Index
It is a white crystalline tricyclic amine salt. It has a melting point of 217 ° C and a pKa of 8.47 at 25 ° C.
If aqueous solutions become alkaline, the free base separates. Cyclobenzaprine hydrochloride is designated chemically as 3- (5H-dibenzo [a, d] cyclohexane-5-ylidene) -N, N-dimethyl-1-propanamide hydrochloride.
Dorixin (cyclobenzaprine hydrochloride or cyclobenzaprine hydrochloride) is available for oral administration in 7.5 mg tablets. Dorixin contains the following inactive ingredients:
- Colloidal silicon dioxide.
- Croscarmellose sodium.
- Dibasic calcium phosphate.
- Hydroxypropyl cellulose.
- Hypromellose, polyethylene glycol.
- Magnesium stearate.
- Microcrystalline cellulose.
- Titanium dioxide.
A single oral dose for adults and children over 14 years is 50 mg, rectally 100 mg, intravenous slowly or intramuscularly 50-100 mg. If the efficacy of parenteral injection is not enough, it is possible to take an oral dose of 50 mg after 20-30 minutes.
Ingredients that match Dorixin
- Clonixin.
Clonixin is reported as an ingredient in Dorixin in the following countries:
- Lebanon.
Clonixin Lysine (a derivative of Clonixin) is reported as an ingredient of Dorixin in the following countries:
- Argentina.
- Costa Rica.
- Ecuador.
- The Savior.
- Guatemala.
- Honduras.
- Mexico.
- Nicaragua.
- Panama.
- Peru.
- Venezuela.
What is dorixin for
Dorixin is a non-steroidal anti-inflammatory drug. It also has analgesic, antipyretic, and platelet inhibitory actions.
It is indicated for treating pain and spasm of smooth muscle located in any part of the digestive tract, genitourinary and hepatolenticular level. Its main indications are:
Gastrointestinal: painful spastic syndrome of the esophagus, pyloric colon, intestinal or irritable colon.
Urinary system: renal colic, ureteral and bladder spasm, cystitis and cistopyelitis, kidney or ureteral stones. It is also used when an instrumental examination of the urinary tract is done.
Female genital tract: functional dysmenorrhea, premenstrual tension, spasm of the tubes, painful adnexal processes, and spastic pains in the puerperium.
Dorixin reduced or abolished skeletal muscle hyperactivity in various animal models. Animal studies indicate that Dorixin does not act at the neuromuscular junction or directly on skeletal muscle.
These studies show that Dorixin acts primarily within the central nervous system in the brain stem instead of levels in the spinal cord. However, its action on the latter may contribute to its overall skeletal muscle relaxant activity.
Evidence suggests that the net effect of Dorixin is a reduction in tonic somatic motor activity, which influences both the gamma (γ) and alpha (α) motor systems.
Pharmacological studies in animals showed a similarity between the effects of Dorixin and structurally related tricyclic antidepressants, including reserpine antagonism, norepinephrine potentiation, potent peripheral and central anticholinergic effects, and sedation.
Pharmacokinetics
Estimates of the mean oral bioavailability of Dorixin range from 33% to 55%.
At steady state in healthy subjects receiving 10 mg tid (n = 18), the maximum plasma concentration was 25.9 ng / mL (range, 12.8-46.1 ng / mL), and the area under the concentration-time curve for a 8 hour dosing interval was 177 ng.hr/mL (range, 80-319 ng.hr/mL).
Elderly
In a pharmacokinetic study in elderly individuals, the mean (n = 10) area values under the Dorixin curve at a steady-state were approximate:
1.7 times (171.0 ng. hr/mL, range 96.1 to 255.3) higher than those observed in a group of eighteen younger adults (101.4 ng. hr/mL, range 36.1 to 182.9) from another study.
Elderly male subjects had the highest observed mean increase, approximately 2.4 times (198.3 ng. hr/mL, range 155.6 to 255.3 versus 83.2 ng. hr/mL, range 41.1 to 142.5 for younger men).
While, levels in older women increased too much less, about 1.2 times (143.8 ng. hr/mL, range 96.1 to 196.3 versus 115.9 ng. hr/mL, range 36.1 to 182.9 for younger women).
In light of these findings, Dorixin therapy in the elderly should be started with a 5 mg dose and titrated slowly upward.
Hepatic impairment
Based on the findings, Dorixin should be used with caution in subjects with mild hepatic impairment starting with the 5 mg dose and slowly titrating upward.
Due to the lack of data in subjects with more severe hepatic impairment, the use of Dorixin is not recommended in subjects with moderate to severe impairment.
