Asendin

Other Cyclic Antidepressants

Oral Administration

May be administered without regard to meals.
The entire daily dose may be administered at one time, preferably at bedtime, provided the dose does not exceed 300 mg/day. If the total daily dosage exceeds 300 mg, give in divided doses.

Severe

tardive dyskinesia / Delayed / 0-1.0
seizures / Delayed / 0-1.0
visual impairment / Early / 0-1.0
vasculitis / Delayed / 0-1.0
SIADH / Delayed / 0-1.0
neuroleptic malignant syndrome / Delayed / 0-1.0
agranulocytosis / Delayed / 0-1.0
suicidal ideation / Delayed / Incidence not known
stroke / Early / Incidence not known
atrial fibrillation / Early / Incidence not known
myocardial infarction / Delayed / Incidence not known
AV block / Early / Incidence not known
ocular hypertension / Delayed / Incidence not known
pancreatitis / Delayed / Incidence not known
ileus / Delayed / Incidence not known
acute generalized exanthematous pustulosis (AGEP) / Delayed / Incidence not known

Moderate

constipation / Delayed / 12.0-12.0
blurred vision / Early / 7.0-7.0
hyperthermia / Delayed / 0-1.0
hypertension / Early / 0-1.0
sinus tachycardia / Rapid / 0-1.0
hypotension / Rapid / 0-1.0
ejaculation dysfunction / Delayed / 0-1.0
urinary retention / Early / 0-1.0
galactorrhea / Delayed / 0-1.0
impotence (erectile dysfunction) / Delayed / 0-1.0
leukopenia / Delayed / 0-1.0
thrombocytopenia / Delayed / 0-1.0
ataxia / Delayed / 1.0
confusion / Early / 1.0
palpitations / Early / 1.0
EEG changes / Delayed / 1.0
edema / Delayed / 1.0
hyperprolactinemia / Delayed / 1.0
hallucinations / Early / Incidence not known
depression / Delayed / Incidence not known
mania / Early / Incidence not known
orthostatic hypotension / Delayed / Incidence not known
cycloplegia / Early / Incidence not known
jaundice / Delayed / Incidence not known
parotitis / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
testicular swelling / Early / Incidence not known
eosinophilia / Delayed / Incidence not known

Mild

drowsiness / Early / 14.0-14.0
xerostomia / Early / 14.0-14.0
paresthesias / Delayed / 0-1.0
tinnitus / Delayed / 0-1.0
syncope / Early / 0-1.0
nasal congestion / Early / 0-1.0
mydriasis / Early / 0-1.0
lacrimation / Early / 0-1.0
diarrhea / Early / 0-1.0
weight gain / Delayed / 0-1.0
abdominal pain / Early / 0-1.0
dysgeusia / Early / 0-1.0
vomiting / Early / 0-1.0
flatulence / Early / 0-1.0
weight loss / Delayed / 0-1.0
photosensitivity / Delayed / 0-1.0
pruritus / Rapid / 0-1.0
urticaria / Rapid / 0-1.0
breast enlargement / Delayed / 0-1.0
libido increase / Delayed / 0-1.0
menstrual irregularity / Delayed / 0-1.0
libido decrease / Delayed / 0-1.0
insomnia / Early / 1.0
nightmares / Early / 1.0
headache / Early / 1.0
dizziness / Early / 1.0
restlessness / Early / 1.0
anxiety / Delayed / 1.0
fatigue / Early / 1.0
asthenia / Delayed / 1.0
tremor / Early / 1.0
nausea / Early / 1.0
appetite stimulation / Delayed / 1.0
rash / Early / 1.0
hyperhidrosis / Delayed / 1.0
anorexia / Delayed / Incidence not known
alopecia / Delayed / Incidence not known
fever / Early / Incidence not known
increased urinary frequency / Early / Incidence not known
petechiae / Delayed / Incidence not known
purpura / Delayed / Incidence not known

Children, suicidal ideation

Amoxapine is not indicated for the treatment of depression in pediatric patients less than 18 years of age. In a pooled analysis of placebo-controlled trials of antidepressants (n = 4,500 pediatrics and 77,000 adults), there was an increased risk for suicidal thoughts and behaviors in children, adolescent and young adult patients 24 years of age and younger receiving an antidepressant versus placebo, with considerable variation in the risk of suicidality among drugs. The difference in absolute risk of suicidal thoughts and behaviors across different indications was highest in those with major depression. The need for an antidepressant in children, adolescents, or young adults for any use must be weighed against the risk of suicidality; it is unknown if this risk extends to long-term use. All patients should be monitored for symptom worsening or suicidality, especially at treatment initiation or after dose changes. Caregivers and/or patients should immediately notify the prescriber of changes in behavior or suicidal ideation. A change to the treatment regimen or discontinuation of amoxapine may be necessary in patients with emerging suicidality or worsening depression. Amoxapine should be used with caution in children and adolescents with a known family history of heart disease. QTc interval prolongation, tachycardia, and other side effects have been reported in children who have taken cyclic antidepressants; there are rare reports of deaths due to cardiovascular side effects. Routine cardiovascular monitoring has been suggested for children receiving cyclic antidepressants due to the potential of these agents to produce adverse cardiac effects.

Asendin

Rx

Norepinephrine reuptake inhibitor with dopamine antagonist properties
Used for the treatment of major depression in adults, including depression with psychotic features, concurrent anxiety, or agitation
Requires close monitoring in pediatrics and young adults due to increased risk of suicidality during the initial stages of treatment

For the treatment of major depression. Oral dosage Adults

50 mg PO 2 to 3 times per day initially. May titrate to 100 mg PO 2 to 3 times per day by the end of the first week of treatment as needed and tolerated. (Initial dosage of 300 mg/day may be given, but notable sedation may occur in some patients during the first few days of therapy.) Dosages above 300 mg/day, given in divided doses, should be used with caution and only if lower doses have been ineffective for at least 2 weeks. When effective dosage is established, may give in a single dose (not to exceed 300 mg/day) at bedtime. Max (outpatients): 400 mg/day PO in divided doses. Max (hospitalized): 600 mg/day PO in at least 2 divided doses (typically 200 mg PO in the morning and 400 mg PO at bedtime, or 300 mg PO twice daily). Onset of action generally occurs within 2 weeks of initiation of therapy.

Geriatric

25 mg PO 2 to 3 times daily as initial dose. If no response is obtained, may titrate, by the end of the first week, to 50 mg PO 2 to 3 times daily. 100 mg/day to 150 mg/day is often adequate for the geriatric adult. Some patients may require higher doses. Max: 300 mg/day PO. Once an effective dosage is established, may give as a single bedtime dose. Onset of action generally occurs within 2 weeks of initiation of therapy.

Hepatic Impairment

Specific guidelines for dosage adjustments in hepatic impairment are not available; amoxapine is extensively metabolized in the liver to active metabolites and should be used with caution.

