolol tartrate.
Mechanism of Action
Metoprolol competitively blocks β1 adrenoceptors. These receptors are found mainly in the heart (sinus node, working myocardium, AV node) and on the juxtaglomerular cells of the kidney. Blockade reduces heart rate and contractility, prolongs atrioventricular conduction time and decreases renin release. The result is a reduction in myocardial oxygen demand and in arterial blood pressure.
At higher doses metoprolol loses its β1 selectivity and also acts on β2 receptors in the bronchi and blood vessels. In patients with asthma this is clinically relevant because the bronchodilatory action of endogenous catecholamines is blunted. Selectivity is better than with non selective propranolol but is not absolute.
In heart failure the central therapeutic effect is not acute haemodynamic unloading but neurohumoral modulation. Chronic sympathetic overactivation in reduced pump function damages myocardial cells and drives remodelling. Long term blockade breaks this cycle, improves left ventricular ejection fraction and reduces mortality.
Indications
- Arterial hypertension: mono or combination therapy, particularly in patients with coronary artery disease, tachycardia or migraine
- Coronary artery disease and stable angina pectoris: reduction of attack frequency and severity
- Secondary prevention after myocardial infarction: reduction in reinfarction rate and all cause mortality
- Chronic heart failure with reduced ejection fraction (HFrEF), NYHA II to IV: mortality reduction, class I guideline recommendation
- Supraventricular tachyarrhythmias: atrial fibrillation (rate control), atrial flutter, AV node reentrant tachycardias
- Migraine prophylaxis: a guideline option in moderate to severe migraine
- Functional cardiac complaints and essential tremor
Dosage and Administration
Hypertension and angina pectoris: start with 47.5 mg once daily, titrate to 95 mg to 190 mg once daily. Migraine prophylaxis: 95 mg once daily, often 47.5 mg is sufficient. Heart failure: very slow up titration, starting at 11.88 mg or 23.75 mg once daily, doubling no earlier than every two weeks, target dose 190 mg.
Dose expressions in milligrams of metoprolol succinate correspond approximately to the equivalent amounts of metoprolol tartrate (23.75 mg succinate approximately equals 25 mg tartrate, 47.5 mg equals 50 mg tartrate, 95 mg equals 100 mg tartrate, 190 mg equals 200 mg tartrate). Renal impairment: no dose adjustment required. Hepatic impairment: in severe impairment dose reduction is advised because of reduced CYP2D6 activity. Take in the morning. The tablet should not be chewed, but it may be halved at the score line in this extended release formulation.
Side Effects
Common (1 to 10 percent): fatigue, dizziness, headache, bradycardia, orthostatic hypotension, cold sensation in hands and feet, exertional dyspnoea, nausea, diarrhoea or constipation.
Uncommon (0.1 to 1 percent): sleep disturbances, nightmares, depressive mood, bronchospasm in predisposed patients, worsening of intermittent claudication, erectile dysfunction, masking of hypoglycaemia in people with diabetes, dry eyes.
Rare: higher grade AV block, severe bradycardia up to cardiac arrest in overdose or in combination with other rate slowing drugs, exacerbation of psoriasis, elevated liver enzymes, allergic skin reactions.
Interactions
- Calcium channel blockers of the verapamil and diltiazem type: strong additive effects on AV conduction and the sinus node, intravenous combination is contraindicated
- Digitalis glycosides: additive bradycardia, frequently an intended combination, ECG monitoring recommended
- Amiodarone, propafenone, flecainide: enhanced negative inotropic and chronotropic effects
- CYP2D6 inhibitors (paroxetine, fluoxetine, bupropion, terbinafine, quinidine): metoprolol plasma levels rise, bradycardia and hypotension intensified
- NSAIDs: can blunt the antihypertensive effect
- Insulin and oral antidiabetics: warning signs of hypoglycaemia (tachycardia, tremor) may be masked
- Alcohol: possible increase in plasma levels and circulatory effects
Special Notes
Discontinuation: never stop metoprolol abruptly. After long term therapy, receptor upregulation can cause rebound tachycardia and hypertension; anginal attacks and, in isolated cases, infarctions have been described. Taper over one to two weeks in stepwise halving.
Bronchial asthma and severe COPD: relative contraindication in severe asthma. In mild asthma or COPD metoprolol may be used at low dose under pulmonology supervision when the cardiological indication is compelling. AV block grade II or III, sick sinus syndrome, shock, severe hypotension, untreated pheochromocytoma: contraindications.
Pregnancy: use possible on a strict indication (hypertension, cardiac disease); possible neonatal effects (bradycardia, hypoglycaemia) therefore require delivery monitoring. Breastfeeding: passage into milk is low, breastfeeding during therapy is possible.
Monitoring: blood pressure and pulse; in heart failure regular weight measurement and follow up of renal retention values and electrolytes. In people with diabetes tight glucose monitoring is advised because adrenergic warning symptoms are blunted.
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Frequently Asked Questions
What is the difference between metoprolol succinate and metoprolol tartrate?
Both contain the same active substance, metoprolol. The succinate is extended release, taken once daily and provides stable plasma concentrations over 24 hours. The tartrate is immediate release, shorter acting and requires two to three doses per day. In heart failure therapy the succinate is preferred because of the MERIT-HF trial.
Why should I not stop metoprolol suddenly?
With long term therapy the β1 receptors of the heart are upregulated. Sudden discontinuation causes an exaggerated adrenergic response with tachycardia, rising blood pressure and anginal attacks. In isolated cases myocardial infarctions have been described after abrupt withdrawal. The dose should be reduced slowly over one to two weeks.
Can I exercise while taking metoprolol?
Yes. Metoprolol does lower heart rate during exertion, so maximum heart rate values from training plans made before therapy are no longer meaningful. Use perceived effort (Borg scale) or ask your cardiologist to redefine the target heart rate. Endurance exercise remains expressly recommended.
Does metoprolol help in migraine?
Metoprolol is anchored in the S1 guidelines of the German Migraine and Headache Society as prophylactic long term therapy in moderate to severe migraine. Efficacy and tolerability are well documented. The effect develops slowly; an assessment is reasonable after two to three months.
Sources
- EMA, European Medicines Agency
- AWMF, National Care Guideline Chronic Heart Failure
- Gelbe Liste, Metoprolol active substance profile
- BfArM, Federal Institute for Drugs and Medical Devices
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