Cyclobenzaprine Side Effects and Warnings

Last Updated: March 26, 2021

Authored by Sharon Levy, MD, MPH

Reviewed by Michael Espelin APRN

Cyclobenzaprine, frequently marketed as Flexeril or Amrix, is one of the most frequently prescribed pain medications according to the Drug Enforcement Administration(DEA). As such, problems related to Cyclobenzaprine side effects are commonly encountered and are of medical importance. Side effects, also known as Adverse Drug Reactions (ADR), are claimed to be the fourth leading cause of death. Adverse drug reactions, including those of Cyclobenzaprine, can be categorized as conditions related to reasonable drug-related symptoms, patient intolerance, individual idiosyncrasies in response to therapy, immunologically mediated allergy, overdose, effects related to unexpected drug-to-drug interactions, and rarely serious, life-threatening events.

This article focuses on the common Cyclobenzaprine side effects and frequent concerns related to its use.

A woman is holding a pill in her hand.

Common Cyclobenzaprine Side Effects

Prescription use of Cyclobenzaprine subjected to the supervision of a licensed doctor is most commonly linked with a non-emergent, tolerable adverse reaction. These reactions develop in ≥3% of the patients and consist of xerostomia, drowsiness, and dizziness all connected to the anticholinergic effects of cyclobenzaprine drug class. As mentioned, these Cyclobenzaprine side effects are tolerable and do not require urgent medical care, and their occurrence may even be preventable or may subside as a physiologic adaptation to cyclobenzaprine use occurs.

The next set of Flexeril side effects, although less common than the ones mentioned previously, are still observed in 1-3% of the patient population, and include:

  • Nervousness
  • Fatigue/tiredness
  • Confusion
  • Headache
  • Blurred vision
  • Asthenia
  • Unpleasant taste
  • Dyspepsia
  • Nausea
  • Constipation

The remaining group of Flexeril side effects are quite uncommon and occur in <1% of the patient population using Cyclobenzaprine.

  • Cardiovascular: Tachyarrhythmia, arrhythmia, conduction defects, and heart block, peripheral vasodilation and hypotension, palpitation, hypertension, myocardial infarction, stroke.
  • Nervous system:  ataxia, seizures and convulsions, dysarthria, double vision, disorientation, depressed mood, insomnia, muscle fasciculations and tremors, paresthesias, vertigo
  • Psychiatric:  anxiety, excitement, agitation, aggression, psychosis, hallucinations and delusions
  • Digestive: Emesis, anorexia, diarrhea, gastritis, polydipsia, flatulence, lingual edema, abnormal hepatic function, hepatitis, jaundice, cholestasis, paralytic ileus, lingual discoloration, stomatitis, parotitis.
  • Endocrine: Syndrome of Inappropriate Antidiuretic Hormone Secretion
  • Haematologic: Pancytopenia, Purpura, eosinophilia
  • Hypersensitivity: anaphylaxis, angioedema, pruritus, facial swelling, urticaria, rash
  • Musculoskeletal: localized hypotonia with weakness, myalgia
  • Respiratory: dyspnea, pharyngitis
  • Integumentary: hyperhidrosis, alopecia
  • Special Senses: ageusia, ringing in the ears
  • Genitourinary: Urinary retention and increased frequency, dysuria, testicular edema,  gynecomastia, impotence, galactorrhea.

Furthermore, it is worth mentioning that the aforementioned signs and symptoms of Cyclobenzaprine side effects are derived from clinical trials conducted by the Food and Drug Association(FDA) as well as from postmarketing experience reports, in which voluntary admissions of all manner of adverse reaction by patients who use this drug or a similar substance to the FDA are compiled. Hence, it is important to contact the primary care provider if one experiences any symptoms while on Сyclobenzaprine therapy.

How Long Do Flexeril Side Effects Last?

