Mitrul® cyclobenzaprine hydrochloride 15mg

Mitrul® cyclobenzaprine hydrochloride 15mg Overview

Mitrul® (cyclobenzaprine hydrochloride extended-release capsules) is used to treat muscle spasms associated with acute, painful musculoskeletal conditions as an adjunct to rest and physical therapy. Relief of muscle spasm and its associated signs and symptoms, such as pain, tenderness, and limitation of motion, indicates progress.

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Use Restrictions

Mitrul should be used for short periods (up to two or three weeks) because adequate evidence of efficacy for longer use is lacking, and muscle spasm associated with acute, painful musculoskeletal conditions is generally of short duration, so specific therapy for longer periods is rarely warranted.
Mitrul has not been shown to be effective in the treatment of spasticity caused by cerebral or spinal cord disease, or in the treatment of children with cerebral palsy.
Dosage (Posology) and administration method

The information provided in Mitrul’s Dosage (Posology) and Method of Administration is based on data from another medicine with the exact same composition as Mitrul. Be cautious and specific in the section Dosage (Posology) and method of administration in the instructions to the drug Mitrul directly from the package or from the pharmacist at the pharmacy.
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For most adults, one (1) Mitrul 15 mg capsule taken once daily is the recommended adult dose. Some patients may require up to 30 mg/day, which is administered as one (1) Mitrul 30 mg capsule once daily or two (2) Mitrul 15 mg capsules once daily.

It is suggested that doses be taken at roughly the same time each day.
Mitrul should not be used for more than two or three weeks at a time.

Contraindications

The information in Mitrul Contraindications is based on data from another medicine with the exact same composition as Mitrul. Be cautious and specific in the section Contraindications in the instructions to the drug Mitrul from the package or from the pharmacist at the pharmacy.
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Hypersensitivity to any of the ingredients in this product. These adverse reactions can manifest as anaphylactic shock, urticaria, swelling of the face and/or tongue, or pruritus. If a hypersensitivity reaction is suspected, discontinue Mitrul.
Use of monoamine oxidase (MAO) inhibitors concurrently or within 14 days of discontinuation. Patients receiving cyclobenzaprine (or structurally similar tricyclic antidepressants) concurrently with MAO inhibitor drugs have experienced hyperpyretic crisis seizures and deaths.
During the acute recovery phase of a myocardial infarction, as well as in patients with arrhythmias, heart block, conduction abnormalities, or congestive heart failure.

Hyperthyroidism.
Special precautions and warnings for use

The information in Special warnings and precautions for Mitrul use is based on data from another medicine with the exact same composition as Mitrul. Be cautious and specific in the section Special warnings and precautions for use in the instructions to the drug Mitrul directly from the package or from the pharmacist at the pharmacy.
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WARNINGS
Included in the PRECAUTIONS section.

PRECAUTIONS

Syndrome of Serotonin

When combined with other drugs, such as selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), tramadol, bupropion, meperidine, verapamil, or MAO inhibitors, cyclobenzaprine has been linked to the development of a potentially fatal serotonin syndrome. The use of Mitrul in conjunction with MAO inhibitors is not recommended. Mental status changes (e.g., confusion, agitation, hallucinations), autonomic instability (e.g., diaphoresis, tachycardia, labile blood pressure, hyperthermia), neuromuscular abnormalities (e.g., tremor, ataxia, hyperreflexia, clonus, muscle rigidity), and/or gastrointestinal symptoms are all possible symptoms of serotonin syndrome (e.g., nausea, vomiting, diarrhea). If any of the above reactions occur, treatment with Mitrul and any concomitant serotonergic agents should be discontinued immediately, and supportive symptomatic treatment should be initiated. If concomitant treatment with Mitrul and other serotonergic drugs is clinically indicated, close monitoring is recommended, especially during treatment initiation or dose increases.

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Effects of Tricyclic Antidepressants

Cyclobenzaprine shares structural similarities with tricyclic antidepressants such as amitriptyline and imipramine. Tricyclic antidepressants have been linked to arrhythmias, sinus tachycardia, and conduction time prolongation, which can lead to myocardial infarction and stroke. Mitrul has the potential to amplify the effects of alcohol, barbiturates, and other CNS depressants.

Some of the more serious CNS reactions observed with tricyclic antidepressants have occurred in short-term studies of cyclobenzaprine for indications other than muscle spasm associated with acute musculoskeletal conditions, and usually at doses slightly higher than those recommended for skeletal muscle spasm. If clinically significant CNS symptoms develop, Mitrul should be stopped.

In Elderly People

Mitrul is not recommended for use in the elderly due to a 40% increase in cyclobenzaprine plasma levels and a 56% increase in plasma half-life following administration in elderly subjects compared to young adults.

