4. Drug-Drug Interactions
Patient profiles will be assessed to identify those drug regimens, which may result in clinically significant drug-drug interactions. Drug-drug interactions considered clinically significant for skeletal muscle relaxants are summarized in Table 3. Only those drug-drug interactions identified as major severity or those considered life threatening which have not been classified will be reviewed.
| Target Drug | Interacting Drug | Interaction | Recommendation | Clinical Significance Level # |
|---|---|---|---|---|
| cyclobenzaprine | MAOIs | combined administration may increase risk of hypertensive crises, convulsions, and death; mechanism not determined but may be due to additive norepinephrine effects or serotonin syndrome | combined use contraindicated; do not use cyclobenzaprine within 14 days of MAOI discontinuation | contraindicated (DrugReax) 1-severe (CP) |
| cyclobenzaprine, tizanidine | QT interval-prolonging medications | Cyclobenzaprine is structurally related to TCAs, which have been associated with QT interval prolongation; combined administration may increase risk of QT interval prolongation; tizanidine also associated with QT interval prolongation in post marketing reports | administer combination cautiously and monitor for QT interval prolongation | contraindicated (DrugReax) 1-severe (CP) |
| cyclobenzaprine | SSRIs/SNRIs | combined administration may increase risk of serotonin syndrome (e.g., tremor, fever, agitation, seizures, coma) due to additive serotonergic effects | administer drug combination cautiously; monitor closely for signs/symptoms of serotonin syndrome | major (DrugReax) 2-major (CP) |
| cyclobenzaprine | tramadol | combined administration may increase seizure risk as cyclobenzaprine is structurally related to TCAs and TCAs may decrease seizure threshold; combined use may also increase risk of serotonin syndrome | avoid combination, if possible, especially in patients predisposed to seizures; if combination necessary, monitor closely for seizure activity and serotonin syndrome sign/ symptoms | major (DrugReax) 3-moderate (CP) |
| orphenadrine | phenothiazines | combined administration may result in decreased phenothiazine serum levels/decreased phenothiazine effectiveness due to orphenadrine anticholinergic effects, which delay phenothiazine gastric emptying and absorption; combined therapy may also produce additive anticholinergic effects | avoid combination, if possible; if combined therapy necessary, adjust phenothiazine doses to effect | moderate (DrugReax) 3-moderate (CP) |
| skeletal muscle relaxants | CNS depressants | increased risk of additive CNS depressant effects (e.g., sedation, respiratory depression) | administer combined therapy cautiously; adjust doses as necessary | major (DrugReax) 3-moderate (CP) |
| tizanidine | potent CYP1A2 inhibitors (e.g., ciprofloxacin, fluvoxamine) | tizanidine is primarily metabolized by CYP1A2; adjunctive administration may result in increased tizanidine levels/enhanced pharmacologic/adverse effects (e.g., hypotension, excessive sedation) due to substantial CYP1A2 | combined use contraindicated | contraindicated (DrugReax) 1-severe (CP) |
| tizanidine | other CYP1A2 inhibitors (e.g., acyclovir, verapamil) | tizanidine primarily metabolized by CYP1A2; adjunctive administration may result in increased tizanidine levels and enhanced pharmacologic/ adverse effects (e.g., hypotension, excessive sedation) due to substantial CYP1A2 inhibition | avoid combination, if possible; if adjunctive therapy necessary, administer cautiously and observe for increased adverse effects | major (DrugReax) 2-major (CP) |
Legend:
- #CP = Clinical Pharmacology
- CNS = central nervous system
- MAOIs = monoamine oxidase inhibitors
- SNRIs = serotonin/norepinephrine reuptake inhibitors
- SSRIs = selective serotonin reuptake inhibitors
- TCAs = tricyclic antidepressant