Norflex

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Norflex

Classes

Muscle Relaxants, Centrally Acting, Plain

Administration
Oral Administration

May be administered without regard to meals.

Injectable Administration

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Orphenadrine is administered intramuscularly or intravenously.

Intravenous Administration

Administer over a period of 5 minutes with the patient in a supine position. The patient should remain in this position for 5—10 minutes following the injection. To minimize adverse reactions, the patient should be assisted from the recumbent position.

Intramuscular Administration

Inject deeply into a large muscle, preferably high into the deltoid muscle. Aspirate prior to injection to avoid injection into a blood vessel.

Adverse Reactions
Severe

ocular hypertension / Delayed / Incidence not known
aplastic anemia / Delayed / Incidence not known
anaphylactoid reactions / Rapid / Incidence not known

Moderate

sinus tachycardia / Rapid / Incidence not known
palpitations / Early / Incidence not known
blurred vision / Early / Incidence not known
confusion / Early / Incidence not known
hallucinations / Early / Incidence not known
constipation / Delayed / Incidence not known
urinary retention / Early / Incidence not known
euphoria / Early / Incidence not known

Mild

agitation / Early / Incidence not known
mydriasis / Early / Incidence not known
vomiting / Early / Incidence not known
xerostomia / Early / Incidence not known
nausea / Early / Incidence not known
drowsiness / Early / Incidence not known
headache / Early / Incidence not known
dizziness / Early / Incidence not known
weakness / Early / Incidence not known
urticaria / Rapid / Incidence not known
syncope / Early / Incidence not known
tremor / Early / Incidence not known
pruritus / Rapid / Incidence not known

Common Brand Names

Banflex, Norflex

Dea Class

Rx

Description

Oral/parenteral centrally acting muscle relaxant; analog of diphenhydramine used primarily as adjunct therapy for acute, painful musculoskeletal conditions.

Dosage And Indications
For adjunctive therapy to rest, physical therapy, and other measures for the relief of musculoskeletal pain associated with acute, painful musculoskeletal conditions. Oral dosage (orphenadrine citrate) Adults

100 mg PO twice daily in the morning and evening.

Intramuscular and Intravenous dosage (orphenadrine citrate) Adults

For acute relief, the usual dosage is 60 mg IV or IM every 12 hours. Oral therapy should replace parenteral therapy as soon as possible.

For use as an adjunct to physical therapy and other medications in the treatment of postencephalic, arteriosclerotic, or idiopathic parkinsonism†. Oral dosage (orphenadrine hydrochloride) Adults

Doses of 150—225 mg PO per day were studied in one small trial (10 patients received orphenadrine). The dosing interval used in this trial was not specified; however, daily doses are divided every 12 hours for other indications. Smaller doses may be used if other antiparkinson medications are being administered concurrently.

†Indicates off-label use

Dosing Considerations
Hepatic Impairment

Orphenadrine is metabolized by the liver and caution is recommended; however, no quantitative recommendations are available.

Renal Impairment

No dosage adjustment needed.