Use in Hepatic Impairment Patients

Mitrul is not recommended in patients with mild, moderate, or severe hepatic impairment due to two-fold higher cyclobenzaprine plasma levels after administration of immediate-release cyclobenzaprine compared to healthy subjects, and because there is limited dosing flexibility with Mitrul.

Action Similar to Atropine

Mitrul should be used with caution in patients with a history of urinary retention, angle-closure glaucoma, increased intraocular pressure, or who are taking anticholinergic medication due to its atropine-like action.

Information on Patient Counseling

Patients should be advised to discontinue Mitrul and to contact their doctor immediately if they experience symptoms of an allergic reaction, such as difficulty breathing, hives, swelling of the face or tongue, or itching.
Inform patients that Mitrul should not be taken with MAO inhibitors or within 14 days of stopping them.
Warn patients about the risk of serotonin syndrome if Mitrul is combined with other medications such as SSRIs, SNRIs, TCAs, tramadol, bupropion, meperidine, verapamil, or MAO inhibitors. Inform patients about the signs and symptoms of serotonin syndrome and tell them to seek medical attention right away if they experience these symptoms.
Advise patients to discontinue Mitrul and notify their doctor immediately if they experience arrhythmias or tachycardia.
Inform patients that Mitrul may increase the effects of alcohol on their ability to drive. These side effects may be seen if Mitrul is combined with other CNS depressants.
Caution patients about driving a car or operating other dangerous machinery until it is reasonably certain that Mitrul therapy will not impair their ability to do so.
Advise patients to take Mitrul at the same time every day.
Toxicology in Nonclinical Settings
Carcinogenesis, Mutagenesis, and Fertility Impairment
Long-term studies with cyclobenzaprine in CD-1 mice and Sprague-Dawley rats were conducted to assess its carcinogenic potential. Metastatic hemangiosarcoma was observed in 3 of 21 male mice in an 81-week carcinogenicity study at 10 mg/kg/day (2 times the MRHD on a mg/m2 basis). Malignant astrocytoma was observed in 3 of 50 male rats in a 105-week carcinogenicity study at 10 mg/kg/day (3 times the MRHD on a mg/m2 basis). In female mice or rats, no tumours were discovered.

In vitro Ames bacterial mutation assay, in vitro Chinese hamster ovary (CHO) cell chromosomal aberration test, and in vivo mouse bone marrow micronucleus assay, cyclobenzaprine HCl was not mutagenic or clastogenic. At oral doses of up to 20 mg/kg/day (6 times the MRHD in mg/m2), cyclobenzaprine HCl had no effect on fertility or reproductive performance in male or female rats.

In Certain Populations

Pregnancy Pregnancy Type B
There have been no adequate and well-controlled Mitrul studies in pregnant women. Mitrul should be used during pregnancy only if clearly needed, because animal reproduction studies are not always predictive of human response. At approximately 3 and 15 times the maximum recommended human dose (MRHD), respectively (on a mg/m2 basis at maternal doses of 20 mg/kg/day in both mice and rabbits), no treatment-related effects on embryofetal development were observed.

Effects are not teratogenic.

Cyclobenzaprine has been shown in rats to have a negative effect on pup postnatal development when dams were given the drug during pregnancy and lactation. In this study, cyclobenzaprine reduced pup body weight and survival by roughly three times the MRHD (on a mg/m2 basis at maternal doses of 10 and 20 mg/kg/day in rats).

Mothers who are breastfeeding

It is unknown whether this medication is excreted in human milk. Because cyclobenzaprine is related to tricyclic antidepressants, some of which are known to be excreted in human milk, Mitrul should be administered with caution to a nursing woman.

Use in Children

Mitrul’s safety and effectiveness in paediatric patients have not been studied.

Geriatric Application

Mitrul clinical trials did not include a large enough number of patients aged 65 and up to determine the drug’s safety and efficacy in the elderly population. When compared to the general patient population, the elderly have significantly higher plasma concentrations and half-lives of cyclobenzaprine. As a result, using Mitrul in the elderly is not advised.

Impaired Hepatic Function

Mitrul should not be used in patients with mild, moderate, or severe hepatic impairment.

Unwanted consequences

The information provided in Mitrul’s Unwanted Side Effects is based on data from another medicine with the exact same composition as Mitrul. Be cautious and specific in the section Unwanted effects in the instructions to the drug Mitrul directly from the package or from the pharmacist at the pharmacy.
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Adverse Reactions Most Common in Mitrul Clinical Trials

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in one drug’s clinical trials cannot be directly compared to rates observed in another drug’s clinical trials and may not reflect rates observed in clinical practise.

