How long does it take for cyclobenzaprine to kick in?

Cyclobenzaprine (Flexeril) Side Effects & Detox Timeline

What is Cyclobenzaprine (Flexeril)?

How cyclobenzaprine (Flexeril) works is not well understood, but it helps alleviate stiffness, pain, and discomfort due to sprains, strains, or injuries to muscles. It is also sometimes prescribed off-label to treat fibromyalgia pain. It is typically only taken one time a day for 2 to 3 weeks. A person should not take cyclobenzaprine for longer than 3 weeks if they have not consulted their healthcare provider.

Cyclobenzaprine may be referred to by the former brand name Flexeril, though generic and other brands exist.

Cyclobenzaprine usually begins working about one hour after it is ingested, relaxing muscles and relieving muscle spasms. Formulations include immediate-release and extended-release. If you are prescribed cyclobenzaprine, follow your healthcare provider’s directions for how to take it.

Cyclobenzaprine’s Effectiveness Timeframe

Cyclobenzaprine works for 4-6 hours. However, the half-life of immediate-release cyclobenzaprine is 18 hours on average, with a range of 8-37 hours. The extended-release form typically has a half-life of 32-33 hours.

Common Cyclobenzaprine Side Effects

Common side effects include:

  • Drowsiness
  • Blurred vision
  • Dry mouth
  • Lightheadedness
  • Dizziness

It is also possible for serious side effects to occur, like seizures, heart arrhythmias, heart attack, or stroke. These are more likely to occur when a person has too much cyclobenzaprine in their system, for instance if their prescription dose is too high or if they are abusing the drug.

Because there is not enough evidence that cyclobenzaprine is effective for long-term use, and because the muscle spasms it is indicated for are generally of short duration, it is not advised to be used for longer than two to three weeks. If cyclobenzaprine is being abused or misused, however, the person may continue to take the medication for much longer and may increase their dose too high, which could lead to dangerous side effects and overdose.

Cyclobenzaprine Interactions With Other Substances

Cyclobenzaprine can increase the effects of CNS depressants, such as alcohol, opioids, allergy medications, and sleeping pills. It can also interact with other medications. If a person is prescribed cyclobenzaprine, they should make sure their health care provider knows all medications they are taking (including over-the-counter medications), as well as if they drink alcohol or use other drugs. This enables the provider to evaluate for any potential interactions and helps them keep the patient safe. Even if it feels like the effects of cyclobenzaprine have worn off, the drug may not be completely eliminated from the body yet and could cause serious interactions with other substances.

Cyclobenzaprine is often prescribed to people who have acute back injuries, including when people report having muscle spasms or significant tightness in their back, or when the back feels like it’s locked, she explained. It’s also prescribed to treat for muscle strains.


Cyclobenzaprine is a skeletal muscle relaxant that works by increasing the release of the chemical norepinephrine from central nervous structures in the brain, Patel said.

It can be taken as either a tablet or an extended release capsule (brand name Amrix). The regular tablet’s usual dosage is two to four times a day, while the extended release capsule is generally taken one to two times a day. The tablets, intended for short-term use, come in 5, 7.5, and 10 mg doses. The usual starting dose, according to the Drug Enforcement Administration, is 5 mg three times a day. The maximum recommended dose is 10 mg three times a day. Patients typically feel better within 10 days.

If stomach upset occurs, take it with food to reduce stomach irritation, Patel said.

According to the Food and Drug Administration (FDA), patients should avoid use of monoamine oxidase (MAO) inhibitors within 14 days of cyclobenzaprine use. These include Marplan, Nardil, Parnate and Matulane. Seizures and even death have occurred in patients who have cyclobenzaprine or other structurally similar tricyclic antidepressants with MAO inhibitor drugs.


A 10-mg dose of cyclobenzaprine in tablet form. (Image credit: National Institutes of Health.)

