AMRIX® (Cyclobenzaprine Hydrochloride Extended-Release Capsules) is a skeletal muscle relaxant which relieves muscle spasm of local origin without interfering with muscle function. The active ingredient in AMRIX® extended-release capsules is cyclobenzaprine hydrochloride, USP. Cyclobenzaprine hydrochloride (HCl) is a white, crystalline tricyclic amine salt with the empirical formula C₂₀H₂₁N·HCl and a molecular weight of 311.9. It has a melting point of 2l7°C, and a pK_a of 8.47 at 25°C. It is freely soluble in water and alcohol, sparingly soluble in isopropanol, and insoluble in hydrocarbon solvents. If aqueous solutions are made alkaline, the free base separates. Cyclobenzaprine HCl is designated chemically as 3-(5H-dibenzo[a,d] cyclohepten-5-ylidene)- N,N-dimethyl-1-propanamine hydrochloride, and has the following structural formula:

AMRIX extended-release capsules for oral administration are supplied in 15 and 30 mg strengths. AMRIX capsules contain the following inactive ingredients: diethyl phthalate NF, ethylcellulose NF (Ethocel Standard 10 Premium), gelatin, Opadry® Clear YS-1-7006, sugar spheres NF (20-25 mesh), and titanium dioxide. AMRIX 15 mg capsules also contain red ferric oxide and yellow ferric oxide. AMRIX 30 mg capsules also contain FD&C blue #1, FD&C blue #2, FD&C red #40, and FD&C yellow #6.

Last updated on RxList: 6/3/2008

AMRIX is indicated as an adjunct to rest and physical therapy for relief of muscle spasm associated with acute, painful musculoskeletal conditions. Improvement is manifested by relief of muscle spasm and its associated signs and symptoms, namely, pain, tenderness, and limitation of motion.

AMRIX should be used only for short periods (up to two or three weeks) because adequate evidence of effectiveness for more prolonged use is not available and because muscle spasm associated with acute, painful musculoskeletal conditions is generally of short duration and specific therapy for longer periods is seldom warranted.

AMRIX has not been found effective in the treatment of spasticity associated with cerebral or spinal cord disease or in children with cerebral palsy.

The recommended adult dose for most patients is one (1) AMRIX (Cyclobenzaprine Hydrochloride Extended-Release Capsules) 15 mg capsule taken once daily. Some patients may require up to 30 mg/day, given as one (1) AMRIX 30 mg capsule taken once daily or as two (2) AMRIX 15 mg capsules taken once daily.

It is recommended that doses be taken at approximately the same time each day. Use of AMRIX for periods longer than two or three weeks is not recommended (see INDICATIONS).

Dosage Considerations for Special Patient Populations: AMRIX should not be used in the elderly or in patients with impaired hepatic function. (see WARNINGS).

AMRIX extended-release capsules are available in 15 and 30 mg strengths, packaged in bottles of 60 capsules. AMRIX 15 mg capsules (NDC 63459-700-60) are orange/orange, are embossed "ECR 15" on each half and bear a single white band. AMRIX 30 mg capsules (NDC 63459-701-60) are blue/orange, are embossed "ECR 30" on each half and bear two white bands.

Dispense in a tight, light-resistant container as defined in the USP/NF. Store at 25°C (77°F); excursions permitted to 15 - 30°C (59 - 86°F); [see USP Controlled Room Temperature].

KEEP THIS AND ALL MEDICATION OUT OF THE REACH OF CHILDREN. IN CASE OF ACCIDENTAL OVERDOSE, SEEK PROFESSIONAL ASSISTANCE OR CONTACT A POISON CONTROL CENTER IMMEDIATELY.

Distributed by Cephalon, Inc., Frazer, PA 19355. Manufactured by Eurand, Inc., Vandalia, Ohio 45377. Rev. 3/2008. FDA Rev date: 3/24/2008

Last updated on RxList: 6/3/2008

The most common adverse reactions in the two 14-day clinical efficacy trials and in the 7-day repeat-dose pharmacokinetic study are presented in Tables 5 and 6, respectively.

