Evoxac

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Evoxac

Classes

Other Agents for Local Oral Treatment

Administration

For storage information, see the specific product information within the the How Supplied section.

Oral Administration

May be administered with food to decrease GI upset.

Adverse Reactions
Severe

visual impairment / Early / 1.0-2.9
peptic ulcer / Delayed / 0-1.0
ileus / Delayed / 0-1.0
GI bleeding / Delayed / 0-1.0
coma / Early / 0-1.0
vasculitis / Delayed / 0-1.0
myocardial infarction / Delayed / 0-1.0
pericarditis / Delayed / 0-1.0
pulmonary embolism / Delayed / 0-1.0
pulmonary fibrosis / Delayed / 0-1.0
bronchospasm / Rapid / 0-1.0
pleural effusion / Delayed / 0-1.0
hearing loss / Delayed / 0-1.0
keratoconjunctivitis / Early / 0-1.0
ocular hemorrhage / Delayed / 0-1.0
keratitis / Delayed / 0-1.0
ocular hypertension / Delayed / 0-1.0
epididymitis / Delayed / 0-1.0
thrombotic thrombocytopenic purpura (TTP) / Delayed / 0-1.0
bradycardia / Rapid / Incidence not known
AV block / Early / Incidence not known
thromboembolism / Delayed / Incidence not known
cholecystitis / Delayed / Incidence not known

Moderate

conjunctivitis / Delayed / 4.3-4.3
stomatitis / Delayed / 1.0-2.9
constipation / Delayed / 1.0-2.9
hypertonia / Delayed / 1.0-2.9
depression / Delayed / 1.0-2.9
migraine / Early / 1.0-2.9
palpitations / Early / 1.0-2.9
chest pain (unspecified) / Early / 1.0-2.9
candidiasis / Delayed / 1.0-2.9
ocular infection / Delayed / 1.0-2.9
cystitis / Delayed / 1.0-2.9
vaginitis / Delayed / 1.0-2.9
anemia / Delayed / 1.0-2.9
peripheral edema / Delayed / 1.0-2.9
hot flashes / Early / 2.4-2.4
dysphagia / Delayed / 0-1.0
hemorrhoids / Delayed / 0-1.0
esophagitis / Delayed / 0-1.0
glossitis / Early / 0-1.0
melena / Delayed / 0-1.0
gastritis / Delayed / 0-1.0
mania / Early / 0-1.0
dysphonia / Delayed / 0-1.0
dysarthria / Delayed / 0-1.0
confusion / Early / 0-1.0
neuropathic pain / Delayed / 0-1.0
hallucinations / Early / 0-1.0
dyskinesia / Delayed / 0-1.0
hypertension / Early / 0-1.0
angina / Early / 0-1.0
ST-T wave changes / Rapid / 0-1.0
phlebitis / Rapid / 0-1.0
supraventricular tachycardia (SVT) / Early / 0-1.0
hypotension / Rapid / 0-1.0
sinus tachycardia / Rapid / 0-1.0
hemoptysis / Delayed / 0-1.0
dyspnea / Early / 0-1.0
photopsia / Delayed / 0-1.0
blepharitis / Early / 0-1.0
cataracts / Delayed / 0-1.0
myopia / Delayed / 0-1.0
contact dermatitis / Delayed / 0-1.0
furunculosis / Delayed / 0-1.0
atopic dermatitis / Delayed / 0-1.0
bullous rash / Early / 0-1.0
skin ulcer / Delayed / 0-1.0
vaginal bleeding / Delayed / 0-1.0
pyuria / Delayed / 0-1.0
urinary incontinence / Early / 0-1.0
hematuria / Delayed / 0-1.0
nephrolithiasis / Delayed / 0-1.0
proteinuria / Delayed / 0-1.0
dysuria / Early / 0-1.0
eosinophilia / Delayed / 0-1.0
lymphadenopathy / Delayed / 0-1.0
hematoma / Early / 0-1.0
thrombocytopenia / Delayed / 0-1.0
leukopenia / Delayed / 0-1.0
hepatitis / Delayed / 0-1.0
cholelithiasis / Delayed / 0-1.0
elevated hepatic enzymes / Delayed / 0-1.0
hypothyroidism / Delayed / 0-1.0
goiter / Delayed / 0-1.0
diabetes mellitus / Delayed / 0-1.0
hypoglycemia / Early / 0-1.0
hypertriglyceridemia / Delayed / 0-1.0
hypokalemia / Delayed / 0-1.0
hyperglycemia / Delayed / 0-1.0
hypercalcemia / Delayed / 0-1.0
dehydration / Delayed / 0-1.0
hyperuricemia / Delayed / 0-1.0
hyponatremia / Delayed / 0-1.0
hypercholesterolemia / Delayed / 0-1.0
hyperlipidemia / Delayed / 0-1.0
edema / Delayed / 0-1.0
osteoporosis / Delayed / Incidence not known
synovitis / Delayed / Incidence not known
myasthenia / Delayed / Incidence not known

