Cyclobenzaprine hydrochloride extended-release capsules are 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.

Limitations of Use:

• Cyclobenzaprine hydrochloride extended-release capsules 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.
• Cyclobenzaprine hydrochloride extended-release capsules have 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) cyclobenzaprine hydrochloride 15 mg extended-release capsule taken once daily. Some patients may require up to 30 mg/day, given as one (1) cyclobenzaprine hydrochloride 30 mg extended-release capsule taken once daily or as two (2) cyclobenzaprine hydrochloride 15 mg extended-release capsules taken once daily.

• It is recommended that doses be taken at approximately the same time each day.
• Use of cyclobenzaprine hydrochloride extended-release capsules for periods longer than two or three weeks is not recommended [see Indications and Usage (1)].

Instruct patients to swallow cyclobenzaprine hydrochloride extended-release capsules intact. Alternatively, the contents of the cyclobenzaprine hydrochloride extended-release capsule may be sprinkled over applesauce and then swallowed. This method is appropriate only for patients able to reliably swallow the applesauce without chewing. Other foods have not been tested and should not be substituted for applesauce. Instruct the patient to:

• Sprinkle the contents of the capsule onto a tablespoon of applesauce and consume immediately without chewing.
• Rinse the mouth to ensure all of the contents have been swallowed.
• Discard any unused portion of the cyclobenzaprine hydrochloride extended-release capsules after the contents have been sprinkled on applesauce.

Extended-release capsules in the following strengths:

• 15 mg: Capsules are orange opaque body and orange opaque cap with "B15" in blue ink on cap.
• 30 mg: Capsules are dark blue opaque body and standard red opaque cap with "B30" in white ink on cap.

• Hypersensitivity to any component of this product. Adverse reactions may include anaphylactic reaction, urticaria, facial and/or tongue swelling, or pruritus. Discontinue cyclobenzaprine hydrochloride extended-release capsules if a hypersensitivity reaction is suspected. 
• 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 or conduction disturbances, or congestive heart failure.
• Hyperthyroidism.

The following clinically significant reactions are described in greater detail, in other sections.

• Serotonin Syndrome [see Warnings and Precautions (5.1)]
• Adverse Cardiovascular Effects [see Warnings and Precautions (5.2)]

Based on its structural similarity to tricyclic antidepressants, cyclobenzaprine hydrochloride extended-release may have life-threatening interactions with MAO inhibitors [see Contraindications (4)], may enhance the effects of alcohol, barbiturates, and other CNS depressants, may enhance the seizure risk in patients taking tramadol, or may block the antihypertensive action of guanethidine and similarly acting compounds.

Postmarketing cases of serotonin syndrome have been reported during combined use of cyclobenzaprine and other drugs, such as SSRIs, SNRIs, TCAs, tramadol, bupropion, meperidine, verapamil, or MAO inhibitors [see Warnings and Precautions (5.1)].

Clinical Presentation

 Although rare, deaths may occur from overdosage with cyclobenzaprine hydrochloride extended-release. 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 most common effects associated with cyclobenzaprine overdose are drowsiness and tachycardia. Less frequent symptoms include tremor, agitation, coma, ataxia, hypertension, slurred speech, confusion, dizziness, nausea, vomiting, and hallucinations. Rare but potentially critical symptoms of overdose are cardiac arrest, chest pain, cardiac dysrhythmias, severe hypotension, seizures, cases of neuroleptic malignant syndrome and rhabdomyolysis have been reported. 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 (6).

Treatment of Overdose

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 symptoms 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 cyclobenzaprine hydrochloride extended-release 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.

Cyclobenzaprine hydrochloride is a skeletal muscle relaxant which relieves muscle spasm of local origin without interfering with muscle function. The active ingredient in cyclobenzaprine hydrochloride 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 217°C, and a pKa 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 hydrochloride is designated chemically as 3-(5H-dibenzo[a,d] cyclohepten-5-ylidene)-N,N-dimethyl-1-propanamine hydrochloride, and has the following structural formula:

Cyclobenzaprine hydrochloride extended-release capsules for oral administration are supplied in 15 mg and 30 mg strengths.  Cyclobenzaprine hydrochloride extended-release 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 to 25 mesh), and titanium dioxide. Cyclobenzaprine hydrochloride 15 mg extended-release capsules also contain D&C yellow #10, FD&C green #3, and FD&C red #40.  Cyclobenzaprine hydrochloride 30 mg extended-release capsules also contain FD&C blue #1, FD&C blue #2, FD&C red #40, and FD&C yellow #6.

