Active ingredient: Cyclobenzaprine hydrochloride;

1 capsule contains 5 mg or 10 mg of Cyclobenzaprine hydrochloride

Excipients: hydroxypropyl cellulose, iron oxide, hydroxypropyl methylcellulose, lactose, starch, magnesium stearate, and titanium dioxide. Flexeril 5 mg also contains Yellow FD&C #6 Aluminum Lake and Yellow D&C #10 Aluminum Lake HT.

Capsules of prolonged action

Muscle relaxants. Other centrally acting muscle relaxants.

ATX code M03B X08.

Pharmacological.

Cyclobenzaprine relieves spasm of skeletal muscles of local origin, without affecting the function of the muscles. The efficacy of cyclobenzaprine in muscle spasms resulting from a disease of the central nervous system (CNS) was not detected. In animals, cyclobenzaprine reduces or eliminates the skeletal muscle hyperactivity. According to preclinical studies, cyclobenzaprine does not affect the neuromuscular synapse or directly the skeletal muscles. Such studies show that it acts on the central nervous system mainly at the level of the brain stem, and not at the level of the spinal cord, although an additional effect on the latter may contribute to the overall ability of cyclobenzaprine to cause skeletal muscle relaxation. Experience shows that the effect of cyclobenzaprine is a decrease in somatic tonic motor activity due to the effect on both gamma (γ) and alpha (α) moto neurons. Pharmacological preclinical studies have demonstrated similarities between the effects of cyclobenzaprine and structurally related tricyclic antidepressants, including antagonism of reserpine, potentiation of the action of norepinephrine, strong peripheral and central anticholinergic effects, as well as sedation. Cyclobenzaprine leads to an increase (from low to moderate degree) of heart rate in animals.

Pharmacokinetics.

Absorption. After applying a single dose of Flexeril by healthy volunteers (n = 15), the C max, AUC 0-168h, AUC 0-∞ indicators increased approximately in proportion to the dose from 15 to 30 mg. The time to reach the maximum concentration of cyclobenzaprine in plasma (T max) is 7-8 hours for both dosages of the drug.

A study of the effects of eating, conducted with the participation of healthy volunteers (n = 15) using a single dose, demonstrated a statistically significant increase in the bioavailability of Flexeril when taken with food compared with an empty stomach. There was an increase in plasma maximum cyclobenzaprine concentration by 35% (C max) and an increase in exposure (AUC 0-168h, AUC 0-∞) by 20% in the presence of food. However, there was no effect on T max or on the level of dependence of the average plasma concentration of cyclobenzaprine on time. Cyclobenzaprine is first detected in blood plasma after 1.5 hours, both when taken with food and on an empty stomach.

Metabolism and excretion. Cyclobenzaprine is extensively metabolized and excreted by the kidneys, primarily in the form of glucuronides. The half-life of cyclobenzaprine is 32 hours (range 8-37 hours, n = 18); clearance – 0.7 l / min after applying a single dose of the drug.

Elimination of muscle spasm, accompanied by acute pain from the musculoskeletal system, in addition to the limited physical activity and physical therapy. The improvement is manifested by the elimination of muscle spasms and associated signs and symptoms, namely pain, hypersensitivity and movement restrictions.

• Hypersensitivity reactions to the components of the drug, including anaphylactic reactions, urticaria, swelling of the face and / or tongue, itching. In case of suspicion of the development of hypersensitivity reactions, the use of Flexeril should be discontinued.
• Simultaneous use with MAO inhibitors (MAO) or within 14 days after their cancellation. There were observed convulsions and death in patients taken cyclobenzaprine (or structurally similar tricyclic antidepressants) concurrently with MAO inhibitors.
• During the recovery phase after acute myocardial infarction and in the presence of cardiac arrhythmias and conduction, including blockade, or congestive heart failure.
• Hyperthyroidism.

Due to its structural similarity with tricyclic antidepressants, Flexeril may have life-threatening interactions with MAO inhibitors (see “Contra-indications”), may increase the effects of alcohol, barbiturates and other drugs that depress the CNS, and may increase the risk of seizures in patients who use tramadol, or can block the antihypertensive effect of guanethidine and similarly acting compounds.

In the post-marketing period of the drug use, cases of serotonin syndrome have been reported in combination with cyclobenzaprine and other drugs, such as selective serotonin reuptake inhibitors (SSRIs), selective serotonin reuptake inhibitors and noradrenaline reuptake inhibitors, tricyclic anti-depressants (88%), and tricyclic anti-depressants (81%), verapamil, or MAO inhibitors.

Restriction of use.

