Data from FDA (Food and Drug Administration, USA) - Curated by EPG Health - Last updated 24 November 2019

Indication(s)

1 INDICATIONS AND USAGE AMRIX® (cyclobenzaprine hydrochloride extended-release capsules) 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. Limitations of Use: 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. AMRIX is a muscle relaxant indicated as an adjunct to rest and physical therapy for relief of muscle spasm associated with acute, painful musculoskeletal conditions. (1) Limitations of Use: AMRIX should be used only for short periods (up to 2 or 3 weeks) (1) AMRIX has not been found effective in the treatment of spasticity or cerebral palsy (1)

Learning Zones

An epgonline.org Learning Zone (LZ) is an area of the site dedicated to providing detailed self-directed medical education about a disease, condition or procedure.

Idiopathic Pulmonary Fibrosis

Idiopathic Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrotic interstitial lung disease that occurs mostly in older adults, is limited to the lungs and often displays a characteristic imaging and histological appearance. Find out how to diagnose IPF and the latest interventions available for patients living with this burden.

Optimising anti-TNF treatment using biosimilars

Optimising anti-TNF treatment using biosimilars

Biosimilars are uniquely placed to change clinical practice in the fields of gastroenterology, rheumatology, and dermatology. The adoption of biosimilars can improve patient access to the most appropriate treatment, at the optimum time, to ensure the best possible long-term disease outcomes.

Chronic Lymphocytic Leukaemia (CLL)

Chronic Lymphocytic Leukaemia (CLL)

Refine your knowledge of chronic lymphocytic leukaemia (CLL) with information on pathophysiology, diagnosis, treatment options and more

+ 1 more

Load more

Related Content

Advisory information

contraindications
4 CONTRAINDICATIONS Hypersensitivity to any component of this product. These adverse reactions may manifest as an anaphylactic reaction, urticaria, facial and/or tongue swelling, or pruritus. Discontinue AMRIX 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. Hypersensitivity to any component of this product (4) Concomitant use of monoamine oxidase (MAO) inhibitors or within 14 days after their discontinuation (4) During acute recovery phase of myocardial infarction, and in patients with arrhythmias, heart block or conduction disturbances, or congestive heart failure (4) Hyperthyroidism (4)
Adverse reactions
6 ADVERSE REACTIONS 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)] Most common adverse reactions (incidence ≥3% in any treatment group and greater than placebo): dry mouth, dizziness, fatigue, constipation, nausea, dyspepsia, and somnolence (6) To report SUSPECTED ADVERSE REACTIONS, contact Teva Pharmaceuticals at 1-888-483-8279 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The data described below reflect exposure to AMRIX in 253 patients in 2 clinical trials. AMRIX was studied in two double-blind, parallel-group, placebo-controlled, active-controlled trials of identical design [see Clinical Studies (14)] . The study population was composed of patients with muscle spasms associated with acute painful musculoskeletal conditions. Patients received 15 mg or 30 mg of AMRIX taken orally once daily, cyclobenzaprine immediate-release (IR) 10 mg three times a day, or placebo for 14 days. The most common adverse reactions (incidence ≥3% in any treatment group and greater than placebo) were dry mouth, dizziness, fatigue, constipation, nausea, dyspepsia, and somnolence (see Table 1). Table 1: Incidence of the Most Common Adverse Reactions Occurring in ≥ 3% of Patients in any Treatment Group* and Greater Than Placebo in the Two Phase 3, Double-Blind AMRIX Trials Placebo AMRIX 15 mg AMRIX 30 mg N=128 N=127 N=126 Dry mouth 2% 6% 14% Dizziness 2% 3% 6% Fatigue 2% 3% 3% Constipation 0% 1% 3% Somnolence 0% 1% 2% Nausea 1% 3% 3% Dyspepsia 1% 0% 4% *AMRIX 15 mg QD, AMRIX 30 mg QD, or cyclobenzaprine IR tablets TID 6.2 Postmarketing Experience The following adverse reactions have been reported in clinical studies or postmarketing experience with AMRIX, cyclobenzaprine IR, or tricyclic drugs. Because some of these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. In a postmarketing surveillance program of cyclobenzaprine IR, the adverse reactions reported most frequently were drowsiness, dry mouth, and dizziness and adverse reactions 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 (AMRIX or cyclobenzaprine IR), in clinical studies of cyclobenzaprine IR (incidence <1%), or in postmarketing experience with other tricyclic drugs: Body as a Whole: Syncope; malaise; chest pain; edema. Cardiovascular: Tachycardia; arrhythmia; vasodilatation; palpitation; hypotension; hypertension; myocardial infarction; heart block; stroke. Digestive: Vomiting; anorexia; diarrhea; gastrointestinal pain; gastritis; thirst; flatulence; edema of the tongue; abnormal liver function and rare reports of hepatitis, jaundice, and cholestasis; paralytic ileus, tongue discoloration; stomatitis; parotid swelling. Endocrine: Inappropriate ADH syndrome. Hematologic and Lymphatic: Purpura; bone marrow depression; leukopenia; eosinophilia; thrombocytopenia. Hypersensitivity: Anaphylaxis; angioedema; pruritus; facial edema; urticaria; rash. Metabolic, Nutritional, and Immune: Elevation and lowering of blood sugar levels; weight gain or loss. Musculoskeletal: Local weakness; myalgia. 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; neuroleptic malignant syndrome; decreased or increased libido; abnormal gait; delusions; aggressive behavior; paranoia; peripheral neuropathy; Bell’s palsy; alteration in EEG patterns; extrapyramidal symptoms. Respiratory: Dyspnea. Skin: Sweating; photosensitization; alopecia. Special Senses: Ageusia; tinnitus. Urogenital: Urinary frequency and/or retention; impaired urination; dilatation of urinary tract; impotence; testicular swelling; gynecomastia; breast enlargement; galactorrhea.