Mild

hyperhidrosis / Delayed / 18.7-18.7
nausea / Early / 13.8-13.8
sinusitis / Delayed / 12.3-12.3
rhinitis / Early / 11.2-11.2
diarrhea / Early / 10.3-10.3
abdominal pain / Early / 7.6-7.6
cough / Delayed / 6.1-6.1
vomiting / Early / 4.6-4.6
back pain / Delayed / 4.5-4.5
arthralgia / Delayed / 3.7-3.7
fatigue / Early / 3.3-3.3
anorexia / Delayed / 1.0-2.9
flatulence / Early / 1.0-2.9
eructation / Early / 1.0-2.9
epistaxis / Delayed / 1.0-2.9
dental pain / Delayed / 1.0-2.9
xerostomia / Early / 1.0-2.9
gastroesophageal reflux / Delayed / 1.0-2.9
vertigo / Early / 1.0-2.9
hyporeflexia / Delayed / 1.0-2.9
tremor / Early / 1.0-2.9
hypoesthesia / Delayed / 1.0-2.9
headache / Early / 1.0-2.9
infection / Delayed / 1.0-2.9
hiccups / Early / 1.0-2.9
fever / Early / 1.0-2.9
otalgia / Early / 1.0-2.9
ocular pain / Early / 1.0-2.9
xerophthalmia / Early / 1.0-2.9
pruritus / Rapid / 1.0-2.9
myalgia / Early / 1.0-2.9
muscle cramps / Delayed / 1.0-2.9
insomnia / Early / 2.4-2.4
hypersalivation / Early / 2.2-2.2
anxiety / Delayed / 1.3-1.3
tenesmus / Delayed / 0-1.0
gingivitis / Delayed / 0-1.0
weight loss / Delayed / 0-1.0
tongue discoloration / Delayed / 0-1.0
dental caries / Delayed / 0-1.0
appetite stimulation / Delayed / 0-1.0
weight gain / Delayed / 0-1.0
hyperkinesis / Delayed / 0-1.0
paresthesias / Delayed / 0-1.0
emotional lability / Early / 0-1.0
agitation / Early / 0-1.0
purpura / Delayed / 0-1.0
laryngitis / Delayed / 0-1.0
diplopia / Early / 0-1.0
tinnitus / Delayed / 0-1.0
mydriasis / Early / 0-1.0
dysgeusia / Early / 0-1.0
parosmia / Delayed / 0-1.0
urticaria / Rapid / 0-1.0
skin discoloration / Delayed / 0-1.0
nail discoloration / Delayed / 0-1.0
seborrhea / Delayed / 0-1.0
hyperkeratosis / Delayed / 0-1.0
xerosis / Delayed / 0-1.0
acne vulgaris / Delayed / 0-1.0
alopecia / Delayed / 0-1.0
photosensitivity / Delayed / 0-1.0
menorrhagia / Delayed / 0-1.0
dysmenorrhea / Delayed / 0-1.0
nocturia / Early / 0-1.0
leukorrhea / Delayed / 0-1.0
mastalgia / Delayed / 0-1.0
amenorrhea / Delayed / 0-1.0
leukocytosis / Delayed / 0-1.0
polydipsia / Early / 0-1.0
malaise / Early / 0-1.0
syncope / Early / 0-1.0
pallor / Early / 0-1.0
asthenia / Delayed / 0.5-0.5
lacrimation / Early / Incidence not known
arthropathy / Delayed / Incidence not known

Common Brand Names

Evoxac

Dea Class

Rx

Description

Derivative of acetylcholine and thus functions as a cholinergic agonist; used for xerostomia secondary to Sjogren's syndrome or radiation therapy; being investigated for Alzheimer's disease.

