Verapamil; Uses, Dosage, Side Effects, Interactions, Pregnancy

Verapamil








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Verapamil is a phenylalkylamine calcium channel blocking agent. Verapamil inhibits the transmembrane influx of extracellular calcium ions into myocardial and vascular smooth muscle cells, causing dilatation of the main coronary and systemic arteries and decreasing myocardial contractility. This agent also inhibits the drug efflux pump P-glycoprotein which is overexpressed in some multi-drug resistant tumors and may improve the efficacy of some antineoplastic agents.

Verapamil is a first generation calcium channel blocker used for the treatment of hypertension, angina pectoris, and superventricular tachyarrhythmias. Verapamil has been linked to a low rate of serum enzyme elevations during therapy and too rare instances of clinically apparent acute liver injury.

Verapamil is a calcium channel blocker that is a class IV anti-arrhythmia agent. The drug is used for the treatment of high blood pressure, chest pain from not enough blood flow to the heart, and supraventricular tachycardia. It may also be used for the prevention of migraines and cluster headaches. It is given by mouth or by injection into a vein.

Mechanism of action of Verapamil

Verapamil inhibits voltage-dependent calcium channels. Specifically, its effect on L-type calcium channels in the heart causes a reduction in ionotropy and chronotropy, this is reducing heart rate and blood pressure. Verapamil’s mechanism of effect in a cluster headache is thought to be linked to its calcium-channel blocker effect, but which channel subtypes are involved is presently not known. Verapamil is an L-type calcium channel blocker that also has antiarrhythmic activity. The R-enantiomer is more effective at reducing blood pressure compared to the S-enantiomer. However, the S-enantiomer is 20 times more potent than the R-enantiomer at prolonging the PR interval in treating arrhythmias.

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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 neuroprotection through a calcium channel-independent pathway and provide a valuable avenue for the development of therapy for inflammation-related neurodegenerative diseases.

Indications of Verapamil

Contra-Indications of Verapamil

Dosage of Verapamil

Strengths

  • 2.5 mg/mL

Tablet

  • 40 mg ;80 mg ;120 mg

Tablet/capsule, extended release

  • 100 mg ;120 mg ;180 mg ;200 mg ;240 mg ;300 mg ;360 mg

Dosage Considerations

Angina

  • Adult, Immediate release: 80 mg orally every 8 hours initially; usual range: 80-120 mg orally every 8 hours; not to exceed 480 mg/day
  • Adult, Extended-release: Covera-HS: 180 mg/day orally at bedtime initially; maintenance: 180-540 mg/day orally at bedtime
  • Geriatric, Immediate release: 80 mg orally every 8 hours initially; usual range: 80-120 mg orally every 8 hours; not to exceed 480 mg/day
  • Geriatric, Extended-release (Covera-HS): 180 mg orally at bedtime initially; maintenance: 180-540 mg orally at bedtime

Hypertension

Adult, Immediate release: 80 mg orally every 8 hours initially; maintenance: 80-320 mg orally every 12 hours

Adult, Extended-release

  • Calan, Isoptin SR: 180 mg/day orally given in morning (120 mg/day initially if patient elderly or of small stature); for desired response, may be increased to 240 mg/day, then to 360 mg/day (either 180 mg every 12 hours or 240 mg in morning and 120 mg in evening)
  • Verelan: 180 mg/day orally (120 mg/day initially if patient elderly or of small stature); for a desired response, may be increased to 240 mg/day orally, then by 120 mg/day at weekly intervals; not to exceed 480 mg/day
  • Verelan PM: 200 mg/day orally at bedtime (100 mg/day if patient elderly or of small stature); may be increased by 100 mg/day at weekly intervals as needed; not to exceed 400 mg/day
  • Covera-HS: 180 mg/day orally at bedtime (120 mg/day initially if patient elderly or of small stature); for the desired response, may be increased to 240 mg/day, then by 120 mg/day at weekly intervals; not to exceed 480 mg/day

Geriatric

  • Immediate release: 40 mg orally every 8 hours initially; maintenance: 80-320 mg orally every 12 hours
  • Extended-release (Calan SR, Isoptin SR, Verelan): 120 mg/day orally given in the morning
  • Extended-release (Covera-HS): 180 mg/day orally at bedtime
  • Extended-release (Verelan PM): 100 mg/day orally at bedtime

Supraventricular Arrhythmia and Atrial Fibrillation/Flutter

  • 2.5-5 mg intravenously (IV) over 2 minutes; 5-10 mg dose may be repeated after 15-30 minutes
  • Alternatively, 0.075-0.15 mg/kg (not to exceed 10 mg) IV over 2 minutes; dose may be repeated once 30 minutes after the first dose

Chronic Atrial Fibrillation and Paroxysmal Supraventricular Tachycardia

  • Treatment of chronic atrial fibrillation (rate control); prevention of paroxysmal supraventricular tachycardia
  • Immediate release: 240-480 mg/day orally divided every 6-8 hours

Supraventricular Tachycardia, Pediatric

  • Children 1-15 years old: 0.1-0.3 mg/kg (not to exceed 5 mg) intravenously (IV) over 2 minutes; second dose (not to exceed 10 mg) may be given after 30 minutes
  • Alternatively (not well established), 4-8 mg/kg/day orally divided every 8 hours

Tardive Dyskinesia

  • 40 mg orally every 8 hours; may be titrated to 120 mg every 8 hours

A migraine (Off-label)

  • Prophylaxis
  • 160-320 mg orally every 6-8 hours

Dosing Modifications

  • Renal impairment: Use with caution; monitor ECG; for Verelan PM, the manufacturer recommends 100 mg at bedtime initially; if CrCl less than 10 mL/min, reduce dose by 25-50%
  • Hepatic impairment: In cirrhosis, reduce dose by 20-50% of normal for oral and intravenous (IV) administration
  • Geriatric: In general, lower initial doses are warranted; doses should be adjusted on basis of clinical response

Side Effects of Verapamil

The most common

Common

Rare

Drug Interactions of Verapamil

Verapamil may interact with following drugs, supplyments, & may change the efficacy of drugs

Pregnancy & Lactation of Verapamil

 FDA Pregnancy Category C

Pregnancy

Verapamil reaches the developing baby if it is taken during pregnancy. This medication should not be used during pregnancy unless the benefits outweigh the risks. If you become pregnant while taking this medication, contact your doctor immediately.

Lactation

This medication passes into breast milk. If you are a breast-feeding mother and are taking verapamil, it may affect your baby. Talk to your doctor about whether you should continue breast-feeding. The safety and effectiveness of using this medication have not been established for children.

References

 

Verapamil

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