Any medication’s duration of action and hence the duration of its adverse reactions is dependent on the rate of its absorption, metabolism, and excretion. Therefore, the following consideration should be taken into account:

  • Cyclobenzaprine absorption is increased by 35% with food
  • It is metabolized by hepatic cytochrome oxidases and excreted via the kidneys, with a plasma clearance of 0.7L/min.

Therefore, in healthy patients with normal hepatic, renal, and heart function, who take therapeutic doses of Flexeril at 5mg every 8 hours, the duration of Сyclobenzaprine side effects is directly proportional to its plasma elimination half-life, which is 24-32 hours.

Other Factors Need to Be Possibly Considered When Flexeril Is Chronically Used or Is Possibly Abused:

  • Prolonged consumption can result in its accumulation in plasma, which may extend the duration of its adverse reactions.
  • The quantity taken is also directly proportional to the period of time it will take for one to experience adverse reactions. Thus taking higher doses than prescribed may cause the adverse reactions to last even longer.
  • Patients with slower metabolic rates, such as those with hypothyroidism, will metabolize Cyclobenzaprine at a lower rate. This will increase the duration of its action.
  • Older patients with poor health will experience adverse reactions for a prolonged period of time.
  • Obese patients or those with large BMIs distribute the drug into peripheral tissues, also prolonging the duration of its adverse reactions.

Cyclobenzaprine Warnings and Precautions

There are several cyclobenzaprine warnings and precautions with use. These syndromes can produce life-threatening complications. Therefore patients should be cautioned against the following cyclobenzaprine warnings.

Serotonin Syndrome

As Cyclobenzaprine belongs to the drug class of cyclic antidepressants, it has inherent serotonergic activity. Although not central to its pharmacodynamics in the management of acute muscle spasms, the serotonergic activity is of clinical importance. If Flexeril use is supplemented with alternative medications which have serotonergic activities such as Selective Serotonin Reuptake Inhibitors(SSRIs), Selective Serotonin Norepinephrine Reuptake Inhibitors(SSNRIs), Monoamine Oxidase Inhibitors(MAOIs), Tramadol, Vilazodone, Trazodone, Buspirone, Vortioxetine, Ondansetron, MDMA, Dextromethorphan, Meperidine,  Triptans, or Linezolid, Serotonin Syndrome can develop owing to serotonin overactivity.

This Syndrome Is a Life-Threatening Syndrome Associated With:

  • Altered consciousness: delirium, agitation, hallucinations
  • Autonomic instability: fever, sweating, tachycardia, variable blood pressure
  • Neuromuscular excitability: muscle rigidity, tremor, ataxia, clonus, and hyperreflexia
  • Gastrointestinal symptoms: diarrhea, nausea, emesis

Thus patients should be warned of these adverse drug reactions, educated on Serotonin Syndrome, and be instructed to seek immediate medical care if they notice respective signs and symptoms.

CNS Depression

As mentioned above, the biochemical relationship to cyclical antidepressants makes Cyclobenzaprine have central depressing effects. These effects can be markedly accentuated if Flexeril use is supplemented with related CNS depressing agents such as alcohol or barbiturates. Furthermore, cardiovascular adverse reactions of TCAs are shared by Cyclobenzaprine and can yield fatal arrhythmias, sinus tachycardia, heart attack, and even stroke.

Cyclobenzaprine Side Effects in Elderly

Elderly patients have higher plasma levels and an increase in plasma half-life of Cyclobenzaprine. This phenomenon can be linked to age-related physiologic changes to liver, kidney, and heart function in the elderly. Therefore, the use of Cyclobenzaprine is contraindicated in patients older than 65, due to the increased risk of Cyclobenzaprine side effects. However, if cyclobenzaprine use is absolutely required in the elderly, these cyclobenzaprine warnings must be clearly discussed with the patients before the prescription.

A woman is holding pills and has pain in stomach.