Table 5: Incidence of the Most Common Adverse Reactions Occurring in ≥ 3% of Subjects in Any Treatment Group in the Two Phase 3, Double- Blind AMRIX Trials.

	AMRIX 15 mg N=127	AMRIX 30 mg N=126	Placebo N=128
Drymouth	6%	14%	2%
Dizziness	3%	6%	2%
Fatigue	3%	3%	2%
Constipation	1%	3%	0%
Somnolence	1%	2%	0%
Nausea	3%	3%	1%
Dyspepsia	0%	4%	1%

Table 6: Incidence of the Most Common Adverse Reactions Occurring in ≥ 3% of Subjects in Any Treatment Group in the Seven -Day Pharmacokinetic Study of AMRIX.

	AMRIX 30 mg N = 36
Somnalence	100%
Dry mouth	58%
Headache NOS	17%
Dizziness	19%
Vision blurred	3%
Nausea	8%
Dysgeusia	6%
palpitations	6%
Tremor	6%
Dry throat	8%
Acne NOS	6%
Disturbance in attention	6%
Insomnia	0%

In a postmarketing surveillance program (7607 patients treated with cyclobenzaprine 10 mg TID), the adverse reactions reported most frequently 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:

Table 7: Most Common Adverse Reactions From Postmarketing Surveillance Program

	Clinical Studies Cyclobenzaprine 10 mg TID	Servillance Program Cyclobenzaprine 10 mg TID
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-marketing experience or with an incidence of less than 1% of patients in clinical trials with the 10 mg TID 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.

Skin: Sweating.

Special Senses: Ageusia; tinnitus.

Urogenital: Urinary frequency and/or retention.

Causal Relationship Unknown Other reactions, reported rarely for cyclobenzaprine 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.

Drug Abuse And Dependence

Pharmacologic similarities among the tricyclic drugs require that certain withdrawal symptoms be considered when AMRIX (Cyclobenzaprine Hydrochloride Extended-Release Capsules) 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.

AMRIX may have life-threatening interactions with MAO inhibitors. (See CONTRAINDICATIONS.) AMRIX 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 (ULTRAM® [tramadol HCl tablets, Ortho-McNeil Pharmaceutical] or ULTRACET® [tramadol HCl and acetaminophen tablets, Ortho-McNeil Pharmaceutical]).

Last updated on RxList: 6/3/2008

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

As a result of a two-fold higher cyclobenzaprine plasma levels in subjects with mild hepatic impairment, as compared to healthy subjects, following administration of immediate-release cyclobenzaprine and because there is limited dosing flexibility with AMRIX, use of AMRIX is not recommended in subjects with mild, moderate or severe hepatic impairment.

As a result of a 40% increase in cyclobenzaprine plasma levels and a 56% increase in plasma half-life following administration of AMRIX in elderly subjects as compared to young adults, use of AMRIX is not recommended in elderly.

General

Because of its atropine-like action, AMRIX (Cyclobenzaprine Hydrochloride Extended-Release Capsules) 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.

Carcinogenesis, Mutagenesis, Impairment of Fertility

In rats treated with cyclobenzaprine 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 doserelated hepatocyte vacuolation with lipidosis. In the higher dose groups, this microscopic change was seen after 26 weeks and even earlier in rats that 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.

A battery of mutagenicity tests using bacterial and mammalian systems for point mutations and cytogenic effects have provided no evidence for a mutagenic potential for cyclobenzaprine. An in vivo mouse bone micronucleus assay, an assessment of chromosomal aberrations (Chinese hamster ovary), and a mammalian microsome reverse mutation assay were negative.

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 cyclobenzaprine. There are, however, no adequate and wellcontrolled 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 AMRIX is administered to a nursing woman.