There are some restrictions as to who can take this drug. The FDA recommends cautious use of cyclobenzaprine in patients with a history of urinary retention and glaucoma or other eye problems. There is no evidence to suggest that the drug causes any issues for pregnant mothers (according to studies done on mice, rats and rabbits), but there have yet to be any adequate and well-controlled studies in pregnant women. As a result, the FDA cautions use during pregnancy only if clearly needed. For nursing mothers, it is unknown if cyclobenzaprine is excreted in human milk. However, because it is closely related to tricyclic antidepressants, which are excreted in human milk, the FDA cautions against breastfeeding if using cyclobenzaprine.

“It’s not known if this medicine can be found in breast milk, and because of that we don’t want to take any chances,” Patel said.

Cyclobenzaprine has not been tested in pediatric patients younger than 15 years of age. The elderly may be at a higher risk for adverse events, including hallucinations and confusion, cardiac events and drug interactions. According to the FDA, the plasma concentration of cyclobenzaprine is increased in the elderly, so the drug should be prescribed only if clearly needed. Initiation should begin with a 5 mg dose and slowly increased, under the careful eye of a doctor.

Side effects

Some common side effects include drowsiness, dry mouth, dizziness, fatigue or upset stomach. If these side effects become severe or cause problems in your everyday life, the National Institutes of Health (NIH) recommends contacting your doctor.

If you experience severe skin rash, swelling of the face or tongue, difficulty breathing or swallowing, irregular heart rate, chest pain, fever or seizures, the NIH recommends contacting a doctor immediately. These side effects, which have been reported in other similar tricyclic antidepressants to the FDA, could be indications of arrhythmias, sinus tachycardia, leading to myocardial infarction and stroke.

The abrupt termination of prolonged use can also cause side effects, including nausea, headache and malaise. However, it is important to note that these withdrawal effects are not indicative of addiction.

Abuse and overdose

A 5-mg dose of cyclobenzaprine in tablet form. (Image credit: National Institutes of Health.)

Cyclobenzaprine may enhance the effects of other central nervous system depressants, such as alcohol, barbiturates, benzodiazepines and narcotics. According to the DEA, abusers often combine cyclobenzaprine with these depressants to produce or enhance psychoactive effects. Though it is not a controlled substance, the DEA has recorded anecdotal reports of use to induce euphoria and relaxation.

Though rare, deaths can occur from cyclobenzaprine overdose, especially in the case of multiple drug ingestion. The FDA recommends that doctors contact a poison control center for current information on treatment for an overdose, as the management of a case is complex. The most common manifestations associated with overdose are drowsiness and an abnormally rapid heart rate (tachycardia). Less common effects include body twitches (tremor), the loss of control of bodily movements (ataxia), hypertension, agitation, slurred speech, nausea, confusion, dizziness, hallucination, vomiting and coma. Rare but critical effects include cardiac arrest, chest pain and seizures.

Drug testing

A formulation of cyclobenzaprine is now being tested to treat combat-related post-traumatic stress disorder (PTSD). Currently, it is in its third trial of drug testing and is being studied on military personnel. Research has found, so far, that the drug can help those with PTDS sleep better and have fewer nightmares.

A 2011, a double-blind randomized placebo-controlled study published by The Journal of Rheumatology found that the drug may also be useful in treating those with fibromyalgia sleep better. A 2016 drug used to deliver cyclobenzaprine into the body of fibromyalgia patients was recently halted during trials. Other drugs using cyclobenzaprine are also being tested to treat fibromyalgia, though. The current form of cyclobenzaprine is not approved by the FDA for the treatment of fibromyalgia.

This article is for informational purposes only, and is not meant to offer medical advice.

Additional reporting by Alina Bradford, Live Science Contributor.

Additional resources

  • Mayo Clinic: Cyclobenzaprine
  • American Family Physician: Cyclobenzaprine in the Treatment of Low Back Pain
  • JAMA: Naproxen with Cyclobenzaprine, Oxycodone/Acetaminophen, or Placebo for Treating Acute Low Back Pain

How Long Does Flexeril Last in Your System?

