Verapamil with Lithium Interaction Details

Brand Names Associated with Verapamil

Brand Names Associated with Lithium

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Dec 03, 2023

Interaction Effect

Loss of mania control, neurotoxicity, bradycardia

Interaction Summary

In case reports, the addition of calcium channel blockers to patients stabilized on lithium therapy (lithium levels 0.6 to 1.2 mEq/L) resulted in a worsening of their mania or development of neurotoxicity. Increased sensitivity to the effects of lithium (neurotoxicity) has been reported during concomitant therapy with verapamil and lithium. Lithium levels have been observed to increase, to decrease, and sometimes to be unchanged .

Severity

Moderate

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Serum lithium levels should be monitored carefully. Patients should be followed closely for signs of mania or psychosis, as well as any symptoms of neurotoxicity such as ataxia, tremors, tinnitus, nausea, vomiting or diarrhea.

Mechanism Of Interaction

Synergistic decrease in calcium ion transport

Literature Reports

A) Concomitant administration of lithium and verapamil has been reported to result in decreases in serum lithium concentrations, resulting in exacerbation of manic psychosis . It is suggested that decreases in serum lithium may be secondary to enhancement of lithium excretion by improved cardiac output due to correction of arrhythmias by verapamil.

B) Concomitant administration of lithium and verapamil was reported to result in neurotoxicity in a 42-year-old woman with rapid-cycling bipolar disorder . Nine days after adding verapamil 80 mg orally three times a day to previous lithium therapy, the patient developed nausea, vomiting, muscular weakness, ataxia and tinnitus. Verapamil was discontinued resulting in resolution of neurotoxic symptoms within 48 hours. Due to worsening of manic symptoms, verapamil 80 mg three times a day was reinstituted, again resulting in improvement in symptoms but recurrence of neurotoxicity; withdrawal of verapamil once again resulted in subsidence of neurotoxic symptoms. At the time of the first occurrence of neurotoxicity, lithium levels were 1.1 mEq/L. The authors suggest that neurotoxic effects in this patient, despite the presence of therapeutic lithium levels, were related to synergistic effects of both agents.

C) A 55-year-old female stabilized for the past 17 years on lithium therapy for a history of bipolar affective disorder experienced severe lithium toxicity following the addition of antihypertensives to her medication regimen. Because of a cerebrovascular accident, she was started on lisinopril 10 mg daily, verapamil 240 mg daily, and aspirin 325 mg daily. Her lithium dose remained at 900 mg per day. Following six weeks of this combined therapy, she presented to the emergency department with slurred speech and confusion, and her lithium level was measured at 4.9 mEq/L. Verapamil and lithium were discontinued and she was started on hemodialysis. Within two days, her lithium level had decreased to 0.8 mEq/L and her mental status gradually improved. Although multiple drugs were involved in this case report, lisinopril has been reported to increase lithium concentrations. Verapamil and lithium coadministration has been associated with an increase in neurotoxicity as manifested by ataxia, dysarthria, tremor, and nausea. The combination of these three agents demonstrate the risks associated with lithium administration .

Verapamil Overview

• Verapamil is used to treat high blood pressure and to control angina (chest pain). The immediate-release tablets are also used alone or with other medications to prevent and treat irregular heartbeats. Verapamil is in a class of medications called calcium-channel blockers. It works by relaxing the blood vessels so the heart does not have to pump as hard. It also increases the supply of blood and oxygen to the heart and slows electrical activity in the heart to control the heart rate.

• High blood pressure is a common condition and when not treated, can cause damage to the brain, heart, blood vessels, kidneys and other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other problems. In addition to taking medication, making lifestyle changes will also help to control your blood pressure. These changes include eating a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 minutes most days, not smoking, and using alcohol in moderation.

Lithium Overview

• Lithium is used to treat and prevent episodes of mania (frenzied, abnormally excited mood) in people with bipolar disorder (manic-depressive disorder; a disease that causes episodes of depression, episodes of mania, and other abnormal moods). Lithium is in a class of medications called antimanic agents. It works by decreasing abnormal activity in the brain.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.