Cyclobenzaprine

Cyclobenzaprine, the generic form of the brand-name drugs Flexeril and Amrix, is a muscle relaxer that relieves pain and discomfort caused by strains, sprains, and other muscle injuries.

It's also available under the brand names Fexmid and FusePaq Tabradol.

This medication is often part of an overall recovery plan that includes rest and physical therapy. Cyclobenzaprine is also prescribed off-label to treat fibromyalgia.

Cyclobenzaprine works on the central nervous system, blocking nerve impulses (or pain sensations) that are sent from sore muscles to your brain. Cyclobenzaprine is chemically related to a class of antidepressants called tricyclic antidepressants.

Cyclobenzaprine was first approved by the Food and Drug Administration (FDA) in 1977 under the brand name Flexeril, which is currently manufactured by PD-RX Pharmaceuticals.

Cyclobenzaprine Warnings

Don't take cyclobenzaprine if you've taken a monoamine oxidase inhibitor (MAOI) in the last two weeks. MAOIs, used to treat depression and Parkinson's disease, include:

• Isocarboxazid (Marplan)
• Linezolid (Zyvox)
• Phenelzine (Nardil)
• Rasagiline (Azilect)
• Selegiline (Emsam)
• Tranylcypromine (Parnate)

The combination of an MAOI with cyclobenzaprine can produce very serious, potentially life-threatening side effects.

Do not take this drug if you have a history of heart problems, including a previous heart attack, heart rhythm problems, blockages, or congestive heart failure.

People who are 65 years and older should not take this drug because the side effects can be more extreme. There are other medications that can be used to treat your condition that are safer and more effective if you are in this age group.

Patients with hepatic impairment (liver failure) are generally more susceptible to drugs with potentially sedating effects like cyclobenzaprine.

Tell your doctor if you are on any medication for depression, seizures, allergies, coughs, or colds, or if you take sedatives, sleeping pills, tranquilizers, or vitamins.

Before prescribing this medication, your healthcare provider should also know if you've ever been diagnosed with overactive thyroid, glaucoma, or if you've ever had difficulty urinating.

You should always tell your healthcare professional about all prescription, non-prescription, over-the-counter, illegal and recreational drugs, herbal remedies, nutritional and dietary supplements, and any other drugs and treatments.

Cyclobenzaprine “High” and Abuse

Numerous online and anecdotal reports suggest that some people abuse cyclobenzaprine for a narcotic-like "high" because it can cause drowsiness.

Cyclobenzaprine can induce moderate to severe anticholinergic effects — meaning, it may disrupt the activity of certain neurotransmitters in your brain — at higher doses. This can lead to physical and mental impairment.

At even higher doses, cyclobenzaprine may cause severe ataxia, a neurologic condition in which you lose control of your muscle movements.

According to the Los Angeles coroner's office, singer Whitney Houston had five drugs in her system when she drowned in her hotel bathtub in 2012, including cyclobenzaprine.

Take cyclobenzaprine only as directed by your doctor, and keep this and all other drugs away from children, teenagers, and anyone for whom the drug was not prescribed.

Pregnancy and Cyclobenzaprine

Discuss a current or planned pregnancy with your doctor before taking cyclobenzaprine.

This drug should only be taken during pregnancy if the benefits outweigh the risks. Your doctor can help you decide if it's right for you.

Also tell your physician if you're breastfeeding or plan to in the future. It's not known if cyclobenzaprine passes into breast milk, but studies show it has happened with similar drugs.

Mechanism of Action

Relieves local skeletal muscle spasm; clinical response similar to diazepam

Structurally related to cyclic antidepressants, and pharmacologic effects are similar, including reserpine antagonism, norepinephrine potentiation, potent peripheral and central anticholinergic effects, and sedation; reduces tonic somatic motor activity influencing alpha and gamma motor neurons

Absorption

Onset: 1 hr

Duration: 12-24 hr

Bioavailability: 33-55%

Peak plasma time: 7-8 hr

Peak plasma concentration: 15-25 ng/mL

Distribution

Protein bound: 93%

Metabolism

Hepatic via CYP3A4, 1A2, and 2D6; may undergo enterohepatic recirculation

Elimination

Half-life: 8-37 hours (immediate release); 32-33 hr (extended release)

Excretion: Urine, feces

Cyclobenzaprine is part of the drug class:

• Other centrally acting agents

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• monoamine oxidase (MAO) inhibitors such as selegiline (Emsam) and phenelzine (Nardil)
• alcohol
• barbiturates such as phenobarbital (Donnatal) or other central nervous system depressants
• guanethidine (Ismelin)
• tramadol (Ultram)
• selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine (Prozac) and sertraline (Zoloft)
• serotonin norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine (Effexor) and duloxetine (Cymbalta)
• tricyclic antidepressants (TCAs) such as amitriptyline (Elavil) or clomipramine (Anafranil)
• anticholinergic medications such as ipratropium (Atrovent) or tiotropium (Spiriva)
• bupropion (Zyban, Wellbutrin)
• meperidine (Demerol)

This is not a complete list of cyclobenzaprine drug interactions. Ask your doctor or pharmacist for more information.