Efficacy was assessed in two double-blind, parallel-group, active-controlled, placebo-controlled studies of identical design of cyclobenzaprine hydrochloride extended-release capsules, 15 mg and 30 mg taken once daily, between 6:00 and 7:00 PM, cyclobenzaprine 10 mg three times a day, or placebo for 14 days 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 cyclobenzaprine hydrochloride extended-release capsules, 15 mg group and the placebo group at Days 4 and 14 in one study and between the cyclobenzaprine hydrochloride extended-release capsules, 30 mg group and the placebo group at Day 4 in the second study.

Table 2: Patients’ Rating of Medication Helpfulness - Study 1*

*Percentages are rounded to the nearest whole percent.

Table 3: Patients’ Rating of Medication Helpfulness - Study 2*

*Percentages are rounded to the nearest whole percent.

In addition, one of the two studies demonstrated significant differences between the cyclobenzaprine hydrochloride extended-release capsules, 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 patient-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.

In both studies, there were no significant treatment differences between the cyclobenzaprine hydrochloride extended-release treatment groups and the placebo group in physician's global assessment, patient-rated restriction in activities of daily living, or quality of nighttime sleep.

See FDA-approved patient labeling (Patient Information).

• Instruct patients to swallow cyclobenzaprine hydrochloride extended-release capsules intact or to sprinkle capsule contents on a tablespoon of applesauce and swallow immediately without chewing.
• Advise patients to stop taking cyclobenzaprine hydrochloride extended-release capsules and to notify their physician right away if they experience symptoms of an allergic reaction, such as difficulty breathing, hives, swelling of face or tongue, or itching.
• Advise patients that cyclobenzaprine hydrochloride extended-release capsules should not be taken with MAO inhibitors or within 14 days after their discontinuation.
• Caution patients about the risk of serotonin syndrome with concomitant use of cyclobenzaprine hydrochloride extended-release and other drugs, such as SSRIs, SNRIs, TCAs, tramadol, bupropion, meperidine, verapamil, or MAO inhibitors. Advise patients of the signs and symptoms of serotonin syndrome [see Warnings and Precautions (5.1)] and instruct patients to seek medical care immediately if they experience these symptoms.
• Advise patients to stop taking cyclobenzaprine hydrochloride extended-release capsules and to notify their physician right away if they experience arrhythmias or tachycardia.
• Advise patients that cyclobenzaprine hydrochloride extended-release capsules may enhance the impairment effects of alcohol. These effects may also be seen if cyclobenzaprine hydrochloride extended-release capsules are taken with other CNS depressants.
• Caution patients about operating an automobile or other hazardous machinery until it is reasonably certain that cyclobenzaprine hydrochloride extended-release capsules therapy will not adversely affect their ability to engage in such activities.
• Advise patients to take cyclobenzaprine hydrochloride extended-release capsules at approximately the same time each day.

Manufactured By:
Adare Pharmaceuticals, Inc.
Vandalia, OH 45377

Distributed by:
Amneal Pharmaceuticals LLC
Bridgewater, NJ 08807

Rev. 05-2025-04

Cyclobenzaprine Hydrochloride
(sye“ kloe ben‘ za preen hye“ droe klor‘ ide)
Extended-Release Capsules

What are cyclobenzaprine hydrochloride extended-release capsules?

Cyclobenzaprine hydrochloride extended-release capsules are a prescription medicine used along with rest and physical therapy to help treat muscle spasm due to acute, painful musculoskeletal problems.

Cyclobenzaprine hydrochloride extended-release capsules should only be used for up to 2 or 3 weeks. It is not known if cyclobenzaprine hydrochloride extended-release capsules are effective when used for longer periods.

It is not known if cyclobenzaprine hydrochloride extended-release capsules are safe and effective in children.

Do not take cyclobenzaprine hydrochloride extended-release capsules if you:

• are allergic to cyclobenzaprine or any of the ingredients in cyclobenzaprine hydrochloride extended-release capsules. See the end of this Patient Information leaflet for a complete list of ingredients in cyclobenzaprine hydrochloride extended-release capsules.
  Talk to your healthcare provider or get medical help right away if you have symptoms of an allergic reaction such as:
  • difficulty breathing
  • hives
  • swelling of your face or tongue
  • itching
• are taking certain antidepressants, known as monoamine oxidase (MAO) inhibitors or it has been 14 days or less since you stopped taking a MAO inhibitor. Ask your healthcare provider or pharmacist for a list of these medicines if you are not sure.
• have had a recent heart attack
• have heart rhythm problems (arrhythmias)
• have heart failure
• have an overactive thyroid (hyperthyroidism)

Talk to your healthcare provider before taking this medicine if you have any of the conditions listed above.