Drug Interactions

Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Acetaminophen; Caffeine; Dihydrocodeine: (Major) Concomitant use of opioid agonists with orphenadrine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking orphenadrine.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Acetaminophen; Chlorpheniramine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Acetaminophen; Codeine: (Major) Concomitant use of opioid agonists with orphenadrine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking orphenadrine.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Additive CNS depression is possible if skeletal muscle relaxants are used concomitantly with other CNS depressants. Dosage adjustments of one or both medications may be necessary.
Acetaminophen; Diphenhydramine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Acetaminophen; Hydrocodone: (Major) Concomitant use of opioid agonists with orphenadrine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking orphenadrine.
Acetaminophen; Oxycodone: (Major) Concomitant use of opioid agonists with orphenadrine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial oxycodone dosage by one-third to one-half when using the extended-release tablets.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Acrivastine; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Alfentanil: (Major) Concomitant use of alfentanil with orphenadrine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Alosetron: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like orphenadrine, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Alprazolam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Amantadine: (Moderate) Additive anticholinergic effects and drowsiness may be seen when orphenadrine is used concomitantly with amantadine.
Amitriptyline: (Moderate) Orphenadrine should be combined cautiously with tricyclic antidepressants due to the potential for additive anticholinergic and CNS depressant effects. Antimuscarinic effects might be seen on GI smooth muscle, bladder function, the eye, and temperature regulation. Consider an alternative skeletal muscle relaxant.
Amobarbital: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Amoxapine: (Moderate) Orphenadrine should be combined cautiously with cyclic antidepressants like amoxapine because they could cause additive sedation or anticholinergic effects. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Patients should be monitored for excessive adverse effects from either agent.
Anxiolytics; Sedatives; and Hypnotics: (Moderate) Additive CNS depressant effects may be seen with combination use of orphenadrine and anxiolytics, sedatives, and hypnotics.
Apomorphine: (Moderate) Apomorphine causes significant somnolence. Concomitant administration of apomorphine and CNS depressants could result in additive depressant effects.
Aspirin, ASA; Butalbital; Caffeine: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Aspirin, ASA; Carisoprodol; Codeine: (Major) Concomitant use of opioid agonists with orphenadrine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking orphenadrine.
Aspirin, ASA; Oxycodone: (Major) Concomitant use of opioid agonists with orphenadrine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial oxycodone dosage by one-third to one-half when using the extended-release tablets.
Atropine: (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other commonly used drugs with moderate to significant anticholinergic effects including orphenadrine. Clinicians should note that anticholinergic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Atropine; Difenoxin: (Moderate) Concurrent administration of diphenoxylate/difenoxin with orphenadrine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other commonly used drugs with moderate to significant anticholinergic effects including orphenadrine. Clinicians should note that anticholinergic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Azelastine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and skeletal muscle relaxants. Concurrent use may result in additive CNS depression.
Azelastine; Fluticasone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of azelastine and skeletal muscle relaxants. Concurrent use may result in additive CNS depression.
Barbiturates: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Belladonna; Opium: (Major) Concomitant use of opoid agonists with orphenadrine may cause respiratory depression, profound sedation, and death. Limit the use of opioid agonists with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. Consider prescribing naloxone for emergency treatment of opioid overdose.
Benzhydrocodone; Acetaminophen: (Major) Concomitant use of benzhydrocodone with orphenadrine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Benzodiazepines: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with other drugs with moderate to significant anticholinergic effects including orphenadrine.
Benztropine: (Moderate) Additive anticholinergic effects may be seen when benztropine is used concomitantly with other drugs that possess anticholinergic properties, such as orphenadrine. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
Botulinum Toxins: (Moderate) Excessive neuromuscular weakness may be exacerbated by coadministration of a botulinum toxin with skeletal muscle relaxants. Advise patients to seek medical assistance if they develop any unusual symptoms (including difficulty with swallowing, speaking, or breathing or walking), or if any existing symptom worsens during use of a botulinum toxin.
Brompheniramine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Brompheniramine; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Brompheniramine; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly with other drugs with moderate to significant anticholinergic effects including orphenadrine.
Buprenorphine: (Moderate) If concurrent use of orphenadrine and buprenorphine is necessary, consider a dose reduction of one or both drugs because of the potential for additive pharmacological effects. Sedation, coma, or respiratory depression may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
