Ziprasidone
Cyclobenzaprine Interactions
NOTE: Based on in vitro data, the CYP3A4 enzyme and CYP1A2 enzyme are primarily responsible for the hepatic metabolism of cyclobenzaprine via N-demethylation in humans. Cyclobenzaprine is a minor substrate for CYP2D6. In addition, cyclobenzaprine is structurally similar to a tricyclic antidepressant agent. Cyclobenzaprine has antimuscarinic and CNS depressant properties, and has potential to prolong the QT interval at higher doses. These factors are considered in regard to potential drug interactions.
Cyclobenzaprine is structurally very similar to tricyclic antidepressants (TCAs) such as amitriptyline. Clinically and in terms of toxicology or side effect profiles, cyclobenzaprine differs little from the TCAs. Such effects include potential for antimuscarinic effects such as dry mouth, urinary difficulty, and impairment of gastrointestinal motility. As with the TCAs, cardiac adverse effects of cyclobenzaprine would be expected in overdose or in cases of excessive pharmacology. In general, the concurrent use of cyclobenzaprine with tricyclic antidepressants should be avoided whenever possible due to the potential for adverse effects resulting from similar pharmacology; consider alternative agents for skeletal muscle relaxation.
Cyclobenzaprine possesses antimuscarinic properties, which can cause dry mouth, urinary difficulties and slowing of gastrointestinal motility. If used with other drugs with antimuscarinic properties, anticholinergic side effects can be additive. Examples of drugs that should be used cautiously with cyclobenzaprine for this reason include: amoxapine; atropine, dicyclomine and other antimuscarinics; bupropion; clozapine; most tricyclic antidepressants; maprotiline; most antipsychotic phenothiazines; and sedating H1-blockers. Particular attention should be paid to GI problems because of the possible development of paralytic ileus.
Cyclobenzaprine may cause additive CNS depression, if used concomitantly with other CNS depressants. such as anxiolytics, sedatives, and hypnotics, benzodiazepines, barbiturates, opiate agonists, buprenorphine, butorphanol, nalbuphine, pentazocine, tricyclic antidepressants, phenothiazines, dronabinol, THC, ethanol, or H1-blockers. The phytomedicinal herbs valerian, Valeriana officinalis or kava kava, Piper methysticum may also interact in this fashion. Combination therapy can cause additive effects of sedation and dizziness, which can impair the patient’s ability to undertake tasks requiring mental alertness. Dosage adjustments of either or both medications may be necessary.
The antihypertensive effects of guanadrel or guanethidine can be decreased by cyclobenzaprine.
Concurrent use of clonidine with tricyclic antidepressants (TCAs) should be avoided when possible. Clonidine’s antihypertensive effect can be reduced by TCAs; occasionally, the hypertension will occur within the first few days of combined therapy. Cyclobenzaprine is structurally related to the TCAs, so caution is also warranted when combining cyclobenzaprine with clonidine. If coadministration with clonidine cannot be avoided, the patient should be closely monitored for increased blood pressure and clonidine dosages adjusted as needed. In addition, concurrent administration of cyclobenzaprine and clonidine may result in additive CNS depression or other side effects; clonidine produces mental depression as a side effect in roughly 1% of patients.
Cyclobenzaprine should not be used concomitantly with MAOIs; possibly fatal adverse reactions can occur. An interval of 14 days should elapse between discontinuation of MAOI therapy and initiation of therapy with cyclobenzaprine. Five to 7 days should elapse between discontinuation of cyclobenzaprine therapy and the beginning of MAOI therapy.
Cyclobenzaprine should be given cautiously with tramadol. Tricyclic compounds that decrease the seizure threshold have been associated with an increased risk of seizures when given concurrently with tramadol.
Cyclobenzaprine is structurally similar to tricyclic antidepressants. Tricyclic antidepressants have reported to prolong the QT interval, especially when given in excessive doses (or in overdosage settings). A case of torsade de pointes (TdP) has been reported with cyclobenzaprine, when given in combination with droperidol (also associated with TdP). It is prudent to use cyclobenzaprine with caution with drugs which prolong the QT interval. Drugs which have been established to have a causal association with QT prolongation and TdP include: Class IA antiarrhythmics (disopyramide, procainamide, quinidine), Class III antiarrhythmics (amiodarone, bretylium, dofetilide, ibutilide, sotalol), astemizole, arsenic trioxide, bepridil, cisapride, chloroquine, clarithromycin, droperidol, erythromycin, grepafloxacin, halofantrine, haloperidol, levomethadyl, methadone, pentamidine, certain phenothiazines (chlorpromazine, mesoridazine, and thioridazine), pimozide, probucol, sparfloxacin, and terfenadine. Other agents associated with a lower, but possible risk for QT prolongation and TdP based on varying levels of documentation (see separate drug monographs) include: abarelix, alfuzosin, amoxapine, apomorphine, beta-agonists, certain quinolones (ofloxacin, ciprofloxacin, gatifloxacin, gemifloxacin, levofloxacin, moxifloxacin, norfloxacin), clozapine, dolasetron, flecainide, halogenated anesthetics, local anesthetics, maprotiline, mefloquine, octreotide, ofloxacin, palonosetron, some phenothiazines (fluphenazine, perphenazine, prochlorperazine, and trifluoperazine), propafenone, ranolazine, risperidone, sertindole, tacrolimus, telithromycin, tricyclic antidepressants when given in excessive doses or overdosage, troleandomycin (based on interactions with macrolides), vardenafil, or ziprasidone. This list is not inclusive of all agents that may cause QT interval prolongation. In addition, some of the listed drugs have CYP3A4 inhibitory properties (e.g., amiodarone, erythromycin, clarithromycin, ranolazine, troleandomycin), and could theoretically inhibit the metabolism of cyclobenzaprine. In addition to avoiding concurrent drug interactions (see Drug Interactions), the potential for TdP can be reduced by avoiding the use of QT prolonging drugs in patients at substantial risk for TdP. Examples of general risk factors for TdP include congenital long QT syndrome, female sex, elderly patients, significant bradycardia, hypokalemia, hypomagnesemia, and underlying cardiac disease (e.g., arrhythmias, cardiomyopathy, acute myocardial ischemia).
Based on in vitro data, the CYP3A4 enzyme and CYP1A2 enzyme are primarily responsible for the hepatic metabolism of cyclobenzaprine via N-demethylation in humans. Theoretically, levels of cyclobenzaprine could rise due to inhibition at the 3A4 enzyme; however, the clinical significance of potential interactions has not been established. Observe the patient for enhanced side effects, such as CNS depression, if cyclobenzaprine and CYP3A4 inhibitors are coadministered. Examples of CYP3A4 inhibitors include: amiodarone, anti-retroviral protease inhibitors, systemic azole antifungals (e.g., ketoconazole, itraconazole, voriconazole, fluconazole), clarithromycin, conivaptan, dalfopristin; quinupristin, delavirdine, diltiazem, efavirenz (induces or inhibits) , erythromycin, imatinib, STI-571, nefazodone, nicardipine, troleandomycin, verapamil, and zafirlukast. This list is not inclusive of all CYP3A4 inhibitors.
Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Cyclobenzaprine should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Because medications that decrease salivation increase the time of sodium iodide I-131 induced radiation exposure to salivary glands, consider discontinuing medications with antimuscarinic activity including cyclobenzaprine prior to sodium iodide I-131 administration.
[ Last revised: 4/4/2006 5:13:00 PM ]
References
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