Pediatric Use

Safety and effectiveness of AMRIX has not been studied in pediatric patients.

Use in the Elderly

The plasma concentration and half-life of cyclobenzaprine are substantially increased in the elderly when compared to the general patient population (see CLINICAL PHARMACOLOGY, Pharmacokinetics, Special Populations, Elderly). Accordingly, AMRIX should not be used in the elderly.

Last updated on RxList: 6/3/2008

Although rare, deaths may occur from overdosage with AMRIX. Multiple drug ingestion (including alcohol) is common in deliberate cyclobenzaprine overdose. As management of overdose is complex and changing, it is recommended that the physician contact a poison control center for current information on treatment. Signs and symptoms of toxicity may develop rapidly after cyclobenzaprine overdose; therefore, hospital monitoring is required as soon as possible. The acute oral LD50 of cyclobenzaprine is approximately 338 and 425 mg/kg in mice and rats, respectively.

Manifestations

The most common effects associated with cyclobenzaprine overdose are drowsiness and tachycardia. Less frequent manifestations include tremor, agitation, coma, ataxia, hypertension, slurred speech, confusion, dizziness, nausea, vomiting, and hallucinations. Rare but potentially critical manifestations of overdose are cardiac arrest, chest pain, cardiac dysrhythmias, severe hypotension, seizures, and neuroleptic malignant syndrome. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of cyclobenzaprine toxicity. Other potential effects of overdosage include any of the symptoms listed under ADVERSE REACTIONS.

Management

General

As management of overdose is complex and changing, it is recommended that the physician contact a poison control center for current information on treatment.

In order to protect against the rare but potentially critical manifestations described above, obtain an ECG and immediately initiate cardiac monitoring. Protect the patient's airway, establish an intravenous line, and initiate gastric decontamination. Observation with cardiac monitoring and observation for signs of CNS or respiratory depression, hypotension, cardiac dysrhythmias and/or conduction blocks, and seizures is necessary. If signs of toxicity occur at any time during this period, extended monitoring is required. Monitoring of plasma drug levels should not guide management of the patient. Dialysis is probably of no value because of low plasma concentrations of the drug.

Gastrointestinal Decontamination

All patients suspected of an overdose with AMRIX should receive gastrointestinal decontamination. This should include large volume gastric lavage followed by activated charcoal. If consciousness is impaired, the airway should be secured prior to lavage and emesis is contraindicated.

Cardiovascular

A maximal limb-lead QRS duration of 0.10 seconds may be the best indication of the severity of the overdose. Serum alkalinization, to a pH of 7.45 to 7.55, using intravenous sodium bicarbonate and hyperventilation (as needed), should be instituted for patients with dysrhythmias and/or QRS widening. A pH > 7.60 or a pCO₂ < 20 mmHg is undesirable.

Dysrhythmias unresponsive to sodium bicarbonate therapy/hyperventilation may respond to lidocaine, bretylium, or phenytoin. Type 1A and 1C antiarrhythmics are generally contraindicated (e.g., quinidine, disopyramide, and procainamide).

CNS

In patients with CNS depression, early intubation is advised because of the potential for abrupt deterioration. Seizures should be controlled with benzodiazepines or, if these are ineffective, other anticonvulsants (e.g., phenobarbital, phenytoin). Physostigmine is not recommended except to treat life-threatening symptoms that have been unresponsive to other therapies, and then only in close consultation with a poison control center.

Psychiatric Follow-up

Since overdosage is often deliberate, patients may attempt suicide by other means during the recovery phase. Psychiatric referral may be appropriate.

Pediatric Management

The principles of management of child and adult overdosage are similar. It is strongly recommended that the physician contact the local poison control center for specific pediatric treatment.