Renal Impairment

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

Abiraterone: (Moderate) Monitor for an increase in amoxapine-related adverse reactions if coadministration with abiraterone is necessary; a dose reduction of amoxapine may be necessary. Amoxapine is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor. Patients who are stable on a given dose of amoxapine may become abruptly toxic when given abiraterone is concomitant therapy.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Acetaminophen; Caffeine; Dihydrocodeine: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking amoxapine. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Acetaminophen; Chlorpheniramine: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent. (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent. (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent. (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Acetaminophen; Codeine: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking amoxapine. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent.
Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent.
Acetaminophen; Dextromethorphan; Phenylephrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent.
Acetaminophen; Dextromethorphan; Pseudoephedrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent.
Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) CNS depressants should be combined cautiously with amoxapine because they could cause additive depressant effects and possible respiratory depression or hypotension. This combination is considered to be safe as long as patients are monitored for excessive adverse effects from either agent. (Moderate) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided.
Acetaminophen; Diphenhydramine: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Acetaminophen; Guaifenesin; Phenylephrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent.
Acetaminophen; Hydrocodone: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Acetaminophen; Oxycodone: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Acetaminophen; Phenylephrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent.
Acetaminophen; Pseudoephedrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent.
Acetazolamide: (Major) Cyclic antidepressants, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. In addition, pharmacokinetic interactions may occur. Monitor patients on anticonvulsants carefully when amoxapine is used concurrently.
Acrivastine; Pseudoephedrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent. (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Adagrasib: (Major) Lower doses of amoxapine may be required during concurrent use of adagrasib due to the potential for increased amoxapine exposure. If adagrasib is discontinued, an increased dose of amoxapine may be necessary. Amoxapine is a CYP2D6 substrate; adagrasib is a CYP2D6 inhibitor.
Alfentanil: (Major) Consider alternative therapy or reduce the dose of one or both drugs if alfentanil is used with another CNS depressant, such as amoxapine. The magnitude and duration of CNS and cardiovascular effects may be enhanced. Monitor patients for hypotension or prolonged respiratory depression and sedation. The respiratory depressant effect of alfentanil may persist longer than the measured analgesic effect; consider the total dose of all opioid agonists before ordering opioid analgesics during recovery from anesthesia.
Alosetron: (Moderate) Alosetron, if combined with drugs that possess anticholinergic properties like amoxapine, may seriously worsen constipation, leading to events such as GI obstruction/impaction or paralytic ileus.
Alprazolam: (Moderate) Amoxapine may enhance the response to the effects of benzodiazepines and other CNS depressants. Patients should be warned of the possibility of drowsiness that may impair performance of potentially hazardous tasks such as driving an automobile or operating machinery.
Amantadine: (Moderate) Medications with significant anticholinergic activity, like amoxapine, may potentiate the anticholinergic effects of amantadine, and may increase the risk of antimuscarinic-related side effects.
Amlodipine; Celecoxib: (Moderate) A dosage adjustment may be warranted for amoxapine if coadministered with celecoxib due to the potential for celecoxib to enhance the exposure and toxicity of amoxapine. Celecoxib is a CYP2D6 inhibitor, and amoxapine is a CYP2D6 substrate.
Amobarbital: (Major) Monitor for excessive sedation and somnolence during coadministration of amoxapine and barbiturates. Concurrent use may result in additive CNS depression.
Amphetamine; Dextroamphetamine Salts: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of indirect-acting sympathomimetics, such as amphetamine, however, the data are not consistent.
Anticholinergics: (Moderate) Depending on the specific agent, additive anticholinergic effects may be seen when amoxapine is used concomitantly with other anticholinergic agents. Clinicians should note that anticholinergic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Additive CNS effects are also possible when these drugs are combined with amoxapine.
Anxiolytics; Sedatives; and Hypnotics: (Moderate) CNS depressants should be combined cautiously with amoxapine because they could cause additive depressant effects and possible respiratory depression or hypotension.
Aripiprazole: (Moderate) Use caution during co-administration of amoxapine and aripiprazole. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of seizure threshold are potential problems with the combined use of amoxapine and antipsychotics.
Artemether; Lumefantrine: (Major) Because most cyclic antidepressants are partially metabolized by CYP2D6, caution is advisable during co-administration of amoxapine and potent CYP2D6 inhibitors such as artemether; lumefantrine. Elevated plasma concentrations of amoxapine may result in more pronounced anticholinergic effects and the risk of seizures may be increased.
Articaine; Epinephrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, such as epinephrine, however, the data are not consistent.
Asenapine: (Moderate) Use caution during co-administration of amoxapine and asenapine. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of seizure threshold are potential problems with the combined use of amoxapine and antipsychotics.
Aspirin, ASA; Butalbital; Caffeine: (Major) Monitor for excessive sedation and somnolence during coadministration of amoxapine and barbiturates. Concurrent use may result in additive CNS depression.
Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Orphenadrine should be combined cautiously with cyclic antidepressants like amoxapine because they could cause additive sedation or anticholinergic effects. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Patients should be monitored for excessive adverse effects from either agent.
Aspirin, ASA; Carisoprodol: (Moderate) Skeletal muscle relaxants should be combined cautiously with cyclic antidepressants like maprotiline because they could cause additive CNS depressant effects. Depending on the specific agent (e.g., cyclobenzaprine, and orphenadrine), additive anticholinergic effects may also be seen. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Patients should be monitored for excessive adverse effects from either agent.
Aspirin, ASA; Carisoprodol; Codeine: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking amoxapine. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Skeletal muscle relaxants should be combined cautiously with cyclic antidepressants like maprotiline because they could cause additive CNS depressant effects. Depending on the specific agent (e.g., cyclobenzaprine, and orphenadrine), additive anticholinergic effects may also be seen. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Patients should be monitored for excessive adverse effects from either agent.
Aspirin, ASA; Oxycodone: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Atazanavir: (Moderate) Atazanavir competitively inhibits the enzymes CYP3A4, CYP1A2 and CYP2C9. Concentrations of drugs that are substrates of these enzymes, such as tricyclic antidepressants, may be increased with concomitant atazanavir use. Amoxapine is related to the tricyclic antidepressants, and until more data is available, similar caution is advised when using amoxapine with atazanavir.
Atazanavir; Cobicistat: (Moderate) Atazanavir competitively inhibits the enzymes CYP3A4, CYP1A2 and CYP2C9. Concentrations of drugs that are substrates of these enzymes, such as tricyclic antidepressants, may be increased with concomitant atazanavir use. Amoxapine is related to the tricyclic antidepressants, and until more data is available, similar caution is advised when using amoxapine with atazanavir.
Atropine; Difenoxin: (Moderate) Diphenoxylate/difenoxin decreases GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. Amoxapine also decreases GI motility and may produce additive effects with diphenoxylate/difenoxin if used concomitantly.
Azelastine: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including amoxapine.
Azelastine; Fluticasone: (Moderate) An enhanced CNS depressant effect may occur when azelastine is combined with other CNS depressants including amoxapine.
Baclofen: (Moderate) Skeletal muscle relaxants should be combined cautiously with cyclic antidepressants like amoxapine because they could cause additive CNS depressant effects. Skeletal muscle relaxants may produce additive CNS depression or other additive effects when combined with tricyclic antidepressants. Depending on the specific agent (e.g., cyclobenzaprine, and orphenadrine), additive anticholinergic effects may also be seen. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Patients should be monitored for excessive adverse effects from either agent.