No significant effect on plasma levels or bioavailability of Dorixin or aspirin was observed when single or multiple doses of the two drugs were administered concomitantly.
Concomitant administration of Dorixin and naproxen or diflunisal was well tolerated, with no unexpected adverse effects. However, the combination therapy of Dorixin with naproxen was associated with more side effects than therapy with naproxen alone, mainly in the form of drowsiness.
There have been no well-controlled studies to indicate that Dorixin improves the clinical effect of aspirin or other pain relievers or whether pain relievers increase the clinical impact of Dorixin in acute musculoskeletal conditions.
Clinical studies
Eight double-blind controlled clinical studies were conducted in 642 patients comparing Dorixin 10 mg, diazepam, and placebo. Muscle spasms, local pain and tenderness, limitation of movement, and restriction in activities of daily living were evaluated.
In three of these studies, there was a significantly more significant improvement with Dorixin than with diazepam, while in the other studies, the improvement after both treatments was comparable.
Although the frequency and severity of adverse reactions observed in patients treated with Dorixin were comparable to those observed in patients treated with diazepam, dry mouth was observed more frequently in patients treated with Dorixin and dizziness more frequently in those treated with diazepam.
The incidence of drowsiness, the most common adverse reaction, was similar with both drugs.
The efficacy of Dorixin 5 mg was demonstrated in two 7-day, double-blind, controlled clinical trials involving 1405 patients. One study compared Dorixin 5 and 10 mg tid to placebo, and a second study compared Dorixin 5 and 2.5 mg tid to placebo.
The primary endpoints for both trials were determined using patient-generated data and included:
- A global impression of change.
- The usefulness of the drug.
- Initial back pain relief.
Each endpoint consisted of a score on a 5-point rating scale. Secondary endpoints included a physician’s assessment of the presence and extent of palpable muscle spasms.
Comparisons of Dorixin 5 mg and placebo groups in both trials established statistically significant superiority of the 5 mg dose for the three primary endpoints on day eight and, in the study comparing 5 and 10 mg, on day 3 or 4.
A similar effect was seen with Dorixin 10 mg (all endpoints). Physician-evaluated secondary endpoints also showed that Dorixin 5 mg was associated with a more significant reduction in palpable muscle spasms than placebo.
Analysis of data from controlled studies shows that Dorixin produces clinical improvement whether sedation occurs or not.
Surveillance program
A post-marketing surveillance program was conducted in 7607 patients with acute musculoskeletal disorders and included 297 patients treated with Dorixin 10 mg for 30 days or more.
The overall effectiveness of Dorixin was similar to that observed in double-blind controlled studies; the overall incidence of adverse effects was lower.
Indications and use
The improvement is manifested by the relief of muscle spasms and their associated signs and symptoms, namely pain, tenderness, limitation of movement, and restriction in activities of daily living.
Dorixin should be used only for short periods (up to two to three weeks) because there is no adequate evidence of effectiveness for more prolonged use. The muscle spasm associated with acute and painful musculoskeletal conditions is generally short-lived and rarely warranted—specific therapy for more extended periods.
Contraindications
The concomitant use of Dorixin with monoamine oxidase inhibitors is contraindicated.
Treatment with Dorixin and any concomitant serotonergic agents should be stopped immediately if the above reactions occur, and supportive symptomatic therapy should be started.
General
Due to its atropine-like action, Dorixin should be used with caution in patients with a history of urinary retention, angle-closure glaucoma, increased intraocular pressure, and anticholinergic medications.
Impaired liver function
Dorixin plasma concentration increases in patients with hepatic impairment.
These patients are generally more susceptible to medications with potentially sedating effects, including Dorixin. Dorixin should be used with caution in subjects with mild hepatic impairment, starting with a 5 mg dose and slowly titrating upward.
Due to the lack of data in subjects with more severe hepatic impairment, the use of Dorixin is not recommended in subjects with moderate to severe impairment.
Information for patients
In the elderly, the frequency and severity of adverse events associated with Dorixin, with or without concomitant medications, increases. In elderly patients, Dorixin should be started with a 5 mg dose and titrated slowly upward.
Patients should be warned about the risk of serotonin syndrome with the concomitant use of Dorixin and other medications, such as:
Selective serotonin reuptake inhibitors, norepinephrine serotonin reuptake inhibitors, tricyclic antidepressants, tramadol, bupropion, meperidine, verapamil, or monoamine oxidase inhibitors.
Patients should be informed of the signs and symptoms of serotonin syndrome and instructed to seek medical attention immediately if they experience these symptoms.
Interactions with other drugs
Dorixin can have life-threatening interactions with monoamine oxidase inhibitors. Monoamine oxidase inhibitors are a possible development of serotonin syndrome.