• Hypersensitivity to any component of this product.
• • Concomitant use of monoamine oxidase (MAO) inhibitors or within 14 days after their discontinuation.
• Hyperpyretic crisis seizures and deaths have occurred in patients receiving cyclobenzaprine (or structurally similar tricyclic antidepressants) concomitantly with MAO inhibitor drugs.
• During the acute recovery phase of myocardial infarction, and in patients with arrhythmias, heart block conduction disturbances, or congestive heart failure.
• Hyperthyroidism.

Last updated on RxList: 6/3/2008

Cyclobenzaprine relieves skeletal muscle spasm of local origin without interfering with muscle function. Cyclobenzaprine has not been shown to be effective in muscle spasm due to central nervous system disease. In animal models, cyclobenzaprine reduced or abolished skeletal muscle hyperactivity. 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 the brain stem as opposed to the spinal cord level, although an overlapping 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 demonstrated 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.

Pharmacokinetics

Absorption

In a single-dose study comprised of healthy adult males (n=15), the dose adjusted ratios of the arithmetic means of AUC_0-168 and AUC_0-∞ indicated that exposure of the AMRIX 30 mg was about 16% and 10% higher than that of AMRIX 15 mg, respectively. The dose-adjusted ratios of the arithmetic means of Cmax indicated that the peak plasma concentration of AMRIX 30 mg was about 20% higher than that of AMRIX 15 mg. The half-lives and time to peak plasma cyclobenzaprine concentration were similar for both AMRIX 15 mg and 30 mg. These data are summarized below.

Table1: Summary of pharmacokinetic Parameters in Healthy Adult Subjects

Parameter Mean±SD	AMRIX 15	AMRIX 30
	(N=15)	(N=14)
AUC0-168 (ng•hr/mL)	318.3 ± 114.7	736.6 ± 259.4
AUC0-∞(ng•hr/mL)	354.1 ± 119.8	779.9 ± 277.6
Cmax(ng/mL)	8.3 ± 2.2	19.9 ± 5.9
Tmax (hrs)	8.1 ± 2.9	7.1 ± 1.6
t½ (hrs)	33.4 ± 10.3	32.0 ± 10.1
SD= Standarard deviation

A food effect study conducted in healthy adult subjects (n=15) utilizing a single dose of AMRIX 30 mg demonstrated a statistically significant increase in bioavailability when AMRIX 30 mg was given with food relative to the fasted state. There was a 35% increase in peak plasma cyclobenzaprine concentration (Cmax) and a 20% increase in exposure (AUC_0-168 and AUC_0-∞) in the presence of food. No effect, however, was noted in T_lag, Tmax, or the shape of the mean plasma cyclobenzaprine concentration versus time profile. Cyclobenzaprine in plasma was first detectable in both the fed and fasted states at 1.5 hours.

In a multiple-dose study utilizing AMRIX 30 mg administered once daily for 7 days in a group of healthy adult volunteers (n=35) a 2.5-fold accumulation of plasma cyclobenzaprine levels was noted at steady-state.

Metabolism and Elimination

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 has an elimination half-life of 32 hours (range 8-37 hours; n=18); plasma clearance is 0.7 L/min following single dose administration of AMRIX.

Special Populations

Elderly

Although there were no notable differences in Cmax or Tmax, cyclobenzaprine plasma AUC is increased by 40% and the plasma half-life of cyclobenzaprine is prolonged in elderly subjects greater than 65 years of age (50 hours) after dosing with AMRIX compared to younger subjects (32 hours). Pharmacokinetic characteristics of cyclobenzaprine following multiple-dose administration of AMRIX in the elderly were not evaluated.