Barbiturates: (Major) Monitor for excessive sedation and somnolence during coadministration of amoxapine and barbiturates. Concurrent use may result in additive CNS depression.
Belladonna; Opium: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Benzhydrocodone; Acetaminophen: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Benzodiazepines: (Moderate) Amoxapine may enhance the response to the effects of benzodiazepines and other CNS depressants. Patients should be warned of the possibility of drowsiness that may impair performance of potentially hazardous tasks such as driving an automobile or operating machinery.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Moderate) Amoxapine should be used cautiously with intravenous methylene blue. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin and norepinephrine in the brain (MAO-A). Amoxapine primarily increases the activity of norepinephrine, with in vitro data suggesting an insignificant binding affinity for serotonin. Therefore, the potential for serotonin syndrome during coadministration of amoxapine and methylene blue is unclear. Monitoring for potential increases in blood pressure is advised due to the potential for additive noradrenergic activity.
Benzphetamine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of indirect-acting sympathomimetics, such as amphetamine, however, the data are not consistent.
Berotralstat: (Major) Lower doses of amoxapine may be required during concurrent use of berotralstat due to the potential for increased amoxapine exposure. If berotralstat is discontinued, an increased dose of amoxapine may be necessary. Amoxapine is a CYP2D6 substrate; berotralstat is a CYP2D6 inhibitor.
Bismuth Subsalicylate: (Moderate) Antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. The concomitant administration of amoxapine may produce additive effects.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Antidiarrheals decrease GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. The concomitant administration of amoxapine may produce additive effects.
Brexpiprazole: (Moderate) Due to the CNS effects of brexpiprazole, caution is advisable when brexpiprazole is given in combination with other centrally-acting medications including heterocyclic antidepressants.
Brompheniramine: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Brompheniramine; Dextromethorphan; Phenylephrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent. (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Brompheniramine; Phenylephrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent. (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Brompheniramine; Pseudoephedrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent. (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent. (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Bupivacaine; Epinephrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, such as epinephrine, however, the data are not consistent.
Buprenorphine: (Major) Concomitant use of buprenorphine with amoxapine may cause excessive sedation and somnolence. Limit the use of buprenorphine and amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Buprenorphine; Naloxone: (Major) Concomitant use of buprenorphine with amoxapine may cause excessive sedation and somnolence. Limit the use of buprenorphine and amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Bupropion: (Major) Concurrent administration of amoxapine with bupropion should be undertaken only with extreme caution due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus may reduce the clearance of amoxapine leading to a potential for increased Cmax, AUC and half-life. Amoxapine appears to be metabolized via CYP2D6. Low initial dosing and gradual dose increases of both drugs should be employed. If bupropion is added to a regimen of a patient already receiving amoxapine, the need to reduce the amoxapine dosage should be considered.
Bupropion; Naltrexone: (Major) Concurrent administration of amoxapine with bupropion should be undertaken only with extreme caution due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus may reduce the clearance of amoxapine leading to a potential for increased Cmax, AUC and half-life. Amoxapine appears to be metabolized via CYP2D6. Low initial dosing and gradual dose increases of both drugs should be employed. If bupropion is added to a regimen of a patient already receiving amoxapine, the need to reduce the amoxapine dosage should be considered.
Buspirone: (Moderate) CNS depressants should be combined cautiously with amoxapine because they could cause additive depressant effects and possible respiratory depression or hypotension. This combination is considered to be safe as long as patients are monitored for excessive adverse effects from either agent.
Butabarbital: (Major) Monitor for excessive sedation and somnolence during coadministration of amoxapine and barbiturates. Concurrent use may result in additive CNS depression.
Butalbital; Acetaminophen: (Major) Monitor for excessive sedation and somnolence during coadministration of amoxapine and barbiturates. Concurrent use may result in additive CNS depression.
Butalbital; Acetaminophen; Caffeine: (Major) Monitor for excessive sedation and somnolence during coadministration of amoxapine and barbiturates. Concurrent use may result in additive CNS depression.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking amoxapine. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Major) Monitor for excessive sedation and somnolence during coadministration of amoxapine and barbiturates. Concurrent use may result in additive CNS depression.
Butalbital; Aspirin; Caffeine; Codeine: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking amoxapine. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Major) Monitor for excessive sedation and somnolence during coadministration of amoxapine and barbiturates. Concurrent use may result in additive CNS depression.
Butorphanol: (Major) Concomitant use of butorphanol with amoxapine may cause excessive sedation and somnolence. Limit the use of butorphanol with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use in necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and amoxapine. CNS depressants can potentiate the effects of cannabidiol.
Capsaicin; Metaxalone: (Moderate) Skeletal muscle relaxants should be combined cautiously with cyclic antidepressants like maprotiline because they could cause additive CNS depressant effects. Depending on the specific agent (e.g., cyclobenzaprine, and orphenadrine), additive anticholinergic effects may also be seen. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Patients should be monitored for excessive adverse effects from either agent.
Carbidopa; Levodopa: (Moderate) Amoxapine exhibits antimuscarinic activity and can decrease gastric motility, decreasing the bioavailability of levodopa. In addition, severe hypertension occurred in a limited number of patients who received levodopa in combination with a tricyclic antidepressant.
Carbidopa; Levodopa; Entacapone: (Moderate) Amoxapine exhibits antimuscarinic activity and can decrease gastric motility, decreasing the bioavailability of levodopa. In addition, severe hypertension occurred in a limited number of patients who received levodopa in combination with a tricyclic antidepressant.
Carbinoxamine: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Cariprazine: (Moderate) Due to the CNS effects of cariprazine, caution is advisable when cariprazine is given in combination with other centrally-acting medications including heterocyclic antidepressants.
Carisoprodol: (Moderate) Skeletal muscle relaxants should be combined cautiously with cyclic antidepressants like maprotiline because they could cause additive CNS depressant effects. Depending on the specific agent (e.g., cyclobenzaprine, and orphenadrine), additive anticholinergic effects may also be seen. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Patients should be monitored for excessive adverse effects from either agent.
Celecoxib: (Moderate) A dosage adjustment may be warranted for amoxapine if coadministered with celecoxib due to the potential for celecoxib to enhance the exposure and toxicity of amoxapine. Celecoxib is a CYP2D6 inhibitor, and amoxapine is a CYP2D6 substrate.
Celecoxib; Tramadol: (Major) Concomitant use of tramadol with amoxapine may cause excessive sedation and somnolence and increase the risk for seizures. Limit the use of tramadol with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and the potential increased risk for seizures. (Moderate) A dosage adjustment may be warranted for amoxapine if coadministered with celecoxib due to the potential for celecoxib to enhance the exposure and toxicity of amoxapine. Celecoxib is a CYP2D6 inhibitor, and amoxapine is a CYP2D6 substrate.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and amoxapine. Concurrent use may result in additive CNS depression.
Cetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with heterocyclic antidepressants should generally be avoided. Coadministration may increase the risk of anticholinergic and CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive anticholinergic effects, sedation, and somnolence.