The data presented below reflect Mitrul exposure in 253 patients across two clinical trials. Mitrul was studied in two identical double-blind, parallel-group, placebo-controlled, active-controlled trials. Patients with muscle spasms associated with acute painful musculoskeletal conditions made up the study population. For 14 days, patients were given either 15 mg or 30 mg of Mitrul orally once daily, cyclobenzaprine immediate-release (IR) 10 mg three times a day, or a placebo.

Dry mouth, dizziness, fatigue, constipation, nausea, dyspepsia, and somnolence were the most common adverse reactions (incidence 3% in any treatment group and greater than placebo) (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 Two Phase 3, Double-Blind Studies. The Mitrul Trials Placebo\sN=128 N=127 Mitrul 15 mg N=126 Mitrul 30 mg N=126
Mouth dryness
2%, 6%, and 14%, respectively
2%, 3%, and 6% experience dizziness.
Fatigue
2%, 3%, and 3%, respectively
0%, 1%, 3%
0% 1% 2%
1 percent 3 percent 3 percent nausea
1 % 0 % 4 % Dyspepsia
Mitrul 15 mg QD, Mitrul 30 mg QD, or cyclobenzaprine IR tablets are all options. TID Adverse Reactions from Clinical Trials and Postmarketing Experience
The following adverse reactions to Mitrul, cyclobenzaprine IR, or tricyclic drugs have been reported in clinical studies or postmarketing experience. Because some of these reactions are reported voluntarily from a small population, it is not always possible to estimate their frequency or establish a causal relationship to drug exposure.

In a postmarketing surveillance programme for cyclobenzaprine IR, the most common adverse reactions reported were drowsiness, dry mouth, and dizziness, with the following adverse reactions reported in 1% to 3% of patients: fatigue/tiredness, asthenia, nausea, constipation, dyspepsia, unpleasant taste, blurred vision, headache, nervousness, and confusion.

In postmarketing experience (Mitrul or cyclobenzaprine IR), clinical studies of cyclobenzaprine IR (incidence 1%), or postmarketing experience with other tricyclic drugs, the following adverse reactions have been reported:

Syncope, malaise, chest pain, and edoema are all symptoms of the body as a whole.

Cardiovascular conditions include tachycardia, arrhythmia, vasodilation, palpitation, hypotension, hypertension, myocardial infarction, heart block, and stroke.

Vomiting, anorexia, diarrhoea, gastrointestinal pain, gastritis, thirst, flatulence, tongue edoema, abnormal liver function, and rare reports of hepatitis, jaundice, and cholestasis; paralytic ileus, tongue discoloration, stomatitis, and parotid swelling

Inappropriate ADH syndrome (endocrine).

Hematologic and lymphatic disorders include purpura, bone marrow depression, leukopenia, eosinophilia, and thrombocytopenia.

Anaphylaxis, angioedema, pruritus, facial edoema, urticaria, and rash are all symptoms of hypersensitivity.

Metabolic, nutritional, and immune: blood sugar elevation and decrease; weight gain or loss

Musculoskeletal: Myalgia; local weakness

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;

Dyspnea in the lungs.

Sweating; photosensitization; alopecia

Ageusia and tinnitus are special senses.

Urogenital symptoms include urinary frequency and/or retention, impaired urination, urinary tract dilatation, impotence, testicular swelling, gynecomastia, breast enlargement, and galactorrhea.

Overdose

The information in Mitrul Overdose is based on data from another medicine with the exact same composition as Mitrul. Be cautious and specific in the section Overdose in the instructions to the drug Mitrul from the package or from the pharmacist at the pharmacy.
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Overdosage with Mitrul can result in death, though this is uncommon. Intentional cyclobenzaprine overdose frequently involves the ingestion of multiple drugs (including alcohol). Because overdose management is complex and changing, it is recommended that the physician contact a poison control centre for the most up-to-date treatment information. Toxic signs and symptoms may appear quickly after a cyclobenzaprine overdose; therefore, hospitalisation is required as soon as possible.

Manifestations

Drowsiness and tachycardia are the most common side effects of cyclobenzaprine overdose. Tremor, agitation, coma, ataxia, hypertension, slurred speech, confusion, dizziness, nausea, vomiting, and hallucinations are less common manifestations. Overdose symptoms include cardiac arrest, chest pain, cardiac dysrhythmias, severe hypotension, seizures, and neuroleptic malignant syndrome. Electrocardiogram changes, particularly changes in the QRS axis or width, are clinically significant indicators of cyclobenzaprine toxicity. Overdosage can also cause any of the symptoms listed under Adverse Reactions (6).

Management

General
Because overdose management is complex and changing, it is recommended that the physician contact a poison control centre for the most up-to-date treatment information. Obtain an ECG and begin cardiac monitoring immediately to protect against the rare but potentially fatal manifestations described above. Safeguard the patient’s airway, start an intravenous line, and begin gastric decontamination. It is necessary to monitor the patient’s heart rate and look for signs of CNS or respiratory depression, hypotension, cardiac dysrhythmias and/or conduction blocks, and seizures. Extensive monitoring is required if signs of toxicity appear at any time during this period. Monitoring plasma drug levels should not be used to guide patient management. Dialysis is probably useless due to the drug’s low plasma concentrations.