• Flexeril should be used only in a short time (up to 2-3 weeks), since there is no sufficient evidence of efficacy in using the drug for a longer time and therefore muscle spasm associated with acute pain by the musculoskeletal system is mostly short , and specific therapy for a long period is rarely justified.
• The efficacy of using Flexeril for the treatment of spasticity associated with diseases of the brain or spinal cord, or with cerebral palsy has not been identified.

Serotonin syndrome. The development of a potentially life-threatening serotonin syndrome was registered with cyclobenzaprine in combination with other drugs, such as SSRIs, tramadol, bupropion, meperidine, verapamil, or MAO inhibitors. The simultaneous use of Flexeril with MAO inhibitors is contraindicated (see “Contra-indications”). Symptoms of serotonin syndrome can include changes in the mental state (for example, confusion, agitation, hallucinations), disorders of the autonomic nervous system (such as, increased sweating, tachycardia, blood pressure lability, hyperthermia), neuromuscular disorders (in particular, tremors, ataxia, hyperreflexia, clonus, muscle stiffness, and / or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). If the above reactions are observed, it is necessary to immediately stop taking medication and any associated serotonergic agents and start symptomatic treatment. If simultaneous treatment with Flexeril and other serotonergic drugs is clinically justified, close monitoring of the patient’s condition is recommended, especially at the beginning of treatment or when the dose is increased.

Effects similar to those that occur when using tricyclic antidepressants. Cyclobenzaprine is structurally similar to tricyclic antidepressants, for example, to amitriptyline and imipramine. In the case of the use of tricyclic antidepressants, cases of arrhythmia, sinus tachycardia, an increase in the time of arousal in the heart leading to the development of myocardial infarction and stroke have been reported (see Section “Contraindications”). It may enhance the effects of alcohol, barbiturates and other drugs that inhibit the central nervous system.

Some of the more serious reactions from the CNS, observed with the use of tricyclic antidepressants, were noted in short-term studies with cyclobenzaprine for other indications, except muscle spasm associated with acute disorders of the musculoskeletal system, and mostly in doses that are somewhat large than those recommended to eliminate skeletal muscle spasm. If you experience clinically significant symptoms of the central nervous system, use of the drug should be discontinued.

Elderly patients. The use of the medication in elderly patients is not recommended due to an increase in plasma levels of cyclobenzaprine by 40% and an increase in the half-life by 56% compared with the corresponding indicators in younger patients.

Patients with liver failure. Use is not recommended for patients with mild, moderate or severe liver failure.

Addiction. The pharmacological similarity of tricyclic drugs leads to the appearance of certain withdrawal symptoms after using Flexeril, even if they are not reported. Sudden withdrawal of the drug after long-term use can sometimes cause nausea, headache and malaise. These symptoms do not indicate the development of addiction.

Pregnancy. Adequate and well controlled studies of Flexeril with the participation of pregnant women were not conducted.

Breastfeeding. No data on the excretion of the drug in breast milk. Since cyclobenzaprine is close to tricyclic antidepressants, some of which are known to be excreted into breast milk, Flexeril should be prescribed with caution during breastfeeding.

It is necessary to take into account the possible development of side effects (see. “Side effects”).

The recommended dose is 15 mg once a day. Some patients need to increase the dose to 30 mg 1 time per day. The drug is taken daily at about the same time.

The use of Flexeril more than 2-3 weeks is not recommended.

Elderly patients (65 years and older). Clinical research on the use of the medication in this category of patients is not enough. The use of the preparation in elderly patients is not recommended.

Patients with liver failure. The use of the medication is not recommended for patients with mild, moderate or severe liver failure (” Specifics of applying”).

Children. Clinical data on the efficacy and safety of the medication in children are absent, so Flexeril is not recommended for use in pediatric practice.

Before using the drug, you should consult with your doctor and familiarize yourself with the annotation approved by the manufacturer. Information about the medication should not be used as a guide to self-treatment.

Symptoms. The most common symptoms of a cyclobenzaprine overdose are drowsiness and tachycardia. Less frequent manifestations include tremor, agitation, coma, ataxia, hypertension, vague speech, confusion, dizziness, nausea, vomiting, and hallucinations. Rare, but potentially critical manifestations of overdose include: cardiac arrest, chest pain, arrhythmia, severe hypotension, convulsions, and neuroleptic malignant syndrome. ECG abnormalities, especially changes in the height or width of the QRS complex, are clinically significant indicators of cyclobenzaprine overdose. Other potential consequences of overdose include any of the symptoms listed in the “Side effects” section.

In case of deliberate cyclobenzaprine overdose, its use in combination with several drugs, as well as with alcohol, is frequent. After an overdose of cyclobenzaprine, symptoms of poisoning can develop quickly, therefore, as soon as possible, monitoring of the patient’s condition in the hospital is necessary. An overdose of Flexeril rarely can be fatal.