Before taking cyclobenzaprine hydrochloride extended-release capsules, tell your healthcare provider about all of your medical conditions, including if you:

• have a history of eye problems including glaucoma
• have heart problems or have had a heart attack
• have liver problems
• have trouble emptying your bladder (urinary retention)
• are pregnant or plan to become pregnant. It is not known if cyclobenzaprine hydrochloride extended-release capsules will harm your unborn baby.
• are breastfeeding or plan to breastfeed. It is not known if cyclobenzaprine passes into your breast milk. Talk to your healthcare provider about the best way to feed your baby if you take cyclobenzaprine hydrochloride extended-release capsules.

Tell your healthcare provider about all the medicines you take including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Especially tell your healthcare provider if you take:

• a medicine to treat depression, mood, anxiety, psychotic, or thought disorders
• a pain medicine called tramadol or meperidine
• barbiturates or other medicines that depress your central nervous system (CNS depressants)
• a medicine that prevents nerve impulses (anticholinergic medicines)
• a medicine to help quit smoking called bupropion
• a blood pressure medicine called verapamil

Know the medicines you take. Keep a list of your medicines and show it to your healthcare provider or pharmacist when you get a new medicine.

How should I take cyclobenzaprine hydrochloride extended-release capsules?

• Take cyclobenzaprine hydrochloride extended-release capsules exactly as your healthcare provider tells you to take it.
• Your healthcare provider will tell you how much cyclobenzaprine hydrochloride extended-release capsules to take and when to take it.
• Your healthcare provider may change your cyclobenzaprine hydrochloride extended-release capsules dose if needed.
• Take cyclobenzaprine hydrochloride extended-release capsules around the same time every day.
• Swallow cyclobenzaprine hydrochloride extended-release capsules whole.
• If you have difficulty swallowing cyclobenzaprine hydrochloride extended-release capsules, tell your healthcare provider. Your healthcare provider may recommend opening the cyclobenzaprine hydrochloride extended-release capsule and mixing the contents with applesauce.
• Cyclobenzaprine hydrochloride extended-release capsules should only be taken for short periods (up to two or three weeks).
• If you take too much cyclobenzaprine hydrochloride extended-release capsules, call your healthcare provider or go to the nearest hospital emergency room right away.

What should I avoid while taking cyclobenzaprine hydrochloride extended-release capsules?

You should not drink alcohol until you know how cyclobenzaprine hydrochloride extended-release capsules affect you. Taking cyclobenzaprine hydrochloride extended-release capsules with alcohol or other medicines that depress your central nervous system can slow your thinking and physical response times.

Do not drive, operate machinery, or do other dangerous activities until you know how cyclobenzaprine hydrochloride extended-release capsules affect you.

What are the possible side effects of cyclobenzaprine hydrochloride extended-release capsules?

Cyclobenzaprine hydrochloride extended-release capsules may cause serious side effects, including:

• Serotonin syndrome is a serious medical condition that may happen when cyclobenzaprine hydrochloride extended-release capsules is taken with certain other medicines. Call your healthcare provider right away or go to the nearest hospital emergency room if you have some or all of these symptoms suggestive of serotonin syndrome:

• agitation, hallucinations, coma, or other changes in mental status
• coordination problems or muscle twitching (overactive reflexes)
• fast heartbeat, high or low blood pressure
• sweating or fever
• nausea, vomiting, or diarrhea
• muscle stiffness or tightness

• Cyclobenzaprine hydrochloride extended-release capsules may cause serious side effects that may lead to heart attack or stroke. Call your healthcare provider right away or go to the nearest hospital emergency room if you have:

• irregular or abnormal heartbeats (arrhythmias)
• fast heartbeat (tachycardia)

The most common side effects of cyclobenzaprine hydrochloride extended-release capsules include:

These are not all the possible side effects of cyclobenzaprine hydrochloride extended-release capsules.

Call your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store cyclobenzaprine hydrochloride extended-release capsules?

• Store cyclobenzaprine hydrochloride extended-release capsules at room temperature between 68°F to 77°F (20°C to 25°C).
• Keep cyclobenzaprine hydrochloride extended-release capsules in a tightly closed container, and keep cyclobenzaprine hydrochloride extended-release capsules out of light.
• Keep cyclobenzaprine hydrochloride extended-release capsules and all medicines out of the reach of children.