If you take too much cyclobenzaprine, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

Administration

Administer orally.101

Dosage

Available as cyclobenzaprine hydrochloride; dosage expressed in terms of the salt.101

Pediatric Patients

Adolescents ≥15 years of age: 5 mg 3 times daily; may increase dosage to 10 mg 3 times daily depending on response.101

Adults

5 mg 3 times daily; may increase dosage to 10 mg 3 times daily depending on response.101

Prescribing Limits

Pediatric Patients

Do not administer for more than 2–3 weeks.101

Adults

Do not administer for more than 2–3 weeks.101

Special Populations

Hepatic Impairment

Initiate with caution in patients with mild hepatic impairment.101 Consider less frequent dosing; start with 5-mg dose and increase slowly.101

Use not recommended in patients with moderate or severe hepatic impairment.101

Geriatric Patients

Consider less frequent dosing; start with 5-mg dose and increase slowly.101

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For cyclobenzaprine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to cyclobenzaprine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of cyclobenzaprine extended-release capsules in the pediatric population. Safety and efficacy have not been established.

Geriatric

Because of the possibility of higher blood levels in the elderly as compared to younger adults, use of cyclobenzaprine extended-release capsules is not recommended in the elderly.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking cyclobenzaprine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using cyclobenzaprine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Amifampridine
• Amisulpride
• Bepridil
• Cisapride
• Dronedarone
• Furazolidone
• Iproniazid
• Isocarboxazid
• Levomethadyl
• Linezolid
• Mesoridazine
• Methylene Blue
• Moclobemide
• Pargyline
• Phenelzine
• Pimozide
• Piperaquine
• Procarbazine
• Rasagiline
• Safinamide
• Saquinavir
• Selegiline
• Sparfloxacin
• Terfenadine
• Thioridazine
• Tranylcypromine
• Ziprasidone

Using cyclobenzaprine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Alfentanil
• Almotriptan
• Amineptine
• Amiodarone
• Amitriptyline
• Amitriptylinoxide
• Amoxapine
• Amphetamine
• Anagrelide
• Aripiprazole
• Aripiprazole Lauroxil
• Arsenic Trioxide
• Artemether
• Asenapine
• Balofloxacin
• Bedaquiline
• Benzphetamine
• Besifloxacin
• Bromazepam
• Buprenorphine
• Buserelin
• Butriptyline
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clomipramine
• Clozapine
• Codeine
• Crizotinib
• Dabrafenib
• Degarelix
• Delamanid
• Desipramine
• Deslorelin
• Desvenlafaxine
• Deutetrabenazine
• Dextroamphetamine
• Dibenzepin
• Dihydrocodeine
• Disopyramide
• Dofetilide
• Dolasetron
• Domperidone
• Donepezil
• Dothiepin
• Doxepin
• Doxylamine
• Droperidol
• Duloxetine
• Efavirenz
• Enoxacin
• Erythromycin
• Escitalopram
• Fentanyl
• Flecainide
• Flibanserin
• Fluconazole
• Flumequine
• Fluoxetine
• Fluvoxamine
• Foscarnet
• Gatifloxacin
• Gemifloxacin
• Gonadorelin
• Goserelin
• Granisetron
• Halofantrine
• Histrelin
• Hydrocodone
• Hydromorphone
• Hydroxychloroquine
• Hydroxytryptophan
• Hydroxyzine
• Ibutilide
• Iloperidone
• Imipramine
• Iprindole
• Ivabradine
• Ketoconazole
• Lapatinib
• Leuprolide
• Levofloxacin
• Levomilnacipran
• Levorphanol
• Lisdexamfetamine
• Lofepramine
• Lomefloxacin
• Lorcaserin
• Lumefantrine
• Melitracen
• Meperidine
• Methadone
• Methamphetamine
• Metronidazole
• Milnacipran
• Mirtazapine
• Morphine
• Morphine Sulfate Liposome
• Moxifloxacin
• Nadifloxacin
• Nafarelin
• Nefazodone
• Nilotinib
• Norfloxacin
• Nortriptyline
• Ofloxacin
• Ondansetron
• Opipramol
• Oxycodone
• Oxymorphone
• Paliperidone
• Palonosetron
• Panobinostat
• Paroxetine
• Pasireotide
• Pazopanib
• Pazufloxacin
• Pefloxacin
• Periciazine
• Pimavanserin
• Pitolisant
• Pixantrone
• Posaconazole
• Propizepine
• Protriptyline
• Prulifloxacin
• Quetiapine
• Quinidine
• Ranolazine
• Remifentanil
• Ribociclib
• Rufloxacin
• Sertraline
• Sevoflurane
• Sibutramine
• Sodium Oxybate
• Sodium Phosphate
• Sotalol
• Sufentanil
• Sulpiride
• Sunitinib
• Tacrolimus
• Tapentadol
• Telithromycin
• Tetrabenazine
• Tianeptine
• Tiotropium
• Tizanidine
• Tramadol
• Trazodone
• Trimipramine
• Triptorelin
• Vandetanib
• Vemurafenib
• Venlafaxine
• Verapamil
• Vilazodone
• Vinflunine
• Voriconazole
• Vortioxetine
• Zolpidem
• Zuclopenthixol