Cyclobenzaprine Pregnancy And Breastfeeding

The United States Food and Drug Association(FDA) categorizes Flexeril as pregnancy risk category B. Category B, refers to the fact that reproduction studies in animals have been unsuccessful in demonstrating a risk to the fetus and there are currently no sufficient and well-organized studies in pregnant women to provide information on whether the use of cyclobenzaprine while pregnant has any teratogenic effects.

Therefore, when considering the use of cyclobenzaprine while pregnant the necessity for maternal use should be weighed against the benefits of breastfeeding in infants. Furthermore, there is no data pertaining to Cyclobenzaprine and breastfeeding according to the FDA, in particular, whether or not Flexeril is excreted in human breast milk in small quantities, whether there are effects on infants or whether there are any effects on milk production. Therefore caution is recommended. However, if indeed Flexeril is excreted in human milk, then its close resemblance to TCAs would give it central sedative properties which would be a relative contraindication for Cyclobenzaprine and breastfeeding.

Signs of Allergic Reactions to Cyclobenzaprine

Allergic reactions are one of the most serious and possibly lethal consequences of Flexeril use. Allergic reactions develop as a result of genetic predisposition, which causes an exaggerated immune response towards the ingested medication.

Symptoms and Signs of Allergic Reaction Include:

  • Hives
  • Difficult breathing
  • Angioedema or Swelling of a patient’s face, lips, tongue, or throat
  • Skin rash
  • Severe dizziness
  • Tightness in chest
  • Changes in the skin color of the face

Patients should be educated about these symptoms and should be told to stop taking Flexeril and notify their primary care physician right away if they experience any of the aforementioned symptoms of an allergic reaction.

Flexeril Overdose

Flexeril overdose is a rare complication that, however, can be fatal to the patient’s health. Overdose can be a result of deliberate drug abuse, accident, or problems with metabolism and excretion of the drug.

The manifestations of Flexeril overdose develop rapidly and manifest initially as drowsiness with tachycardia. Overdose can manifest with any of the adverse side effects mentioned previously in this article.

In Addition, Some Potentially Lethal Manifestations Include:

  • cardiac arrest
  • angina
  • dysrhythmias
  • hypertension
  • seizures
  • neuroleptic malignant syndrome

The management of Flexeril overdose is complicated and ever-changing. However, the first step should always be to contact a poison control center for current information on treatment which may involve intubation, gastrointestinal decontamination, close cardiac monitoring, and monitoring for signs of the central nervous system or respiratory depression.

Preventing Flexeril Side Effects

Prevention of adverse drug reaction of any medication, including Flexeril, is best achieved with proper patient education and counseling. The following precautions should be discussed with patients before starting Flexeril in order to avoid associated adverse drug reactions:

  • Patients with urinary retention, angle-closure glaucoma, or increased intraocular pressure should not be prescribed this medication.
  • Patients with recent MI, arrhythmias, congestive heart failure, and hyperthyroidism should also not be prescribed this medication.
  • Older patients(>65) and ones with impaired hepatorenal function should not be prescribed this medication.
  • All medications taken should be discussed and the patient should be counseled on possible drug-to-drug interactions.
  • Flexeril should only be prescribed for a short course of 2-3 weeks.
  • Patients should be counseled to take Flexeril at the same time each day.
  • Patients should be counseled on proper storage and told that out-of-date medication cannot be used.
  • Patients should be educated about symptoms of allergic drug reactions and advised to stop taking medication and notify their physician immediately if they notice any of the following symptoms: difficulty breathing, hives, swelling of face or tongue, or itching.
  • Patients should be counseled not to combine Flexeril with MAO inhibitors or any other serotonergic drugs to avoid the risk of Serotonin Syndrome.
  • Patients should be counseled on recognizing symptoms and signs of serotonin syndrome and recommended that they seek urgent medical help upon experiencing any of the symptoms.
  • Patients should be counseled to stop taking their medication and contact their physician if they develop cardiovascular complications like arrhythmias or tachycardia.
  • Patients should be counseled and cautioned against using alcohol with Flexeril, as they have additive CNS depressive effects and can lead to respiratory depression.
  • Patients should be counseled to avoid driving until they are sure they are not experiencing any of the common side effects such as drowsiness or dizziness.