Usage information

Dosing and administration
2 DOSAGE AND ADMINISTRATION The recommended adult dose for most patients is one (1) AMRIX 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 and Usage (1) ]. Instruct patients to swallow AMRIX capsules intact. Alternatively, the contents of the AMRIX 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 AMRIX capsules after the contents have been sprinkled on applesauce. Recommended adult dose for most patients is 15 mg taken once daily. Some patients may require 30 mg taken once daily (2) Recommended to take doses at approximately same time each day (2) Instruct patients to swallow AMRIX capsules intact or to sprinkle capsule contents on a tablespoon of applesauce and swallow immediately without chewing (2) Use for periods longer than 2 or 3 weeks is not recommended (2)
Use in special populations
8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Risk Summary Available data from case reports with AMRIX use in pregnancy have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In rats, decreased pup body weight and survival was noted at cyclobenzaprine doses ≥10 mg/kg/day (approximately ≥3 times the maximum recommended human dose (MRHD) of 30 mg/day), when administered orally during pregnancy and lactation (see Data). The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data No adverse embryofetal effects were reported following oral administration of cyclobenzaprine during organogenesis to mice and rabbits at maternal doses up to 20 mg/kg/day (approximately 3 and 15 times the MRHD, respectively, on a mg/m2 basis). Maternal toxicity characterized by decreased body weight gain was observed only in mice at the highest tested dose of 20 mg/kg/day. Decreased pup body weight and survival were reported in a prenatal and postnatal study where pregnant rats were treated orally with cyclobenzaprine during pregnancy and lactation with maternal doses of 10 and 20 mg/kg/day (approximately 3 and 6 times the MRHD on a mg/m2 basis). Maternal toxicity, characterized by a decreased body weight gain, was observed only at the highest tested dose of 20 mg/kg/day. 8.2 Lactation Risk Summary There are no data on the presence of cyclobenzaprine in either human or animal milk, the effects on a breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for AMRIX and any potential adverse effects on the breastfed child from AMRIX or from the underlying maternal condition. 8.4 Pediatric Use Safety and effectiveness of AMRIX have not been studied in pediatric patients. 8.5 Geriatric Use Clinical studies of AMRIX did not include sufficient numbers of patients aged 65 and over to determine the safety and efficacy of AMRIX in the elderly population. The plasma concentration and half-life of cyclobenzaprine are substantially increased in the elderly when compared to the general patient population. Accordingly, use of AMRIX is not recommended in the elderly [see Warnings and Precautions (5.3) and Clinical Pharmacology (12.3)]. 8.6 Hepatic Impairment The use of AMRIX is not recommended in patients with mild, moderate, or severe hepatic impairment [ see Warnings and Precautions (5.4 ) and Clinical Pharmacology (12.3)].

Interactions

7 DRUG INTERACTIONS Based on its structural similarity to tricyclic antidepressants, AMRIX 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)]. MAO Inhibitors: Life-threatening interactions may occur (4, 7) Serotonergic Drugs: Serotonin syndrome has been reported (5.1, 7) CNS Depressants: Effects of alcohol, barbiturates, and other CNS depressants may be enhanced (5.2, 7) Tramadol: Seizure risk may be enhanced (7) Guanethidine: Antihypertensive effect may be blocked (7)

More information

Category Value
Authorisation number NDA021777
Agency product number 0VE05JYS2P
Orphan designation No
Product NDC 63459-700,63459-701
Date Last Revised 21-05-2019
Type HUMAN PRESCRIPTION DRUG
RXCUI 828355
Storage and handling 16.2 Storage and Handling 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].
Marketing authorisation holder Cephalon, Inc.