Buprenorphine; Naloxone: (Moderate) If concurrent use of orphenadrine and buprenorphine is necessary, consider a dose reduction of one or both drugs because of the potential for additive pharmacological effects. Sedation, coma, or respiratory depression may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
Butabarbital: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Butalbital; Acetaminophen: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Butalbital; Acetaminophen; Caffeine: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Concomitant use of opioid agonists with orphenadrine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking orphenadrine. (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Concomitant use of opioid agonists with orphenadrine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking orphenadrine. (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Butorphanol: (Moderate) Concomitant use of butorphanol with other CNS depressants can potentiate the effects of butorphanol on respiratory depression, CNS depression, and sedation.
Calcium, Magnesium, Potassium, Sodium Oxybates: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with skeletal muscle relaxants.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and orphenadrine. CNS depressants can potentiate the effects of cannabidiol.
Carbidopa; Levodopa; Entacapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including skeletal muscle relaxants, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Carbinoxamine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Celecoxib; Tramadol: (Major) Concomitant use of tramadol with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and orphenadrine. Concurrent use may result in additive CNS depression.
Cetirizine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and skeletal muscle relaxants due to the risk for additive CNS depression.
Cetirizine; Pseudoephedrine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and skeletal muscle relaxants due to the risk for additive CNS depression.
Chlophedianol; Dexbrompheniramine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Chlorcyclizine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Chlordiazepoxide: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Chlordiazepoxide; Amitriptyline: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation. (Moderate) Orphenadrine should be combined cautiously with tricyclic antidepressants due to the potential for additive anticholinergic and CNS depressant effects. Antimuscarinic effects might be seen on GI smooth muscle, bladder function, the eye, and temperature regulation. Consider an alternative skeletal muscle relaxant.
Chlordiazepoxide; Clidinium: (Moderate) Additive anticholinergic effects may be seen when orphenadrine is used concomitantly with other antimuscarinics. (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Chlorpheniramine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Chlorpheniramine; Codeine: (Major) Concomitant use of opioid agonists with orphenadrine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking orphenadrine. (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Chlorpheniramine; Dextromethorphan: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) Concomitant use of opioid agonists with orphenadrine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking orphenadrine. (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Chlorpheniramine; Hydrocodone: (Major) Concomitant use of opioid agonists with orphenadrine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking orphenadrine. (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Chlorpheniramine; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Chlorpheniramine; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Chlorpromazine: (Moderate) Additive anticholinergic effects may be seen when chlorpromazine is used concomitantly with other drugs having antimuscarinic activity such as orphenadrine. Additive sedation may also occur.
Clemastine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Clomipramine: (Moderate) Orphenadrine should be combined cautiously with tricyclic antidepressants due to the potential for additive anticholinergic and CNS depressant effects. Antimuscarinic effects might be seen on GI smooth muscle, bladder function, the eye, and temperature regulation. Consider an alternative skeletal muscle relaxant.
Clonazepam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Clorazepate: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Clozapine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like clozapine and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Codeine: (Major) Concomitant use of opioid agonists with orphenadrine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking orphenadrine.
Codeine; Guaifenesin: (Major) Concomitant use of opioid agonists with orphenadrine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking orphenadrine.
Codeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of opioid agonists with orphenadrine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking orphenadrine.
Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of opioid agonists with orphenadrine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking orphenadrine. (Moderate) Additive anticholinergic effects may be seen when promethazine is used concomitantly with other drugs having antimuscarinic activity such as orphenadrine. Additive sedation may also occur.
Codeine; Promethazine: (Major) Concomitant use of opioid agonists with orphenadrine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking orphenadrine. (Moderate) Additive anticholinergic effects may be seen when promethazine is used concomitantly with other drugs having antimuscarinic activity such as orphenadrine. Additive sedation may also occur.