Cetirizine; Pseudoephedrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent. (Moderate) Concurrent use of cetirizine/levocetirizine with heterocyclic antidepressants should generally be avoided. Coadministration may increase the risk of anticholinergic and CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive anticholinergic effects, sedation, and somnolence.
Chlophedianol; Dexbrompheniramine: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent. (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Chlorcyclizine: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Chlordiazepoxide: (Moderate) Amoxapine may enhance the response to the effects of benzodiazepines and other CNS depressants. Patients should be warned of the possibility of drowsiness that may impair performance of potentially hazardous tasks such as driving an automobile or operating machinery.
Chlordiazepoxide; Amitriptyline: (Moderate) Amoxapine may enhance the response to the effects of benzodiazepines and other CNS depressants. Patients should be warned of the possibility of drowsiness that may impair performance of potentially hazardous tasks such as driving an automobile or operating machinery.
Chlordiazepoxide; Clidinium: (Moderate) Amoxapine may enhance the response to the effects of benzodiazepines and other CNS depressants. Patients should be warned of the possibility of drowsiness that may impair performance of potentially hazardous tasks such as driving an automobile or operating machinery.
Chlorpheniramine: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Chlorpheniramine; Codeine: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking amoxapine. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Chlorpheniramine; Dextromethorphan: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent. (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent. (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent. (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking amoxapine. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Chlorpheniramine; Hydrocodone: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent. (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Chlorpheniramine; Phenylephrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent. (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Chlorpheniramine; Pseudoephedrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent. (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Chlorpromazine: (Moderate) Use caution during coadministration of amoxapine and chlorpromazine. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of seizure threshold are potential problems with the combined use of amoxapine and chlorpromazine.
Chlorthalidone; Clonidine: (Major) Concurrent use of clonidine with amoxapine should be avoided when possible, due to multiple possible interactions. Clonidine's antihypertensive effect can be reduced by cyclic antidepressants; occasionally, the hypertension will occur within the first few days of combined therapy. If coadministration of amoxapine with clonidine cannot be avoided, the patient should be closely monitored for increased blood pressure and clonidine dosages adjusted as needed. In addition, concurrent administration of a cyclic antidepressant and clonidine may result in additive CNS depression or other side effects; clonidine produces mental depression as a side effect in roughly 1% of patients. In rats, the coadministration of a cyclic antidepressant (amitriptyline) with clonidine resulted in corneal lesions, but the human implications of these animal study findings are unknown.
Chlorzoxazone: (Moderate) Skeletal muscle relaxants should be combined cautiously with cyclic antidepressants like maprotiline because they could cause additive CNS depressant effects. Depending on the specific agent (e.g., cyclobenzaprine, and orphenadrine), additive anticholinergic effects may also be seen. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Patients should be monitored for excessive adverse effects from either agent.
Cholinergic agonists: (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.
Cimetidine: (Moderate) Cimetidine can inhibit the systemic clearance of drugs that undergo oxidative metabolism, such as amoxapine, resulting in increased plasma levels of the antidepressant. Patients should be monitored for amoxapine-related side effects and toxicity if cimetidine is added; when possible, choose an alternative H2-blocker for treatment.
Cinacalcet: (Major) Lower doses of amoxapine may be required during concurrent use of cinacalcet due to the potential for increased amoxapine exposure. If cinacalcet is discontinued, an increased dose of amoxapine may be necessary. Amoxapine is a CYP2D6 substrate; cinacalcet is a CYP2D6 inhibitor.
Clemastine: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Clobazam: (Moderate) Amoxapine may enhance the response to benzodiazepines and other CNS depressants. Patients should be warned of the possibility of drowsiness that may impair performance of potentially hazardous tasks such as driving an automobile or operating machinery.
Clonazepam: (Moderate) Amoxapine may enhance the response to the effects of benzodiazepines and other CNS depressants. Patients should be warned of the possibility of drowsiness that may impair performance of potentially hazardous tasks such as driving an automobile or operating machinery.
Clonidine: (Major) Concurrent use of clonidine with amoxapine should be avoided when possible, due to multiple possible interactions. Clonidine's antihypertensive effect can be reduced by cyclic antidepressants; occasionally, the hypertension will occur within the first few days of combined therapy. If coadministration of amoxapine with clonidine cannot be avoided, the patient should be closely monitored for increased blood pressure and clonidine dosages adjusted as needed. In addition, concurrent administration of a cyclic antidepressant and clonidine may result in additive CNS depression or other side effects; clonidine produces mental depression as a side effect in roughly 1% of patients. In rats, the coadministration of a cyclic antidepressant (amitriptyline) with clonidine resulted in corneal lesions, but the human implications of these animal study findings are unknown.
Clorazepate: (Moderate) Amoxapine may enhance the response to the effects of benzodiazepines and other CNS depressants. Patients should be warned of the possibility of drowsiness that may impair performance of potentially hazardous tasks such as driving an automobile or operating machinery.
Clozapine: (Moderate) Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when clozapine is given concurrently. In addition, additive anticholinergic effects and sedation are possible, as well as lowering of the seizure threshold.
Cocaine: (Moderate) Monitor patients for increased CNS stimulation during coadministration of cocaine and amoxapine. Concurrent use of cocaine and cyclic antidepressants may increase the risk for excessive sympathetic CNS activity leading to symptoms such as tachycardia, hypertension, diaphoresis, agitation, cardiac arrythmias, or convulsions.
Codeine: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking amoxapine. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Codeine; Guaifenesin: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking amoxapine. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Codeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent. (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking amoxapine. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent. (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking amoxapine. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Additive anticholinergic effects are possible during coadministration of promethazine and amoxapine. Additive drowsiness and sedation are also possible. Anticholinergic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Codeine; Promethazine: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking amoxapine. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Moderate) Additive anticholinergic effects are possible during coadministration of promethazine and amoxapine. Additive drowsiness and sedation are also possible. Anticholinergic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
COMT inhibitors: (Major) COMT inhibitors should be given cautiously with other agents that cause CNS depression, such as heterocyclic antidepressants, due to the possibility of additive sedation. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Cyclizine: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Cyclobenzaprine: (Major) Cyclobenzaprine shares structural similarity to amoxapine; concurrent use of cyclobenzaprine should generally be avoided in patients taking cyclic antidepressants due to the additive risk of similar pharmacology, and side effects such as sedation and anticholinergic effects. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Patients should be monitored for excessive anticholinergic adverse effects, such as constipation or urinary retention. Additive CNS effects such as drowsiness or dizziness may also occur.
Cyproheptadine: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Dacomitinib: (Moderate) Monitor for increased toxicity of amoxapine, such as increased anticholinergic effects, if coadministered with dacomitinib. Coadministration may increase serum concentrations of amoxapine. Amoxapine is a CYP2D6 substrate; dacomitinib is a strong CYP2D6 inhibitor.
Dantrolene: (Moderate) Skeletal muscle relaxants should be combined cautiously with cyclic antidepressants like maprotiline because they could

