Pruritus: Topical: Apply a thin film 4 times/day with at least 3- to 4-hour interval between applications; not recommended for use >8 days.
Note: Risk of systemic side effects is greater when applying to over 10% of body surface area. If excessive drowsiness occurs it may be necessary to decrease the BSA treated, decrease the frequency of applications and/or the amount of cream applied or discontinue therapy.
Neuropathic pain (off-label use): Topical: 3.3% cream (extemporaneous preparation): Apply a thin film to painful area 3 times daily (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
There are no dosage adjustments provided in the manufacturer’s labeling.
Refer to adult dosing; use with caution.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
>10%:
Dermatologic: Burning sensation of skin (≤23%), stinging of the skin (≤23%)
Nervous system: Drowsiness (22%)
1% to 10%:
Cardiovascular: Edema (1%)
Gastrointestinal: Dysgeusia (2%), xerostomia (10%)
Nervous system: Dizziness (2%), emotional lability (2%), fatigue (3%)
<1%:
Gastrointestinal: Nausea
Nervous system: Anxiety, nervousness, numbness of tongue
Miscellaneous: Fever
Postmarketing: Dermatologic: Contact dermatitis
Hypersensitivity to doxepin or any component of the formulation; untreated narrow-angle glaucoma; tendency to urinary retention
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to other dibenzoxepins compounds; use in children <12 years of age
Concerns related to adverse effects:
• Anticholinergic effects: May cause anticholinergic effects (dry mouth, thirst, taste changes, dry eyes).
• CNS depression: May cause CNS depression, which may impair physical or mental abilities; patients must be cautioned about performing tasks that require mental alertness (eg, operating machinery or driving). Drowsiness has been reported in >20% of patients; risk is increased with greater body surface area (>10%) application.
• Hypersensitivity: May cause contact sensitization; use for >8 days may increase risk.
• QT prolongation: May cause QT prolongation.
Special populations:
• Older adult: May cause confusion and oversedation in the elderly; use with caution; monitor closely.
Dosage form specific issues:
• Benzyl alcohol and derivatives: Some dosage forms may contain benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension and cardiovascular collapse (AAP 1997; CDC 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol with caution in neonates. See manufacturer’s labeling.
• Topical: For external use only (not for ophthalmic, vaginal, or oral use); avoid contact with eyes. Doxepin is significantly absorbed following topical administration; plasma levels may be similar to those achieved with oral administration.
Cream is not recommended for use in pediatric patients; overdoses from topical administration in children have been reported.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Cream, External, as hydrochloride:
Prudoxin: 5% (45 g) [contains benzyl alcohol, cetyl alcohol]
Zonalon: 5% (30 g, 45 g) [contains benzyl alcohol, cetyl alcohol]
Generic: 5% (45 g)
Yes
Cream (Doxepin HCl External)
5% (per gram): $16.05 - $16.94
Cream (Prudoxin External)
5% (per gram): $17.83
Cream (Zonalon External)
5% (per gram): $23.71
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Topical: For external use only (not for ophthalmic, vaginal, or oral use); avoid contact with eyes. Apply thin film to affected area; do not use occlusive dressings (may increase absorption).
Pruritus: Short-term (≤8 days) management of moderate pruritus in adults with atopic dermatitis or lichen simplex chronicus.