COMT inhibitors: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including skeletal muscle relaxants, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Cyclizine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Cyclobenzaprine: (Major) Orphenadrine has mild anticholinergic activity. Additive anticholinergic effects may be seen when orphenadrine is used concomitantly with other antimuscarinics, such as cyclobenzaprine. Clinicians should note that anticholinergic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Cyproheptadine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Darifenacin: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like darifenacin are used concomitantly with orphenadrine.
Desipramine: (Moderate) Orphenadrine should be combined cautiously with tricyclic antidepressants due to the potential for additive anticholinergic and CNS depressant effects. Antimuscarinic effects might be seen on GI smooth muscle, bladder function, the eye, and temperature regulation. Consider an alternative skeletal muscle relaxant.
Deutetrabenazine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as orphenadrine, may have additive effects and worsen drowsiness or sedation.
Dexbrompheniramine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Dexchlorpheniramine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Dexmedetomidine: (Moderate) Due to the anesthetic effects of dexmedetomidine, concurrent use with other CNS depressants, such as skeletal muscle relaxants, could result in additive sedative effects and possibly prolong recovery from anesthesia. Dosage adjustments of either or both medications may be necessary.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Diazepam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Dicyclomine: (Moderate) Additive anticholinergic effects may be seen when dicyclomine is used concomitantly with other drugs that possess anticholinergic properties, such as orphenadrine. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive drowsiness may also occur.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Dimenhydrinate: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Diphenhydramine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Diphenhydramine; Ibuprofen: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Diphenhydramine; Naproxen: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Diphenhydramine; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Diphenoxylate; Atropine: (Moderate) Concurrent administration of diphenoxylate/difenoxin with orphenadrine can potentiate the CNS-depressant effects of diphenoxylate/difenoxin. Use caution during coadministration. (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other commonly used drugs with moderate to significant anticholinergic effects including orphenadrine. Clinicians should note that anticholinergic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Disopyramide: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties like disopyramide and orphenadrine are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation.
Donepezil: (Moderate) The therapeutic benefits of donepezil may be diminished when co-administered with drugs known to exhibit anticholinergic properties, such as orphenadrine, the functional antagonists of the cholinesterase inhibitors.
Donepezil; Memantine: (Moderate) The therapeutic benefits of donepezil may be diminished when co-administered with drugs known to exhibit anticholinergic properties, such as orphenadrine, the functional antagonists of the cholinesterase inhibitors.
Doxepin: (Moderate) Orphenadrine should be combined cautiously with tricyclic antidepressants due to the potential for additive anticholinergic and CNS depressant effects. Antimuscarinic effects might be seen on GI smooth muscle, bladder function, the eye, and temperature regulation. Consider an alternative skeletal muscle relaxant.
Doxylamine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Doxylamine; Pyridoxine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Dronabinol: (Moderate) Concomitant use of skeletal muscle relaxants with dronabinol can result in additive CNS depression and dizziness, which can impair the ability to undertake tasks requiring mental alertness. Utilize appropriate caution if these drugs are given together.
Droperidol: (Moderate) Additive CNS depressant effects may be seen with combination use of orphenadrine and droperidol. Dosage reduction and/or discontinuance of one or both drugs is recommended.
Entacapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including skeletal muscle relaxants, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Esketamine: (Major) Closely monitor patients receiving esketamine and skeletal muscle relaxants for sedation and other CNS depressant effects. Patients who receive a dose of esketamine should not drive or engage in other activities requiring alertness until the next day after a restful sleep.
Estazolam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Eszopiclone: (Moderate) Additive CNS depressant effects may be seen with combination use of orphenadrine and anxiolytics, sedatives, and hypnotics.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
Etomidate: (Moderate) General anesthetics potentiate the effects of other CNS depressants, including skeletal muscle relaxants.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and orphenadrine. Concurrent use may result in additive CNS depression.
Fentanyl: (Major) Concomitant use of fentanyl with orphenadrine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Fesoterodine: (Moderate) Coadministration of fesoterodine and other drugs with moderate to significant anticholinergic effects such as orphenadrine may increase the frequency and/or severity of anticholinergic effects such as blurred vision, constipation, xerostomia, and urinary retention. Additive effects may be seen on GI smooth muscle, bladder function, the CNS, the eye, and temperature regulation.
Flavoxate: (Moderate) Additive anticholinergic effects may be seen when orphenadrine is used concomitantly with other antimuscarinics.
Fluphenazine: (Moderate) Additive anticholinergic effects may be seen when fluphenazine is used concomitantly with other drugs having antimuscarinic activity such as orphenadrine.
