7 Tizanidine Interactions You Should Know About

Tizanidine (Zanaflex) is a muscle relaxer that’s FDA approved to treat muscle spasticity. Spasticity occurs when your muscles are tight and stiff. 

If you’re prescribed tizanidine, knowing about possible tizanidine warnings, including drug interactions, can help keep you safe. Tizanidine interactions can change the way tizanidine works in your body or could raise the risk of side effects. Some tizanidine interactions should be avoided entirely. But others may only require closer monitoring.

Below, we’ll cover seven of the most important tizanidine interactions you should know.

1. Medications that increase tizanidine levels, such as ciprofloxacin

Tizanidine is metabolized (broken down) in the liver. But some medications block the liver enzymes (proteins) that metabolize tizanidine. This may cause higher tizanidine levels in the body which can make side effects more likely. Possible tizanidine side effects include low blood pressure, sleepiness, and dry mouth.

Examples of medications that can block tizanidine metabolism include:

• Fluvoxamine (Luvox)

• Ciprofloxacin (Cipro) and other fluoroquinolone antibiotics

• Zileuton (Zyflo)

• Acyclovir (Zovirax)

• Antiarrhythmics like amiodarone (Pacerone)

• Histamine-2 antagonists like famotidine (Pepcid AC, Zantac 360) and cimetidine (Tagamet HB)

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These medications don’t increase tizanidine levels to the same degree. For example, ciprofloxacin and fluvoxamine may significantly increase tizanidine levels in the body. These medications shouldn’t be used with tizanidine. 

The other medications listed here may not increase tizanidine levels as much. But you should talk to your healthcare team before taking them. They might consider lowering your tizanidine dose. Or they may just ask you to watch out for tizanidine side effects.

Be sure to share your medication list with your healthcare team so they can help check for possible interactions.

2. Birth control pills like Sprintec and Yasmin

Birth control pills are often used to prevent an unplanned pregnancy. These pills contain hormones like estrogen and/or progestin. But like the medications discussed above, birth control pills may block tizanidine metabolism. This can increase tizanidine levels in the body and lead to side effects.

This may be especially true for birth control pills containing ethinyl estradiol or desogestrel. Ethinyl estradiol is a type of estrogen and desogestrel is a type of progestin. Examples of birth control pills that contain these hormones include:

• Desogestrel / ethinyl estradiol (Apri, Kariva, Viorele)

• Norethindrone acetate / ethinyl estradiol (Junel, Lo Loestrin FE)

• Levonorgestrel / ethinyl estradiol (Vienva, Portia)

• Norgestimate / ethinyl estradiol (Sprintec, Tri-Sprintec)

• Drospirenone / ethinyl estradiol (Yasmin, Yaz)

EXPERT PICKS: WHAT TO READ NEXT

• Tizanidine side effects: Learn about possible tizanidine side effects and how to best manage them.

• Avoiding tizanidine and alcohol: Muscle relaxers and alcohol are best avoided, here’s why.

• Comparing muscle relaxers: Read on for the differences and similarities between several muscle relaxers available to treat muscle stiffness.

If you’re taking birth control pills, it's usually best to avoid tizanidine. But if your prescriber thinks you need both medications, they may start you on a lower tizanidine dose. They may raise your dose slowly based on how you respond.

If you take tizanidine and birth control pills, monitor for tizanidine side effects. Examples includelow blood pressure (hypotension) or slowed heart rate. Signs of these side effects may include dizziness, fainting, or shortness of breath. You should also watch for feelings of extreme tiredness. 

3. Alpha-2 agonists, such as clonidine

Alpha-2 adrenergic receptor agonists (alpha-2 agonists) are medications that have many functions in the body. This includes lowering blood pressure and causing sedation. Examples include clonidine (Catapres) and guanfacine (Intuniv ER).

Tizanidine is also an alpha-2 agonist. Combining tizanidine with other alpha-2 agonists could cause dangerous side effects. These include hypotension and excessive sleepiness.

It’s not recommended to take tizanidine with other alpha-2 agonists.