Dosage And Indications
For the treatment of xerostomia and/or dry eye disease† in persons with Sjogren's syndrome. Oral dosage Adults

30 mg PO 3 times daily.

Dosing Considerations
Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Renal Impairment

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Drug Interactions

Acebutolol: (Major) Cevimeline should be administered with caution to patients taking beta adrenergic antagonists, because of the possibility of conduction disturbances. Cevimeline can potentially alter cardiac conduction and/or heart rate. Patients with significant cardiovascular disease treated with beta-blockers may potentially be unable to compensate for transient changes in hemodynamics or rhythm induced by cevimeline. If use of these drugs together cannot be avoided, close monitoring of blood pressure, heart rate and cardiac function is advised.
Amoxapine: (Major) Amoxapine may antagonize some of the effects of parasympathomimetics. However, bethanechol has occasionally been used therapeutically to offset some of the adverse antimuscarinic effects of cyclic antidepressants. Due to their anticholinergic actions, some cyclic antidepressants, such as amoxapine, may potentially antagonize the therapeutic actions of cholinergic agonists.
Anticholinergics: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Atenolol: (Major) Cevimeline should be administered with caution to patients taking beta adrenergic antagonists, because of the possibility of conduction disturbances. Cevimeline can potentially alter cardiac conduction and/or heart rate. Patients with significant cardiovascular disease treated with beta-blockers may potentially be unable to compensate for transient changes in hemodynamics or rhythm induced by cevimeline. If use of these drugs together cannot be avoided, close monitoring of blood pressure, heart rate and cardiac function is advised.
Atenolol; Chlorthalidone: (Major) Cevimeline should be administered with caution to patients taking beta adrenergic antagonists, because of the possibility of conduction disturbances. Cevimeline can potentially alter cardiac conduction and/or heart rate. Patients with significant cardiovascular disease treated with beta-blockers may potentially be unable to compensate for transient changes in hemodynamics or rhythm induced by cevimeline. If use of these drugs together cannot be avoided, close monitoring of blood pressure, heart rate and cardiac function is advised.
Atropine: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Atropine; Difenoxin: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Belladonna; Opium: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Benztropine: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Beta-blockers: (Major) Cevimeline should be administered with caution to patients taking beta adrenergic antagonists, because of the possibility of conduction disturbances. Cevimeline can potentially alter cardiac conduction and/or heart rate. Patients with significant cardiovascular disease treated with beta-blockers may potentially be unable to compensate for transient changes in hemodynamics or rhythm induced by cevimeline. If use of these drugs together cannot be avoided, close monitoring of blood pressure, heart rate and cardiac function is advised.
Betaxolol: (Major) Cevimeline should be administered with caution to patients taking beta adrenergic antagonists, because of the possibility of conduction disturbances. Cevimeline can potentially alter cardiac conduction and/or heart rate. Patients with significant cardiovascular disease treated with beta-blockers may potentially be unable to compensate for transient changes in hemodynamics or rhythm induced by cevimeline. If use of these drugs together cannot be avoided, close monitoring of blood pressure, heart rate and cardiac function is advised.
Bethanechol: (Moderate) Cevimeline and bethanechol are both cholinergic agonists. Coadministration is expected to result in additive parasympathomimetic effects.
Bisoprolol: (Major) Cevimeline should be administered with caution to patients taking beta adrenergic antagonists, because of the possibility of conduction disturbances. Cevimeline can potentially alter cardiac conduction and/or heart rate. Patients with significant cardiovascular disease treated with beta-blockers may potentially be unable to compensate for transient changes in hemodynamics or rhythm induced by cevimeline. If use of these drugs together cannot be avoided, close monitoring of blood pressure, heart rate and cardiac function is advised.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Major) Cevimeline should be administered with caution to patients taking beta adrenergic antagonists, because of the possibility of conduction disturbances. Cevimeline can potentially alter cardiac conduction and/or heart rate. Patients with significant cardiovascular disease treated with beta-blockers may potentially be unable to compensate for transient changes in hemodynamics or rhythm induced by cevimeline. If use of these drugs together cannot be avoided, close monitoring of blood pressure, heart rate and cardiac function is advised.