Post-marketing cases of serotonin syndrome have been reported during the combined use of Dorixin.
Medications that provide a depressing effect on the central nervous system or with ethanol may increase tramadol’s main nervous system depressant effects.
Serotonin reuptake inhibitors, tricyclic antidepressants, antipsychotics, and other means of lowering the threshold of seizure readiness, increase the risk of seizures.
Warfarin and phenprocoumon increase the anticoagulant effect. Carbamazepine reduced the plasma concentration of tramadol and its analgesic effect. Paroxetine describes cases of serotonin syndrome and seizures.
Long-term use of opioids or barbiturate analgesics encourages the development of cross-tolerance.
Naloxone activates respiration, eliminating analgesia after opioid pain relievers.
Carcinogenesis, mutagenesis, impaired fertility
At oral doses up to 10 times the human dose, Dorixin did not adversely affect male or female rats’ reproductive performance or fertility.
Dorixin did not demonstrate mutagenic activity in the male mouse at dose levels up to 20 times the human dose.
Nursing mothers
It is not known whether this drug is excreted in human milk.
Pediatric use
The safety and efficacy of Dorixin in pediatric patients under 15 years of age have not been established. For children 1 to 14 years old, set the dose rate to 1-2 mg/kg.
The duration of treatment is determined individually. The maximum dose for adults and children over 14 years of age, regardless of the method of administration, is 400 mg/day.
Use in the elderly
Dorixin plasma concentration increases in the elderly. The elderly may also be at increased risk for adverse central nervous system events, such as hallucinations and confusion, cardiac events resulting in falls or other sequelae, and drug-drug and drug-disease interactions.
For these reasons, in the elderly, Dorixina should be used only if necessary. Dorixin should be started at a 5 mg dose and titrated upward in such patients.
Adverse reactions
Adverse reactions that were reported in 1% to 3% of patients were:
Abdominal pain, acid regurgitation, constipation, diarrhea, dizziness, nausea, irritability, decreased mental alertness, nervousness, upper respiratory infection, and pharyngitis.
The most frequently reported adverse reactions with Dorixin were drowsiness, dry mouth, and dizziness.
The list of adverse reactions is based on experience in 473 patients treated with Dorixin 10 mg in additional controlled clinical studies, 7607 patients in the post-marketing surveillance program, and reports received since the medicine was marketed.
The overall incidence of adverse reactions among patients in the surveillance program was lower than the incidence in controlled clinical studies.
The following adverse reactions were reported in post-marketing experience or with an incidence of less than 1% of patients in clinical trials with the 10 mg tablet:
Body as a whole: syncope; discomfort.
Special senses: Ageusia (alteration in the sense of taste); tinnitus.
Urogenital : urinary frequency and / or retention.
Central nervous system: dizziness, weakness, drowsiness, confusion, and, in some cases, seizures and convulsions of brain origin (for intravenous uses in high doses or with the concomitant administration of neuroleptics).
Cardiovascular system: tachycardia, orthostatic hypotension, collapse.
Digestive system: dry mouth, nausea, vomiting.
Metabolism: increased sweating.
Musculoskeletal system: miosis.
Note: Dorixin 10 mg tablets date from a clinical trial. Dorixin 5 mg tablets and placebo data are from two studies.
Abuse and dependency
The pharmacological similarities between tricyclic drugs require that specific withdrawal symptoms be considered when Dorixin is given, although they have not been reported to occur with this drug.
After prolonged administration, the abrupt discontinuation of treatment can rarely cause nausea, headache, and general malaise. These are not indicative of addiction.
Overdose
Although rare, deaths can occur from overdose with Dorixin. Ingestion of multiple drugs (including alcohol) is common in deliberate Dorixin overdose.
Signs and symptoms of toxicity can develop rapidly after a Dorixin overdose; therefore, hospital monitoring is required as soon as possible.
Management
Central Nervous System
In patients with central nervous system depression, early intubation is recommended due to the potential for abrupt deterioration. Seizures should be controlled with benzodiazepines or, if ineffective, with other anticonvulsants (e.g., phenobarbital, phenytoin).
Psychiatric follow-up
Since overdose is often deliberate, patients may attempt suicide by other means during the recovery phase. A psychiatric referral may be appropriate.
Pediatric management
The principles of overdose treatment for children and adults are similar. It is strongly recommended that the physician contact the local poison control center for specific pediatric treatment.
Dosage
For most patients, the recommended dose of Dorixin is 5 mg three times a day. Depending on the patient’s response, the dose can be increased to 7.5 mg or 10 mg three times a day. The use of Dorixina for periods longer than two or three weeks is not recommended.