Flexeril (cyclobenzaprine) generally starts working within about an hour after taking it, MedScape explains. It remains active in the bloodstream for about 12 to 24 hours.

It can remain in your system for much longer, up to several days.

Flexeril Basics

Flexeril is a muscle relaxant medication prescribed to treat muscle spasms that occur as a result of painful and acute musculoskeletal conditions. The active ingredient, cyclobenzaprine, is chemically similar to tricyclic antidepressants (TCAs).
While the mechanism of action is not entirely understood, it is known that Flexeril acts like a central nervous system (CNS) depressant. It slows down some CNS activity and nerve firings to calm muscle spasms and related pain.

Flexeril is an effective treatment for pain and muscle spasms for a relatively short period of time — usually between four and 12 hours. It can remain in the bloodstream for much longer — up to a few days.
Even if it is still present in the system, it may seem like it isn’t working. This can encourage people to take too much.
Flexeril is only designed to be taken for a short timeframe. The U.S. Food and Drug Administration (FDA) recommends that cyclobenzaprine is only to be prescribed for a maximum of two to three weeks.
When taking Flexeril, it is important to follow medical recommendations to minimize potential complications.

Effectiveness vs. Elimination Timeline

As an immediate-release formulation, cyclobenzaprine is generally given in 5 mg doses three times per day. Doses should not exceed 30 mg per day, per PDR, the Prescriber’s Digital Reference.
The extended-release formulation of Flexeril may be dosed twice per day in 15 mg doses.
The immediate-release formulation generally remains effective for about four to six hours, while the extended-release can work for about 12 hours on pain and muscle spasms.
Flexeril has a long and variable half-life. It can stay in the body long after its effectiveness has worn off.
According to BioMed Research International, cyclobenzaprine has a half-life that may range from eight to 37 hours for the immediate-release version and between 32 and 33 hours for the extended-release version.
A half-life for medication is the length of time it takes for half of the drug to be broken down by the body. With this in mind, Flexeril can potentially stay in the body for up to three days.


It may seem as if Flexeril is no longer working, which may make it tempting to take more. If more is taken, it can trigger a wide range of side effects, not the least of which is the potential for overdose.

A cyclobenzaprine overdose can come on suddenly and rapidly. The U.S. National Library of Medicine (NLM) explains that the most common side effects are tachycardia (irregular heart rate) and drowsiness.

  • Nausea and vomiting
  • Dizziness
  • Tremors
  • Chest pain
  • Agitation
  • Muscle weakness
  • Slurred speech
  • Hallucinations
  • Mental confusion
  • High blood pressure
  • Coma
  • Seizures

The U.S. Drug Enforcement Administration (DEA) published in 2010 that there were more than 12,000 emergency room visits that involved cyclobenzaprine. Over 10,000 case mentions of exposure to cyclobenzaprine were reported to the American Association of Poison Control Centers.
Misuse of Flexeril or combining it with other drugs or alcohol can amplify the potential side effects as well as the risk for fatal overdose.

Factors Impacting Metabolism

The length of time Flexeril stays in your body will depend on several factors. Not everyone metabolizes drugs the same way.
Cyclobenzaprine is excreted through the kidneys, so individuals with kidney damage or less function in the kidneys may struggle to process the drug out as quickly.

The FDA publishes that Flexeril takes longer to process out of the elderly and those with hepatic impairment; therefore, dosages should be lowered for these populations.
As you age, your metabolism slows down. This means that it can take longer for a drug to process out of the body.
Hepatic impairment involves the liver — which is the primary organ involved in flushing toxins out of the body — so issues with the liver can impede Flexeril metabolism. This slows the rate at which it is processed out of the system.

