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Interactions between Cyclobenzaprine and Trihexyphenidyl

1 drug interaction and 24 additional warnings found for the following 2 drugs:

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Drug interactions

Moderate drug interactions

Moderate:

cyclobenzaprine trihexyphenidyl

Applies to: cyclobenzaprine and trihexyphenidyl
Monitor

Agents with anticholinergic properties (e.g., sedating antihistamines; antispasmodics; neuroleptics; phenothiazines; skeletal muscle relaxants; tricyclic antidepressants; disopyramide) may have additive effects when used in combination. Excessive parasympatholytic effects may result in paralytic ileus, hyperthermia, heat stroke, and the anticholinergic intoxication syndrome. Peripheral symptoms of intoxication commonly include mydriasis, blurred vision, flushed face, fever, dry skin and mucous membranes, tachycardia, urinary retention, and constipation. Central symptoms may include memory loss, disorientation, incoherence, hallucinations, psychosis, delirium, hyperactivity, twitching or jerking movements, stereotypy, and seizures. Central nervous system-depressant effects may also be additively or synergistically increased when these agents are combined, especially in elderly or debilitated patients. Use of neuroleptics in combination with other neuroleptics or anticholinergic agents may increase the risk of tardive dyskinesia. In addition, some neuroleptics and tricyclic antidepressants may cause prolongation of the QT interval and theoretically, concurrent use of two or more drugs that can cause QT interval prolongation may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death.

Management

Caution is advised when agents with anticholinergic properties are combined, particularly in the elderly and those with underlying organic brain disease, who tend to be more sensitive to the central anticholinergic effects of these drugs and in whom toxicity symptoms may be easily overlooked. Patients should be advised to notify their physician promptly if they experience potential symptoms of anticholinergic intoxication such as abdominal pain, fever, heat intolerance, blurred vision, confusion, and/or hallucinations. Ambulatory patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them. A reduction in anticholinergic dosages may be necessary if excessive adverse effects develop.

References (15)
  1. Stadnyk AN, Glezos JD (1983) "Drug-induced heat stroke." Can Med Assoc J, 128, p. 957-9
  2. Zelman S, Guillan R (1970) "Heat stroke in phenothiazine-treated patients: a report of three fatalities." Am J Psychiatry, 126, p. 1787-90
  3. Mann SC, Boger WP (1978) "Psychotropic drugs, summer heat and humidity, and hyperplexia: a danger restated." Am J Psychiatry, 135, p. 1097-100
  4. Warnes H, Lehmann HE, Ban TA (1967) "Adynamic ileus during psychoactive medication: a report of three fatal and five severe cases." Can Med Assoc J, 96, p. 1112-3
  5. Gershon S, Neubauer H, Sundland DM (1965) "Interaction between some anticholinergic agents and phenothiazines." Clin Pharmacol Ther, 6, p. 749-56
  6. Sarnquist F, Larson CP Jr (1973) "Drug-induced heat stroke." Anesthesiology, 39, p. 348-50
  7. Johnson AL, Hollister LE, Berger PA (1981) "The anticholinergic intoxication syndrome: diagnosis and treatment." J Clin Psychiatry, 42, p. 313-7
  8. Lee BS (1986) "Possibility of hyperpyrexia with antipsychotic and anticholinergic drugs." J Clin Psychiatry, 47, p. 571
  9. Forester D (1978) "Fatal drug-induced heat stroke." JACEP, 7, p. 243-4
  10. Moreau A, Jones BD, Banno V (1986) "Chronic central anticholinergic toxicity in manic depressive illness mimicking dementia." Can J Psychiatry, 31, p. 339-41
  11. Hvizdos AJ, Bennett JA, Wells BG, Rappaport KB, Mendel SA (1983) "Anticholinergic psychosis in a patient receiving usual doses of haloperidol." Clin Pharm, 2, p. 174-8
  12. Cohen MA, Alfonso CA, Mosquera M (1994) "Development of urinary retention during treatment with clozapine and meclizine [published erratum appears in Am J Psychiatry 1994 Jun;151(6):952]." Am J Psychiatry, 151, p. 619-20
  13. (2001) "Product Information. Cogentin (benztropine)." Merck & Co., Inc
  14. Kulik AV, Wilbur R (1982) "Delirium and stereotypy from anticholinergic antiparkinson drugs." Prog Neuropsychopharmacol Biol Psychiatry, 6, p. 75-82
  15. (2001) "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories

Food/lifestyle interactions

Moderate food/lifestyle interactions

Moderate:

cyclobenzaprine Food/Lifestyle

Applies to: cyclobenzaprine
Generally avoid

Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

Management

Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References (4)
  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka America Pharmaceutical, Inc.
Moderate:

trihexyphenidyl Alcohol (Ethanol)

Applies to: trihexyphenidyl
Generally avoid

Use of anticholinergic agents with alcohol may result in sufficient impairment of attention so as to render driving and operating machinery more hazardous. In addition, the potential for abuse may be increased with the combination. The mechanism of interaction is not established but may involve additive depressant effects on the central nervous system. No effect of oral propantheline or atropine on blood alcohol levels was observed in healthy volunteers when administered before ingestion of a standard ethanol load. However, one study found impairment of attention in subjects given atropine 0.5 mg or glycopyrrolate 1 mg in combination with alcohol.

Management

Alcohol should generally be avoided during therapy with anticholinergic agents. Patients should be counseled to avoid activities requiring mental alertness until they know how these agents affect them.

References (1)
  1. Linnoila M (1973) "Drug effects on psychomotor skills related to driving: interaction of atropine, glycopyrrhonium and alcohol." Eur J Clin Pharmacol, 6, p. 107-12

Disease interactions

22 potential interactions Applies to: 19 conditions, including High Blood Pressure, Heart Failure, Arrhythmia, Hypotension, and Hyperthyroidism.

Arrhythmia

Major:

trihexyphenidyl

Trihexyphenidyl has a major potential interaction with Arrhythmia.

Patients with tachycardia should be supervised closely during treatment with anticholinergic agents. Tachycardia is produced by blocking normal vagal inhibition of the SA node. Paradoxically, bradycardia may occur due to central vagal stimulation which may occur prior to peripheral cholinergic blockade.

Autonomic Neuropathy

Major:

trihexyphenidyl

Trihexyphenidyl has a major potential interaction with Autonomic Neuropathy.

Agents with anticholinergic activity can exacerbate many of the manifestations of autonomic neuropathy, including tachycardia, anhidrosis, bladder atony, obstipation, dry mouth and eyes, cycloplegia and blurring of vision, and sexual impotence in males. Therapy with antimuscarinic agents and higher dosages of antispasmodic agents (e.g., dicyclomine or oxybutynin) should be administered cautiously in patients with autonomic neuropathy.

Cardiovascular Conditions and Disorders

Major:

cyclobenzaprine

Cyclobenzaprine has a major potential interaction with Cardiovascular Conditions and Disorders.

The manufacturers consider the use of cyclobenzaprine to be contraindicated in the acute recovery phase following myocardial infarction and in patients with hyperthyroidism, congestive heart failure, arrhythmias, heart block, and/or conduction disturbances. Cyclobenzaprine is structurally related to the tricyclic antidepressants, which have been reported to cause tachycardia, arrhythmias, heart block, hypertension, hypotension (particularly orthostatic hypotension), thrombosis, thrombophlebitis, myocardial infarction, strokes, congestive heart failure, and ECG abnormalities such as PR and QT interval prolongation. Therapy with cyclobenzaprine should be administered cautiously in patients with a history of cardiovascular or cerebrovascular disease or a predisposition to hypotension, particularly if the intended dosage exceeds those normally used for musculoskeletal conditions. Tachycardia, arrhythmia, palpitation, and hypotension have been reported with the use of cyclobenzaprine in less than 1% of patients.

Cerebrovascular Insufficiency

Major:

cyclobenzaprine

Cyclobenzaprine has a major potential interaction with Cerebrovascular Insufficiency.

The manufacturers consider the use of cyclobenzaprine to be contraindicated in the acute recovery phase following myocardial infarction and in patients with hyperthyroidism, congestive heart failure, arrhythmias, heart block, and/or conduction disturbances. Cyclobenzaprine is structurally related to the tricyclic antidepressants, which have been reported to cause tachycardia, arrhythmias, heart block, hypertension, hypotension (particularly orthostatic hypotension), thrombosis, thrombophlebitis, myocardial infarction, strokes, congestive heart failure, and ECG abnormalities such as PR and QT interval prolongation. Therapy with cyclobenzaprine should be administered cautiously in patients with a history of cardiovascular or cerebrovascular disease or a predisposition to hypotension, particularly if the intended dosage exceeds those normally used for musculoskeletal conditions. Tachycardia, arrhythmia, palpitation, and hypotension have been reported with the use of cyclobenzaprine in less than 1% of patients.