General information about the safe and effective use of cyclobenzaprine hydrochloride extended-release capsules.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use cyclobenzaprine hydrochloride extended-release capsules for a condition for which it was not prescribed. Do not give cyclobenzaprine hydrochloride extended-release capsules to other people, even if they have the same symptoms you have. It may harm them.

You can ask your pharmacist or healthcare provider for information about cyclobenzaprine hydrochloride extended-release capsules that is written for healthcare professionals.

What are the ingredients in cyclobenzaprine hydrochloride extended-release capsules?

Active Ingredient: cyclobenzaprine hydrochloride USP

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.

Cyclobenzaprine hydrochloride 15 mg extended-release capsules also contain: D&C yellow #10, FD&C green #3, and FD&C red #40.

Cyclobenzaprine hydrochloride 30 mg extended-release capsules also contain: FD&C blue #1, FD&C blue #2, FD&C red #40, and FD&C yellow #6.

Distributed by:                                                                 Manufactured By:
Amneal Pharmaceuticals LLC                                   Adare Pharmaceuticals, Inc.
Bridgewater, NJ 08807                                                  Vandalia, OH 45377

For more information, go to www.amneal.com or call toll-free 1-877-835-5472.

This Patient Information has been approved by the U.S. Food and Drug Administration                                
Revised: May 2025

INSTRUCTIONS FOR USE
Cyclobenzaprine Hydrochloride
(sye“ kloe ben‘ za preen hye“ droe klor‘ ide)
Extended-Release Capsules

Read this Instructions for Use before you prepare your first dose of cyclobenzaprine hydrochloride extended-release capsules mixed with applesauce using the capsule sprinkle method, each time you get a refill, and as needed. There may be new information. Ask your healthcare provider or pharmacist if you have any questions about how to mix or give a dose of cyclobenzaprine hydrochloride extended-release capsules using the capsule sprinkle method.

Important Information:

• Do not chew cyclobenzaprine hydrochloride extended-release capsules or the granules that are in the capsules.
• The capsule sprinkle method for mixing the contents of cyclobenzaprine hydrochloride extended-release capsules with applesauce may be used for adults who cannot swallow capsules. Do not use any other food in the place of applesauce.

Preparing a dose of cyclobenzaprine hydrochloride extended-release capsules using the capsule sprinkle method.

Before you prepare a dose of cyclobenzaprine hydrochloride extended-release capsules mixed with applesauce using the capsule sprinkle method, gather the following supplies:

• paper towels
• tablespoon
• applesauce
• cup of water

Step 1: Choose a clean, flat work surface. Place a clean paper towel on the work surface. Then place the other supplies on the paper towel.
Step 2: Wash and dry your hands well.
Step 3: Check the dose that was prescribed by your healthcare provider. Take out the number of cyclobenzaprine hydrochloride extended-release capsules needed to prepare your dose. Place them on the paper towel.
Step 4: Place enough applesauce to fill your tablespoon. Set the tablespoon down on the paper towel.
Step 5: Hold the cyclobenzaprine hydrochloride extended-release capsule in an upright position (vertical) directly over the tablespoon. Hold each end of the cyclobenzaprine hydrochloride extended-release capsule between your thumbs and index (pointer) fingers.
Step 6: Carefully twist both ends of the cyclobenzaprine hydrochloride extended-release capsule in opposite directions to open it. Be careful not to spill the capsule contents.
Step 7: Sprinkle the contents of the cyclobenzaprine hydrochloride extended-release capsule onto the applesauce. Check the capsule shells to make sure they are empty. Throw away the empty capsule shells. If the total prescribed dose is more than 1 capsule, repeat Steps 5 through 7 for each capsule. Do not add more applesauce. Then follow the rest of the steps below.
Step 8: Pick up the tablespoon and swallow the cyclobenzaprine hydrochloride extended-release capsule contents and applesauce mixture right away. Do not chew the cyclobenzaprine hydrochloride extended-release capsule contents and applesauce mixture.
Step 9: Rinse your mouth with a sip of water and swallow to make sure that all of the cyclobenzaprine hydrochloride extended-release granules have been swallowed.
Step 10: Throw away any unused cyclobenzaprine hydrochloride extended-release capsule content and applesauce mixture. Do not keep any cyclobenzaprine hydrochloride extended-release capsule content and applesauce mixture for future use.

How should I store cyclobenzaprine hydrochloride extended-release capsules?

• Store cyclobenzaprine hydrochloride extended-release capsules at room temperature between 68°F to 77°F (20°C to 25°C).

Keep cyclobenzaprine hydrochloride extended-release capsules and all medicines out of the reach of children.

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Issued: May 2019