Frequently Asked Questions

Can Cyclobenzaprine Side Effects Cause Death?

The use of Cyclobenzaprine in those patients in whom its use is contraindicated due to Cyclobenzaprine warnings, hypersensitivity reactions to its use, or Flexeril overdose with concomitant alcohol use can all lead to death from Cyclobenzaprine side effects of respiratory and cardiovascular depression.

Does Flexeril Cause Weight Gain?

No definite information exists whether weight gain is one of the Cyclobenzaprine side effects. Anecdotal evidence, however, suggests that small weight gain can occur during acute use of Flexeril. This weight gain is thought to be attributed to a period of physical inactivity caused by muscle relaxant use. Information on whether long-term use of Flexeril has any impact on weight gain is unknown.

Does Cyclobenzaprine Make you Sleepy or Tired?

As previously mentioned, one of the most commonly encountered adverse drug reactions of therapeutic Cyclobenzaprine use seen in  ≥3% of the patients is drowsiness. Drowsiness manifests as feelings of tiredness, sluggishness, and lessened reaction time. Patients should be advised to exercise caution when driving or operating machinery. But for the safety of other road users, patients taking Flexeril are not encouraged to drive.

Does Flexeril Increase or Decrease Blood Pressure?

Flexeril does not lower blood pressure. Instead, as previously mentioned, it can cause hypertension or increased blood pressure in the event of taking an excessive amount of the drug or Flexeril overdose.

However, it should be noted that Flexeril can cause peripheral vasodilation leading to hypotension as an adverse reaction, but this is only transient. Furthermore, some which are used for the treatment of blood pressure, like guanethidine, can have their efficacies lowered when used concomitantly with Flexeril. Thus, if antihypertensive medications are used in conjunction with Flexeril, their efficacy will be reduced, and hypertension will ensue.

 

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Page Sources

  1. DailyMed - CYCLOBENZAPRINE- cyclobenzaprine hydrochloride tablet, film coated. (2019, December). Dailymed.Nlm.Nih.Gov. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=b12fb4ea-182e-462b-b6ed-cfd2f6bb71e8
  2. Mestres, J., Seifert, S. A., & Oprea, T. I. (2011, October 5). Linking Pharmacology to Clinical Reports: Cyclobenzaprine and Its Possible Association With Serotonin Syndrome. Ncbi.Nlm.Nih.Gov/. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3809033/
  3. Prescriber’s Digital Reference. (n.d.). PDR.Net Error. PDR.Net. Retrieved March 2021, fromhttps://www.pdr.net/drug-summary/Cyclobenzaprine-Hydrochloride-cyclobenzaprine-hydrochloride-3089.1153
  4. Shprecher, D., Sloan, C. T., & Sederholm, B. (2013, May). Neuropsychiatric side effects of cyclobenzaprine. Ncbi.Nlm.Nih.Gov. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669814/
  5. U.S. Food and Drug Administration. (2019, April). AMRIX® (cyclobenzaprine hydrochloride extended-release capsules), for oral use. Accessdata.Fda.Gov. https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/021777s017lbl.pdf

Published on: November 30th, 2018

Updated on: March 26th, 2021

About Author

Sharon Levy, MD, MPH

After successful graduation from Boston University, MA, Sharon gained a Master’s degree in Public Health. Since then, Sharon devoted herself entirely to the medical niche. Sharon Levy is also a certified addiction recovery coach.

Medically Reviewed by

Michael Espelin APRN

8 years of nursing experience in wide variety of behavioral and addition settings that include adult inpatient and outpatient mental health services with substance use disorders, and geriatric long-term care and hospice care.  He has a particular interest in psychopharmacology, nutritional psychiatry, and alternative treatment options involving particular vitamins, dietary supplements, and administering auricular acupuncture.