Dehydration

Major:

cyclobenzaprine

Cyclobenzaprine has a major potential interaction with Dehydration.

The manufacturers consider the use of cyclobenzaprine to be contraindicated in the acute recovery phase following myocardial infarction and in patients with hyperthyroidism, congestive heart failure, arrhythmias, heart block, and/or conduction disturbances. Cyclobenzaprine is structurally related to the tricyclic antidepressants, which have been reported to cause tachycardia, arrhythmias, heart block, hypertension, hypotension (particularly orthostatic hypotension), thrombosis, thrombophlebitis, myocardial infarction, strokes, congestive heart failure, and ECG abnormalities such as PR and QT interval prolongation. Therapy with cyclobenzaprine should be administered cautiously in patients with a history of cardiovascular or cerebrovascular disease or a predisposition to hypotension, particularly if the intended dosage exceeds those normally used for musculoskeletal conditions. Tachycardia, arrhythmia, palpitation, and hypotension have been reported with the use of cyclobenzaprine in less than 1% of patients.

Esophageal Obstruction

Major:

trihexyphenidyl

Trihexyphenidyl has a major potential interaction with Esophageal Obstruction.

Anticholinergics are contraindicated in patients with obstructive diseases such as achalasia, esophageal stricture or stenosis, pyloroduodenal stenosis, stenosing peptic ulcer, pyloric obstruction, and paralytic ileus. Anticholinergics may further suppress intestinal motility with resultant precipitation or aggravation of toxic megacolon.

Fever

Minor:

trihexyphenidyl

Trihexyphenidyl has a minor potential interaction with Fever.

Atropine-like agents may increase the risk of hyperthermia in patients with fever by producing anhidrosis. Therapy with atropine-like agents should be administered cautiously in febrile patients.

Gastrointestinal Obstruction

Major:

trihexyphenidyl

Trihexyphenidyl has a major potential interaction with Gastrointestinal Obstruction.

Anticholinergics are contraindicated in patients with obstructive diseases such as achalasia, esophageal stricture or stenosis, pyloroduodenal stenosis, stenosing peptic ulcer, pyloric obstruction, and paralytic ileus. Anticholinergics may further suppress intestinal motility with resultant precipitation or aggravation of toxic megacolon.

Moderate:

cyclobenzaprine

Cyclobenzaprine has a moderate potential interaction with Gastrointestinal Obstruction.

Cyclobenzaprine has anticholinergic activity, to which elderly patients are particularly sensitive. Therapy with cyclobenzaprine should be administered cautiously in patients with preexisting conditions that are likely to be exacerbated by anticholinergic activity, such as urinary retention or obstruction; angle-closure glaucoma, untreated intraocular hypertension, or uncontrolled primary open-angle glaucoma; and gastrointestinal obstructive disorders. Glaucoma should be treated and under control prior to initiation of cyclobenzaprine therapy, and intraocular pressure monitored during therapy.

Glaucoma/Intraocular Hypertension

Major:

trihexyphenidyl

Trihexyphenidyl has a major potential interaction with Glaucoma/Intraocular Hypertension.

Anticholinergic agents are contraindicated in patients with primary glaucoma, a tendency toward glaucoma (narrow anterior chamber angle), or adhesions (synechiae) between the iris and lens, as well as for the elderly and others in whom undiagnosed glaucoma or excessive pressure in the eye may be present. Because anticholinergics cause mydriasis, they may exacerbate these conditions.

Moderate:

cyclobenzaprine

Cyclobenzaprine has a moderate potential interaction with Glaucoma/Intraocular Hypertension.

Cyclobenzaprine has anticholinergic activity, to which elderly patients are particularly sensitive. Therapy with cyclobenzaprine should be administered cautiously in patients with preexisting conditions that are likely to be exacerbated by anticholinergic activity, such as urinary retention or obstruction; angle-closure glaucoma, untreated intraocular hypertension, or uncontrolled primary open-angle glaucoma; and gastrointestinal obstructive disorders. Glaucoma should be treated and under control prior to initiation of cyclobenzaprine therapy, and intraocular pressure monitored during therapy.

Heart Failure

Major:

cyclobenzaprine

Cyclobenzaprine has a major potential interaction with Heart Failure.