Flurazepam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Gabapentin: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and orphenadrine. Concomitant use of gabapentin with orphenadrine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
Galantamine: (Moderate) The therapeutic benefits of galantamine may be diminished when co-administered with drugs known to exhibit anticholinergic properties, such as orphenadrine.
General anesthetics: (Moderate) General anesthetics potentiate the effects of other CNS depressants, including skeletal muscle relaxants.
Glycopyrrolate: (Moderate) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly with other drugs with moderate to significant anticholinergic effects including orphenadrine.
Glycopyrrolate; Formoterol: (Moderate) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly with other drugs with moderate to significant anticholinergic effects including orphenadrine.
Guaifenesin; Hydrocodone: (Major) Concomitant use of opioid agonists with orphenadrine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking orphenadrine.
Haloperidol: (Moderate) Orphenadrine has mild anticholinergic activity. Concomitant use of orphenadrine and haloperidol may worsen schizophrenic symptoms. Tardive dyskinesia may also develop.
Homatropine; Hydrocodone: (Major) Concomitant use of opioid agonists with orphenadrine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking orphenadrine. (Moderate) The anticholinergic effects of homatropine may be enhanced when combined with other drugs with moderate to significant anticholinergic effects including orphenadrine.
Hydrocodone: (Major) Concomitant use of opioid agonists with orphenadrine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking orphenadrine.
Hydrocodone; Ibuprofen: (Major) Concomitant use of opioid agonists with orphenadrine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking orphenadrine.
Hydrocodone; Pseudoephedrine: (Major) Concomitant use of opioid agonists with orphenadrine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Avoid prescribing opioid cough medication in patients taking orphenadrine.
Hydromorphone: (Major) Concomitant use of opioid agonists with orphenadrine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations.
Hydroxyzine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Hyoscyamine: (Moderate) Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with other drugs with moderate to significant anticholinergic effects including orphenadrine.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with other drugs with moderate to significant anticholinergic effects including orphenadrine.
Ibuprofen; Oxycodone: (Major) Concomitant use of opioid agonists with orphenadrine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial oxycodone dosage by one-third to one-half when using the extended-release tablets.
Imipramine: (Moderate) Orphenadrine should be combined cautiously with tricyclic antidepressants due to the potential for additive anticholinergic and CNS depressant effects. Antimuscarinic effects might be seen on GI smooth muscle, bladder function, the eye, and temperature regulation. Consider an alternative skeletal muscle relaxant.
Indacaterol; Glycopyrrolate: (Moderate) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly with other drugs with moderate to significant anticholinergic effects including orphenadrine.
Isoflurane: (Moderate) General anesthetics potentiate the effects of other CNS depressants, including skeletal muscle relaxants.
Ketamine: (Moderate) General anesthetics potentiate the effects of other CNS depressants, including skeletal muscle relaxants.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and orphenadrine. Concurrent use may result in additive CNS depression.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and orphenadrine. Dosage adjustments of lemborexant and orphenadrine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Levocetirizine: (Moderate) Monitor for unusual drowsiness and sedation during coadministration of cetirizine and skeletal muscle relaxants due to the risk for additive CNS depression.
Levorphanol: (Major) Concomitant use of opioid agonists with orphenadrine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial levorphanol dosage by 50% or more.
Lofexidine: (Major) Monitor for excessive hypotension and sedation during coadministration of lofexidine and orphenadrine. Lofexidine can potentiate the effects of CNS depressants.
Lorazepam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Loxapine: (Moderate) Loxapine and orphenadrine both have anticholinergic activity. The concomitant use of these drugs can increase the risk of anticholinergic adverse reactions including exacerbation of glaucoma, constipation, and urinary retention. Loxapine is a central nervous system (CNS) depressant. The concurrent use of loxapine with other CNS depressants (e.g., muscle relaxants such as orphenadrine) can increase the risk of respiratory depression, hypotension, profound sedation, and syncope. Therefore, consider reducing the dose of CNS depressants if used concomitantly with loxapine.
Lumateperone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lumateperone and skeletal muscle relaxants. Concurrent use may result in additive CNS depression.
Maprotiline: (Moderate) Skeletal muscle relaxants should be combined cautiously with cyclic antidepressants like maprotiline because they could cause additive CNS depressant effects. Depending on the specific agent (e.g., cyclobenzaprine, and orphenadrine), additive anticholinergic effects may also be seen. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Patients should be monitored for excessive adverse effects from either agent.
Meclizine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Meperidine: (Major) Concomitant use of opioid agonists with orphenadrine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations.
Meprobamate: (Moderate) Additive CNS depressant effects may be seen with combination use of orphenadrine and anxiolytics, sedatives, and hypnotics.
Methadone: (Major) Concomitant use of methadone with orphenadrine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequ

ate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with other drugs with moderate to significant anticholinergic effects including orphenadrine.
Methohexital: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Methscopolamine: (Moderate) Additive anticholinergic effects may be seen when orphenadrine is used concomitantly with other antimuscarinics.
Midazolam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Mirtazapine: (Moderate) Skeletal muscle relaxants like orphenadrine may cause additive CNS depression if used concomitantly with other drugs with CNS depressant properties such as mirtazapine. Combination therapy may amplify sedation and dizziness, which can impair the patient's ability to perform tasks requiring mental alertness. Dosage adjustments of either or both medications may be necessary in some instances.
Molindone: (Moderate) Simultaneous use of skeletal muscle relaxants and other CNS depressants, such as molindone, can increase CNS depression. In addition, antipsychotics are associated with anticholinergic effects; therefore, additive effects may be seen during concurrent use of molindone and other drugs having anticholinergic activity. Clinicians should note that antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Morphine: (Major) Concomitant use of morphine with orphenadrine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation.
Morphine; Naltrexone: (Major) Concomitant use of morphine with orphenadrine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. For extended-release morphine tablets (MS Contin and Morphabond), start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of respiratory depression and sedation.
Nabilone: (Major) Avoid use together if possible. Use of nabilone with skeletal muscle relaxants can potentiate the CNS depressant effects of nabilone on sedation, dizziness and other side effects, which can impair the ability to undertake tasks requiring mental alertness.
Nalbuphine: (Major) Concomitant use of nalbuphine with orphenadrine may cause excessive sedation and somnolence. Limit the use of nalbuphine with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations.
Neostigmine; Glycopyrrolate: (Moderate) Additive anticholinergic effects may be seen when glycopyrrolate is used concomitantly with other drugs with moderate to significant anticholinergic effects including orphenadrine.
Nortriptyline: (Moderate) Orphenadrine should be combined cautiously with tricyclic antidepressants due to the potential for additive anticholinergic and CNS depressant effects. Antimuscarinic effects might be seen on GI smooth muscle, bladder function, the eye, and temperature regulation. Consider an alternative skeletal muscle relaxant.
Olanzapine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like olanzapine and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Olanzapine; Fluoxetine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like olanzapine and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Olanzapine; Samidorphan: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like olanzapine and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Oliceridine: (Major) Concomitant use of oliceridine with orphenadrine may cause excessive sedation and somnolence. Limit the use of oliceridine with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Opicapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including skeletal muscle relaxants, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Oxazepam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Oxybutynin: (Moderate) Additive anticholinergic effects may be seen when oxybutynin is used concomitantly with other drugs that have moderate to significant anticholinergic effects, including orphenadrine. Clinicians should note that anticholinergic effects might be seen not only on bladder smooth muscle, but also on GI function, the eye, and temperature regulation. Additive drowsiness may also occur.
Oxycodone: (Major) Concomitant use of opioid agonists with orphenadrine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial oxycodone dosage by one-third to one-half when using the extended-release tablets.
Oxymorphone: (Major) Concomitant use of opioid agonists with orphenadrine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Reduce the initial oxymorphone dosage by one-third to one-half.
Paroxetine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like paroxetine and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation.
Pentazocine: (Major) Concomitant use of pentazocine with orphenadrine may cause respiratory depression, profound sedation, and death. Limit the use of pentazocine with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. Consider prescribing naloxone for the emergency treatment of opioid overdose.
Pentazocine; Naloxone: (Major) Concomitant use of pentazocine with orphenadrine may cause respiratory depression, profound sedation, and death. Limit the use of pentazocine with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation. Consider prescribing naloxone for the emergency treatment of opioid overdose.
Pentobarbital: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Perphenazine: (Moderate) Additive anticholinergic effects may be seen when perphenazine is used concomitantly with other drugs having antimuscarinic activity such as orphenadrine. Additive sedation may also occur.
Perphenazine; Amitriptyline: (Moderate) Additive anticholinergic effects may be seen when perphenazine is used concomitantly with other drugs having antimuscarinic activity such as orphenadrine. Additive sedation may also occur. (Moderate) Orphenadrine should be combined cautiously with tricyclic antidepressants due to the potential for additive anticholinergic and CNS depressant effects. Antimuscarinic effects might be seen on GI smooth muscle, bladder function, the eye, and temperature regulation. Consider an alternative skeletal muscle relaxant.
Phenobarbital: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Additive anticholinergic effects may be seen when hyoscyamine is used concomitantly with other drugs with moderate to significant anticholinergic effects including orphenadrine. (Moderate) Additive anticholinergic effects may be seen when scopolamine is used concomitantly with other drugs with moderate to significant anticholinergic effects including orphenadrine. (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation. (Moderate) The anticholinergic effects of atropine may be enhanced when combined with other commonly used drugs with moderate to significant anticholinergic effects including orphenadrine. Clinicians should note that anticholinergic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Pregabalin: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and orphenadrine. Concomitant use of pregabalin with orphenadrine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
Primidone: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Prochlorperazine: (Moderate) Additive anticholinergic effects may be seen when prochlorperazine is used concomitantly with other drugs having antimuscarinic activity such as orphenadrine. Additive sedation may also occur.
Promethazine: (Moderate) Additive anticholinergic effects may be seen when promethazine is used concomitantly with other drugs having antimuscarinic activity such as orphenadrine. Additive sedation may also occur.