Neuropathic pain
Doxepin may be confused with digoxin, doxapram, doxazosin, Doxidan, doxycycline
Zonalon may be confused with Zone-A
Doxal [Finland] may be confused with Doxil brand name for doxorubicin (liposomal) [US, Israel]
Doxal brand name for doxepin [Finland] but also brand name for pyridoxine/thiamine [Brazil]
Substrate of CYP1A2 (minor), CYP2C19 (minor), CYP2D6 (minor), CYP3A4 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Acetylcholinesterase Inhibitors: May diminish the therapeutic effect of Agents with Clinically Relevant Anticholinergic Effects. Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Risk C: Monitor therapy
Aclidinium: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid combination
Adagrasib: May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Adagrasib may increase the serum concentration of QT-prolonging Antidepressants (Moderate Risk). Management: Consider alternatives to this combination. If combined, monitor for increased antidepressant toxicities including QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Agents with Clinically Relevant Anticholinergic Effects: May enhance the adverse/toxic effect of other Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy
Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Risk C: Monitor therapy
Alizapride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Almotriptan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Alosetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Alpha-/Beta-Agonists: Tricyclic Antidepressants may enhance the vasopressor effect of Alpha-/Beta-Agonists. Management: Avoid, if possible, the use of alpha-/beta-agonists in patients receiving tricyclic antidepressants. If combined, monitor for evidence of increased pressor effects and consider reductions in initial dosages of the alpha-/beta-agonist. Risk D: Consider therapy modification
Alpha1-Agonists: Tricyclic Antidepressants may enhance the therapeutic effect of Alpha1-Agonists. Tricyclic Antidepressants may diminish the therapeutic effect of Alpha1-Agonists. Risk C: Monitor therapy
Alpha2-Agonists: Tricyclic Antidepressants may diminish the antihypertensive effect of Alpha2-Agonists. Management: Consider avoiding this combination. If used, monitor for decreased effects of the alpha2-agonist. Exercise great caution if discontinuing an alpha2-agonist in a patient receiving a TCA. Risk D: Consider therapy modification
Alpha2-Agonists (Ophthalmic): Tricyclic Antidepressants may diminish the therapeutic effect of Alpha2-Agonists (Ophthalmic). Risk C: Monitor therapy
Altretamine: May enhance the orthostatic hypotensive effect of Tricyclic Antidepressants. Risk C: Monitor therapy
Amantadine: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy
Amifampridine: Agents With Seizure Threshold Lowering Potential may enhance the neuroexcitatory and/or seizure-potentiating effect of Amifampridine. Risk C: Monitor therapy
Amisulpride (Oral): May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk C: Monitor therapy
Amisulpride (Oral): Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Amisulpride (Oral). Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Amphetamines: Tricyclic Antidepressants may enhance the adverse/toxic effect of Amphetamines. Tricyclic Antidepressants may potentiate the cardiovascular effects of Amphetamines. Amphetamines may enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased cardiovascular effects when these agents are combined. Risk C: Monitor therapy
Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
ARIPiprazole: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of ARIPiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
ARIPiprazole Lauroxil: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of ARIPiprazole Lauroxil. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Asenapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Asenapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Azelastine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Baclofen: Tricyclic Antidepressants may enhance the adverse neuromuscular effect of Baclofen. Baclofen may enhance the CNS depressant effect of Tricyclic Antidepressants. Risk C: Monitor therapy
Barbiturates: May increase the metabolism of Tricyclic Antidepressants. Management: Monitor for decreased efficacy of tricyclic antidepressants if a barbiturate is initiated/dose increased, or increased effects if a barbiturate is discontinued/dose decreased. Tricyclic antidepressant dose adjustments are likely required. Risk D: Consider therapy modification
Benperidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Benperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Benperidol: Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Benperidol. Risk C: Monitor therapy
Beta2-Agonists: Tricyclic Antidepressants may enhance the adverse/toxic effect of Beta2-Agonists. Risk C: Monitor therapy
Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Management: Use caution if coadministering blonanserin and CNS depressants; dose reduction of the other CNS depressant may be required. Strong CNS depressants should not be coadministered with blonanserin. Risk D: Consider therapy modification
Botulinum Toxin-Containing Products: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy
Brexanolone: CNS Depressants may enhance the CNS depressant effect of Brexanolone. Risk C: Monitor therapy
Brexpiprazole: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Brexpiprazole. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Bromopride: May enhance the adverse/toxic effect of Tricyclic Antidepressants. Risk X: Avoid combination
Bromperidol: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine at lower doses in patients already receiving CNS depressants. Risk D: Consider therapy modification
BuPROPion: Tricyclic Antidepressants may enhance the neuroexcitatory and/or seizure-potentiating effect of BuPROPion. BuPROPion may increase the serum concentration of Tricyclic Antidepressants. Risk C: Monitor therapy
BusPIRone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Cannabinoid-Containing Products: Tricyclic Antidepressants may enhance the tachycardic effect of Cannabinoid-Containing Products. Blood pressure raising effects and drowsiness may also be enhanced. Risk C: Monitor therapy
Cannabinoid-Containing Products: Agents with Clinically Relevant Anticholinergic Effects may enhance the tachycardic effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
Cannabinoid-Containing Products: CNS Depressants may enhance the CNS depressant effect of Cannabinoid-Containing Products. Risk C: Monitor therapy
CarBAMazepine: May decrease the serum concentration of Tricyclic Antidepressants. Risk C: Monitor therapy
Cariprazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Cariprazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Chloral Betaine: May enhance the adverse/toxic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy
Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Risk D: Consider therapy modification
Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Risk C: Monitor therapy
Chlorprothixene: Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Chlorprothixene. Risk C: Monitor therapy
Cimetidine: May increase the serum concentration of Tricyclic Antidepressants. Risk C: Monitor therapy
Cimetropium: Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Cimetropium. Risk X: Avoid combination
Citalopram: May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Citalopram may enhance the serotonergic effect of QT-prolonging Antidepressants (Moderate Risk). This could result in serotonin syndrome. Citalopram may increase the serum concentration of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and serotonin syndrome when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Clothiapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Clothiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
CloZAPine: Agents with Clinically Relevant Anticholinergic Effects may enhance the constipating effect of CloZAPine. Management: Consider alternatives to this combination whenever possible. If combined, monitor closely for signs and symptoms of gastrointestinal hypomotility and consider prophylactic laxative treatment. Risk D: Consider therapy modification
CloZAPine: QT-prolonging Antidepressants (Moderate Risk) may enhance the constipating effect of CloZAPine. CloZAPine may enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Consider alternatives to this combination whenever possible. If combined, consider prophylactic laxatives and monitor closely for signs and symptoms of gastrointestinal hypomotility, QTc prolongation, and serotonin syndrome. Risk D: Consider therapy modification
CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Risk C: Monitor therapy
Cocaine (Topical): May enhance the adverse/toxic effect of Tricyclic Antidepressants. Risk C: Monitor therapy
Cyclobenzaprine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
CYP2D6 Inhibitors (Moderate): May increase the serum concentration of Doxepin (Topical). Risk C: Monitor therapy
CYP2D6 Inhibitors (Strong): May increase the serum concentration of Doxepin (Topical). Risk C: Monitor therapy
Dabrafenib: May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Dapoxetine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Do not use serotonergic agents (high risk) with dapoxetine or within 7 days of serotonergic agent discontinuation. Do not use dapoxetine within 14 days of monoamine oxidase inhibitor use. Dapoxetine labeling lists this combination as contraindicated. Risk X: Avoid combination
Daridorexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dose reduction of daridorexant and/or any other CNS depressant may be necessary. Use of daridorexant with alcohol is not recommended, and the use of daridorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Desmopressin: Tricyclic Antidepressants may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy
DexmedeTOMIDine: CNS Depressants may enhance the CNS depressant effect of DexmedeTOMIDine. Management: Monitor for increased CNS depression during coadministration of dexmedetomidine and CNS depressants, and consider dose reductions of either agent to avoid excessive CNS depression. Risk D: Consider therapy modification
Dexmethylphenidate-Methylphenidate: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Dextromethorphan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Difelikefalin: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Dimethindene (Systemic): Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Dimethindene (Systemic). Risk C: Monitor therapy
Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Domperidone: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Domperidone. Risk X: Avoid combination
Doxylamine: CNS Depressants may enhance the CNS depressant effect of Doxylamine. Risk C: Monitor therapy
Dronedarone: QT-prolonging Antidepressants (Moderate Risk) may enhance the QTc-prolonging effect of Dronedarone. Risk X: Avoid combination
DroPERidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (eg, opioids, barbiturates) with concomitant use. Risk D: Consider therapy modification
DULoxetine: May enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome. DULoxetine may increase the serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations and effects if these agents are combined. Risk C: Monitor therapy
Eletriptan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Eluxadoline: Agents with Clinically Relevant Anticholinergic Effects may enhance the constipating effect of Eluxadoline. Risk X: Avoid combination
Encorafenib: May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Epinephrine (Racemic): Tricyclic Antidepressants may enhance the adverse/toxic effect of Epinephrine (Racemic). Risk X: Avoid combination
Ergot Derivatives: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Escitalopram: May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Escitalopram may enhance the serotonergic effect of QT-prolonging Antidepressants (Moderate Risk). This could result in serotonin syndrome. Risk C: Monitor therapy
Esketamine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Fenfluramine: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Risk C: Monitor therapy
Fexinidazole: QT-prolonging Antidepressants (Moderate Risk) may enhance the QTc-prolonging effect of Fexinidazole. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Flunarizine: CNS Depressants may enhance the CNS depressant effect of Flunarizine. Risk X: Avoid combination
Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Management: Reduce the dose of CNS depressants when combined with flunitrazepam and monitor patients for evidence of CNS depression (eg, sedation, respiratory depression). Use non-CNS depressant alternatives when available. Risk D: Consider therapy modification
Fluorouracil Products: May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
FLUoxetine: May enhance the serotonergic effect of Tricyclic Antidepressants. FLUoxetine may increase the serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations/effects if these agents are combined. Risk D: Consider therapy modification
Flupentixol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Flupentixol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
FluPHENAZine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of FluPHENAZine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
FluvoxaMINE: May enhance the serotonergic effect of Tricyclic Antidepressants. FluvoxaMINE may increase the serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations/effects if these agents are combined. Risk C: Monitor therapy
Gastrointestinal Agents (Prokinetic): Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Risk C: Monitor therapy
Gepirone: May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Gepirone may enhance the serotonergic effect of QT-prolonging Antidepressants (Moderate Risk). This could result in serotonin syndrome. Risk C: Monitor therapy
Gilteritinib: QT-prolonging Antidepressants (Moderate Risk) may enhance the QTc-prolonging effect of Gilteritinib. Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Glucagon: Agents with Clinically Relevant Anticholinergic Effects may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Risk C: Monitor therapy
Glycopyrrolate (Oral Inhalation): Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Risk X: Avoid combination
Glycopyrronium (Topical): May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid combination
Guanethidine: Tricyclic Antidepressants may diminish the therapeutic effect of Guanethidine. Risk C: Monitor therapy
Haloperidol: QT-prolonging Antidepressants (Moderate Risk) may enhance the QTc-prolonging effect of Haloperidol. Haloperidol may enhance the serotonergic effect of QT-prolonging Antidepressants (Moderate Risk). This could result in serotonin syndrome. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and serotonin syndrome/serotonin toxicity (SS/ST) or NMS when these agents are combined. Patients with additional risk factors for QTc prolongation or SS/ST may be at even higher risk. Risk C: Monitor therapy
Haloperidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Haloperidol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Management: Consider a decrease in the CNS depressant dose, as appropriate, when used together with hydroxyzine. Increase monitoring of signs/symptoms of CNS depression in any patient receiving hydroxyzine together with another CNS depressant. Risk D: Consider therapy modification
Iloperidone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iloperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Iobenguane Radiopharmaceutical Products: Tricyclic Antidepressants may diminish the therapeutic effect of Iobenguane Radiopharmaceutical Products. Management: Discontinue all drugs that may inhibit or interfere with catecholamine transport or uptake for at least 5 biological half-lives before iobenguane administration. Do not administer these drugs until at least 7 days after each iobenguane dose. Risk X: Avoid combination
Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic antiseizure drugs. Risk D: Consider therapy modification
Ipratropium (Nasal): May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy
Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid combination
Itopride: Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Itopride. Risk C: Monitor therapy
Ixabepilone: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kava Kava: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Kratom: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Landiolol: Tricyclic Antidepressants may enhance the hypotensive effect of Landiolol. Risk C: Monitor therapy
Lasmiditan: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Lemborexant: May enhance the CNS depressant effect of CNS Depressants. Management: Dosage adjustments of lemborexant and of concomitant CNS depressants may be necessary when administered together because of potentially additive CNS depressant effects. Close monitoring for CNS depressant effects is necessary. Risk D: Consider therapy modification
Levoketoconazole: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Levoketoconazole. Risk X: Avoid combination
Levosulpiride: Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Levosulpiride. Risk X: Avoid combination
Linezolid: May enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome. Risk X: Avoid combination
Lisuride: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Lofexidine: May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). QT-prolonging Antidepressants (Moderate Risk) may enhance the QTc-prolonging effect of Lofexidine. QT-prolonging Antidepressants (Moderate Risk) may diminish the therapeutic effect of Lofexidine. Management: Consider avoiding this combination when possible. Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Lorcaserin (Withdrawn From US Market): May enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome. Lorcaserin (Withdrawn From US Market) may increase the serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations and effects if these agents are combined. Risk C: Monitor therapy
Loxapine: CNS Depressants may enhance the CNS depressant effect of Loxapine. Risk D: Consider therapy modification
Lumateperone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Lumateperone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Lurasidone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Lurasidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Metaxalone: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Methadone: Doxepin-Containing Products may enhance the QTc-prolonging effect of Methadone. Management: Consider alternatives to this drug combination. If combined, monitor for QTc interval prolongation and ventricular arrhythmias. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk D: Consider therapy modification
Methotrimeprazine: CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Methotrimeprazine may enhance the CNS depressant effect of CNS Depressants. Management: Reduce the usual dose of CNS depressants by 50% if starting methotrimeprazine until the dose of methotrimeprazine is stable. Monitor patient closely for evidence of CNS depression. Risk D: Consider therapy modification
Methylene Blue: Tricyclic Antidepressants may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Risk X: Avoid combination
Metoclopramide: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Metoclopramide: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Consider monitoring for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Risk C: Monitor therapy
Mianserin: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk C: Monitor therapy
Minocycline (Systemic): May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Mirabegron: Agents with Clinically Relevant Anticholinergic Effects may enhance the adverse/toxic effect of Mirabegron. Risk C: Monitor therapy
Molindone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Molindone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Monoamine Oxidase Inhibitors (Antidepressant): May enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome. Risk X: Avoid combination
Nabilone: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Nefazodone: Tricyclic Antidepressants may enhance the serotonergic effect of Nefazodone. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Nicorandil: Tricyclic Antidepressants may enhance the hypotensive effect of Nicorandil. Risk C: Monitor therapy
Nitroglycerin: Agents with Clinically Relevant Anticholinergic Effects may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Risk C: Monitor therapy
Nonsteroidal Anti-Inflammatory Agents: Tricyclic Antidepressants may enhance the adverse/toxic effect of Nonsteroidal Anti-Inflammatory Agents. Specifically, the risk of major adverse cardiac events (MACE), hemorrhagic stroke, ischemic stroke, and heart failure may be increased. Tricyclic Antidepressants may enhance the antiplatelet effect of Nonsteroidal Anti-Inflammatory Agents. Risk C: Monitor therapy
OLANZapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of OLANZapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Olopatadine (Nasal): May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Ondansetron: May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Ondansetron may enhance the serotonergic effect of QT-prolonging Antidepressants (Moderate Risk). This could result in serotonin syndrome. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and serotonin syndrome when these agents are combined. Patients with additional risk factors for QTc prolongation or serotonin syndrome may be at even higher risk. Risk C: Monitor therapy
Opioid Agonists: CNS Depressants may enhance the CNS depressant effect of Opioid Agonists. Management: Avoid concomitant use of opioid agonists and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Risk X: Avoid combination
Oxatomide: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid combination
Oxitriptan: Serotonergic Agents (High Risk) may enhance the serotonergic effect of Oxitriptan. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Risk X: Avoid combination
Oxybate Salt Products: CNS Depressants may enhance the CNS depressant effect of Oxybate Salt Products. Management: Consider alternatives to this combination when possible. If combined, dose reduction or discontinuation of one or more CNS depressants (including the oxybate salt product) should be considered. Interrupt oxybate salt treatment during short-term opioid use Risk D: Consider therapy modification
OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Risk D: Consider therapy modification
Ozanimod: May enhance the adverse/toxic effect of Serotonergic Agents (High Risk). Risk C: Monitor therapy
Paliperidone: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Paliperidone. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Risk X: Avoid combination
PARoxetine: May enhance the serotonergic effect of Tricyclic Antidepressants. PARoxetine may increase the serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations/effects if these agents are combined. Risk D: Consider therapy modification
Pentamidine (Systemic): May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
Perampanel: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Periciazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Periciazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Perphenazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Perphenazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Pimozide: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Pipamperone [INT]: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Pipamperone [INT]. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Piperaquine: QT-prolonging Agents (Moderate Risk) may enhance the QTc-prolonging effect of Piperaquine. Risk X: Avoid combination
Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Risk C: Monitor therapy
Pitolisant: Tricyclic Antidepressants may diminish the therapeutic effect of Pitolisant. Risk X: Avoid combination
Polyethylene Glycol-Electrolyte Solution: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Polyethylene Glycol-Electrolyte Solution. Specifically, the risk of seizure may be increased. Risk C: Monitor therapy
Potassium Chloride: Agents with Clinically Relevant Anticholinergic Effects may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Risk X: Avoid combination
Potassium Citrate: Agents with Clinically Relevant Anticholinergic Effects may enhance the ulcerogenic effect of Potassium Citrate. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium citrate. Risk X: Avoid combination
Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Risk C: Monitor therapy
Pramlintide: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. These effects are specific to the GI tract. Risk X: Avoid combination
Procarbazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Prochlorperazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Prochlorperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Promazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Promazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Psilocybin: Antidepressants may diminish the therapeutic effect of Psilocybin. Risk C: Monitor therapy
QT-prolonging Agents (Highest Risk): May enhance the QTc-prolonging effect of Doxepin-Containing Products. Management: Consider alternatives to this combination. Patients with other risk factors (eg, older age, female sex, bradycardia, hypokalemia, hypomagnesemia, heart disease, and higher drug concentrations) are likely at greater risk for these toxicities. Risk D: Consider therapy modification