Brimonidine; Timolol: (Major) Cevimeline should be administered with caution to patients taking beta adrenergic antagonists, because of the possibility of conduction disturbances. Cevimeline can potentially alter cardiac conduction and/or heart rate. Patients with significant cardiovascular disease treated with beta-blockers may potentially be unable to compensate for transient changes in hemodynamics or rhythm induced by cevimeline. If use of these drugs together cannot be avoided, close monitoring of blood pressure, heart rate and cardiac function is advised.
Budesonide; Glycopyrrolate; Formoterol: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Bupropion: (Moderate) Cevimeline is partially metabolized by CYP2D6. Inhibitors of this isoenzyme, like bupropion, would be expected to lead to an increase in cevimeline plasma concentrations.
Bupropion; Naltrexone: (Moderate) Cevimeline is partially metabolized by CYP2D6. Inhibitors of this isoenzyme, like bupropion, would be expected to lead to an increase in cevimeline plasma concentrations.
Carteolol: (Major) Cevimeline should be administered with caution to patients taking beta adrenergic antagonists, because of the possibility of conduction disturbances. Cevimeline can potentially alter cardiac conduction and/or heart rate. Patients with significant cardiovascular disease treated with beta-blockers may potentially be unable to compensate for transient changes in hemodynamics or rhythm induced by cevimeline. If use of these drugs together cannot be avoided, close monitoring of blood pressure, heart rate and cardiac function is advised.
Carvedilol: (Major) Cevimeline should be administered with caution to patients taking beta adrenergic antagonists, because of the possibility of conduction disturbances. Cevimeline can potentially alter cardiac conduction and/or heart rate. Patients with significant cardiovascular disease treated with beta-blockers may potentially be unable to compensate for transient changes in hemodynamics or rhythm induced by cevimeline. If use of these drugs together cannot be avoided, close monitoring of blood pressure, heart rate and cardiac function is advised.
Chlordiazepoxide; Clidinium: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Cholinesterase inhibitors: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
Dacomitinib: (Moderate) Monitor for increased toxicity of cevimeline if coadministered with dacomitinib. Coadministration may increase serum concentrations of cevimeline. Cevimeline is a CYP2D6 substrate; dacomitinib is a strong CYP2D6 inhibitor.
Dextromethorphan; Bupropion: (Moderate) Cevimeline is partially metabolized by CYP2D6. Inhibitors of this isoenzyme, like bupropion, would be expected to lead to an increase in cevimeline plasma concentrations.
Dextromethorphan; Quinidine: (Moderate) Cevimeline is metabolized by cytochrome P450 3A4 and CYP2D6. Concurrent administration of inhibitors of these enzymes, such as quinidine, may lead to increased cevimeline plasma concentrations.
Dicyclomine: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Diphenoxylate; Atropine: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Disopyramide: (Moderate) Disopyramide possesses clinically significant antimuscarinic properties and these appear to be dose-related. It is possible that disopyramide could antagonize the muscarinic actions of cholinergic agonists. Clinicians should be alert to this possibility.
Donepezil: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
Donepezil; Memantine: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
Dorzolamide; Timolol: (Major) Cevimeline should be administered with caution to patients taking beta adrenergic antagonists, because of the possibility of conduction disturbances. Cevimeline can potentially alter cardiac conduction and/or heart rate. Patients with significant cardiovascular disease treated with beta-blockers may potentially be unable to compensate for transient changes in hemodynamics or rhythm induced by cevimeline. If use of these drugs together cannot be avoided, close monitoring of blood pressure, heart rate and cardiac function is advised.
Esmolol: (Major) Cevimeline should be administered with caution to patients taking beta adrenergic antagonists, because of the possibility of conduction disturbances. Cevimeline can potentially alter cardiac conduction and/or heart rate. Patients with significant cardiovascular disease treated with beta-blockers may potentially be unable to compensate for transient changes in hemodynamics or rhythm induced by cevimeline. If use of these drugs together cannot be avoided, close monitoring of blood pressure, heart rate and cardiac function is advised.
Flavoxate: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Fluoxetine: (Moderate) Monitor for an increase in cevimeline-related adverse effects if concomitant use of fluoxetine is necessary. Concomitant use may increase cevimeline exposure. Cevimeline is a CYP2D6 substrate; fluoxetine is a strong CYP2D6 inhibitor.
Galantamine: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
Glycopyrrolate: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Glycopyrrolate; Formoterol: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Guanidine: (Moderate) Cevimeline and guanidine are both cholinergic agonists. Coadministration is expected to result in additive parasympathomimetic effects.
