From the Guidelines
Cyclobenzaprine use is associated with several side effects, including anticholinergic effects such as hallucinations, confusion, drowsiness, constipation, urinary retention, and dry mouth, as well as potential interactions with sedatives and anesthetic agents 1. When considering the side effects of cyclobenzaprine, it is essential to note that these can be attributed to its mechanism of action as a centrally acting 5-HT2 receptor antagonist and its structural relation to amitriptyline. The most common side effects include:
- Drowsiness
- Confusion
- Constipation
- Urinary retention
- Dry mouth These side effects are a result of cyclobenzaprine's anticholinergic activity, which can also lead to norepinephrine potentiation 1. Additionally, long-term use of cyclobenzaprine can lead to withdrawal symptoms such as malaise, nausea, and headache upon discontinuation, although these symptoms are not life-threatening and can be mitigated by tapering the medication over 2 to 3 weeks 1. It is also crucial to be aware of potential drug interactions, such as the increased risk of serotonin syndrome when cyclobenzaprine is used concomitantly with monoamine oxidase inhibitors 1. Given the potential for these side effects, it is recommended to closely monitor patients taking cyclobenzaprine, especially in the perioperative period, and to exercise caution when combining it with other medications that may exacerbate its effects 1.
From the FDA Drug Label
Adverse Reactions Section Incidence of most common adverse reactions in the 2 double-blind‡, placebo-controlled 5 mg studies (incidence of > 3% on cyclobenzaprine hydrochloride tablets 5 mg): Cyclobenzaprine Hydrochloride Tablets 5 mg N=464 Cyclobenzaprine Hydrochloride Tablets 10 mg N=249 Placebo N=469 Drowsiness 29% 38% 10% Dry Mouth 21% 32% 7% Fatigue 6% 6% 3% Headache 5% 5% 8% Adverse reactions which were reported in 1% to 3% of the patients were: abdominal pain, acid regurgitation, constipation, diarrhea, dizziness, nausea, irritability, mental acuity decreased, nervousness, upper respiratory infection, and pharyngitis The following list of adverse reactions is based on the experience in 473 patients treated with cyclobenzaprine hydrochloride tablets 10 mg in additional controlled clinical studies, 7607 patients in the post-marketing surveillance program, and reports received since the drug was marketed The overall incidence of adverse reactions among patients in the surveillance program was less than the incidence in the controlled clinical studies. The adverse reactions reported most frequently with cyclobenzaprine hydrochloride were drowsiness, dry mouth and dizziness The incidence of these common adverse reactions was lower in the surveillance program than in the controlled clinical studies: ‡Note: Cyclobenzaprine hydrochloride tablets 10 mg data are from one clinical trial. Cyclobenzaprine hydrochloride tablets 5 mg and placebo data are from two studies Clinical Studies with Cyclobenzaprine Hydrochloride Tablets 10 mg Surveillance Program with Cyclobenzaprine Hydrochloride Tablets 10 mg Drowsiness 39% 16% Dry Mouth 27% 7% Dizziness 11% 3% Among the less frequent adverse reactions, there was no appreciable difference in incidence in controlled clinical studies or in the surveillance program Adverse reactions which were reported in 1% to 3% of the patients were: fatigue/tiredness, asthenia, nausea, constipation, dyspepsia, unpleasant taste, blurred vision, headache, nervousness, and confusion The following adverse reactions have been reported in post-marking experience or with an incidence of less than 1% of patients in clinical trials with the 10 mg tablet: Body as a Whole: Syncope; malaise. Cardiovascular: Tachycardia; arrhythmia; vasodilatation; palpitation; hypotension Digestive: Vomiting; anorexia; diarrhea; gastrointestinal pain; gastritis; thirst; flatulence; edema of the tongue; abnormal liver function and rare reports of hepatitis, jaundice and cholestasis. Hypersensitivity: Anaphylaxis; angioedema; pruritus; facial edema; urticaria; rash. Musculoskeletal: Local weakness Nervous System and Psychiatric: Seizures, ataxia; vertigo; dysarthria; tremors; hypertonia; convulsions; muscle twitching; disorientation; insomnia; depressed mood; abnormal sensations; anxiety; agitation; psychosis, abnormal thinking and dreaming; hallucinations; excitement; paresthesia; diplopia, serotonin syndrome. Skin: Sweating. Special Senses: Ageusia; tinnitus Urogenital: Urinary frequency and/or retention. Causal Relationship Unknown Other reactions, reported rarely for cyclobenzaprine hydrochloride under circumstances where a causal relationship could not be established or reported for other tricyclic drugs, are listed to serve as alerting information to physicians: Body as a Whole: Chest pain; edema Cardiovascular: Hypertension; myocardial infarction; heart block; stroke. Digestive: Paralytic ileus; tongue discoloration; stomatitis; parotid swelling. Endocrine: Inappropriate ADH syndrome. Hematic and Lymphatic: Purpura; bone marrow depression; leukopenia; eosinophilia; thrombocytopenia. Metabolic, Nutritional and Immune: Elevation and lowering of blood sugar levels; weight gain or loss Musculoskeletal: Myalgia. Nervous System and Psychiatric: Decreased or increased libido; abnormal gait; delusions; aggressive behavior; paranoia; peripheral neuropathy; Bell's palsy; alteration in EEG patterns; extrapyramidal symptoms. Respiratory: Dyspnea. Skin: Photosensitization; alopecia Urogenital: Impaired urination; dilatation of urinary tract; impotence; testicular swelling; gynecomastia; breast enlargement; galactorrhea.
The common side effects of cyclobenzaprine include:
- Drowsiness
- Dry mouth
- Fatigue
- Headache
- Dizziness The less common side effects of cyclobenzaprine include:
- Abdominal pain
- Acid regurgitation
- Constipation
- Diarrhea
- Nausea
- Irritability
- Mental acuity decreased
- Nervousness
- Upper respiratory infection
- Pharyngitis
- Seizures
- Ataxia
- Vertigo
- Dysarthria
- Tremors
- Hypertonia
- Convulsions
- Muscle twitching
- Disorientation
- Insomnia
- Depressed mood
- Abnormal sensations
- Anxiety
- Agitation
- Psychosis
- Abnormal thinking and dreaming
- Hallucinations
- Excitement
- Paresthesia
- Diplopia
- Serotonin syndrome 2
From the Research
Common Side Effects of Cyclobenzaprine
- Sedation: The most common adverse event associated with the use of cyclobenzaprine at the usual dosage of 10 mg TID 3
- Dry mouth: Due to cyclobenzaprine's anticholinergic action, dry mouth is a common side effect 3, 4
- Drowsiness: Mild degrees of drowsiness were encountered more often than with diazepam or placebo 4
- Somnolence: The most common adverse effect, which is mild and dose-related 3
Serious Side Effects of Cyclobenzaprine
- Serotonin syndrome: A potentially lethal adverse drug reaction that may occur in patients taking proserotoninergic medications, including cyclobenzaprine 5, 6
- Delirium and hyperkinetic movement disorders: Unusual side effects that may occur when cyclobenzaprine is initiated, especially when combined with other medications such as oxycodone 6