Treatment.

General. To prevent the occurrence of rare but potentially critical manifestations described above, it is necessary to make an ECG and immediately start monitoring cardiac activity. It is also necessary to protect the patient’s airway, provide intravenous access and begin decontamination of the stomach. Monitoring is also needed to detect signs of CNS depression or respiration, hypotension, cardiac arrhythmia, and / or cardiac conduction blockage. If signs of poisoning occur at any time during this period, extended surveillance will be required.

Decontamination of the gastrointestinal tract. All patients with overdose are required to undergo decontamination of the gastrointestinal tract. It should include gastric lavage with large volumes of fluid followed by the use of activated charcoal.

Cardiovascular system. A maximum duration of QRS duration in standard 0.10 seconds may be the best indicator of the severity of an overdose. Alkalinization of blood serum to a pH level of 7.45-7.55 by administering sodium bicarbonate and hyperventilation (if necessary) should be carried out in patients with arrhythmia and / or expansion of the QRS complex. Level of pH > 7.60 or pCO 2 <20 mm Hg is undesirable. Arrhythmias that do not respond to sodium bicarbonate therapy / hyperventilation may respond to treatment with lidocaine, bretilium or phenytoin. Antiarrhythmic drugs of class 1A and 1C (for example, quinidine, disopyramide and procainamide) are usually contraindicated.

CNS. Patients with CNS depression are recommended early intubation due to the possibility of a sharp deterioration. Convulsions need to be controlled with benzodiazepines or, if the latter are ineffective, with other anticonvulsants (for example, phenobarbital, phenytoin).

Treatment of overdose in children. The principles of overdose in children and adults are similar.

The most common side effects in clinical studies of Flexeril.

The most common adverse reactions that have been reported with a frequency of ≥ 3% are: dry mouth, dizziness, fatigue, constipation, nausea, dyspepsia, and drowsiness.

Additional adverse reactions that have been observed in clinical studies and in post-marketing use. Below you can see adverse reactions that were recorded in clinical studies or post-marketing use of cyclobenzaprine with prolonged action, immediate release cyclobenzaprine or tricyclic preparations.

In the post-registration monitoring program for immediate-release cyclobenzaprine, frequent adverse reactions are: drowsiness, dry mouth and dizziness, and adverse reactions that occurred in 1-3% of patients are: fatigue / fatigue, asthenia, nausea, constipation, dyspepsia, unpleasant taste, blurred vision, headache, nervousness and confusion.

Below adverse reactions that were recorded during post-marketing use of prolonged-release cyclobenzaprine or immediate release cyclobenzaprine in clinical studies (<1%) or during post-marketing use of other tricyclic preparations:

Common disorders: fainting, malaise, chest pain, swelling.

Cardiovascular system: tachycardia, arrhythmia, vasodilation, palpitations, arterial hypotension, arterial hypertension, myocardial infarction, blockade of cardiac conduction, stroke.

Digestive system: vomiting, anorexia, diarrhea, abdominal pain, gastritis, thirst, flatulence, swelling of the tongue, abnormal liver function and rare cases of hepatitis, jaundice and cholestasis, paralytic intestinal obstruction, discoloration of the tongue, stomatitis, swelling of the parotid salivary gland .

Endocrine system: inadequate secretion syndrome.

Blood and lymphatic system: purpura, bone marrow suppression, leukopenia, eosinophilia, thrombocytopenia.

Hypersensitivity reactions: anaphylactic shock, angioedema, pruritus, swelling of the face, urticaria, rash.

Metabolic, nutritional and immune disorders: increase or decrease in blood sugar levels, increase or loss of body weight.

Musculoskeletal system: local muscle weakness, myalgia.

Nervous system: convulsive seizures, ataxia, vertigo, dysarthria, tremor, hypertension, convulsions, muscle twitching, disorientation, insomnia, depressed mood, unusual sensations, anxiety, agitation, psychosis, abnormal thoughts and dreams, hallucinations, unrest , paresthesias, diplopia, serotonin syndrome, neuroleptic malignant syndrome, decreased or increased libido, gait disturbance, delirium, aggressive behavior, paranoia, peripheral neuropathy.

Respiratory system: shortness of breath.

Skin and subcutaneous tissues: sweating, photosensitivity, alopecia.

Kidneys and urinary tract: increase and / or decrease the frequency of urination, impaired urination, dilatation of the urinary tract, impotence, testicular edema, gynecomastia, breast augmentation, galactorrhea.

Four years

Store at a temperature not exceeding 25 ° C. Keep out of the reach of children!

14 capsules in the blister, on 1 blister in a cardboard box.

Cyclobenzaprine, Amrix