Homatropine; Hydrocodone: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Hyoscyamine: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Indacaterol; Glycopyrrolate: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Labetalol: (Major) Cevimeline should be administered with caution to patients taking beta adrenergic antagonists, because of the possibility of conduction disturbances. Cevimeline can potentially alter cardiac conduction and/or heart rate. Patients with significant cardiovascular disease treated with beta-blockers may potentially be unable to compensate for transient changes in hemodynamics or rhythm induced by cevimeline. If use of these drugs together cannot be avoided, close monitoring of blood pressure, heart rate and cardiac function is advised.
Levobunolol: (Major) Cevimeline should be administered with caution to patients taking beta adrenergic antagonists, because of the possibility of conduction disturbances. Cevimeline can potentially alter cardiac conduction and/or heart rate. Patients with significant cardiovascular disease treated with beta-blockers may potentially be unable to compensate for transient changes in hemodynamics or rhythm induced by cevimeline. If use of these drugs together cannot be avoided, close monitoring of blood pressure, heart rate and cardiac function is advised.
Maprotiline: (Major) Maprotiline may antagonize some of the effects of parasympathomimetics. However, bethanechol has occasionally been used therapeutically to offset some of the adverse antimuscarinic effects of cyclic antidepressants. Due to their anticholinergic actions, some cyclic antidepressants like maprotiline may potentially antagonize the therapeutic actions of the cholinesterase-inhibitors used for the treatment of dementia.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Methscopolamine: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Metoprolol: (Major) Cevimeline should be administered with caution to patients taking beta adrenergic antagonists, because of the possibility of conduction disturbances. Cevimeline can potentially alter cardiac conduction and/or heart rate. Patients with significant cardiovascular disease treated with beta-blockers may potentially be unable to compensate for transient changes in hemodynamics or rhythm induced by cevimeline. If use of these drugs together cannot be avoided, close monitoring of blood pressure, heart rate and cardiac function is advised.
Metoprolol; Hydrochlorothiazide, HCTZ: (Major) Cevimeline should be administered with caution to patients taking beta adrenergic antagonists, because of the possibility of conduction disturbances. Cevimeline can potentially alter cardiac conduction and/or heart rate. Patients with significant cardiovascular disease treated with beta-blockers may potentially be unable to compensate for transient changes in hemodynamics or rhythm induced by cevimeline. If use of these drugs together cannot be avoided, close monitoring of blood pressure, heart rate and cardiac function is advised.
Nadolol: (Major) Cevimeline should be administered with caution to patients taking beta adrenergic antagonists, because of the possibility of conduction disturbances. Cevimeline can potentially alter cardiac conduction and/or heart rate. Patients with significant cardiovascular disease treated with beta-blockers may potentially be unable to compensate for transient changes in hemodynamics or rhythm induced by cevimeline. If use of these drugs together cannot be avoided, close monitoring of blood pressure, heart rate and cardiac function is advised.
Nebivolol: (Major) Cevimeline should be administered with caution to patients taking beta adrenergic antagonists, because of the possibility of conduction disturbances. Cevimeline can potentially alter cardiac conduction and/or heart rate. Patients with significant cardiovascular disease treated with beta-blockers may potentially be unable to compensate for transient changes in hemodynamics or rhythm induced by cevimeline. If use of these drugs together cannot be avoided, close monitoring of blood pressure, heart rate and cardiac function is advised.
Nebivolol; Valsartan: (Major) Cevimeline should be administered with caution to patients taking beta adrenergic antagonists, because of the possibility of conduction disturbances. Cevimeline can potentially alter cardiac conduction and/or heart rate. Patients with significant cardiovascular disease treated with beta-blockers may potentially be unable to compensate for transient changes in hemodynamics or rhythm induced by cevimeline. If use of these drugs together cannot be avoided, close monitoring of blood pressure, heart rate and cardiac function is advised.
Neostigmine: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
Neostigmine; Glycopyrrolate: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided. (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Olanzapine; Fluoxetine: (Moderate) Monitor for an increase in cevimeline-related adverse effects if concomitant use of fluoxetine is necessary. Concomitant use may increase cevimeline exposure. Cevimeline is a CYP2D6 substrate; fluoxetine is a strong CYP2D6 inhibitor.
Oxybutynin: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Paroxetine: (Moderate) Monitor for an increase in cevimeline-related adverse effects if concomitant use of paroxetine is necessary. Concomitant use may increase cevimeline exposure. Cevimeline is a CYP2D6 substrate; paroxetine is a strong CYP2D6 inhibitor.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Physostigmine: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