cause additive CNS depressant effects. Depending on the specific agent (e.g., cyclobenzaprine, and orphenadrine), additive anticholinergic effects may also be seen. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Patients should be monitored for excessive adverse effects from either agent.
Darifenacin: (Moderate) Monitor for increased toxicity of amoxapine, such as increased anticholinergic effects, if coadministered with darifenacin. Coadministration may increase serum concentrations of amoxapine. Amoxapine is a CYP2D6 substrate; darifenacin is a moderate CYP2D6 inhibitor.
Delavirdine: (Moderate) Lower doses of amoxapine may be required during concurrent use of delavirdine due to the potential for increased amoxapine exposure. Amoxapine is a CYP2D6 substrate and delavirdine is a CYP2D6 inhibitor.
Desloratadine; Pseudoephedrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent.
Deutetrabenazine: (Moderate) Monitor for signs and symptoms of neuroleptic malignant syndrome (NMS), restlessness, and agitation. If NMS is diagnosed, immediately discontinue deutetrabenazine, and provide intensive symptomatic treatment and medical monitoring. Recurrence of NMS has been reported with resumption of drug therapy. If akathisia or parkinsonism develops during treatment, the deutetrabenazine dose should be reduced; discontinuation may be required. Deutetrabenazine is a reversible, dopamine depleting drug and amoxapine is a dopamine antagonist. The risk for parkinsonism, NMS, or akathisia may be increased with concomitant administration. Also, advise patients that concurrent use of deutetrabenazine and drugs that cause CNS depression, such as amoxapine, may have additive effects and worsen drowsiness or sedation.
Dexbrompheniramine: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Dexbrompheniramine; Pseudoephedrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent. (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Dexchlorpheniramine: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent. (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Dextromethorphan; Bupropion: (Major) Concurrent administration of amoxapine with bupropion should be undertaken only with extreme caution due to the potential for increased risk of seizures from the lowering of seizure threshold. In addition, bupropion inhibits the hepatic isozyme CYP2D6 and thus may reduce the clearance of amoxapine leading to a potential for increased Cmax, AUC and half-life. Amoxapine appears to be metabolized via CYP2D6. Low initial dosing and gradual dose increases of both drugs should be employed. If bupropion is added to a regimen of a patient already receiving amoxapine, the need to reduce the amoxapine dosage should be considered.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent. (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent.
Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent.
Dextromethorphan; Quinidine: (Major) Because most cyclic antidepressants are partially metabolized by CYP2D6, caution is advisable during co-administration of amoxapine and potent CYP2D6 inhibitors such as quinidine. Elevated plasma concentrations of amoxapine may result in more pronounced anticholinergic effects and the risk of seizures may be increased. Anti-arrhythmics that are less potent inhibitors of CYP2D6, such as propafenone, may similarly interact with amoxapine. CYP2D6 substrates including flecainide may compete with amoxapine for the same metabolic pathway.
Diazepam: (Moderate) Amoxapine may enhance the response to the effects of benzodiazepines and other CNS depressants. Patients should be warned of the possibility of drowsiness that may impair performance of potentially hazardous tasks such as driving an automobile or operating machinery.
Diethylpropion: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants decrease the pressor response to indirect-acting sympathomimetics, such as diethylpropion, however, the data are not consistent.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Dimenhydrinate: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Diphenhydramine: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Diphenhydramine; Ibuprofen: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Diphenhydramine; Naproxen: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Diphenhydramine; Phenylephrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent. (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Diphenoxylate; Atropine: (Moderate) Diphenoxylate/difenoxin decreases GI motility. Agents that inhibit intestinal motility or prolong intestinal transit time have been reported to induce toxic megacolon. Amoxapine also decreases GI motility and may produce additive effects with diphenoxylate/difenoxin if used concomitantly.
Disopyramide: (Moderate) Additive anticholinergic effects may be seen when drugs with anticholinergic properties like disopyramide and amoxapine are used concomitantly. Adverse effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation.
Disulfiram: (Moderate) Limited data suggest that the combination of cyclic antidepressants with disulfiram can produce transient delirium. Disulfiram is known to inhibit some of the hepatic cytochrome P450 isoenzymes involved in cyclic antidepressant metabolism.
Dobutamine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent.
Donepezil: (Major) Amoxapine may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of donepezil. Donepezil exerts its therapeutic effect by inhibiting acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine.
Donepezil; Memantine: (Major) Amoxapine may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of donepezil. Donepezil exerts its therapeutic effect by inhibiting acetylcholinesterase, the enzyme responsible for the degradation of acetylcholine, and improves the availability of acetylcholine.
Dopamine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent.
Doxylamine: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Doxylamine; Pyridoxine: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Dronabinol: (Moderate) Use caution if coadministration of dronabinol with amoxapine is necessary. Concurrent use of dronabinol, THC with amoxapine may result in additive drowsiness, hypertension, tachycardia, and possibly cardiotoxicity.
Ephedrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent.
Ephedrine; Guaifenesin: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent.
Epinephrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, such as epinephrine, however, the data are not consistent.
Erythromycin: (Moderate) Erythromycin may be used to stimulate GI motility, such as in patients with diabetic gastroparesis. Some cyclic antidepressants with substantial antimuscarinic properties, such as amoxapine, may counteract erythromycin's effectiveness in enhancing GI motility.
Esketamine: (Major) Closely monitor patients receiving esketamine and amoxapine for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
Estazolam: (Moderate) Amoxapine may enhance the response to the effects of benzodiazepines and other CNS depressants. Patients should be warned of the possibility of drowsiness that may impair performance of potentially hazardous tasks such as driving an automobile or operating machinery.
Eszopiclone: (Moderate) CNS depressants should be combined cautiously with amoxapine because they could cause additive depressant effects and possible respiratory depression or hypotension.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking CNS depressants. Alcohol consumption may result in additive CNS depression.
Ethiodized Oil: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Amoxapine should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Ethotoin: (Moderate) Amoxapine, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Pharmacokinetic interactions may occur, since hydantoins may induce hepatic metabolism of certain antidepressants. Monitor patients on anticonvulsants carefully when amoxapine is used concurrently.
Everolimus: (Moderate) Monitor for an increase in amoxapine-related adverse reactions if coadministration with everolimus is necessary. Amoxapine is a CYP2D6 substrate and everolimus is a weak CYP2D6 inhibitor; concomitant use may increase plasma concentrations of amoxapine.
Fedratinib: (Moderate) Monitor for increased toxicity of amoxapine, such as increased anticholinergic effects, if coadministered with fedratinib. Coadministration may increase serum concentrations of amoxapine. Amoxapine is a CYP2D6 substrate; fedratinib is a moderate CYP2D6 inhibitor.
Felbamate: (Moderate) Amoxapine, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and amoxapine. Concurrent use may result in additive CNS depression.
Fentanyl: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Fexofenadine; Pseudoephedrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent.
Flecainide: (Moderate) CYP2D6 substrates including flecainide may compete with amoxapine for the same metabolic pathway.
Flumazenil: (Major) Particular caution is necessary when using flumazenil in cases of mixed drug overdosage since the toxic effects (such as convulsions and cardiac dysrhythmias) of other drugs taken in overdose (especially cyclic antidepressants like amoxapine) may emerge with the reversal of the benzodiazepine effect by flumazenil. The reversal of benzodiazepine effects may be associated with the onset of seizures in certain high-risk populations; concurrent cyclic antidepressant poisoning is a risk factor for seizures. Flumazenil is not recommended in cases of serious cyclic antidepressant poisoning, as manifested by motor abnormalities (twitching, rigidity, focal seizure), dysrhythmia (wide QRS, ventricular dysrhythmia, heart block), anticholinergic signs (mydriasis, dry mucosa, hypoperistalsis), and cardiovascular collapse at presentation. In such cases flumazenil should be withheld and the patient should be allowed to remain sedated (with ventilatory and circulatory support as needed) until the signs of antidepressant toxicity have subsided. Treatment with flumazenil has no known benefit to the seriously ill mixed-overdose patient other than reversing sedation and should not be used in cases where seizures (from any cause) are likely.
Fluoxetine: (Moderate) Fluoxetine, a potent CYP2D6 inhibitor, may increase the plasma concentrations of the tetracyclic antidepressant amoxapine, which is partially metabolized by CYP2D6. In several cases, symptoms of toxicity, including seizures, have been reported when tricyclic antidepressants were coadministered with an SSRI, including fluoxetine. At least one case report exists of a death thought to be due to impaired clearance of the tricyclic antidepressant amitriptyline by fluoxetine. Also, this combination may represent duplicative therapy. Patients receiving amoxapine should be monitored closely for toxicity if fluoxetine is added. Monitoring should be continued for several weeks following the discontinuation of fluoxetine due to the long half-life of norfluoxetine, the active metabolite of fluoxetine which has a half-life of 7 to 9 days and is a CYP2D6 inhibitor.
Fluphenazine: (Moderate) Use caution during co-administration of amoxapine and antipsychotics. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of seizure threshold are potential problems with the combined use of amoxapine and antipsychotics.
Flurazepam: (Moderate) Amoxapine may enhance the response to the effects of benzodiazepines and other CNS depressants. Patients should be warned of the possibility of drowsiness that may impair performance of potentially hazardous tasks such as driving an automobile or operating machinery.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Fosphenytoin: (Moderate) Amoxapine, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Pharmacokinetic interactions may occur, since hydantoins may induce hepatic metabolism of certain antidepressants. Monitor patients on anticonvulsants carefully when amoxapine is used concurrently.
Gabapentin: (Major) Initiate gabapentin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of gabapentin and amoxapine. Concomitant use of gabapentin with amoxapine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
Galantamine: (Moderate) Due to their anticholinergic actions, some cyclic antidepressants, including amoxapine, may antagonize the therapeutic actions of the cholinesterase-inhibitors such as galantamine, which are used for the treatment of dementia. Consider alternatives if concurrent therapy is needed. If alternative therapy is not possible, monitor for deceased efficacy of galantamine.
General anesthetics: (Moderate) Because amoxapine can cause sedation, an enhanced CNS depressant effect may occur during combined use with general anesthetics such as enflurane.
Givosiran: (Major) Avoid concomitant use of givosiran and amoxapine due to the risk of increased amoxapine-related adverse reactions. If use is necessary, consider decreasing the amoxapine dose. Monitor amoxapine serum concentrations. Amoxapine is a CYP2D6 substrate. Givosiran may moderately reduce hepatic CYP2D6 enzyme activity because of its pharmacological effects on the hepatic heme biosynthesis pathway.
Goserelin: (Major) Avoid coadministration of goserelin with amoxapine due to the risk of reduced efficacy of goserelin. Amoxapine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; goserelin is a GnRH analog.
Guaifenesin; Hydrocodone: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Guaifenesin; Phenylephrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent.
Guaifenesin; Pseudoephedrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent.
Guanfacine: (Major) Cyclic antidepressants like amoxapine can inhibit the hypotensive effects of guanfacine, causing an increase in blood pressure if given concomitantly. Increased dosages of guanfacine may be required in patients who are receiving amoxapine concurrently. In addition, concurrent amoxapine use may enhance the potential for rebound hypertension following guanfacine discontinuation. If guanfacine is withdrawn in the presence of amoxapine or other cyclic antidepressants, guanfacine should be tapered gradually and the patient should be monitored for potential hypertension.
Guselkumab: (Moderate) Clinically relevant drug interactions may occur when guselkumab is administered with sensitive substrates of CYP2D6, such as amoxapine. Monitor amoxapine concentrations if guselkumab is initiated or discontinued; the amoxapine dose may need to be adjusted. During chronic inflammation, increased levels of certain cytokines can alter the formation of CYP450 enzymes. Thus, the formation of CYP2D6 could be normalized during guselkumab administration.
Haloperidol: (Moderate) Use caution during co-administration of amoxapine and antipsychotics. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. Clinically significant anticholinergic activity may also be seen with loxapine, olanzapine, and clozapine. In addition, amoxapine is metabolized by CYP2D6. Haloperidol is an inhibitor of hepatic CYP2D6, and coadministration with amoxapine may lead to elevated amoxapine serum concentrations.
Histrelin: (Major) Avoid coadministration of histrelin with amoxapine due to the risk of reduced efficacy of histrelin. Amoxapine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; histrelin is a GnRH analog.
Homatropine; Hydrocodone: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Hydantoins: (Moderate) Amoxapine, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Pharmacokinetic interactions may occur, since hydantoins may induce hepatic metabolism of certain antidepressants. Monitor patients on anticonvulsants carefully when amoxapine is used concurrently.
Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) Amoxapine, as a cyclic antidepressant, can block the action of methyldopa, preventing or significantly reducing the expected antihypertensive effects. Avoid use of amoxapine concurrently with methyldopa when possible.
Hydrocodone: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Hydrocodone; Ibuprofen: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Hydrocodone; Pseudoephedrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent. (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Hydromorphone: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Hydroxyzine: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Moderate) Amoxapine should be used cautiously with intravenous methylene blue. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin and norepinephrine in the brain (MAO-A). Amoxapine primarily increases the activity of norepinephrine, with in vitro data suggesting an insignificant binding affinity for serotonin. Therefore, the potential for serotonin syndrome during coadministration of amoxapine and methylene blue is unclear. Monitoring for potential increases in blood pressure is advised due to the potential for additive noradrenergic activity.
Ibuprofen; Oxycodone: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Ibuprofen; Pseudoephedrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent.
Iloperidone: (Moderate) Use caution during co-administration of amoxapine and iloperidone. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of seizure threshold are potential problems with the combined use of amoxapine and antipsychotics.
Imatinib: (Moderate) Imatinib is a potent inhibitor of cytochrome P450 2D6 and may increase concentrations of other drugs metabolized by this enzyme including amoxapine.
Iodixanol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Amoxapine should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iohexol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Amoxapine should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iomeprol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Amoxapine should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iopamidol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Amoxapine should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Iopromide: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Amoxapine should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Ioversol: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Amoxapine should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Isocarboxazid: (Contraindicated) Amoxapine, a heterocyclic antidepressant, is contraindicated for use with monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders or within 14 days of discontinuing treatment with an MAOI. Conversely, an MAOI should not be initiated within 14 days of stopping amoxapine. Hyperpyretic crisis, severe convulsions, and deaths have occurred in patients receiving other cyclic antidepressants and MAOIs simultaneously.
Isoproterenol: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent.
Isosulfan Blue: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Amoxapine should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Labetalol: (Moderate) An increased incidence of labetalol-induced tremor has been reported in patients being treated concurrently with tricyclic antidepressants. Similar interactions would be expected with the related cyclic antidepressant amoxapine.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and amoxapine. Concurrent use may result in additive CNS depression.
Lemborexant: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lemborexant and amoxapine. Dosage adjustments of lemborexant and amoxapine may be necessary when administered together because of potentially additive CNS effects. The risk of next-day impairment, including impaired driving, is increased if lemborexant is taken with other CNS depressants.
Leuprolide: (Major) Avoid coadministration of leuprolide with amoxapine due to the risk of reduced efficacy of leuprolide. Amoxapine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
Leuprolide; Norethindrone: (Major) Avoid coadministration of leuprolide with amoxapine due to the risk of reduced efficacy of leuprolide. Amoxapine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; leuprolide is a GnRH analog.
Levocetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with heterocyclic antidepressants should generally be avoided. Coadministration may increase the risk of anticholinergic and CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive anticholinergic effects, sedation, and somnolence.
Levodopa: (Moderate) Amoxapine exhibits antimuscarinic activity and can decrease gastric motility, decreasing the bioavailability of levodopa. In addition, severe hypertension occurred in a limited number of patients who received levodopa in combination with a tricyclic antidepressant.
Levorphanol: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Reduce the initial dose of levorphanol by approximately 50% or more. Educate patients about the risks and symptoms of excessive CNS depression.
Lidocaine; Epinephrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, such as epinephrine, however, the data are not consistent.
Linezolid: (Moderate) Amoxapine should be used cautiously with linezolid. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO), an enzyme responsible for the catabolism of serotonin, norepinephrine, and dopamine in the brain. Amoxapine primarily increases the activity of norepinephrine, with in vitro data suggesting an insignificant binding affinity for serotonin. Therefore, the potential for serotonin syndrome during coadministration of amoxapine and linezolid is unclear. Monitoring for potential increases in blood pressure is advised due to the potential for additive noradrenergic activity.
Lofexidine: (Moderate) Monitor for excessive hypotension and sedation during coadministration of lofexidine and amoxapine. Lofexidine can potentiate the effects of CNS depressants.
Lopinavir; Ritonavir: (Major) Ritonavir potently inhibits CYP2D6, and may inhibit the metabolism of amoxapine. Since the magnitude of the interaction with the amoxapine is difficult to predict but may be significant, monitor patients receiving ritonavir and amoxapine concurrently closely. Adjust the dosage of the coadministered drug based on therapeutic response. Amoxapine serum concentration monitoring may be useful to guide adjustments and prevent toxicity.
Loratadine; Pseudoephedrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent.
Lorazepam: (Moderate) Amoxapine may enhance the response to the effects of benzodiazepines and other CNS depressants. Patients should be warned of the possibility of drowsiness that may impair performance of potentially hazardous tasks such as driving an automobile or operating machinery.
Loxapine: (Major) Amoxapine is a metabolite of loxapine and this combination is generally not prescribed. Use caution during coadministration of amoxapine and loxapine. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. Clinically significant anticholinergic activity and sedation are also possible.
Lumateperone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lumateperone and amoxapine. Concurrent use may result in additive CNS depression.
Lurasidone: (Moderate) Use caution during co-administration of amoxapine and lurasidone. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of seizure threshold are potential problems with the combined use of amoxapine and antipsychotics.
Maprotiline: (Contraindicated) The use of amoxapine with chemically-related cyclic antidepressants like maprotiline or tricyclic antidepressants (TCAs) is not generally recommended, due to the duplicative nature of therapy and the risk for side effects. Additive cardiac effects (e.g., prolonged QT interval), CNS effects, or antimuscarinic effects may occur. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Meclizine: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Meperidine: (Moderate) Concomitant use of mepridine with amoxapine may cause additive sedation and somnolence. Limit the use of opioid pain medications to patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. Monitor for other additive effects, such as constipation or urinary retention.
Meprobamate: (Moderate) CNS depressants should be combined cautiously with amoxapine because they could cause additive depressant effects and possible respiratory depression or hypotension.
Metaxalone: (Moderate) Skeletal muscle relaxants should be combined cautiously with cyclic antidepressants like maprotiline because they could cause additive CNS depressant effects. Depending on the specific agent (e.g., cyclobenzaprine, and orphenadrine), additive anticholinergic effects may also be seen. Clinicians should note that antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Patients should be monitored for excessive adverse effects from either agent.
Methadone: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Methamphetamine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of indirect-acting sympathomimetics, such as methamphetamine, however, the data are not consistent.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Moderate) Amoxapine should be used cautiously with intravenous methylene blue. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin and norepinephrine in the brain (MAO-A). Amoxapine primarily increases the activity of norepinephrine, with in vitro data suggesting an insignificant binding affinity for serotonin. Therefore, the potential for serotonin syndrome during coadministration of amoxapine and methylene blue is unclear. Monitoring for potential increases in blood pressure is advised due to the potential for additive noradrenergic activity.
Methohexital: (Major) Monitor for excessive sedation and somnolence during coadministration of amoxapine and barbiturates. Concurrent use may result in additive CNS depression.
Methyldopa: (Moderate) Amoxapine, as a cyclic antidepressant, can block the action of methyldopa, preventing or significantly reducing the expected antihypertensive effects. Avoid use of amoxapine concurrently with methyldopa when possible.
Methylene Blue: (Moderate) Amoxapine should be used cautiously with intravenous methylene blue. Methylene blue is a thiazine dye that is also a potent, reversible inhibitor of the enzyme responsible for the catabolism of serotonin and norepinephrine in the brain (MAO-A). Amoxapine primarily increases the activity of norepinephrine, with in vitro data suggesting an insignificant binding affinity for serotonin. Therefore, the potential for serotonin syndrome during coadministration of amoxapine and methylene blue is unclear. Monitoring for potential increases in blood pressure is advised due to the potential for additive noradrenergic activity.
Methylphenidate Derivatives: (Moderate) Methylphenidate derivatives and amoxapine may lower the seizure threshold; therefore, caution is particularly advisable when this combination is administered to patients susceptible to seizures. In addition, methylphenidate is thought to exert some of its beneficial effects through dopamine re-uptake blockade while amoxapine has central dopamine antagonist properties. In theory, the therapeutic effects of either agent may be reduced.
Metoclopramide: (Major) Metoclopramide is a central dopamine antagonist and may cause extrapyramidal reactions (e.g., acute dystonic reactions, pseudo-parkinsonism, akathisia, or tardive dyskinesia), and rarely, neuroleptic malignant syndrome. Metoclopramide is contraindicated with other drugs that are likely to cause extrapyramidal effects since the risk of these effects may be increased. Case reports and case series have implicated tricyclic antidepressants in causing a variety of extrapyramidal symptoms (EPS). Although the occurrence is infrequent compared to antipsychotic-induced EPS, the risk of these events may be increased during concurrent use of metoclopramide and tricyclic antidepressants compared to monotherapy with either agent. The related cyclic compound amoxapine has significant anti-dopaminergic properties, and several cases of EPS have been reported during use of this drug. It is advisable to avoid coadministration of metoclopramide and amoxapine if possible.
Midazolam: (Moderate) Amoxapine may enhance the response to the effects of benzodiazepines and other CNS depressants. Patients should be warned of the possibility of drowsiness that may impair performance of potentially hazardous tasks such as driving an automobile or operating machinery.
Midodrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent.
Minocycline: (Minor) Injectable minocycline contains magnesium sulfate heptahydrate. Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants such as heterocyclic antidepressants (i.e., amoxapine, maprotiline, mirtazapine, and trazodone). Caution should be exercised when using these agents concurrently.
Mirabegron: (Major) Concomitant use of amoxapine with drugs that can inhibit cytochrome P450 2D6, such as mirabegron, may require lower doses than usually prescribed for either amoxapine or mirabegron. Furthermore, whenever mirabegron is withdrawn from co-therapy, an increased dose of the amoxapine may be required. It is desirable to monitor amoxapine plasma levels whenever amoxapine is going to be co-administered with another drug known to be an inhibitor of P450 2D6.
Mirtazapine: (Major) Monitor for excessive sedation and somnolence during coadministration of amoxapine and mirtazapine. Concurrent use may result in additive CNS depression.
Molindone: (Moderate) Use caution during co-administration of amoxapine and molindone. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of seizure threshold are potential problems with the combined use of amoxapine and antipsychotics.
Monoamine oxidase inhibitors: (Contraindicated) Amoxapine, a heterocyclic antidepressant, is contraindicated for use with monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders or within 14 days of discontinuing treatment with an MAOI. Conversely, an MAOI should not be initiated within 14 days of stopping amoxapine. Hyperpyretic crisis, severe convulsions, and deaths have occurred in patients receiving other cyclic antidepressants and MAOIs simultaneously.
Morphine: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. For extended-release morphine tablets, start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of excessive CNS depression.
Morphine; Naltrexone: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. For extended-release morphine tablets, start with 15 mg every 12 hours. Morphine; naltrexone should be initiated at 1/3 to 1/2 the recommended starting dosage. Educate patients about the risks and symptoms of excessive CNS depression.
Nabilone: (Moderate) Nabilone or other CNS depressants should be combined cautiously with heterocyclic antidepressants because they could cause additive depressant effects and possible respiratory depression or hypotension.
Nalbuphine: (Major) Concomitant use of nalbuphine with amoxapine may cause excessive sedation and somnolence. Limit the use of nalbuphine with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use in necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Naproxen; Pseudoephedrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent.
Neostigmine: (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 neostigmine. Consider alternatives if concurrent therapy is needed.
Neostigmine; Glycopyrrolate: (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 neostigmine. Consider alternatives if concurrent therapy is needed.
Niraparib; Abiraterone: (Moderate) Monitor for an increase in amoxapine-related adverse reactions if coadministration with abiraterone is necessary; a dose reduction of amoxapine may be necessary. Amoxapine is a CYP2D6 substrate and abiraterone is a moderate CYP2D6 inhibitor. Patients who are stable on a given dose of amoxapine may become abruptly toxic when given abiraterone is concomitant therapy.
Nirmatrelvir; Ritonavir: (Major) Ritonavir potently inhibits CYP2D6, and may inhibit the metabolism of amoxapine. Since the magnitude of the interaction with the amoxapine is difficult to predict but may be significant, monitor patients receiving ritonavir and amoxapine concurrently closely. Adjust the dosage of the coadministered drug based on therapeutic response. Amoxapine serum concentration monitoring may be useful to guide adjustments and prevent toxicity.
Nitroglycerin: (Minor) Nitroglycerin can cause hypotension. This action may be additive with other agents that can cause hypotension such as heterocyclic antidepressants. Patients should be monitored more closely for hypotension if nitroglycerin is used concurrently with these antidepressants.
Non-Ionic Contrast Media: (Major) Use of medications that lower the seizure threshold should be carefully evaluated when considering the use of intrathecal radiopaque contrast agents. Amoxapine should be discontinued at least 48 hours before myelography and should not be resumed for at least 24 hours postprocedure.
Norepinephrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, such as norepinephrine, however, the data are not consistent.
Olanzapine: (Moderate) Use caution during coadministration of amoxapine and olanzapine. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of seizure threshold are potential problems with the combined use of amoxapine and olanzapine.
Olanzapine; Fluoxetine: (Moderate) Fluoxetine, a potent CYP2D6 inhibitor, may increase the plasma concentrations of the tetracyclic antidepressant amoxapine, which is partially metabolized by CYP2D6. In several cases, symptoms of toxicity, including seizures, have been reported when tricyclic antidepressants were coadministered with an SSRI, including fluoxetine. At least one case report exists of a death thought to be due to impaired clearance of the tricyclic antidepressant amitriptyline by fluoxetine. Also, this combination may represent duplicative therapy. Patients receiving amoxapine should be monitored closely for toxicity if fluoxetine is added. Monitoring should be continued for several weeks following the discontinuation of fluoxetine due to the long half-life of norfluoxetine, the active metabolite of fluoxetine which has a half-life of 7 to 9 days and is a CYP2D6 inhibitor. (Moderate) Use caution during coadministration of amoxapine and olanzapine. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of seizure threshold are potential problems with the combined use of amoxapine and olanzapine.
Olanzapine; Samidorphan: (Moderate) Use caution during coadministration of amoxapine and olanzapine. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of seizure threshold are potential problems with the combined use of amoxapine and olanzapine.
Oliceridine: (Major) Concomitant use of oliceridine with amoxapine may cause excessive sedation and somnolence. Limit the use of oliceridine with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Orphenadrine: (Moderate) Orphenadrine should be combined cautiously with cyclic antidepressants like amoxapine because they could cause additive sedation or anticholinergic effects. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation. Patients should be monitored for excessive adverse effects from either agent.
Osilodrostat: (Moderate) Monitor for an increase in amoxapine-related adverse reactions if coadministration with osilodrostat is necessary; a dose reduction of amoxapine may be necessary. Concurrent use may increase exposure of amoxapine. Amoxapine is a CYP2D6 substrate and osilodrostat is a CYP2D6 inhibitor.
Oxazepam: (Moderate) Amoxapine may enhance the response to the effects of benzodiazepines and other CNS depressants. Patients should be warned of the possibility of drowsiness that may impair performance of potentially hazardous tasks such as driving an automobile or operating machinery.
Oxycodone: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Oxymorphone: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Reduce the initial oxymorphone dosage by 1/3 to 1/2. Educate patients about the risks and symptoms of excessive CNS depression.
Ozanimod: (Contraindicated) Do not use amoxapine in patients taking MAOIs or within 14 days of stopping them. An active metabolite of ozanimod inhibits MAO-B, and interactions with amoxapine may manifest as serotonin syndrome, hypertensive crisis, QT prolongation or other serious side effects. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving cyclic antidepressants and MAO inhibiting drugs simultaneously. Consider an alternative to amoxapine. Ozanimod is a monoamine oxidase inhibitor that may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs and there are limited data for the use of amoxapine in combination with other QT-prolonging drugs.
Paliperidone: (Moderate) Use caution during coadministration of amoxapine and paliperidone. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics, such as paliperidone, are given concurrently. Sedation, orthostatic hypotension, anticholinergic effects, and lowering of seizure threshold are potential problems with the combined use of amoxapine and antipsychotics.
Paroxetine: (Moderate) Paroxetine, a potent CYP2D6 inhibitor, may increase the plasma concentrations of the tetracyclic antidepressant amoxapine, which is partially metabolized by CYP2D6. In several cases, symptoms of toxicity, including seizures, have been reported when tricyclic antidepressants were coadministered with a selective serotonin reuptake inhibitor (SSRI). At least one case report exists of a death thought to be due to impaired clearance of the tricyclic antidepressant amitriptyline by fluoxetine. Additive anticholinergic effects are possible. This combination may represent duplicative therapy. Patients receiving amoxapine should be monitored closely for toxicity if paroxetine is added.
Pentazocine: (Major) Concomitant use of pentazocin and amoxapine may cause excessive sedation and somnolence. Limit the use of pentazocine and amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Pentazocine; Naloxone: (Major) Concomitant use of pentazocin and amoxapine may cause excessive sedation and somnolence. Limit the use of pentazocine and amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Pentobarbital: (Major) Monitor for excessive sedation and somnolence during coadministration of amoxapine and barbiturates. Concurrent use may result in additive CNS depression.
Perampanel: (Moderate) Co-administration of perampanel with CNS depressants, including ethanol, may increase CNS depression. The combination of perampanel (particularly at high doses) with ethanol has led to decreased mental alertness and ability to perform complex tasks (such as driving), as well as increased levels of anger, confusion, and depression; similar reactions should be expected with concomitant use of other CNS depressants, such as amoxapine. In addition, cyclic antidepressants, when used concomitantly with anticonvulsants, may also lower the seizure threshold, leading to pharmacodynamic interactions.
Perphenazine: (Moderate) Use caution during coadministration of amoxapine and perphenazine. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of seizure threshold are potential problems with the combined use of amoxapine and antipsychotics.
Perphenazine; Amitriptyline: (Moderate) Use caution during coadministration of amoxapine and perphenazine. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of seizure threshold are potential problems with the combined use of amoxapine and antipsychotics.
Phendimetrazine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent.
Phenelzine: (Contraindicated) Amoxapine, a heterocyclic antidepressant, is contraindicated for use with monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders or within 14 days of discontinuing treatment with an MAOI. Conversely, an MAOI should not be initiated within 14 days of stopping amoxapine. Hyperpyretic crisis, severe convulsions, and deaths have occurred in patients receiving other cyclic antidepressants and MAOIs simultaneously.
Phenobarbital: (Major) Monitor for excessive sedation and somnolence during coadministration of amoxapine and barbiturates. Concurrent use may result in additive CNS depression.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Monitor for excessive sedation and somnolence during coadministration of amoxapine and barbiturates. Concurrent use may result in additive CNS depression.
Phentermine: (Moderate) Use phentermine and amoxapine together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of weight loss treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Amoxapine has pharmacologic activity similar to tricylclic antidepressant agents. Phentermine is a sympathomimetic agent related to the amphetamines and may cause additive sympathomimetic effects when combined with amoxapine. CNS effects, such as dizziness, are also possible.
Phentermine; Topiramate: (Moderate) Use phentermine and amoxapine together with caution and close clinical monitoring. Regularly assess blood pressure, heart rate, the efficacy of weight loss treatment, and the emergence of sympathomimetic/adrenergic adverse events. Carefully adjust dosages as clinically indicated. Amoxapine has pharmacologic activity similar to tricylclic antidepressant agents. Phentermine is a sympathomimetic agent related to the amphetamines and may cause additive sympathomimetic effects when combined with amoxapine. CNS effects, such as dizziness, are also possible.
Phenylephrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent.
Phenytoin: (Moderate) Amoxapine, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions. Pharmacokinetic interactions may occur, since hydantoins may induce hepatic metabolism of certain antidepressants. Monitor patients on anticonvulsants carefully when amoxapine is used concurrently.
Physostigmine: (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 physostigmine. Consider alternatives if concurrent therapy is needed.
Pimozide: (Major) Avoid co-administration of amoxapine and pimozide if possible, due to additive CNS effects. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of seizure threshold are also potential problems with the combined use of amoxapine and antipsychotics.
Pramipexole: (Moderate) Pramipexole may cause additive drowsiness when combined with amoxapine.
Pregabalin: (Major) Initiate pregabalin at the lowest recommended dose and monitor patients for symptoms of sedation and somnolence during coadministration of pregabalin and amoxapine. Concomitant use of pregabalin with amoxapine may cause additive CNS depression. Educate patients about the risks and symptoms of excessive CNS depression.
Prilocaine; Epinephrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, such as epinephrine, however, the data are not consistent.
Primidone: (Major) Monitor for excessive sedation and somnolence during coadministration of amoxapine and barbiturates. Concurrent use may result in additive CNS depression.
Procarbazine: (Major) Procarbazine is a chemotherapy agent with monoamine oxidase inhibitor (MAOI) activity, and concurrent use with amoxapine should be avoided if possible. Amoxapine, a heterocyclic antidepressant, is contraindicated for use with monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders or within 14 days of discontinuing treatment with an MAOI. Conversely, an MAOI should not be initiated within 14 days of stopping amoxapine. Hyperpyretic crisis, severe convulsions, hypertensive crisis, and deaths have occurred in patients receiving other cyclic antidepressants and MAOIs simultaneously.
Prochlorperazine: (Moderate) Use caution during coadministration of amoxapine and prochlorperazine. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, or anticholinergic effects are potential problems with the combined use of amoxapine and many antipsychotics, such as phenothiazines.
Promethazine: (Moderate) Additive anticholinergic effects are possible during coadministration of promethazine and amoxapine. Additive drowsiness and sedation are also possible. Anticholinergic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Promethazine; Dextromethorphan: (Moderate) