VERAPAMIL 2,5 mg/ml RBC

Indications

• Hypertension
• Angina pectoris
• Supraventricular tachycardias
• Atrial fibrillation or flutter (rate control)

Dosage

Adults: Refer to the BNF for specific dosing guidelines based on the condition being treated. Common dosing includes 80-240 mg daily in divided doses for hypertension, and for

Mechanism of action

Verapamil inhibits L-type calcium channels by binding to the alpha-1 subunit (Cav1.2), which is prevalent in vascular smooth muscle and myocardial tissue. This binding occurs in a voltage- and frequency-dependent manner, increasing as the membrane potential decreases and with excessive depolarization. The inhibition of calcium influx prevents muscle contraction and promotes relaxation of blood vessels, thus lowering systemic vascular resistance and blood pressure. Additionally, it affects electrical conduction through the AV node, which can lower heart rate.

Pharmacodynamics

Verapamil exhibits antiarrhythmic, antianginal, and antihypertensive properties. It is classified as a negative inotropic agent, meaning it reduces myocardial contractility. Due to this effect, it is contraindicated in patients with severe left ventricular dysfunction or hypertrophic cardiomyopathy, as it may exacerbate these conditions. Immediate-release forms require multiple daily doses, while extended-release options facilitate once-daily administration.

Pharmacokinetics

Verapamil is well-absorbed from the gastrointestinal tract, but it undergoes extensive first-pass metabolism in the liver, which significantly reduces its bioavailability. The drug is metabolized primarily by the liver enzymes CYP3A4 and CYP2C8. Its half-life varies depending on the formulation, with immediate-release forms having a shorter half-life compared to extended-release forms. The drug is primarily excreted in urine as metabolites, with only a small fraction eliminated unchanged.

Contra-indications

• Severe left ventricular dysfunction
• Hypertrophic cardiomyopathy
• Known hypersensitivity to verapamil or any of its components

Adverse effects

• Constipation
• Dizziness
• Headache
• Nausea
• Bradycardia
• Hypotension
• Peripheral edema

Interactions

• Severe: amiodarone (increases risk of cardiodepression)
• Severe: non-selective beta-blockers (increases risk of cardiovascular adverse effects)
• Severe: intravenous dantrolene (increases risk of acute hyperkalaemia and cardiovascular collapse)
• Severe: grapefruit juice (increases exposure)
• Moderate: miconazole (increases exposure)
• Moderate: bictegravir (increases exposure)
• Moderate: panobinostat (increases exposure)
• Moderate: thrombin inhibitors (increases exposure)
• Moderate: dabigatran (increases exposure)
• Unknown: enzalutamide (decreases exposure)

Precautions

• Caution in patients with renal impairment
• Caution in patients with liver impairment
• Monitor heart rate and blood pressure regularly during treatment
• Consider alternative therapies in patients with severe cardiac conditions

Pregnancy

Verapamil should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Consult relevant guidelines for specific recommendations.

Breast-feeding

Verapamil is excreted in breast milk. Caution should be exercised when administering to nursing women.

Storage

Store at room temperature, away from light and moisture. Keep out of reach of children.

Formulations

• Immediate-release tablets
• Extended-release tablets
• Injection solution

Indications

• Hypertension
• Supraventricular arrhythmias
• Angina pectoris

Dosage

Children: Not licensed for use in children. Consult the BNF for Children for any potential off-label uses and specific dosing recommendations.

Adults: For hypertension, the usual starting dose is 80 mg to 120 mg daily, which can be adjusted based on blood pressure response. The maintenance dose may range up to 240 mg daily. For supraventricular arrhythmias, initial intravenous doses can vary. Refer to specific product literature for detailed dosing.

Mechanism of action

Verapamil hydrochloride selectively inhibits L-type calcium channels in the cardiac and vascular smooth muscle. By blocking these channels, it reduces intracellular calcium concentrations, leading to decreased myocardial contractility, heart rate, and vascular resistance. This mechanism is crucial in managing conditions like hypertension and arrhythmias.

Pharmacodynamics

Verapamil produces a dose-dependent decrease in heart rate and myocardial contractility. It also causes vasodilation, which contributes to its antihypertensive effects. The drug can have varying effects on peripheral vascular resistance and may influence the autonomic nervous system, particularly through its impact on heart rate.

Pharmacokinetics

Verapamil is well absorbed from the gastrointestinal tract, but undergoes extensive first-pass metabolism in the liver, resulting in lower bioavailability. It is highly protein-bound, primarily to albumin. The drug is metabolized by the liver, with a half-life ranging from 3 to 7 hours. Its metabolites are excreted via the kidneys. Dosage adjustments may be necessary in patients with hepatic impairment.

Contra-indications

• Cardiogenic shock
• Severe aortic stenosis
• Severe hypotension
• Pregnancy with multiple gestations

Adverse effects

• Constipation
• Malaise
• Oedema
• Allergic reactions
• Angioedema

Interactions

• Caution with other calcium channel blockers
• Increased risk of serious hypotension when used with antihypertensives

Precautions

• Monitor blood pressure and heart rate regularly
• Use with caution in hepatic and renal impairment
• Consider dose adjustment in severe impairment

Pregnancy

May inhibit labor and is not recommended in multiple pregnancies due to risks of severe maternal hypotension and fetal hypoxia.

Breast-feeding

Manufacturer advises avoidance as it is present in breast milk.

Storage

Store at room temperature, away from moisture and heat.

Formulations

• Tablets
• Modified-release capsules

Mechanism of action

Verapamil inhibits L-type calcium channels by binding to a specific area of their alpha-1 subunit,Cav1.2, which is highly expressed on L-type calcium channels in vascular smooth muscle and myocardial tissue where these channels are responsible for the control of peripheral vascular resistance and heart contractility. Calcium influx through these channels allows for the propagation of action potentials necessary for the contraction of muscle tissue and the heart's electrical pacemaker activity. Verapamil binds to these channels in a voltage- and frequency-dependent manner, meaning affinity is increased 1) as vascular smooth muscle membrane potential is reduced, and 2) with excessive depolarizing stimulus. Verapamil's mechanism of action in the treatment of angina and hypertension is likely due to the mechanism described above. Inhibition of calcium influx prevents the contraction of vascular smooth muscle, causing relaxation/dilation of blood vessels throughout the peripheral circulation - this lowers systemic vascular resistance (i.e. afterload) and thus blood pressure. This reduction in vascular resistance also reduces the force against which the heart must push, decreasing myocardial energy consumption and oxygen requirements and thus alleviating angina. Electrical activity through the AV node is responsible for determining heart rate, and this activity is dependent upon calcium influx through L-type calcium channels. By inhibiting these channels and decreasing the influx of calcium, verapamil prolongs the refractory period of the AV node and slows conduction, thereby slowing and controlling the heart rate in patients with arrhythmia. Verapamil's mechanism of action in the treatment of cluster headaches is unclear, but is thought to result from an effect on other calcium channels (e.g. N-, P-, Q-, or T-type). Verapamil is known to interact with other targets, including other calcium channels, potassium channels, and adrenergic receptors. Calcium antagonists inhibit excitation-contraction coupling in myocardial and smooth muscle by blocking the transmembrane carrier of calcium. This results in decreased myocardial contractility and in vasodilatation. ... /Salt not specified/ Verapamil has been shown to be neuroprotective in several acute neurotoxicity models due to blockade of calcium entry into neurons. However, the potential use of verapamil to treat chronic neurodegenerative diseases has not been reported. Using rat primary mesencephalic neuron/glia cultures, we report that verapamil significantly inhibited LPS-induced dopaminergic neurotoxicity in both pre- and post-treatment experiments. Reconstituted culture studies revealed that the presence of microglia was essential in verapamil-elicited neuroprotection. Mechanistic studies showed that decreased production of inflammatory mediators from LPS-stimulated microglia underlay neuroprotective property of verapamil. Further studies demonstrated that microglial NADPH oxidase (PHOX), the key superoxide-producing enzyme, but not calcium channel in neurons, is the site of action for the neuroprotective effect of verapamil. This conclusion was supported by the following two observations: 1) Verapamil failed to show protective effect on LPS-induced dopaminergic neurotoxicity in PHOX-deficient (deficient in the catalytic subunit of gp91(phox)) neuron/glia cultures; 2) Ligand binding studies showed that the binding of (3)H-verapamil onto gp91(phox) transfected COS7 cell membranes was higher than the non-transfected control. The calcium channel-independent neuroprotective property of verapamil was further supported by the finding that R(+)-verapamil, a less active form in blocking calcium channel, showed the same potency in neuroprotection, inhibition of pro-inflammatory factors production and binding capacity to gp91(phox) membranes as R(-)-verapamil, the active isomer of calcium channel blocker. In conclusion, our results demonstrate a new indication of verapamil-mediated

Pharmacodynamics

Verapamil is an L-type calcium channel blocker with antiarrhythmic, antianginal, and antihypertensive activity. Immediate-release verapamil has a relatively short duration of action, requiring dosing 3 to 4 times daily, but extended-release formulations are available that allow for once-daily dosing. As verapamil is a negative inotropic medication (i.e. it decreases the strength of myocardial contraction), it should not be used in patients with severe left ventricular dysfunction or hypertrophic cardiomyopathy as the decrease in contractility caused by verapamil may increase the risk of exacerbating these pre-existing conditions.