The manufacturers consider the use of cyclobenzaprine to be contraindicated in the acute recovery phase following myocardial infarction and in patients with hyperthyroidism, congestive heart failure, arrhythmias, heart block, and/or conduction disturbances. Cyclobenzaprine is structurally related to the tricyclic antidepressants, which have been reported to cause tachycardia, arrhythmias, heart block, hypertension, hypotension (particularly orthostatic hypotension), thrombosis, thrombophlebitis, myocardial infarction, strokes, congestive heart failure, and ECG abnormalities such as PR and QT interval prolongation. Therapy with cyclobenzaprine should be administered cautiously in patients with a history of cardiovascular or cerebrovascular disease or a predisposition to hypotension, particularly if the intended dosage exceeds those normally used for musculoskeletal conditions. Tachycardia, arrhythmia, palpitation, and hypotension have been reported with the use of cyclobenzaprine in less than 1% of patients.

High Blood Pressure

Minor:

trihexyphenidyl

Trihexyphenidyl has a minor potential interaction with High Blood Pressure.

Cardiovascular effects of anticholinergics may exacerbate hypertension. Therapy with anticholinergic agents should be administered cautiously in patients with hypertension.

History - Cerebrovascular Disease

Major:

cyclobenzaprine

Cyclobenzaprine has a major potential interaction with History - Cerebrovascular Disease.

The manufacturers consider the use of cyclobenzaprine to be contraindicated in the acute recovery phase following myocardial infarction and in patients with hyperthyroidism, congestive heart failure, arrhythmias, heart block, and/or conduction disturbances. Cyclobenzaprine is structurally related to the tricyclic antidepressants, which have been reported to cause tachycardia, arrhythmias, heart block, hypertension, hypotension (particularly orthostatic hypotension), thrombosis, thrombophlebitis, myocardial infarction, strokes, congestive heart failure, and ECG abnormalities such as PR and QT interval prolongation. Therapy with cyclobenzaprine should be administered cautiously in patients with a history of cardiovascular or cerebrovascular disease or a predisposition to hypotension, particularly if the intended dosage exceeds those normally used for musculoskeletal conditions. Tachycardia, arrhythmia, palpitation, and hypotension have been reported with the use of cyclobenzaprine in less than 1% of patients.

History - Myocardial Infarction

Major:

cyclobenzaprine

Cyclobenzaprine has a major potential interaction with History - Myocardial Infarction.

The manufacturers consider the use of cyclobenzaprine to be contraindicated in the acute recovery phase following myocardial infarction and in patients with hyperthyroidism, congestive heart failure, arrhythmias, heart block, and/or conduction disturbances. Cyclobenzaprine is structurally related to the tricyclic antidepressants, which have been reported to cause tachycardia, arrhythmias, heart block, hypertension, hypotension (particularly orthostatic hypotension), thrombosis, thrombophlebitis, myocardial infarction, strokes, congestive heart failure, and ECG abnormalities such as PR and QT interval prolongation. Therapy with cyclobenzaprine should be administered cautiously in patients with a history of cardiovascular or cerebrovascular disease or a predisposition to hypotension, particularly if the intended dosage exceeds those normally used for musculoskeletal conditions. Tachycardia, arrhythmia, palpitation, and hypotension have been reported with the use of cyclobenzaprine in less than 1% of patients.

Hyperthyroidism

Major:

cyclobenzaprine

Cyclobenzaprine has a major potential interaction with Hyperthyroidism.

The manufacturers consider the use of cyclobenzaprine to be contraindicated in the acute recovery phase following myocardial infarction and in patients with hyperthyroidism, congestive heart failure, arrhythmias, heart block, and/or conduction disturbances. Cyclobenzaprine is structurally related to the tricyclic antidepressants, which have been reported to cause tachycardia, arrhythmias, heart block, hypertension, hypotension (particularly orthostatic hypotension), thrombosis, thrombophlebitis, myocardial infarction, strokes, congestive heart failure, and ECG abnormalities such as PR and QT interval prolongation. Therapy with cyclobenzaprine should be administered cautiously in patients with a history of cardiovascular or cerebrovascular disease or a predisposition to hypotension, particularly if the intended dosage exceeds those normally used for musculoskeletal conditions. Tachycardia, arrhythmia, palpitation, and hypotension have been reported with the use of cyclobenzaprine in less than 1% of patients.

Hypotension

Major:

cyclobenzaprine

Cyclobenzaprine has a major potential interaction with Hypotension.