Other things that can influence how long Flexeril will stay in the system and how the drug is metabolized can include:

  • The method and manner in which the drug is taken. Crushing and snorting or chewing Flexeril tablets can interfere with the way the drug is meant to be metabolized. This can impact the speed at which it processes out of the system.
  • Concurrent substance use. Taking other drugs or drinking alcohol with Flexeril can exacerbate the effects of each substance. This also impacts drug metabolism and the rate at which Flexeril will process out of the body.
  • Co-occurring disorders. The presence of a medical or mental health disorder can change how a drug is metabolized and how long it may stay in the system.
  • Biological and genetic influences. Sex, age, and race can all impact drug metabolism.

Tolerance and Drug Dependence

Another factor is based on how much and how often you take Flexeril.
When you take a drug that interacts with brain chemistry, your brain can get used to certain amounts of it. This means that you can become tolerant to the drug, and it will take more of it to feel the same effects. This can lead to escalating dosages of Flexeril, and more taken in between doses. Flexeril can then build up in the body, and it can take even longer for it to process out.
Physical drug dependence may form with regular use of Flexeril, which can lead to difficult withdrawal symptoms when it leaves the body. These symptoms may include malaise, nausea, and headache.
The more often you take Flexeril, the longer you’ve been taking it, and the higher the doses taken each time, the more significant the level of dependence will be. Higher levels of dependence mean it will take longer to leave your system.

Variations of Use

Flexeril is not intended for use longer than two to three weeks. It is generally prescribed as an adjunct treatment to be used in conjunction with other methods.

Dependence is a precursor to substance abuse and addiction, for some people. Specialized treatment programs involving medical detox can help manage addiction while allowing Flexeril to process safely out of the system.

Other drugs including TCAs, MOAIs (monoamine oxidase inhibitors), SNRIs (serotonin and norepinephrine reuptake inhibitors), and SSRIs (selective serotonin reuptake inhibitors) can interact negatively with Flexeril. It is important that Flexeril is completely processed out of the body before introducing one of these medications.

The length of time Flexeril lasts in the system will vary from person to person. A medical professional can give you the best idea of a specific timeline for your unique situation.

(April 2013). Pharmacokinetics and Bioequivalence Evaluation of Cyclobenzaprine Tablets. Biomed Research International. Retrieved February 2019 from

Flexeril: 7 things you should know

3. Downsides

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

  • Sedation is a major side effect which may impair reaction skills and affect a person’s ability to drive or operate machinery. Alcohol should be avoided.
  • Dry mouth, tiredness, dizziness, headache, difficulty with urination, nausea, an increase in eye pressure and blurred vision have also been reported.
  • Heart palpitations, seizures and an increased risk of heart attack have rarely been associated with Flexeril.
  • Effects may be similar to those seen with tricyclic antidepressants (TCAs) as Flexeril is structurally related to TCAs.
  • Abrupt cessation of Flexeril may cause sickness, headache and tiredness; however, these are not indicative of addiction.
  • Should only be used short-term (for periods of up to two to three weeks only).
  • Not effective for muscle spasm occurring as a result of cerebral or spinal cord disease, or in children with cerebral palsy.
  • Flexeril should never be given within 14 days of monoamine oxidase (MAO) inhibitor antidepressants, as the combination may be fatal.
  • Interaction with other drugs that also increase serotonin (such as antidepressants, tramadol, St John’s Wort, bupropion) may cause serotonin syndrome. Symptoms include mental status changes (such as agitation, hallucinations, coma, delirium), fast heart rate, dizziness, flushing, muscle tremor or rigidity and stomach symptoms (including nausea, vomiting, and diarrhea).
  • Flexeril may enhance the effects or side effects of tricyclic antidepressants (for example, amitriptyline and imipramine), alcohol, and other CNS depressants.
  • May not be suitable for people with arrhythmias, heart block or conduction disturbances, heart failure, hyperthyroidism, or immediately following a heart attack.
  • The dosage of Flexeril should be reduced in people with mild liver disease. It should not be taken by people with moderate-to-severe liver disease.
  • Flexeril may also not be suitable for people with glaucoma or increased intraocular pressure, a history of urinary retention, or taking other drugs that also have anticholinergic side effects (anticholinergic side effects include constipation, blurred vision and an increase in eye pressure).
  • Elderly people may be more sensitive to the effects of Flexeril, and the dosage should be kept low if the benefits of using it in seniors outweigh the risks.