Promethazine; Dextromethorphan: (Moderate) Additive anticholinergic effects may be seen when promethazine is used concomitantly with other drugs having antimuscarinic activity such as orphenadrine. Additive sedation may also occur.
Promethazine; Phenylephrine: (Moderate) Additive anticholinergic effects may be seen when promethazine is used concomitantly with other drugs having antimuscarinic activity such as orphenadrine. Additive sedation may also occur.
Propantheline: (Moderate) Additive anticholinergic effects may be seen when orphenadrine is used concomitantly with other antimuscarinics.
Propofol: (Moderate) General anesthetics potentiate the effects of other CNS depressants, including skeletal muscle relaxants.
Protriptyline: (Moderate) Orphenadrine should be combined cautiously with tricyclic antidepressants due to the potential for additive anticholinergic and CNS depressant effects. Antimuscarinic effects might be seen on GI smooth muscle, bladder function, the eye, and temperature regulation. Consider an alternative skeletal muscle relaxant.
Pseudoephedrine; Triprolidine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Pyrilamine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Quazepam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Remifentanil: (Major) Concomitant use of remifentanil with orphenadrine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Remimazolam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Rivastigmine: (Moderate) Concurrent use of certain muscle relaxants, such as cyclobenzaprine or orphenadrine, with rivastigmine should be avoided if possible. Rivastigmine inhibits acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine. Use of cyclobenzaprine or high doses of orphenadrine may result in significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Scopolamine: (Moderate) Additive anticholinergic effects may be seen when scopolamine is used concomitantly with other drugs with moderate to significant anticholinergic effects including orphenadrine.
Secobarbital: (Moderate) Concomitant use of skeletal muscle relaxants with barbiturates can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take barbiturates with another CNS depressant for symptoms of excess sedation.
Sedating H1-blockers: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Sevoflurane: (Moderate) General anesthetics potentiate the effects of other CNS depressants, including skeletal muscle relaxants.
Sodium Oxybate: (Major) Sodium oxybate should not be used in combination with CNS depressant anxiolytics, sedatives, and hypnotics or other sedative CNS depressant drugs. Additive CNS depressant effects may be possible when sodium oxybate is used concurrently with skeletal muscle relaxants.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and orphenadrine. CNS depressants can potentiate the effects of stiripentol.
Sufentanil: (Major) Concomitant use of sufentanil with orphenadrine may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Tapentadol: (Major) Concomitant use of opioid agonists with orphenadrine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with orphenadrine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations.
Temazepam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Thalidomide: (Major) Avoid the concomitant use of thalidomide with other central nervous system depressants such as skeletal muscle relaxants due to the potential for additive sedative effects.
Thioridazine: (Moderate) Additive anticholinergic effects may be seen when thioridazine is used concomitantly with other drugs having antimuscarinic activity such as orphenadrine. Additive sedation may also occur.
Thiothixene: (Moderate) Thiothixene can potentiate the CNS-depressant action of other drugs, such skeletal muscle relaxants. Caution should be exercised during simultaneous use of these agents due to potential excessive CNS effects or additive hypotension.
Tolcapone: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including skeletal muscle relaxants, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Tolterodine: (Moderate) Additive anticholinergic effects may be seen when orphenadrine is used concomitantly with other drugs known to possess anticholinergic properties including tolterodine. Clinicians should note that anticholinergic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Tramadol: (Major) Concomitant use of tramadol with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Tramadol; Acetaminophen: (Major) Concomitant use of tramadol with a skeletal muscle relaxant may cause respiratory depression, hypotension, profound sedation, and death. Limit the use of opioid pain medications with a skeletal muscle relaxant to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, reduce initial dosage and titrate to clinical response; use the lowest effective doses and minimum treatment durations. Educate patients about the risks and symptoms of respiratory depression and sedation.
Trazodone: (Moderate) CNS depressants, such as skeletal muscle relaxants, should be used cautiously in patients receiving trazodone because of additive CNS-depressant effects, including possible respiratory depression or hypotension. A dose reduction of one or both drugs may be warranted.
Triazolam: (Moderate) Concomitant use of skeletal muscle relaxants with benzodiazepines can result in additive CNS depression. The severity of this interaction may be increased when additional CNS depressants are given. Monitor patients who take benzodiazepines with another CNS depressant for symptoms of excess sedation.
Tricyclic antidepressants: (Moderate) Orphenadrine should be combined cautiously with tricyclic antidepressants due to the potential for additive anticholinergic and CNS depressant effects. Antimuscarinic effects might be seen on GI smooth muscle, bladder function, the eye, and temperature regulation. Consider an alternative skeletal muscle relaxant.
Trifluoperazine: (Moderate) Additive anticholinergic effects may be seen when trifluoperazine is used concomitantly with other drugs having antimuscarinic activity such as orphenadrine. Additive sedation may also occur.
Trihexyphenidyl: (Moderate) Additive anticholinergic effects may be seen when orphenadrine is used concomitantly with other antimuscarinics.
Trimipramine: (Moderate) Orphenadrine should be combined cautiously with tricyclic antidepressants due to the potential for additive anticholinergic and CNS depressant effects. Antimuscarinic effects might be seen on GI smooth muscle, bladder function, the eye, and temperature regulation. Consider an alternative skeletal muscle relaxant.
Triprolidine: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties, like sedating H1-blockers and orphenadrine, are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Trospium: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like trospium are used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects including orphenadrine. Clinicians should note that anticholinergic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Zaleplon: (Moderate) Additive CNS depressant effects may be seen with combination use of orphenadrine and anxiolytics, sedatives, and hypnotics.
Ziprasidone: (Moderate) Ziprasidone has the potential to impair cognitive and motor skills. Additive CNS depressant effects are possible when ziprasidone is used concurrently with any CNS depressant, including orphenadrine.
Zolpidem: (Moderate) Additive CNS depressant effects may be seen with combination use of orphenadrine and anxiolytics, sedatives, and hypnotics.

How Supplied

Banflex/Norflex/Orphenadrine Citrate Intramuscular Inj Sol: 1mL, 30mg
Banflex/Norflex/Orphenadrine Citrate Intravenous Inj Sol: 1mL, 30mg
Norflex/Orphenadrine Citrate Oral Tab ER: 100mg

Maximum Dosage
Adults

200 mg/day PO; 120 mg/day IV/IM.

Elderly

200 mg/day PO; 120 mg/day IV/IM.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Mechanism Of Action

Mechanism of Action: The exact mechanism of action of orphenadrine has not been determined. Orphenadrine may reduce skeletal muscle spasm, possibly through actions on cerebral motor centers or on the medulla. Orphenadrine does not have a direct skeletal muscle relaxant effect. The drug does have analgesic activity, which may contribute to its skeletal muscle relaxant properties. Orphenadrine also possesses postganglionic anticholinergic effects and some antihistaminic and local anesthetic action. The antihistaminic activity is less than that of diphenhydramine; contrary to the sedative effect of diphenhydramine, orphenadrine produces a mild CNS stimulation.

Pharmacokinetics

Orphenadrine is administered intramuscularly, intravenously, and orally. Distribution of the drug has not been fully determined. Animal data suggest that the drug and/or its metabolites are distributed to all organs, particularly those with high perfusion (e.g., lungs). Orphenadrine may cross the placenta. It is not known if the drug is distributed into human milk. The metabolism of orphenadrine has not been fully characterized; the drug is almost completely metabolized to at least 8 metabolites. Orphenadrine is excreted primarily in the urine as metabolites and, in small amounts, as unchanged drug. The elimination half-life is approximately 14 hours.

Oral Route

Following oral administration, orphenadrine is readily absorbed from the gastrointestinal tract.

Pregnancy And Lactation
Pregnancy

Orphenadrine is classified as pregnancy risk category C. Animal reproduction studies have not been performed. It is also not known whether orphenadrine can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. In one large surveillance study, 411 newborns had been exposed to orphenadrine during the first trimester. Eleven major birth defects were observed and 16 were expected. However, because these pregnancy outcome data are too limited to be conclusive, orphenadrine should be used during pregnancy only if clearly needed. The effects of orphenadrine during labor and delivery are unknown.

Manufacturer recommendations for breast-feeding mothers are not available for orphenadrine. It is not known if orphenadrine is distributed into breast milk and there is no information available on the effects of orphenadrine in a nursing infant. If treatment with orphenadrine cannot be avoided during breast-feeding, the infant should be monitored for commonly encountered adverse effects of orphenadrine therapy including drowsiness and constipation. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.