The manufacturers consider the use of cyclobenzaprine to be contraindicated in the acute recovery phase following myocardial infarction and in patients with hyperthyroidism, congestive heart failure, arrhythmias, heart block, and/or conduction disturbances. Cyclobenzaprine is structurally related to the tricyclic antidepressants, which have been reported to cause tachycardia, arrhythmias, heart block, hypertension, hypotension (particularly orthostatic hypotension), thrombosis, thrombophlebitis, myocardial infarction, strokes, congestive heart failure, and ECG abnormalities such as PR and QT interval prolongation. Therapy with cyclobenzaprine should be administered cautiously in patients with a history of cardiovascular or cerebrovascular disease or a predisposition to hypotension, particularly if the intended dosage exceeds those normally used for musculoskeletal conditions. Tachycardia, arrhythmia, palpitation, and hypotension have been reported with the use of cyclobenzaprine in less than 1% of patients.

Infectious Gastroenteritis

Major:

trihexyphenidyl

Trihexyphenidyl has a major potential interaction with Infectious Gastroenteritis.

The use of drugs with antiperistaltic activity (primarily antidiarrheal and antimuscarinic agents, but also antispasmodic agents such as dicyclomine or oxybutynin at high dosages) is contraindicated in patients with diarrhea due to pseudomembranous enterocolitis or enterotoxin-producing bacteria. These drugs may prolong and/or worsen diarrhea associated with organisms that invade the intestinal mucosa, such as toxigenic E. coli, Salmonella and Shigella, and pseudomembranous colitis due to broad-spectrum antibiotics. Other symptoms and complications such as fever, shedding of organisms and extraintestinal illness may also be increased or prolonged. In general, because antiperistaltic agents decrease gastrointestinal motility, they may delay the excretion of infective gastroenteric organisms or toxins and should be used cautiously in patients with any infectious diarrhea, particularly if accompanied by high fever or pus or blood in the stool. Some cough and cold and other combination products may occasionally include antimuscarinic agents for their drying effects and may, therefore, require careful selection when necessary.

Psychosis

Moderate:

trihexyphenidyl

Trihexyphenidyl has a moderate potential interaction with Psychosis.

Toxic psychosis manifested as confusion, disorientation, agitation, excitation, memory impairment, delusions and hallucinations may develop at toxic and therapeutic dosages of antimuscarinic agents. Therapy with these agents should be administered cautiously in patients with mental disorders receiving antimuscarinic agents for control of drug-induced extrapyramidal effects, especially at the beginning of therapy or during dosage adjustment. Psychiatric deterioration and psychotic flare-ups have also been reported following withdrawal of therapy. Symptoms include delusions, hallucinations, aggression or violent behavior, and suicidal tendencies. In high dosages, antimuscarinic agents may sometimes produce euphorigenic effects. For this reason, it can be a drug of abuse.

Tardive Dyskinesia

Major:

trihexyphenidyl

Trihexyphenidyl has a major potential interaction with Tardive Dyskinesia.

Anticholinergic agents and agents with secondary anticholinergic activity may aggravate tardive dyskinesia or induce previously suppressed symptoms. Therapy with these agents should be avoided, if possible, or administered cautiously in patients with preexisting tardive dyskinesia, particularly in the elderly. If tardive dyskinesia symptoms develop or worsen during treatment with an anticholinergic agent, prompt withdrawal of therapy will provide better chances of improving the condition.

Urinary Retention

Major:

trihexyphenidyl

Trihexyphenidyl has a major potential interaction with Urinary Retention.

In general, the use of anticholinergic agents is contraindicated in patients with urinary retention and bladder neck obstruction caused by prostatic hypertrophy. Dysuria may occur and may require catheterization. Also, anticholinergic drugs may aggravate partial obstructive uropathy. Caution is advised even when using agents with mild to moderate anticholinergic activity, particularly in elderly patients.

Moderate:

cyclobenzaprine

Cyclobenzaprine has a moderate potential interaction with Urinary Retention.

Cyclobenzaprine has anticholinergic activity, to which elderly patients are particularly sensitive. Therapy with cyclobenzaprine should be administered cautiously in patients with preexisting conditions that are likely to be exacerbated by anticholinergic activity, such as urinary retention or obstruction; angle-closure glaucoma, untreated intraocular hypertension, or uncontrolled primary open-angle glaucoma; and gastrointestinal obstructive disorders. Glaucoma should be treated and under control prior to initiation of cyclobenzaprine therapy, and intraocular pressure monitored during therapy.

More resources

cyclobenzaprine

A total of 466 drugs are known to interact with cyclobenzaprine.

trihexyphenidyl

A total of 353 drugs are known to interact with trihexyphenidyl.

Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.