Flexeril

Name: Flexeril

What side effects can this medication cause?

Cyclobenzaprine may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

  • dry mouth
  • dizziness
  • nausea
  • constipation
  • heartburn
  • extreme tiredness

If you experience any of the following symptoms, call your doctor immediately:

  • skin rash
  • hives
  • swelling of the face or tongue
  • difficulty breathing or swallowing
  • irregular or fast heart rate
  • chest pain

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

What brand names are available for cyclobenzaprine?

  • Amrix, Fexmid are the brand names available for cyclobenzaprine in the US.
  • Flexeril brand name has been discontinued and is no longer available in the US.

Which drugs or supplements interact with cyclobenzaprine (Amrix, Fexmid)?

  • Cyclobenzaprine is chemically related to the tricyclic class of antidepressants, for example, amitriptyline (Elavil, Endep), nortriptyline  Pamelor). As such, it should not be taken with or within two weeks of any monoamine oxidase (MAO) inhibitor, for example, isocarboxazid (Marplan), phenelzine (Nardil), tranylcypromine (Parnate), and procarbazine (Matulane). High fever, convulsions, and even death can occur when these drugs are used together.
  • Cyclobenzaprine interacts with other medications and drugs that slow the brain's processes, such as
    • alcohol,
    • barbiturates,
    • benzodiazepines, for example, diazepam (Valium), lorazepam (Ativan), and
    • narcotics.

Cyclobenzaprine Side Effects

Common side effects of cyclobenzaprine include:

  • Drowsiness
  • Dizziness
  • Dry mouth
  • Constipation
  • Fatigue

Let your physician know if any of these side effects persist or get worse.

Serious side effects of cycolobenzaprine include:

  • Fast or irregular heartbeat
  • Mood or mental changes (like confusion or hallucinations)
  • Trouble urinating
  • Chest pain
  • Fever
  • Seizures

A very serious allergic reaction is rare but seek immediate medical attention if you develop any of the following:

  • Rash
  • Itching
  • Swelling (especially in the face, tongue, or throat)
  • Severe dizziness
  • Trouble breathing

Combining this drug with some antidepressant medications could lead to serotonin syndrome and can be fatal. Symptoms of serotonin syndrome include:

  • Confusion
  • Agitation or restlessness
  • Dilated pupils
  • Headache
  • Changes in blood pressure
  • Changes in body temperature
  • Nausea or vomiting
  • Severe diarrhea
  • Rapid heart rate
  • Loss of muscle coordination or twitching
  • Shivering or goosebumps
  • Heavy sweating

Cyclobenzaprine Dosage

Cyclobenzaprine is taken by mouth. It comes as a tablet and an extended-release capsule.

Your doctor is likely to start you on 5 milligrams of the regular release tablet, three times a day.

The extended-release tablet is dosed once a day. This dose could be increased if you aren't getting relief from pain.

This drug is not meant to be taken long-term. Studies show it decreases pain for the first two weeks, peaking in the first few days but has no proven benefit after that.

Don't take this drug for more than three weeks without talking to your physician.

Patients with liver problems or who are over 65 years old may start at lower doses.

Always take cyclobenzaprine with a full glass of water and always swallow the medication whole.

Cyclobenzaprine Overdose

Symptoms of cyclobenzaprine overdose include:

  • Chest pain
  • Convulsions
  • Hallucinations
  • Vomiting
  • Rapid heartbeat
  • Drowsiness
  • Slurred speech

If you suspect an overdose, seek emergency medical attention or call a poison-control help line at 1-800-222-1222.

Missed Dose of Cyclobenzaprine

Take the missed dose of cyclobenzaprine as soon as you remember.

Skip the missed dose if it is almost time for your next scheduled dose.

Don't "double up" on this medication to make up for a missed dose.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. 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. .

Flexeril Interactions

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 oxide (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 Flexeril drug interactions. Ask your doctor or pharmacist for more information.

Flexeril Precautions

Serious side effects have been reported with Flexeril including:

  • General: Flexeril should be used with caution in certain patients. Tell your doctor if you:
    • have a history of urinary retention
    • have a history of glaucoma or of high intraocular pressure (high pressure of the fluid in the eyes)
    • take anticholinergic medication such as atropine (Atroposil) and ipratropium (Atrovent)
  • Impaired liver function: Flexeril can increase liver tests and impair the liver’s function. Tell your doctor if you have a history of liver disease.
  • Serotonin syndrome: Tell your healthcare provider right away if you have some or all of the following symptoms of serotonin syndrome:
    • confusion
    • agitation
    • hallucinations
    • high body temperature
    • fast heartbeat
    • tremors
    • nausea
    • vomiting
    • diarrhea
  • Hypersensitivity (allergic) reaction: Tell your healthcare provider right away if you have some or all of the following symptoms of an allergic reaction:
    • swelling
    • itchy skin
    • hives
    • rash
    • difficulty breathing or swallowing
    • hoarseness

Flexeril can cause dizziness and drowsiness. Do not drive or operate machinery until you know how Flexeril affects you. Do not drink alcohol while taking Flexeril. Alcohol may intensify this side effect.

Do not take Flexeril if you:

  • are allergic to Flexeril or any of its ingredients 
  • have used monoamine oxidase (MAO) inhibitors such as selegiline (Emsam) and phenelzine (Nardil) in the last 14 days
  • have a history of heart problems such as a heart attack, arrhythmia (abnormal heart beat or rhythm), heart block, conduction disturbances, or heart failure
  • have hyperthyroidism, or an overactive thyroid

What is cyclobenzaprine (amrix, comfort pac with cyclobenzaprine, fexmid, flexeril)?

Cyclobenzaprine is a muscle relaxant. It works by blocking nerve impulses (or pain sensations) that are sent to your brain.

Cyclobenzaprine is used together with rest and physical therapy to treat skeletal muscle conditions such as pain or injury.

Cyclobenzaprine may also be used for other purposes not listed in this medication guide.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Cyclobenzaprine Hydrochloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Tablets, film-coated

5 mg

Flexeril

McNeil

10 mg*

Flexeril

McNeil

Precautions

General

Because of its atropine-like action, Flexeril should be used with caution in patients with a history of urinary retention, angle-closure glaucoma, increased intraocular pressure, and in patients taking anticholinergic medication.

Impaired Hepatic Function

The plasma concentration of cyclobenzaprine is increased in patients with hepatic impairment (see CLINICAL PHARMACOLOGY, Pharmacokinetics,Hepatic Impairment). These patients are generally more susceptible to drugs with potentially sedating effects, including cyclobenzaprine. Flexeril should be used with caution in subjects with mild hepatic impairment starting with a 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.

Information for Patients

Flexeril, especially when used with alcohol or other CNS depressants, may impair mental and/or physical abilities required for performance of hazardous tasks, such as operating machinery or driving a motor vehicle. In the elderly, the frequency and severity of adverse events associated with the use of cyclobenzaprine, with or without concomitant medications, is increased. In elderly patients, Flexeril should be initiated with a 5 mg dose and titrated slowly upward.

Drug Interactions

Flexeril may have life-threatening interactions with MAO inhibitors. (See CONTRAINDICATIONS.)

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

Tricyclic antidepressants may block the antihypertensive action of guanethidine and similarly acting compounds.

Tricyclic antidepressants may enhance the seizure risk in patients taking tramadol.2

2 ULTRAM® (tramadol HCl tablets, Ortho-McNeil Pharmaceutical)
ULTRACET® (tramadol HCl and acetaminophen tablets, Ortho-McNeil Pharmaceutical)

Carcinogenesis, Mutagenesis, Impairment of Fertility

In rats treated with Flexeril for up to 67 weeks at doses of approximately 5 to 40 times the maximum recommended human dose, pale, sometimes enlarged, livers were noted and there was a dose-related hepatocyte vacuolation with lipidosis. In the higher dose groups this microscopic change was seen after 26 weeks and even earlier in rats which died prior to 26 weeks; at lower doses, the change was not seen until after 26 weeks.

Cyclobenzaprine did not affect the onset, incidence or distribution of neoplasia in an 81-week study in the mouse or in a 105-week study in the rat.

At oral doses of up to 10 times the human dose, cyclobenzaprine did not adversely affect the reproductive performance or fertility of male or female rats. Cyclobenzaprine did not demonstrate mutagenic activity in the male mouse at dose levels of up to 20 times the human dose.

Pregnancy

Pregnancy Category B: Reproduction studies have been performed in rats, mice and rabbits at doses up to 20 times the human dose, and have revealed no evidence of impaired fertility or harm to the fetus due to Flexeril. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

It is not known whether this drug is excreted in human milk. Because cyclobenzaprine is closely related to the tricyclic antidepressants, some of which are known to be excreted in human milk, caution should be exercised when Flexeril is administered to a nursing woman.

Pediatric Use

Safety and effectiveness of Flexeril in pediatric patients below 15 years of age have not been established.

Use in the Elderly

The plasma concentration of cyclobenzaprine is increased in the elderly (see CLINICAL PHARMACOLOGY, Pharmacokinetics,Elderly). The elderly may also be more at risk for CNS adverse events such as hallucinations and confusion, cardiac events resulting in falls or other sequelae, drug-drug and drug-disease interactions. For these reasons, in the elderly, cyclobenzaprine should be used only if clearly needed. In such patients Flexeril should be initiated with a 5 mg dose and titrated slowly upward.

Flexeril Dosage and Administration

For most patients, the recommended dose of Flexeril is 5 mg three times a day. Based on individual patient response, the dose may be increased to 10 mg three times a day. Use of Flexeril for periods longer than two or three weeks is not recommended. (see INDICATIONS AND USAGE).

Less frequent dosing should be considered for hepatically impaired or elderly patients (see PRECAUTIONS, Impaired Hepatic Function, and Use in the Elderly).

How is Flexeril Supplied

Flexeril tablets are available in 5 mg and 10 mg dosage strengths. The 5 mg tablets are yellow-orange, 5-sided D-shaped, film coated tablets, coded FLEX over 5 on one side and without coding on the other. The 10 mg tablets are butterscotch yellow, 5-sided D-shaped, film coated tablets, coded Flexeril on one side and without coding on the other. The two dosage strengths are supplied as follows:

  5 mg 100 count bottle NDC 50580-280-10
10 mg 100 count bottle NDC 50580-874-11

STORAGE

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F). [see USP Controlled Room Temperature].

Rx Only

For more information call 1-888-440-7903
or visit www.Flexeril.info

McNeil Consumer & Specialty Pharmaceuticals
DIVISION OF MCNEIL-PPC, INC.
Fort Washington, PA 19034

Edition: February 2005
7629222

Flexeril is a registered trademark of ALZA Corporation
Copyright ©ALZA Corporation, 2001
All rights reserved.

Flexeril 
cyclobenzaprine hydrochloride tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:50580-280
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
cyclobenzaprine hydrochloride (cyclobenzaprine) cyclobenzaprine 5 mg
Inactive Ingredients
Ingredient Name Strength
hydroxypropyl cellulose  
hypromellose  
lactose  
magnesium stearate  
starch  
titanium dioxide  
Yellow D&C #10 Aluminum Lake HT  
Yellow FD&C #6 Aluminum Lake  
Product Characteristics
Color YELLOW (Yellow) , ORANGE (Orange) Score no score
Shape PENTAGON (5 sided) (PENTAGON (5 sided)) Size 8mm
Flavor Imprint Code FLEX;5
Contains     
Coating true Symbol false
Packaging
# Item Code Package Description
1 NDC:50580-280-10 100 TABLET, FILM COATED (100 TABLET) in 1 BOTTLE
Flexeril 
cyclobenzaprine hydrochloride tablet, film coated
Product Information
Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:50580-874
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
cyclobenzaprine hydrochloride (cyclobenzaprine) cyclobenzaprine 10 mg
Inactive Ingredients
Ingredient Name Strength
hydroxypropyl cellulose  
hypromellose  
iron oxide  
lactose  
magnesium stearate  
starch  
titanium dioxide  
Product Characteristics
Color YELLOW (Butterscotch-Yellow) Score no score
Shape PENTAGON (5 sided) (PENTAGON (5 sided)) Size 8mm
Flavor Imprint Code Flexeril
Contains     
Coating true Symbol false
Packaging
# Item Code Package Description
1 NDC:50580-874-11 100 TABLET, FILM COATED (100 TABLET) in 1 BOTTLE
Labeler - McNeil Consumer and Specialty Pharmaceuticals
Revised: 11/2006   McNeil Consumer and Specialty Pharmaceuticals

How should I take Flexeril?

Take this medication exactly as it was prescribed for you. Do not take Flexeril in larger amounts, or take it for longer than recommended by your doctor. Follow the directions on your prescription label.

Take this medicine with a full glass of water.

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

What happens if I miss a dose?

Take the missed dose as soon as you remember. If it is almost time for your next dose, skip the missed dose and take the medicine at the next regularly scheduled time. Do not take extra medicine to make up the missed dose.

For the Consumer

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

Along with its needed effects, cyclobenzaprine (the active ingredient contained in Flexeril) 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:

Rare
  • 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:

Symptoms of overdose
  • 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:

More common
  • Blurred vision
  • dizziness, drowsiness, or lightheadedness
  • dryness of the mouth
Less common or rare
  • 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

For Healthcare Professionals

Applies to cyclobenzaprine: compounding powder, oral capsule extended release, oral tablet, oral and topical kit

General

The most frequently occurring adverse reactions have included dry mouth, dizziness, fatigue, constipation, nausea, dyspepsia, and somnolence.[Ref]

Nervous system

Very common (10% or more): Drowsiness (up to 38%)
Common (1% to 10%): Dizziness, somnolence
Postmarketing reports: Headache, serotonin syndrome, seizures, ataxia, tremors, hypertonia, convulsions, abnormal sensations, paresthesia, ageusia[Ref]

Elderly patients may be particularly susceptible to the sedation and confusion which may accompany cyclobenzaprine therapy.[Ref]

Psychiatric

Common (1% to 10%): Irritability, mental acuity decreased, nervousness
Postmarketing reports: Nervousness, confusion, disorientation, insomnia, depressed mood, anxiety, agitation, psychosis, abnormal thinking and dreaming, hallucinations, excitement[Ref]

Hypersensitivity

Postmarketing reports: Anaphylaxis, angioedema, pruritus, facial edema, urticaria, rash[Ref]

Gastrointestinal

Very common (10% or more): Dry mouth (up to 32%)
Common (1% to 10%): Constipation, nausea, dyspepsia, abdominal pain, acid regurgitation, diarrhea
Postmarketing reports: Unpleasant taste, vomiting, anorexia, gastritis, thirst, flatulence, tongue edema[Ref]

Hepatic

Postmarketing reports: Abnormal liver function, hepatitis, jaundice, cholestasis[Ref]

Cardiovascular

Postmarketing reports: Syncope, tachycardia, arrhythmia, vasodilation, palpitation, hypotension[Ref]

Other

Common (1% to 10%): Fatigue
Postmarketing reports: Asthenia, malaise, vertigo[Ref]

Dermatologic

Postmarketing reports: Sweating[Ref]

Genitourinary

Postmarketing reports: Urinary frequency and/or retention[Ref]

Musculoskeletal

Postmarketing reports: Local weakness, dysarthria, muscle twitching[Ref]

Ocular

Postmarketing reports: Blurred vision, diplopia, tinnitus[Ref]

Respiratory

Common (1% to 10%): Upper respiratory infection, pharyngitis[Ref]

Some side effects of Flexeril may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

How it works

  • Flexeril is a brand (trade) name for cyclobenzaprine. Cyclobenzaprine relaxes muscles by reducing muscle hyperactivity through an action on both gamma and alpha motor systems (these are nerve fibres that directly connect with skeletal muscle and are responsible for muscle contraction). Cyclobenzaprine acts primarily through the brain stem rather than the spinal cord and does not act directly on skeletal muscle.
  • Flexeril will not reduce muscle spasm due to central nervous system (CNS) disease, such as cerebral palsy.
  • Flexeril belongs to a class of drugs known as muscle relaxants.
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