Pilocarpine: (Moderate) Cevimeline and pilocarpine are both cholinergic agonists. Coadministration is expected to result in additive parasympathomimetic effects.
Pindolol: (Major) Cevimeline should be administered with caution to patients taking beta adrenergic antagonists, because of the possibility of conduction disturbances. Cevimeline can potentially alter cardiac conduction and/or heart rate. Patients with significant cardiovascular disease treated with beta-blockers may potentially be unable to compensate for transient changes in hemodynamics or rhythm induced by cevimeline. If use of these drugs together cannot be avoided, close monitoring of blood pressure, heart rate and cardiac function is advised.
Pralidoxime: (Moderate) Cevimeline and pralidoxime are both cholinergic agonists. Coadministration is expected to result in additive parasympathomimetic effects.
Propantheline: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Propranolol: (Major) Cevimeline should be administered with caution to patients taking beta adrenergic antagonists, because of the possibility of conduction disturbances. Cevimeline can potentially alter cardiac conduction and/or heart rate. Patients with significant cardiovascular disease treated with beta-blockers may potentially be unable to compensate for transient changes in hemodynamics or rhythm induced by cevimeline. If use of these drugs together cannot be avoided, close monitoring of blood pressure, heart rate and cardiac function is advised.
Propranolol; Hydrochlorothiazide, HCTZ: (Major) Cevimeline should be administered with caution to patients taking beta adrenergic antagonists, because of the possibility of conduction disturbances. Cevimeline can potentially alter cardiac conduction and/or heart rate. Patients with significant cardiovascular disease treated with beta-blockers may potentially be unable to compensate for transient changes in hemodynamics or rhythm induced by cevimeline. If use of these drugs together cannot be avoided, close monitoring of blood pressure, heart rate and cardiac function is advised.
Pyridostigmine: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
Quinidine: (Moderate) Cevimeline is metabolized by cytochrome P450 3A4 and CYP2D6. Concurrent administration of inhibitors of these enzymes, such as quinidine, may lead to increased cevimeline plasma concentrations.
Rivastigmine: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
Scopolamine: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Sotalol: (Major) Cevimeline should be administered with caution to patients taking beta adrenergic antagonists, because of the possibility of conduction disturbances. Cevimeline can potentially alter cardiac conduction and/or heart rate. Patients with significant cardiovascular disease treated with beta-blockers may potentially be unable to compensate for transient changes in hemodynamics or rhythm induced by cevimeline. If use of these drugs together cannot be avoided, close monitoring of blood pressure, heart rate and cardiac function is advised.
Tacrine: (Major) Cholinergic agonists can cause additive pharmacodynamic effects if used concomitantly with cholinesterase inhibitors. Concurrent use is unlikely to be tolerated by the patient and should be avoided.
Terbinafine: (Moderate) Cevimeline is partially metabolized by CYP2D6. Inhibitors of this isoenzyme, like terbinafine, would be expected to lead to an increase in cevimeline plasma concentrations.
Timolol: (Major) Cevimeline should be administered with caution to patients taking beta adrenergic antagonists, because of the possibility of conduction disturbances. Cevimeline can potentially alter cardiac conduction and/or heart rate. Patients with significant cardiovascular disease treated with beta-blockers may potentially be unable to compensate for transient changes in hemodynamics or rhythm induced by cevimeline. If use of these drugs together cannot be avoided, close monitoring of blood pressure, heart rate and cardiac function is advised.
Tricyclic antidepressants: (Moderate) Tricyclic antidepressants (TCAs) may antagonize some of the effects of parasympathomimetics (e.g., cholinesterase inhibitors) due to their anticholinergic activity. However, parasympathomimetics like bethanechol have occasionally been used historically to offset some of the adverse peripheral antimuscarinic (anticholinergic) effects of TCAs, such as dry mouth, constipation, or urinary retention. For years, physostigmine was used as an adjunct to the treatment of TCA overdose; however, its efficacy was limited to addressing anticholinergic effects. Additionally, case reports suggest that harmful effects such as seizures and bradyarrhythmias progressing to asystole, especially in patients with cardiac conduction abnormalities at baseline, are possible. For these reasons, physostigmine is no longer considered a standard of care in the treatment of TCA overdose.
Trihexyphenidyl: (Major) The muscarinic actions of drugs known as parasympathomimetics, including both direct cholinergic receptor agonists and cholinesterase inhibitors, can antagonize the antimuscarinic actions of anticholinergic drugs, and vice versa.
Trospium: (Moderate) Pharmacologically, parasympathomimetic drugs enhance muscarinic/cholinergic function. Because trospium is an antimuscarinic, the muscarinic actions of drugs known as parasympathomimetics, including direct cholinergic agonists, could be antagonized when used concomitantly with trospium.