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using cyclobenzaprine with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use cyclobenzaprine, or give you special instructions about the use of food, alcohol, or tobacco.

• Tobacco

Other Medical Problems

The presence of other medical problems may affect the use of cyclobenzaprine. Make sure you tell your doctor if you have any other medical problems, especially:

• Congestive heart failure or
• Heart attack, recent or
• Heart block or
• Heart rhythm problems (eg, arrhythmia) or
• Hyperthyroidism (overactive thyroid)—Should not be used in patients with these conditions.

• Glaucoma, angle closure, history of or
• Trouble urinating, history of—Use with caution. May these conditions worse.

• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body. .

Serotonin Syndrome

The development of a potentially life-threatening serotonin syndrome has been reported with Cyclobenzaprine Hydrochloride when used in combination with other drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), tramadol, bupropion, meperidine, verapamil, or MAO inhibitors. The concomitant use of Cyclobenzaprine Hydrochloride with MAO inhibitors is contraindicated (see CONTRAINDICATIONS). Serotonin syndrome symptoms may include mental status changes (e.g., confusion, agitation, hallucinations), autonomic instability (e.g., diaphoresis, tachycardia, labile blood pressure, hyperthermia), neuromuscular abnormalities (e.g., tremor, ataxia, hyperreflexia, clonus, muscle rigidity), and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Treatment with Cyclobenzaprine Hydrochloride and any concomitant serotonergic agents should be discontinued immediately if the above reactions occur and supportive symptomatic treatment should be initiated. If concomitant treatment with Cyclobenzaprine Hydrochloride and other serotonergic drugs is clinically warranted, careful observation is advised, particularly during treatment initiation or dose increases (see PRECAUTIONS, Drug Interactions).

Cyclobenzaprine is closely related to the tricyclic antidepressants, e.g., amitriptyline and imipramine. In short term studies for indications other than muscle spasm associated with acute musculoskeletal conditions, and usually at doses somewhat greater than those recommended for skeletal muscle spasm, some of the more serious central nervous system reactions noted with the tricyclic antidepressants have occurred (see WARNINGS, below, and ADVERSE REACTIONS).

Tricyclic antidepressants have been reported to produce arrhythmias, sinus tachycardia, prolongation of the conduction time leading to myocardial infarction and stroke.

Cyclobenzaprine HCl may enhance the effects of alcohol, barbiturates, and other CNS depressants.

Incidence of most common adverse reactions in the 2 double-blind‡, placebo-controlled 5 mg studies (incidence of > 3% on Cyclobenzaprine HCl 5 mg):

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 HCl 10 mg in additional controlled clinical studies, 7607 patients in the postmarketing 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 HCl 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:

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 postmarketing 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 HCl 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.

To report SUSPECTED ADVERSE REACTIONS, contact Actavis at 1-800-272-5525 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Pharmacologic similarities among the tricyclic drugs require that certain withdrawal symptoms be considered when Cyclobenzaprine HCl is administered, even though they have not been reported to occur with this drug. Abrupt cessation of treatment after prolonged administration rarely may produce nausea, headache, and malaise. These are not indicative of addiction.

Acute jaw pain due to temporomandibular disorder

Data from two randomized, double-blind, placebo-controlled trials in patients experiencing jaw pain upon wakening supports the use of cyclobenzaprine at bedtime for the treatment of this condition [Alencar 2014], [Herman 2002]. Of note, one study demonstrated significant improvement in pain scores with treatment; however, no significant differences were seen when compared to placebo [Alencar 2014]. Additional trials may be necessary to further define the role of cyclobenzaprine in the treatment of acute jaw pain due to temporomandibular disorder.

Hypersensitivity to cyclobenzaprine or any component of the formulation; during or within 14 days of MAO inhibitors; hyperthyroidism; heart failure; arrhythmias; heart block or conduction disturbances; acute recovery phase of MI

Capsule, extended release: Use not recommended.

Tablet, immediate release: Initial: 5 mg; titrate dose slowly and consider less frequent dosing.

You should not use cyclobenzaprine if you have a thyroid disorder, heart block, congestive heart failure, a heart rhythm disorder, or you have recently had a heart attack.

Do not use cyclobenzaprine if you have taken an MAO inhibitor in the past 14 days. A dangerous drug interaction could occur. MAO inhibitors include isocarboxazid, linezolid, phenelzine, rasagiline, selegiline, and tranylcypromine.

Cyclobenzaprine is usually taken once daily for only 2 or 3 weeks. Follow all directions on your prescription label. Do not take this medicine in larger or smaller amounts or for longer than recommended.

Take the medicine at the same time each day.

Do not crush, chew, break, or open an extended-release capsule. Swallow it whole.

You may have unpleasant withdrawal symptoms when you stop taking cyclobenzaprine after long-term use. Ask your doctor how to avoid withdrawal symptoms when you stop using this medicine.

Cyclobenzaprine is only part of a complete program of treatment that may also include rest, physical therapy, or other pain relief measures. Follow your doctor's instructions.

Store at room temperature away from moisture, heat, and light.

Taking cyclobenzaprine with other drugs that make you sleepy or slow your breathing can cause dangerous or life-threatening side effects. Ask your doctor before taking cyclobenzaprine with a sleeping pill, narcotic pain medicine, prescription cough medicine, a muscle relaxer, or medicine for anxiety, depression, or seizures.

This list is not complete. Other drugs may interact with cyclobenzaprine, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.

Applies to cyclobenzaprine: oral capsule extended release, oral suspension, oral tablet

Along with its needed effects, cyclobenzaprine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking cyclobenzaprine:

• Clumsiness or unsteadiness
• confusion
• fainting
• mental depression
• problems in urinating
• ringing or buzzing in the ears
• skin rash, hives, or itching occurring without other symptoms of an allergic reaction listed above
• unusual thoughts or dreams
• yellow eyes or skin

Get emergency help immediately if any of the following symptoms of overdose occur while taking cyclobenzaprine:

• Convulsions (seizures)
• drowsiness (severe)
• dry, hot, flushed skin
• fast or irregular heartbeat
• hallucinations (seeing, hearing, or feeling things that are not there)
• increase or decrease in body temperature
• troubled breathing
• unexplained muscle stiffness
• unusual nervousness or restlessness (severe)
• vomiting (occurring together with other symptoms of overdose)

Some side effects of cyclobenzaprine may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Blurred vision
• dizziness, drowsiness, or lightheadedness
• dryness of the mouth

• Bloated feeling or gas, indigestion, nausea or vomiting, or stomach cramps or pain
• constipation
• diarrhea
• excitement or nervousness
• frequent urination
• general feeling of discomfort or illness
• headache
• muscle twitching
• numbness, tingling, pain, or weakness in hands or feet
• pounding heartbeat
• problems in speaking
• trembling
• trouble sleeping
• unpleasant taste or other taste changes
• unusual muscle weakness
• unusual tiredness

• Relieves muscle spasm associated with acute, painful, musculoskeletal conditions.
• Improves pain, tenderness, and range of motion associated with muscle spasms and increases a person's ability to perform their day-to-day activities.
• Cyclobenzaprine is the most studied skeletal muscle relaxant.
• Relieves skeletal muscle spasm without interfering with muscle function.
• The sedative effects of cyclobenzaprine may help those experiencing insomnia as a result of muscle spasms.
• Long-lasting effects.
• Cyclobenzaprine has not been associated with addiction; however, abrupt discontinuation may produce symptoms such as nausea, headache, and a general feeling of discomfort. The dosage of cyclobenzaprine is best tapered off slowly on discontinuation.
• Generic cyclobenzaprine is available.

Taking cyclobenzaprine with other drugs that make you sleepy or slow your breathing can cause dangerous or life-threatening side effects. Ask your doctor before taking a sleeping pill, narcotic pain medicine, prescription cough medicine, a muscle relaxer, or medicine for anxiety, depression, or seizures.

This list is not complete. Other drugs may interact with cyclobenzaprine, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.