Tizanidine hydrochloride is a skeletal muscle relaxant. Zanaflex is the brand name, while tizanidine is the generic version of this muscle relaxant. It is a popular option as it reduces pain by obstructing nerve signals responsible for pain in the brain. It is one of the only three medications approved by the United States Food and Drug Administration (FDA) to treat muscle spasticity.
There are several benefits to using tizanidine; however, there are side effects of tizanidine that one must be aware of. These risks are even more evident when someone is taking other medications, as unwanted interactions may occur. Along with disclosing any medications—prescription and over-the-counter (OTC), social habits such as drinking and illicit drug use must be discussed. Even interactions with vitamins, minerals, and food/diet are considered when medications are initiated.
Key takeaways:
- Drugs that significantly affect the liver reduce the metabolism of tizanidine, sedatives, and Alpha-2 adrenergic receptor agonist medications should be avoided altogether while using tizanidine. Some serious interactions to be aware of while using these combinations involve excessive sleepiness or reduced heart rates that can be life-threatening.
- Adverse effects from tizanidine interactions include:
- Common side effects-dry mouth, sleepiness, weakness, dizziness, hypotension, urinary tract infection, elevated liver enzymes, constipation, vomiting, speech disturbance, increased urinary frequency, blurred vision, flu-like symptoms, involuntary movements, nervousness, sore throat, stuffy nose, and hallucinations.
- Severe side effects—liver damage, severe hypotension and heart rate, fainting, withdrawal symptoms, and severe allergic reactions.
- Contact your healthcare professional immediately for medical advice if there is any interaction when you take tizanidine.
Tizanidine-drug interactions
Several drug interactions are associated with the use of tizanidine. Medications that increase the effects of tizanidine are of great concern as increased drowsiness or lightheadedness may occur.
Alpha-2 adrenergic receptor agonists
Alpha-2 agonist drugs are not recommended to be used in combination with tizanidine. Tizanidine is a type of alpha-2 agonist that helps relax muscles. Alpha-2 agonist medications are historically for lowering blood pressure however, tizanidine is not approved for hypertension and has milder effects on lowering blood pressure. However, when this muscle relaxant is added with other alpha-2 agonists, it can cause excessive drowsiness, dizziness, or even too low of a heart rate and hypotension. Serious consequences like overdose or even death can occur, so adding these medications together must be taken seriously. An alternative to tizanidine is required while taking other alpha-2 agonist drugs.
Example of alpha-2 agonists:
Birth control medications
Birth control is usually safe when used with other medications but must be cautioned when combined with tizanidine. Medications containing hormones may act to change the chemical process of other medications that are absorbed or used in the body—this includes tizanidine. When using birth control or hormone replacement medications, the change in metabolism of tizanidine causes increased levels of the medication in the body. The increased levels may raise the chances of unwanted side effects.
Your healthcare provider may modify your dose of tizanidine if they are made aware that you are on birth control pills. If there are no unwanted side effects, but your pain remains, they may gradually increase the amount of tizanidine prescribed. While on birth control pills and tizanidine, close monitoring of potential symptoms should be done. If symptoms such as excessive drowsiness, dizziness, or shortness of breath occur, contact your healthcare provider right away.
Example of oral contraceptives/hormone replacement:
- Estradiol (contraceptive)
- estrogens (hormone replacement)
- Ethinyl estradiol (contraceptive)
Opioids
Narcotic pain medication should be avoided with the use of tizanidine. Both categories cause central nervous system (CNS) depression which slows breathing, causes low blood pressure, and lowers the heart rate. Increased symptoms of sleepiness, dizziness, impaired judgment, and decreased coordination may occur and are worse when both are used simultaneously. Your doctor may offer an alternative to tizanidine if you are required to remain on opioids for pain management. Lower doses of tizanidine or your opioids may also be an alternative if both are needed.
Examples of opioids:
Sedatives
Medications used for the treatment of anxiety, depression, seizures, or sleeping problems are usually categorized as sedatives. These medications are known to slow brain activity (CNS depressants) which causes drowsiness, poor coordination, slurred speech, and reduced heart rate or hypotension. When in combination with tizanidine, these symptoms may increase. In more serious cases, overdose, unconsciousness, or even death may occur. Tizanidine should be avoided with these medications or at least closely monitored if there are no alternatives available.
Lower doses of tizanidine may be initially provided if sedatives are needed for various conditions and can not be avoided due to allergies to other medications or inability to stop the sedative in a timely fashion, as they usually require a weaning off period when used for long periods of time or with high doses. If at any time shortness of breath, increased sleepiness, or unconsciousness occurs while using these medications together, immediately contact the poison control center.
