Tizanidine and Lisinopril: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Tizanidine
No brand names on recordLisinopril
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
Both of these medicines can lower your blood pressure, and together they can lower it more than expected. Lisinopril is a blood pressure medicine, and tizanidine is a muscle relaxer that also relaxes blood vessels. When you take them together, your blood pressure can drop, sometimes quickly.
Some people have felt very dizzy, lightheaded, or even faint, and in a few reported cases people had a slow heartbeat or felt confused. This can happen soon after starting tizanidine. The good news is your care team can manage this by starting tizanidine low, raising it slowly, and keeping an eye on your blood pressure. Tell them if you feel dizzy or weak.
Effect: Additive/potentiated hypotension. Tizanidine, a central alpha(2)-adrenergic agonist, produces dose-related hypotension that can compound the antihypertensive effect of lisinopril (ACE inhibitor). This is a pharmacodynamic interaction; neither agent is a prodrug and no PK change drives it.
- Direction: Increased hypotensive response (additive BP lowering).
- Onset: Rapid (case reports: profound hypotension within 2 hours; hypotension and bradycardia within 2 days of tizanidine initiation).
- Evidence: Probable; severity moderate.
- Management: Use caution with concurrent antihypertensives. Initiate tizanidine at low single doses and titrate gradually; monitor BP, heart rate, and symptoms of hypotension.
What happens
Potentiation of hypotensive response
Interaction Deep Dive
As an alpha(2)-adrenergic agonist, tizanidine has the potential to cause hypotension in a dose-related manner1. In one case, a woman aged 48 experienced marked hypotension along with altered consciousness within a 2-hour window after being given lisinopril together with tizanidine3; separately, a man aged 85 who had been on lisinopril for an extended period developed pronounced hypotension and bradycardia within two days of initiating tizanidine 2 mg2. Prescribers should exercise caution whenever tizanidine is used in patients already taking anti-hypertensive agents. Beginning tizanidine at single doses of 4 mg and titrating the dose upward slowly helps limit the extent of hypotension. Patients should be observed closely for any signs and symptoms indicating hypotension1.
Why it happens (mechanism)
Unknown
How to manage this interaction
This interaction is manageable with sensible dosing and monitoring. Keep taking both medicines as prescribed unless your prescriber tells you otherwise.
- Your team will typically start tizanidine at a low dose and raise it slowly to limit blood pressure drops.
- Expect closer blood pressure (and possibly heart rate) monitoring, especially in the first days after starting or changing tizanidine.
- Rise slowly from sitting or lying down to reduce dizziness.
- Call your pharmacist or doctor if you feel dizzy, lightheaded, faint, unusually weak, or notice a slow heartbeat.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
2 reports — tap to read
a) An 85-year-old man receiving long-term lisinopril therapy developed severe hypotension and bradycardia after taking 3 doses of tizanidine. His medical background included several conditions, such as type 2 diabetes mellitus, congestive heart failure, and severe chronic back pain. After 3 doses of tizanidine 2 mg every 8 hours, he developed marked 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). On admission, medications including tizanidine, lisinopril, theophylline, omeprazole, and simvastatin were withheld. Laboratory testing showed his WBC count within normal limits, and his serum creatinine (SCr), BUN, serum potassium, and serum sodium were 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. Every medication except tizanidine was restarted at discharge. At follow-up, the patient reported that he had experienced no further episodes. The authors of the case report assign a Naranjo adverse reaction probability rating of 'probable' to the likelihood that tizanidine caused this patient's reaction, and a probability rating of 'possible' to the likelihood that this was a drug interaction between lisinopril and tizanidine 2.
b) Profound hypotension occurred in a 48-year-old woman after she received combined therapy with lisinopril and tizanidine. The patient had been taking lisinopril 10 milligrams (mg) daily (along with amlodipine, nimodipine, and labetalol) for 3 weeks to manage high blood pressure before tizanidine 2 mg was added to her regimen to treat spasticity resulting from an intracranial hemorrhage. Within 2 hours of the first tizanidine dose, her blood pressure fell sharply from 130/85 millimeters mercury (mmHg) to 66/42 mmHg, along with an altered level of consciousness. Tizanidine was stopped together with all antihypertensive medications, and dopamine was given for blood pressure support. Within 5 hours, her blood pressure returned to 120/50 mmHg, allowing dopamine to be discontinued 20 hours later. Labetalol, amlodipine, nimodipine, and tizanidine were reintroduced one after another 42 hours later to manage elevated blood pressures, and no adverse events occurred. The authors of the case report assign a Naranjo probability rating of 'possible' to the likelihood of a drug interaction between lisinopril and tizanidine 3.
Common questions
Can I take Tizanidine and Lisinopril together?
Taking tizanidine with lisinopril can lower your blood pressure more than either alone, sometimes quickly. Your care team can manage this by starting tizanidine low, titrating slowly, and monitoring your blood pressure, so report any dizziness or fainting. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Tizanidine and Lisinopril interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How is the Tizanidine and Lisinopril interaction managed?
This interaction is manageable with sensible dosing and monitoring. Keep taking both medicines as prescribed unless your prescriber tells you otherwise. Your team will typically start tizanidine at a low dose and raise it slowly to limit blood pressure drops. Expect closer blood pressure (and possibly heart rate) monitoring, especially in the first days after starting or changing tizanidine. Rise… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Tizanidine or Lisinopril need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there anything you'd monitor while I'm on both?
References (3)
- Product Information: tizanidine hcl tablets, tizanidine hcl tablets. Corepharma,LLC, Middlesex, NJ, 2006. DailyMed
- Publow SW & Branam DL: Hypotension and bradycardia associated with concomitant tizanidine and lisinopril therapy. Am J Health Syst Pharm 2010; 67(19):1606-1610. PubMed
- Kao C-D, Chang J-B, Chen J-T, et al: Hypotension due to interaction between lisinopril and tizanidine. Ann Pharmacother 2004; 38:1840-1843. PubMed
Keep reading about Tizanidine
Keep reading about Lisinopril
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist