Verapamil

Selective L-channel blocker (L stands for "long-lasting" ) used to treat cardiovascular diseases (coronary heart disease, various forms of angina pectoris) in order to improve the oxygen supply to the heart. It has both cardiodepressive and vasodilating effects in the same concentration range. Verapamil is bound to 90% of plasma proteins.

Further indications for verapamil are hypertension and hypertrophic obstructive cardiomyopathy (HOCM). As an antiarrhythmic agent, verapamil is mainly used in supraventricular tachyarrhythmias as well as atrial fibrillation and atrial flutter with rapid AV transition (with the exception of WPW syndrome or Lown-Ganong-Levine syndrome). Rare applications of verapamil are also the prophylaxis of cluster headaches and the therapy of plaque deposits in cases of hardening of the penile erectile tissue(induratio penis plastica).

Verapamil is available as salt, verapamil hydrochloride, in tablets, retard tablets and in injection solutions.

Verapamil is extensively metabolised in the liver by CYP3A4, CYP1A2, CYP2C8, CYP2C9 and CYP2C18. Identified were 12 metabolites of which only norverapamil has a significant pharmacological effect (about 20% of verapamil). After oral administration the elimination half-life is three to seven hours. About 50% of the administered dose is eliminated renally within 24 hours, 70% within five days. Up to 16% is eliminated with the faeces.

Verapamil belongs to the group of phenylalkylamines and blocks the influx of calcium through voltage-dependent calcium channels into the cells of the heart muscles. This leads to a reduction of the heart's beating power and a lowered beat frequency. As a result, the heart is relieved. In addition, verapamil has a dilating effect especially in the coronary arteries. This improves the oxygen supply to the myocardium and alleviates the symptoms typical of angina pectoris. In addition, peripheral resistance decreases, cardiac output increases and blood pressure drops. The antiarrythmogenic effect is based on an extended transition time at the AV node.

After oral administration, more than 90% of verapamil is rapidly absorbed from the small intestine. The bioavailability after a single administration of verapamil tablets is 22%, and about 32% for retarded verapamil. Verapamil is subject to a pronounced first-pass metabolism. After administration of verapamil tablets, maximum plasma levels are reached after one to two hours, after administration of retarded verapamil after four to five hours. After several times daily administration, the steady state is reached after three to four days.

Limited renal function: Verapamil should be used with caution and under close observation in patients with limited renal function.

Liver dysfunction: In patients with liver dysfunction, verapamil metabolism is slowed, which can significantly increase the bioavailability of verapamil and increase or prolong its effects. Therefore, low initial doses of 80 - 120 mg verapamil per day are recommended initially.

Verapamil is placenta-compatible and in addition, reproductive toxicity has been shown in animal studies. Verapamil should therefore not be taken orally during the first and second trimester of pregnancy. Verapamil should only be taken in the third trimester of pregnancy if there is a compelling indication and after a strict risk-benefit analysis.

Intravenous administration of verapamil during pregnancy is contraindicated. There is a risk of hypotension and thus a decrease in uteroplacental perfusion with the risk of fetal hypoxia.

Breastfeeding

Verapamil passes into breast milk in small amounts after oral administration, so verapamil should only be used orally during lactation after a strict risk-benefit assessment. Intravenous administration of verapamil is contraindicated during lactation. If there is a compelling indication, breastfeeding must be interrupted for the duration of treatment.

There is also evidence that hyperprolactinaemia and galactorrhoea may be caused.

Oral use:

Hypertension in adults and adolescents over 50 kg body weight: The recommended dosage is 240 mg - 360 mg verapamil per day.

Coronary heart disease in adults and adolescents over 50 kg body weight: The recommended dosage is 240 mg - 480 mg verapamil per day. In patients with angina pectoris after myocardial infarction, verapamil should not be used until 7 days after the acute infarction event.

Children:

• older preschoolers up to 6 years of age: The recommended dosage is 80 mg - 120 mg verapamil per day.
• School children 6 - 14 years of age: The recommended dosage is 80 mg - 360 mg verapamil hydrochloride per day.

Parenteral use:

Paroxysmal, supraventricular tachycardia, atrial fibrillation and for initial treatment of unstable angina pectoris when nitrates and/or beta-receptor blockers are not indicated:

Adults and adolescents over 50 kg body weight: Initial dose 5 mg verapamil i.v., if necessary after 5-10 minutes another 5 mg verapamil.

Subsequently, a continuous drip infusion of 5-10 mg verapamil/hour, on average up to a total dose of 100 mg verapamil/day, can be given. If the therapy of unstable angina pectoris is started intravenously with verapamil, it should be switched to oral therapy as soon as possible.

The very common side effects of verapamil include gastrointestinal complaints such as nausea, constipation and bloating. Serious common adverse effects include cardiac arrhythmias and blood pressure regulation disorders and worsening of existing heart failure. Allergic reactions with skin redness, itching or hives as well as fatigue, headache, ankle edema and dizziness are some of the other common side effects of verapamil.

Serious consequences likely - in certain cases contraindicated (verapamil as CYP3A4 inhibitor):

• H2-blocker: Simultaneous use not recommended:
• Amiodarone: Additive cardiodepressive effect possible
• Enzyme inducers (CYP3A4): Reduced effects of calcium antagonists
• Rifampicin: Reduced effects of nifedipine and its derivatives
• Colchicine: Risk of colchicine intoxication

Hypersensitivity to verapamil

Cardiovascular Shock

Pronounced stimulation conduction disorders (such as SA or AV block II and III degrees; except in patients with pacemakers)

Sinus node syndrome (except for patients with pacemakers)

Heart failure with a reduced ejection fraction of less than 35% and/or an occlusion pressure of more than 20 mmHg (unless caused by supraventricular tachycardia responsive to verapamil)

Atrial fibrillation/flutter and simultaneous presence of accessory pathways (e.g. WPW or Down-Ganong-Levine syndrome). In these patients, verapamil administration increases the risk of developing ventricular tachycardia, including ventricular fibrillation

The simultaneous intravenous administration of beta-receptor blockers must not be performed in patients during treatment with verapamil (except for intensive care)

Treatment with verapamil requires regular medical supervision. Individual differences in response may alter the ability to react to the treatment to such an extent that the ability to actively participate in road traffic or to operate machinery is impaired. This is particularly true at the start of treatment and when the dose is increased.