Notes: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. For a complete list of all side effects, .



Cyclobenzaprine HCl relieves skeletal muscle spasm of local origin without interfering with muscle function. It is ineffective in muscle spasm due to central nervous system disease.

Cyclobenzaprine reduced or abolished skeletal muscle hyperactivity in several animal models. Animal studies indicate that cyclobenzaprine does not act at the neuromuscular junction or directly on skeletal muscle. Such studies show that cyclobenzaprine acts primarily within the central nervous system at brain stem as opposed to spinal cord levels, although its action on the latter may contribute to its overall skeletal muscle relaxant activity. Evidence suggests that the net effect of cyclobenzaprine is a reduction of tonic somatic motor activity, influencing both gamma (γ) and alpha (α) motor systems.

Pharmacological studies in animals showed a similarity between the effects of cyclobenzaprine and the structurally related tricyclic antidepressants, including reserpine antagonism, norepinephrine potentiation, potent peripheral and central anticholinergic effects, and sedation. Cyclobenzaprine caused slight to moderate increase in heart rate in animals.


Estimates of mean oral bioavailability of cyclobenzaprine range from 33% to 55%. Cyclobenzaprine exhibits linear pharmacokinetics over the dose range 2.5 mg to 10 mg, and is subject to enterohepatic circulation. It is highly bound to plasma proteins. Drug accumulates when dosed three times a day, reaching steady-state within 3-4 days at plasma concentrations about four-fold higher than after a single dose. At steady state in healthy subjects receiving 10 mg t.i.d. (n=18), peak plasma concentration was 25.9 ng/mL (range, 12.8-46.1 ng/mL), and area under the concentration-time (AUC) curve over an 8-hour dosing interval was 177 (range, 80-319

Cyclobenzaprine is extensively metabolized, and is excreted primarily as glucuronides via the kidney. Cytochromes P-450 3A4, 1A2, and, to a lesser extent, 2D6, mediate N-demethylation, one of the oxidative pathways for cyclobenzaprine. Cyclobenzaprine is eliminated quite slowly, with an effective half-life of 18 hours (range 8-37 hours; n=18); plasma clearance is 0.7 L/min.

The plasma concentration of cyclobenzaprine is generally higher in the elderly and in patients with hepatic impairment. (See PRECAUTIONS, Use in the Elderly and PRECAUTIONS, Impaired Hepatic Function.)


In light of these findings, therapy with FLEXERIL in the elderly should be initiated with a 5 mg dose and titrated slowly upward.

Hepatic Impairment

In a pharmacokinetic study of sixteen subjects with hepatic impairment (15 mild, 1 moderate per Child-Pugh score), both AUC and Cmax were approximately double the values seen in the healthy control group. Based on the findings, FLEXERIL should be used with caution in subjects with mild hepatic impairment starting with the 5 mg dose and titrating slowly upward. Due to the lack of data in subjects with more severe hepatic insufficiency, the use of FLEXERIL in subjects with moderate to severe impairment is not recommended.

No significant effect on plasma levels or bioavailability of FLEXERIL or aspirin was noted when single or multiple doses of the two drugs were administered concomitantly. Concomitant administration of FLEXERIL and naproxen or diflunisal was well tolerated with no reported unexpected adverse effects. However combination therapy of FLEXERIL with naproxen was associated with more side effects than therapy with naproxen alone, primarily in the form of drowsiness. No well-controlled studies have been performed to indicate that FLEXERIL enhances the clinical effect of aspirin or other analgesics, or whether analgesics enhance the clinical effect of FLEXERIL in acute musculoskeletal conditions.