Decontamination of the Gastrointestine

All patients suspected of taking too much Mitrul should have their gastrointestinal tract decontaminated. Large volume gastric lavage should be followed by activated charcoal. If consciousness is impaired, the airway should be secured before lavage, and emesis should be avoided.

Cardiovascular

A maximum limb-lead QRS duration of 0.10 seconds may be the best indicator of overdose severity. Patients with dysrhythmias and/or QRS widening should have their serum alkalinized to a pH of 7.45 to 7.55 using intravenous sodium bicarbonate and hyperventilation (as needed). A pH greater than 7.60 or a pCO2 greater than 20 mmHg is undesirable. Dysrhythmias that do not respond to sodium bicarbonate therapy or hyperventilation may benefit from lidocaine, bretylium, or phenytoin. Antiarrhythmics of type 1A and 1C are generally contraindicated (e.g., quinidine, disopyramide, and procainamide).

Because of the risk of sudden deterioration in patients with CNS depression, early intubation is recommended. Seizures should be treated with benzodiazepines or, if these fail, with other anticonvulsants (e.g., phenobarbital, phenytoin). Physostigmine should only be used to treat life-threatening symptoms that have not responded to other treatments, and only in close consultation with a poison control centre.

Follow-up Psychiatric Care

Because overdosage is frequently intentional, patients may attempt suicide by other means during the recovery phase. A psychiatric referral may be necessary.

Management of Children

The principles of child and adult overdosage management are similar. It is strongly advised that the doctor contact the local poison control centre for paediatric treatment.

Pharmacokinetic characteristics

The data in Pharmacokinetic properties of Mitrul are based on data from another medicine with the exact same composition as Mitrul. Be cautious and specific in the section Pharmacokinetic properties in the instructions to the drug Mitrul from the package or from the pharmacist at the pharmacy.
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Absorption

Cmax, AUC0-168h, and AUC0- increased approximately doseproportionally from 15 mg to 30 mg in healthy adult subjects (n=15) after single-dose administration of Mitrul 15 mg and 30 mg. For both Mitrul doses, the time to peak plasma cyclobenzaprine concentration (Tmax) was 7 to 8 hours.

A food effect study in healthy adult subjects (n=15) using a single dose of Mitrul 30 mg revealed a statistically significant increase in bioavailability when Mitrul 30 mg was administered with food compared to fasting. In the presence of food, peak plasma cyclobenzaprine concentration (Cmax) increased by 35% and exposure (AUC0-168h and AUC0-) increased by 20%. Tmax and the shape of the mean plasma cyclobenzaprine concentration versus time profile, on the other hand, showed no effect. At 1.5 hours, cyclobenzaprine in plasma was detectable in both fed and fasted states.

A 2.5-fold accumulation of plasma cyclobenzaprine levels was observed at steady-state in a multiple-dose study involving Mitrul 30 mg administered once daily for 7 days in a group of 35 healthy adult subjects.

Excretion and Metabolism

Cyclobenzaprine is extensively metabolised and is primarily excreted as glucuronides through the kidney. Cytochromes P-450 3A4, 1A2, and, to a lesser extent, 2D6 mediate N-demethylation, one of the cyclobenzaprine oxidative pathways. Cyclobenzaprine has an elimination half-life of 32 hours (range 8-37 hours; n=18); plasma clearance after a single dose of Mitrul is 0.7 L/min.

FQAs

Will cyclobenzaprine put me to sleep?

Cyclobenzaprine oral tablet can make you drowsy and dizzy. This is more likely to occur within a few hours of taking it.

Cyclobenzaprine, what is it, and is it a narcotic?

Narcotic Painkiller

Cyclobenzaprine is classified as a separate chemical because of its muscle relaxing properties. Flexeril works by blocking certain nerve impulses that are sent to the brain, but it can be just as addictive as other opioids on the market that are used for similar purposes.

What are the side effects of cyclobenzaprine?

Drowsiness, dizziness, dry mouth, constipation, or tiredness are all possible side effects. Inform your doctor or pharmacist right away if any of these side effects persist or worsen.
Uses, Side Effects, and Dosage of Cyclobenzaprine Oral

Who should avoid taking cyclobenzaprine?

Cyclobenzaprine is not recommended for children under the age of 15. If you have taken an MAO inhibitor within the last 14 days, do not take cyclobenzaprine. A dangerous drug interaction is possible. Isocarboxazid, linezolid, phenelzine, rasagiline, selegiline, and tranylcypromine are all MAO inhibitors.