Table2: Summary of pharmacokinetic Parameters of AMRIX 30 mg Extended-Release Capsules, By Age Group

Parameter Mean±SD	AMRIX 30 QD	AMRIX 30 QD
	18 to 45 Years (N=18)	65 to 75 Years (N=17)
AUC0-168 (ng•hr/mL)	715.1 ± 264.2	945.9 ± 255.2
AUC0-∞(ng•hr/mL)	751.2 ± 271.5	779.9 ± 277.6
Cmax(ng/mL)*	19.2 ± 5.6	19.2 ± 5.1
Tmax (hrs)*	6.8 ± 1.9	8.5 ± 2.3
t½ (hrs)	32.4 ± 8.1	49.0 ± 8.3
* measured over the entire 24 hour period SD= Standarard deviation

Hepatic Impairment

In a pharmacokinetic study of immediate-release cyclobenzaprine in 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. The pharmacokinetics of cyclobenzaprine in subjects with severe hepatic impairment is not known.

Clinical Studies

Efficacy was assessed in two double-blind, parallel-group, placebocontrolled studies of identical design of AMRIX (Cyclobenzaprine Hydrochloride Extended-Release Capsules) 15 mg and 30 mg taken once daily in patients with muscle spasms associated with acute painful musculoskeletal conditions.

There were significant differences in the primary efficacy analysis, the patient's rating of medication helpfulness, between the AMRIX 15 mg group and the placebo group at Days 4 and 14 in one study and between the AMRIX 30 mg group and the placebo group at Day 4 in the second study.

Table 3: Subject's Rating of Medication Helpfulness - Study 1105

	Day 4		Day 14
	Number of Subjects (%)		Number of Subjects (%)
	Placebo (N=64)	AMRIX 30 mg (N=64)	Placebo (N=64)	AMRIX 30 mg (N=64)
Excellent	1 (1.6%)	3 (4.7%)	12 (18.8%)	15 (23.4%)
Very Good	5 (7.8%)	13 (20.3%)	9 (14.1%)	19 (29.7%)
Good	15 (23.4%)	22 (34.4%)	10 (15.6%)	15 (23.4%)
Fair	24 (37.5%)	20 (31.3%)	16 (25.0%)	10 (15.6%)
Poor	10 (15.6%)	5 (7.8%)	9 (14.1%)	4 (6.3%)
Missing	9 (14.1%)	1 (1.6%)	8 (12.5%)	1 (1.6%)

Table 4: Subject's Rating of Medication Helpfulness - Study 1108

	Day 4		Day 14
	Number of Subjects (%)		Number of Subjects (%)
	Placebo (N=64)	AMRIX 15 mg (N=63)	Placebo (N=64)	AMRIX 15 mg (N=63)
Excellent	1 (1.6%)	2 (3.2%)	10 (15.6%)	13 (20.6%)
Very Good	10 (15.6%)	12 (19.0%)	12 (18.8%)	21 (33.3%)
Good	14 (21.9%)	21 (33.3%)	13 (20.3%)	9(14.3%)
Fair	16 (25.0%)	17 (27.0%)	14 (21.9%)	10 (15.9%)
Poor	19 (29.7%)	6 (9.5%)	12 (18.8%)	5 (7.9%)
Missing	4 (6.3%)	5 (17.9%)	3(4.7%)	5 (7.9%)

In addition, one of the two studies demonstrated significant differences between the AMRIX 30 mg group and the placebo group in terms of patient-rated relief from local pain due to muscle spasm at Day 4 and Day 8, in subject-rated restriction of movement at Day 4 and Day 8, and in patient-rated global impression of change at Day 4, Day 8, and Day 14.

There were no significant treatment differences between the AMRIX treatment groups and the placebo group in physician's global assessment, in subject-rated restriction in activities of daily living, or quality of night-time sleep.

Last updated on RxList: 6/3/2008

AMRIX, 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.

Last updated on RxList: 6/3/2008

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

CYCLOBENZAPRINE EXTENDED-RELEASE - ORAL

(sye-klo-BENZ-uh-preen)

COMMON BRAND NAME(S): Amrix

USES: This medication relaxes muscles. It is used along with rest and physical therapy to decrease muscle pain and spasms associated with strains, sprains, or other muscle injuries.