4. Benzodiazepines, such as Xanax

Medications called sedatives can slow down brain activity. They’re prescribed for several conditions, including anxiety, sleep problems, and seizures. Benzodiazepines are one type of sedative. Examples include:

• Xanax (alprazolam)

• Klonopin (clonazepam)

• Ativan (lorazepam)

• Valium (diazepam)

Sedatives can cause sleepiness, dizziness, and poor coordination. They may also have mental health effects, such as causing or worsening depression or aggression. Although tizanidine isn’t a benzodiazepine, it can also have sedative-like effects. It can be dangerous then to take a benzodiazepine like Xanax with tizanidine. In severe cases, this combination increases your risk of overdose, coma, and death.

In general, it’s best to avoid combining sedatives like benzodiazepines with tizanidine.

5. Opioids, such as oxycodone

Although tizanidine isn’t a narcotic (opioid), both muscle relaxers and opioids have sedative-like effects. So taking them together can be dangerous. It can lead to excessive sleepiness, slowed breathing, and overdose. Examples of opioids include:

• Oxycodone (Roxicodone, Oxycontin)

• Hydrocodone (Hysingla ER) and hydrocodone / acetaminophen

• Tramadol (Qdolo, ConZip)

• Methadone (Methadose)

Make sure your prescriber knows if you take an opioid before starting oxycodone. If you regularly take opiods, an alternative to tizanidine may be a better option.

6. Other medications that affect the brain, such as Benadryl

Some other medications can also have sedative-like effects similar to tizanidine. And as discussed, when you combine multiple medications that have sedative properties, dangerous side effects are more likely. These include excessive sleepiness and dizziness, which can lead to falls, slowed breathing, and overdose.

Examples of other sedative-like medications include:

• “Z-drugs,” such as zolpidem (Ambien, Edluar, and ZolpiMist)

• Antidepressants, such as trazodone

• Gabapentin (Neurontin)

• Benadryl (diphenhydramine)

• Other muscle relaxers, such as methocarbamol

• Barbiturates like phenobarbital

In general, it’s best to avoid driving or any activity that requires alertness until you know how tizanidine affects you. This is especially true if you take other medications that can cause sedation. 

Ask your prescriber if you’re taking any medications or supplements that cause sedation. They may recommend an alternative to tizanidine to avoid side effects. Or they may prescribe a lower dose of tizanidine and ask you to watch for symptoms of oversedation. 

7. Alcohol

Alcohol affects the body in many ways. It can change your mood, coordination, and level of alertness. And similar to sedatives, alcohol can make you more sleepy. 

In short, drinking alcohol and taking muscle relaxers isn’t recommended. Alcohol and tizanidine can cause excessive sedation when taken together. It can also lower your blood pressure, leading to fainting or potential injuries. This is especially true if you drink large amounts of alcohol.

What’s more, alcohol may increase tizanidine levels in the body. This increases the risk of tizanidine side effects even more so. In severe cases, this combination could cause slowed breathing and overdose.

It’s best to avoid alcohol while taking tizanidine. If you drink alcohol, talk with your prescriber. They can talk to you about the risks of this interaction, and let you know if you should avoid tizanidine entirely.

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Written by:

Austin Ulrich, PharmD, BCACP

Austin Ulrich, PharmD, BCACP, is a board-certified ambulatory care clinical pharmacist. In his early career, he provided direct patient care in a variety of settings, including hospital and community pharmacies, and in a primary care clinic as a clinical pharmacist.

Edited by:

Amy B. Gragnolati, PharmD, BCPS

Amy Gragnolati, PharmD, BCPS, is a pharmacy editor for GoodRx. Amy currently holds her pharmacist license in Georgia and California.

Reviewed by:

Alex Brewer, PharmD, MBA

Alex Brewer, PharmD, MBA, is a licensed pharmacist specializing in chronic disease and health and wellness. Upon completing his residency, he worked in the managed care field, conducting medication therapy management and adherence counseling sessions with Medicaid, Medicare, and private insurance patients, before transitioning to a career in medical writing.

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