Clinical Studies

Eight double-blind controlled clinical studies were performed in 642 patients comparing FLEXERIL 10 mg, diazepam, and placebo. Muscle spasm, local pain and tenderness, limitation of motion, and restriction in activities of daily living were evaluated. In three of these studies there was a significantly greater improvement with FLEXERIL than with diazepam, while in the other studies the improvement following both treatments was comparable.

Although the frequency and severity of adverse reactions observed in patients treated with FLEXERIL were comparable to those observed in patients treated with diazepam, dry mouth was observed more frequently in patients treated with FLEXERIL and dizziness more frequently in those treated with diazepam. The incidence of drowsiness, the most frequent adverse reaction, was similar with both drugs.

The efficacy of FLEXERIL 5 mg was demonstrated in two seven-day, double-blind, controlled clinical trials enrolling 1405 patients. One study compared FLEXERIL 5 mg and 10 mg t.i.d. to placebo; and a second study compared FLEXERIL 5 mg and 2.5 mg t.i.d. to placebo. Primary endpoints for both trials were determined by patient-generated data and included global impression of change, medication helpfulness, and relief from starting backache. Each endpoint consisted of a score on a 5-point rating scale (from 0 or worst outcome to 4 or best outcome).

Comparisons of FLEXERIL 5 mg and placebo groups in both trials established the statistically significant superiority of the 5 mg dose for all three primary endpoints at day 8 and, in the study comparing 5 and 10 mg, at day 3 or 4 as well. A similar effect was observed with FLEXERIL 10 mg (all endpoints). Physician-assessed secondary endpoints also showed that FLEXERIL 5 mg was associated with a greater reduction in palpable muscle spasm than placebo.

Analysis of the data from controlled studies shows that FLEXERIL produces clinical improvement whether or not sedation occurs.

Secondary endpoints included a physician’s evaluation of the presence and extent of palpable muscle spasm.

Surveillance Program

A post-marketing surveillance program was carried out in 7607 patients with acute musculoskeletal disorders, and included 297 patients treated with FLEXERIL 10 mg for 30 days or longer. The overall effectiveness of FLEXERIL was similar to that observed in the double-blind controlled studies; the overall incidence of adverse effects was less (see ADVERSE REACTIONS).

This essay reports on a better way to use Flexeril, a way that improves sleep and pain, but actually lessens feelings of daytime fatigue.

Two key innovations:

  1. By taking a lower than usual dose of Flexeril at night —
    in the 2 mg to 5 mg at night instead of the usual 10 mg dose.
  2. By taking Flexeril every night for many weeks,
    not just as an intermittent sleeping pill.

The lead author of this key research study is Harvey Moldofsky, M.D., now Professor Emeritus at the University of Toronto. Dr. Moldofsky’s career-long research on fibromyalgia has been made major contributions to understanding our field. For example, Dr. Moldofsky’s 1975 article was the first to prove the relationship between fibromyalgia pain and abnormal patterns of sleep. His most recent publication on fibromyalgia was in 2015.

In a 2011 study, Dr. Moldofsky’s Toronto team conducted a double blind study of 36 patients with FM. Half were given “low dose” Flexeril/cyclobenzaprine starting at 1 mg and working up to the 4 mg range. The others received a placebo. These were taken every night over 8 weeks.

The outcomes: low dose cyclobenzaprine made a positive difference with very few major side effects. Patients on placebo did not improve.

Here are the main numbers:

Pain intensity levels were scored prior to starting treatment and after 8 weeks.
For the Flexeril group, pain severity decreased by 26.1%.

The “P value” was less than .01. (That is, the probability (P) of this result being obtained by chance was less than 1 chance in 100. A P value of <.05 is considered to be “statistically significant”.)

The placebo group had no change in their pain.