HOW TO USE: Take this medication by mouth usually once a day or as directed by your doctor. Dosage is based on your medical condition and response to treatment. Do not increase your dose or take it more often than prescribed because doing so increases the risk of side effects.

Swallow the capsules whole. Do not crush or chew the capsules. Doing so can destroy the long action of the drug and may increase side effects.

For best results, take the medication at the same time each day.

This medication is intended for short-term use, usually no longer than 3 weeks, unless otherwise directed by your doctor. If your condition does not improve in 2 to 3 weeks, contact your doctor.

SIDE EFFECTS: Drowsiness, dry mouth, fatigue, dizziness, lightheadedness, constipation, or blurred vision may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

Tell your doctor immediately if any of these unlikely but serious side effects occur: mental/mood changes (e.g., confusion, hallucinations), difficulty urinating, loss of coordination.

Tell your doctor immediately if any of these rare but very serious side effects occur: fast/pounding/irregular heartbeat, fainting, yellowing eyes/skin, stomach/abdominal pain, persistent nausea/vomiting/lack of appetite, dark urine, seizures.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before taking cyclobenzaprine, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.

This medication should not be used if you have certain medical conditions. Before using this medicine, consult your doctor or pharmacist if you have: an overactive thyroid (hyperthyroidism), certain heart problems (irregular heartbeat, congestive heart failure, heart block/rhythm disorders, recent heart attack).

Before using this medication, tell your doctor or pharmacist your medical history, especially of: severe difficulty urinating (urinary retention), high pressure inside the eyes (glaucoma), liver disease.

This drug may make you dizzy or drowsy. Use caution while driving, using machinery, or doing any activity that requires alertness. Alcohol may worsen dizziness or drowsiness. Limit alcoholic beverages.

To lower your risk of dizziness and lightheadedness, get up slowly when rising from a sitting or lying position.

This medication is not recommended for use in the elderly. They may be more sensitive to its side effects, especially drowsiness, dizziness, and confusion, which can increase the risk of falling.

During pregnancy, this medication should be used only when clearly needed. Discuss the risks and benefits with your doctor.

This medication may pass into breast milk. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with them first.

Avoid taking MAO inhibitors (e.g., furazolidone, isocarboxazid, linezolid, moclobemide, phenelzine, procarbazine, rasagiline, selegiline, tranylcypromine) within 2 weeks before, during, and after treatment with this medication. In some cases a serious (possibly fatal) drug interaction may occur.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use, especially of: certain types of asthma drugs (e.g., albuterol, salmeterol), cimetidine, clonidine, guanethidine, guanadrel, SSRI antidepressants (e.g., fluoxetine, citalopram), stimulants and weight loss products (e.g., ephedrine, dextroamphetamine, phenylephrine), tramadol, tricyclic antidepressants (e.g., amitriptyline, imipramine).

Tell your doctor or pharmacist if you also take drugs that cause drowsiness such as: some antihistamines (e.g., diphenhydramine), anti-seizure drugs (e.g., carbamazepine), medicine for sleep or anxiety (e.g., alprazolam, diazepam, zolpidem), muscle relaxants, narcotic pain relievers (e.g., codeine), psychiatric medicines (e.g., chlorpromazine, risperidone, trazodone).

Check the labels on all your medicines (e.g., cough-and-cold products, diet aids, acid reducers) because they may contain ingredients that could increase the risk of side effects with cyclobenzaprine. Ask your pharmacist about using those products safely.

This document does not contain all possible interactions. Therefore, before using this product, tell your doctor or pharmacist of all the products you use. Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center. Symptoms of overdose may include: severe drowsiness, fast/irregular heartbeat, slurred speech, hallucinations, chest pain, seizures, increased muscle stiffness with fever and sweating.

NOTES: Do not share this medication with others.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature at 77 degrees F (25 degrees C) away from light and moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Do not store in the bathroom. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.