QT-prolonging Antidepressants (Moderate Risk): May enhance the anticholinergic effect of other QT-prolonging Antidepressants (Moderate Risk). QT-prolonging Antidepressants (Moderate Risk) may enhance the CNS depressant effect of other QT-prolonging Antidepressants (Moderate Risk). QT-prolonging Antidepressants (Moderate Risk) may enhance the QTc-prolonging effect of other QT-prolonging Antidepressants (Moderate Risk). QT-prolonging Antidepressants (Moderate Risk) may enhance the serotonergic effect of other QT-prolonging Antidepressants (Moderate Risk). This could result in serotonin syndrome. Management: Monitor for QTc interval prolongation, ventricular arrhythmias, and serotonin syndrome when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Class IC Antiarrhythmics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-Prolonging Inhalational Anesthetics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias, including torsades de pointes when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Kinase Inhibitors (Moderate Risk): QT-prolonging Antidepressants (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Kinase Inhibitors (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Miscellaneous Agents (Moderate Risk): QT-prolonging Antidepressants (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Miscellaneous Agents (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk): QT-prolonging Antidepressants (Moderate Risk) may enhance the QTc-prolonging effect of QT-prolonging Moderate CYP3A4 Inhibitors (Moderate Risk). Risk C: Monitor therapy
QT-prolonging Quinolone Antibiotics (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Management: Monitor for QTc interval prolongation and ventricular arrhythmias when these agents are combined. Patients with additional risk factors for QTc prolongation may be at even higher risk. Risk C: Monitor therapy
QT-prolonging Strong CYP3A4 Inhibitors (Moderate Risk): May enhance the QTc-prolonging effect of QT-prolonging Antidepressants (Moderate Risk). Risk C: Monitor therapy
QUEtiapine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of QUEtiapine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Ramosetron: Agents with Clinically Relevant Anticholinergic Effects may enhance the constipating effect of Ramosetron. Risk C: Monitor therapy
Ramosetron: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Rasagiline: May enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome. Risk X: Avoid combination
Revefenacin: Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Revefenacin. Risk X: Avoid combination
RisperiDONE: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of RisperiDONE. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Rivastigmine: Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Rivastigmine. Rivastigmine may diminish the therapeutic effect of Agents with Clinically Relevant Anticholinergic Effects. Management: Use of rivastigmine with an anticholinergic agent is not recommended unless clinically necessary. If the combination is necessary, monitor for reduced anticholinergic effects. Risk D: Consider therapy modification
Ropeginterferon Alfa-2b: CNS Depressants may enhance the adverse/toxic effect of Ropeginterferon Alfa-2b. Specifically, the risk of neuropsychiatric adverse effects may be increased. Management: Avoid coadministration of ropeginterferon alfa-2b and other CNS depressants. If this combination cannot be avoided, monitor patients for neuropsychiatric adverse effects (eg, depression, suicidal ideation, aggression, mania). Risk D: Consider therapy modification
ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Risk C: Monitor therapy
Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Risk C: Monitor therapy
Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Risk C: Monitor therapy
Safinamide: May enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome. Risk X: Avoid combination
Secretin: Agents with Clinically Relevant Anticholinergic Effects may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Risk D: Consider therapy modification
Selegiline: May enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome. Risk X: Avoid combination
Serotonergic Agents (High Risk, Miscellaneous): Tricyclic Antidepressants may enhance the serotonergic effect of Serotonergic Agents (High Risk, Miscellaneous). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Serotonergic Non-Opioid CNS Depressants: Tricyclic Antidepressants may enhance the CNS depressant effect of Serotonergic Non-Opioid CNS Depressants. Tricyclic Antidepressants may enhance the serotonergic effect of Serotonergic Non-Opioid CNS Depressants. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and CNS depression when these agents are combined. Risk C: Monitor therapy
Serotonergic Opioids (High Risk): Tricyclic Antidepressants may enhance the CNS depressant effect of Serotonergic Opioids (High Risk). Serotonergic Opioids (High Risk) may enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome. Management: Consider alternatives to this drug combination. If combined, monitor for signs and symptoms of serotonin syndrome/serotonin toxicity and CNS depression. Risk D: Consider therapy modification
Serotonin 5-HT1D Receptor Agonists (Triptans): May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Serotonin/Norepinephrine Reuptake Inhibitors: May enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes when these agents are combined. Risk C: Monitor therapy
Sertindole: May enhance the QTc-prolonging effect of QT-prolonging Agents (Moderate Risk). Risk X: Avoid combination
Sertraline: May enhance the serotonergic effect of Tricyclic Antidepressants. Sertraline may increase the serum concentration of Tricyclic Antidepressants. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) and increased TCA concentrations/effects if these agents are combined. Risk C: Monitor therapy
Sodium Phosphates: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Sodium Phosphates. Specifically, the risk of seizure or loss of consciousness may be increased in patients with significant sodium phosphate-induced fluid or electrolyte abnormalities. Risk C: Monitor therapy
St John's Wort: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. St John's Wort may decrease the serum concentration of Serotonergic Agents (High Risk). Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Sulpiride: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Sulpiride. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Risk D: Consider therapy modification
Syrian Rue: May enhance the serotonergic effect of Serotonergic Agents (High Risk). This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) when these agents are combined. Risk C: Monitor therapy
Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Risk X: Avoid combination
Thiazide and Thiazide-Like Diuretics: Agents with Clinically Relevant Anticholinergic Effects may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy
Thioridazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Thioridazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Thiothixene: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Thiothixene. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Thyroid Products: May enhance the arrhythmogenic effect of Tricyclic Antidepressants. Thyroid Products may enhance the stimulatory effect of Tricyclic Antidepressants. Risk C: Monitor therapy
Tiotropium: Agents with Clinically Relevant Anticholinergic Effects may enhance the anticholinergic effect of Tiotropium. Risk X: Avoid combination
Topiramate: Agents with Clinically Relevant Anticholinergic Effects may enhance the adverse/toxic effect of Topiramate. Risk C: Monitor therapy
Tricyclic Antidepressants: May enhance the anticholinergic effect of other Tricyclic Antidepressants. Tricyclic Antidepressants may enhance the CNS depressant effect of other Tricyclic Antidepressants. Tricyclic Antidepressants may enhance the serotonergic effect of other Tricyclic Antidepressants. This could result in serotonin syndrome. Management: Monitor closely for increased TCA adverse effects, including serotonin syndrome/serotonin toxicity, CNS depression, and anticholinergic effects. Risk C: Monitor therapy
Trifluoperazine: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Trifluoperazine. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Umeclidinium: May enhance the anticholinergic effect of Agents with Clinically Relevant Anticholinergic Effects. Risk X: Avoid combination
Valerian: May enhance the CNS depressant effect of CNS Depressants. Risk C: Monitor therapy
Valproate Products: May increase the serum concentration of Tricyclic Antidepressants. Risk C: Monitor therapy
Vasopressin: Drugs Suspected of Causing SIADH may enhance the therapeutic effect of Vasopressin. Specifically, the pressor and antidiuretic effects of vasopressin may be increased. Risk C: Monitor therapy
Vilazodone: Tricyclic Antidepressants may enhance the serotonergic effect of Vilazodone. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) if these agents are combined. Risk C: Monitor therapy
Vortioxetine: Tricyclic Antidepressants may enhance the serotonergic effect of Vortioxetine. This could result in serotonin syndrome. Management: Monitor for signs and symptoms of serotonin syndrome/serotonin toxicity (eg, hyperreflexia, clonus, hyperthermia, diaphoresis, tremor, autonomic instability, mental status changes) if these agents are combined. Risk C: Monitor therapy
Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Risk D: Consider therapy modification
Zuclopenthixol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Zuclopenthixol. Specifically, the risk of seizures may be increased. Risk C: Monitor therapy
Zuranolone: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to the use of zuranolone with other CNS depressants or alcohol. If combined, consider a zuranolone dose reduction and monitor patients closely for increased CNS depressant effects. Risk D: Consider therapy modification
Following topical application, plasma levels may be similar to those achieved with oral administration. Refer to the Doxepin (Systemic) monograph for additional information.
Following topical application, plasma levels may be similar to those achieved with oral administration. Refer to the Doxepin (Systemic) monograph for additional information.
Doxepin is present in breast milk following oral administration. Following topical application, plasma levels may be similar to those achieved with oral administration. Due to the potential for serious adverse reactions in the breastfed infant, the manufacturer recommends a decision be made whether to discontinue breastfeeding or to discontinue the drug, taking into account the importance of treatment to the mother. Refer to the Doxepin (Systemic) monograph for additional information.
Excessive drowsiness or other systemic effects (may be increased if topical formulation is applied to >10% of body surface area)
Doxepin has H1 and H2 histamine receptor blocking actions, the exact mechanism by which it exerts its antipruritic effect is unknown.
Absorption: Plasma levels may be similar to those achieved with oral administration.
Metabolism: Hepatic; desmethyldoxepin (active metabolite)
Half-life elimination: 28 to 52 hours (desmethyldoxepin)
Excretion: Urine
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