For those taking Flexeril, fatigue scores decreased by 14%.
This difference was statistically significant (P=.039). For those on placebo, daytime fatigue did not improve.

Patients taking Flexeril increased their average sleep time by about one half hour.

Those on placebo slept about the same as they did before. Flexeril may also have improved the quality of sleep by reducing the occurrence of disruptive brain wave patterns.

Many patients with chronic fibromyalgia suffer a degree of anxiety and/or depression.

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After 8 weeks, patients taking low dose Flexeril improved on their anxiety/depression score by 24.1%. (P=.012).

The placebo group’s anxiety/depression score decreased also, but by just 3.8%.

After 8 weeks, patients were asked to rate whether they had improved since starting treatment. Those taking low dose Flexeril tended to rate themselves as improved (P=.001). Those taking placebo did not.

The treating doctors (who did not know which person was taking Flexeril versus placebo) agreed that Flexeril patients had improved, while placebo patients had not.

Side effects in this relatively small study were mild and occurred about as often in both groups. The only adverse event that was rated as severe was a headache, occurred in a patient taking placebo.

Clinical thoughts:

As medicines go, Flexeril at 5 mgs (the lowest commercially available dose) is relatively safe and relatively inexpensive.

Therefore, if you have fibromyalgia, consider discussing an option like this with your clinician: Perhaps start with a 2.5 mg dose at night (one half of a 5 mg pill). If 2.5 mgs doesn’t make you too tired the next day, then consider increasing to 5 mg each night for an 8 week-long trial. If 5 mg makes you tired, go back to 2.5. Don’t prejudge whether Flexeril actually helps until the full trial is done.

(I contacted Dr. Moldofsky, who said that there were no interim measures of effectiveness done between baseline and 8 weeks. My guess is that the maximum benefit from low dose Flexeril would take more than a few days to be noted, but fewer than 8 weeks.)

Side effects: The most serious potential side effect for Flexeril (cyclobenzaprine) is prolongation of the QT interval on the electrocardiogram. This can be important since a long QT interval increases the risk for serious heart rhythm problems.

In fact, a fair number of medicines you might use also increase the QT interval. Among these: antibiotics (e.g. Zithromax, Biaxin, Cipro, Levaquin); heart medicines (Amiodorone, Flecainide); several cancer medicines; anti-nausea drugs (Odansetron/Zofran, procholorperazine/ Compazine); many antipsychotic medicines, and tricyclic antidepressants such as Elavil (amitryptiline), or Pamelor nortriptyline). Clinicians might consider which patients should have an EKG read out of their QT interval.

Also, several commonly used medicines tend to increase the blood level of Flexeril/cyclobenzaprine, thereby increasing Flexeril’s effect on prolonging the QT interval. This interaction is most likely for medicines that compete with Flexeril for the same liver detoxification pathways.

Your doctor probably has not memorized all these potential interactions. But your pharmacist’s computer should know. Ask your pharmacist specifically whether any of your medicines increase the QT interval and whether any of your medicines use the same liver pathways as Flexeril (Cytochromes P450 3A4 or P450 1A2, or to a lesser extent P450 2 D6).

Persons with liver disease, certain heart rhythm abnormalities or a known prolongation of their QT interval might best avoid Flexeril (and other drugs that prolong the QT interval).

Key Article:
Moldofsky, H, et al., Effects of Bedtime Very Low Dose Cyclobenzaprine on Symptoms and Sleep Physiology with Fibromyalgia Syndrome: A Double-blind Randomized Placebo-controlled Study, The Journal of Rheumatology, 38: 2653-2663, 2011.

Richard Podell, M.D., MPH, is a graduate of Harvard Medical School and the Harvard School of Public Health. He has been treating patients with ME-CFS and Fibromyalgia for more than 20 years. A clinical professor at New Jersey’s Robert Wood Johnson Medical School, Dr. Podell see patients at his Summit, NJ and Somerset, NJ offices.

His website is

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