Tizanidine with Lisinopril Interaction Details

Brand Names Associated with Tizanidine

Brand Names Associated with Lisinopril

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 14, 2023

Interaction Effect

Potentiation of hypotensive response

Interaction Summary

Tizanidine is an alpha(2)-adrenergic agonist and can produce dose-related hypotension. A 48-year-old woman developed profound hypotension and alteration of consciousness within 2 hours of receiving concomitant therapy with lisinopril and tizanidine , and an 85-year-old male on long-term lisinopril treatment developed severe hypotension and bradycardia within two days of starting on tizanidine 2 mg . Caution is advised when tizanidine is prescribed in patients receiving concurrent anti-hypertensive therapy. To minimize the degree of hypotension, tizanidine treatment should be started with single-doses of 4 mg and gradually titrated upwards. Monitor patient carefully for signs and symptoms of hypotension .

Severity

Moderate

Onset

Rapid

Evidence

Probable

How To Manage Interaction

Tizanidine is an alpha(2)-adrenergic agonist and can produce dose-related hypotension. Caution is advised when tizanidine is prescribed in patients receiving concurrent anti-hypertensive therapy. To minimize the degree of hypotension, tizanidine treatment should be started with single-doses of 4 mg and gradually titrated upwards. Monitor patient carefully for signs and symptoms of hypotension.

Mechanism Of Interaction

Unknown

Literature Reports

A) An 85-year-old male on long-term lisinopril treatment developed severe hypotension and bradycardia after taking 3 doses of tizanidine. His medical history consisted of multiple diseases, including type 2 diabetes mellitus, congestive heart failure, and severe chronic back pain. Following 3 doses of tizanidine 2 mg every 8 hours, he experienced notable weakness and was admitted to the hospital with a blood pressure (BP) of 60/32 mmHg, and sinus bradycardia on ECG with a heart rate of 37 beats per minute (bpm). Medications, including tizanidine, lisinopril, theophylline, omeprazole, and simvastatin were held on admission. Laboratory work showed his WBC count to be within normal limits, and his serum creatinine (SCr), BUN, serum potassium, and serum sodium to be 1.9 mg/dL (170 mcmol/L), 21 mg/dL (7.5 mmol/L), 5.5 mEq/L (5.5 mmol/L), and 128 mEq/L (128 mmol/L), respectively. Within 24 hours of receiving IV fluids (100 mL/hr), his BP was 158/70 mmHg and his heart rate 65 bpm; his SCr, BUN, serum potassium and serum sodium levels improved to 1.6 mg/dL (140 mcmol/L), 19 mg/dL (6.8 mmol/L), 4.8 mEq/L (4.8 mmol/L), and 132 mEq/L (132 mmol/L), respectively. All medications except tizanidine, were reinstated upon discharge. At follow-up, the patient stated he had not experienced any further episodes. The case report authors assign a Naranjo adverse reaction probability rating of 'probable' to the likelihood of tizanidine causing this patients reaction, and a probability rating of 'possible' to the likelihood of this being a drug interaction between lisinopril and tizanidine .

B) Profound hypotension developed in a 48-year-old woman after receiving concomitant therapy with lisinopril and tizanidine. The patient had been receiving lisinopril 10 milligrams (mg) daily (as well as amlodipine, nimodipine, and labetalol) for 3 weeks to control high blood pressure prior to having tizanidine 2 mg added to her treatment regimen for management of spasticity arising from an intracranial hemorrhage. Within 2 hours of receiving the first dose of tizanidine, her blood pressure declined dramatically from 130/85 millimeters mercury (mmHg) to 66/42 mmHg, accompanied by an alteration of consciousness. Tizanidine was discontinued along with all antihypertensive medications, and dopamine was administered for blood pressure support. Within 5 hours, her blood pressure was restored to 120/50 mmHg, enabling discontinuation of dopamine 20 hours later. Labetalol, amlodipine, nimodipine, and tizanidine were added successively 42 hours later to control high blood pressures, and no adverse events occurred. The case report authors assign a Naranjo probability rating of 'possible' to the likelihood of a drug interaction between lisinopril and tizanidine .

Tizanidine Overview

• Tizanidine is used to relieve the spasms and increased muscle tone caused by multiple sclerosis (MS, a disease in which the nerves do not function properly and patients may experience weakness, numbness, loss of muscle coordination and problems with vision, speech, and bladder control), stroke, or brain or spinal injury. Tizanidine is in a class of medications called skeletal muscle relaxants. It works by slowing action in the brain and nervous system to allow the muscles to relax.

Lisinopril Overview

• Lisinopril is used alone or in combination with other medications to treat high blood pressure in adults and children 6 years of age and older. It is used in combination with other medications to treat heart failure. Lisinopril is also used to improve survival after a heart attack. Lisinopril is in a class of medications called angiotensin-converting enzyme (ACE) inhibitors. It works by decreasing certain chemicals that tighten the blood vessels, so blood flows more smoothly and the heart can pump blood more efficiently.

• 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.

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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.