How Supplied

Cevimeline/Evoxac Oral Cap: 30mg

Maximum Dosage
Adults

90 mg/day PO.

Elderly

90 mg/day PO.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Mechanism Of Action

Cevimeline is a muscarinic receptor agonist. Muscarinic receptors occur in cardiovascular, exocrine gland, gastrointestinal, ocular, pulmonary, and urinary tissues. Effects of muscarinic agonists on these tissues may include bradycardia or other alterations in cardiac conduction, vasodilation, secretion from lacrimal, salivary and sweat glands, increased GI motility, miosis and accommodation, increased bronchial secretions and bronchoconstriction, and biliary or urinary tract contraction. Cevimeline has partial direct M1-receptor agonist activity in the CNS and has high binding affinity for muscarinic M3 receptors on lacrimal and salivary gland epithelium. Binding to other muscarinic receptor subtypes has been reported to varying degrees depending upon the tissue and assay used. As a muscarinic receptor agonist, cevimeline increases secretion of exocrine glands, such salivary and sweat glands and increases tone of the smooth muscle in the gastrointestinal tract and urinary tract.

Pharmacokinetics

Cevimeline is administered orally. It has a high volume of distribution with little protein binding, suggesting high binding to tissues; however, specific tissue binding sites are not known. Cevimeline is metabolized by liver cytochrome P450 isoenzymes (CYP) 2D6 and 3A4. It has no induction or inhibitory effects on any CYP isoenzymes. The mean half-life is 5 hours and it is mostly excreted in the urine.
 
Affected cytochrome P450 isoenzymes: CYP2D6, CYP3A4

Oral Route

Following oral administration of cevimeline, Tmax occurs within 1.5—2 hours. When cevimeline is administered with food the Tmax increases to 2.86 hours and the Cmax is decreased by 17.3%.

Pregnancy And Lactation
Pregnancy

Use cevimeline during pregnancy only if the benefit to the mother justifies the potential risk to the infant. No adequate and well-controlled studies have been conducted in pregnant women, and its ability to cause fetal harm or affect reproductive capacity is unknown. Passage through the placenta to the infant should be expected based on the drugs' low molecular weight. In animal studies, a reduction in the mean number of implantations were observed in pregnant rats following administration of doses 5-times the maximum recommended human dose. This effect may have been secondary to maternal toxicity.

Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from cevimeline, a decision should be made whether to discontinue breast-feeding or discontinue the drug, taking into account the importance of the drug to the mother. It is not known whether cevimeline is secreted in human milk.