Examples of sedatives:
- Antidepressants
- Barbiturates
- pentobarbital
- Phenobarbital
- Benzodiazepines
- Sleeping aids
- Eszopiclone
- Gabapentin (off-label)
- Zaleplon
- Zolpidem
- Anti-histamines
- Diphenhydramine (Benadryl)
- Doxepin
Other medications
Many medications may be metabolized in the liver, which can block enzymes that break down tizanidine in the body. This can cause increased levels of the medication within the bloodstream resulting in serious side effects. Types of medication impacting the liver may be antibiotics, antiarrhythmics, and GERD medications. Some of these medications must be fully avoided, while others must be closely monitored, and the dose may just be adjusted.
Examples of other medications:
- Acyclovir
- Amiodarone
- Atenolol
- Cimetidine
- Ciprofloxacin (Cipro)
- Famotidine
- Fluvoxamine
- Levofloxacin
- Quinidine
- Sotalol
- Verapamil
- Zileuton
Other muscle relaxants
Taking multiple muscle relaxants at once is not usually recommended. Since they work similarly and pose the same side effects, multiple muscle relaxants will increase the chances of negative reactions. You may not be aware that you are already taking a muscle relaxant or something similar with sedative-like properties, so it is important to disclose all medications—either prescription or OTC—with your doctor. If you are already taking a muscle relaxant that is not improving your symptoms, a higher dose may be offered or a different medication altogether. If more than one muscle relaxant is provided, usually lower doses are initiated and monitored closely. This must be under the supervision of your healthcare provider.
Other muscle relaxers:
- Baclofen
- Carisoprodol
- Chlorzoxazone
- Cyclobenzaprine
- Dantrolene
- Methocarbamol
- Metaxalone
- Orphenadrine
Tizanidine-food interactions
There are no known food interactions at this time with tizanidine. In general, it is important to stay hydrated with lots of water during the day. Drinking liquids with electrolytes especially when exercising, may also help with treating and preventing muscle aches and pains.
Other tizanidine interactions
Although prescription drugs and OTC medications are widely known to have interactions with prescription muscle relaxants, patients should also be aware of other interactions from non-pharmaceuticals that may impact tizanidine use.
Tizanidine and alcohol
Mixing tizanidine with alcohol is similar to the effects that occur with sedatives. It is a CNS depressant and slows down brain activity. Since alcohol is known to cause drowsiness, impair coordination, and judgment alone, muscle relaxants such as tizanidine should be avoided. These symptoms may become more severe when used together. If alcohol is consumed while taking tizanidine, monitor symptoms closely. If any slowed breathing, decreased heart rate, or fainting occurs, contact your doctor immediately.
Tizanidine and caffeine
Beware of coffee and sodas while on tizanidine. Caffeine can increase the levels of this medication, increasing the side effects of the medication. When starting this muscle relaxant, monitor symptoms closely. If symptoms occur, the dose may be lowered, or an alternative may be given.
Tizanidine and disease/CBD/illicit drugs/vitamins/herbal supplements/etc.
Along with drug interactions to be mindful of, certain medical conditions may put you at risk of negative side effects while taking tizanidine. Patients with known liver disease, a history of hypotension, kidney disease, and mental illness should avoid tizanidine. This medication requires close monitoring and individual dose adjustments when these conditions are considered. Regular lab work is needed to test liver function and the kidneys while on this muscle relaxer. Hallucinations are associated with tizanidine use, so this must be discussed with those who have known psychiatric disorders.
Drowsiness, poor coordination, mental impairment, and dizziness may be seen when tizanidine, cannabidiol (CBD), and illicit drugs are combined. Be honest with your healthcare provider if you are using these things so alternatives can be reviewed for managing your muscle aches and pain.
How to minimize tizanidine interactions
The thought of minimizing drug interactions can feel overwhelming. It is important that you are aware of all drug information when taking any medication. This includes supplements, vitamins, and OTC medications. Keeping track of what prescriptions you are taking is helpful. This will allow you to inform your healthcare providers, which reduces your chances tremendously of having unwanted symptoms or serious adverse effects.
When to talk to a healthcare provider about tizanidine interactions
Again, speaking openly with your healthcare provider is vital when taking any medication. Tizanidine may be very beneficial in improving muscle aches and pains that traditional OTC medications cannot help. However, at any time, if symptoms- mild or severe- begin to arise, you should contact your doctor for further evaluation. A decision may be made to closely monitor things, reduce the dosage and or/frequency, or there may be a need to discontinue the medication completely. This must be done strategically to help reduce occasional withdrawal symptoms sometimes associated with this medication. These adjustments must be under the guidance of your doctor. At any time, if unconsciousness, shortness of breath, or decreased blood pressure/heart rate is present, go immediately to the hospital.
Sources
- Tizanidine, Stat Pearls (2022)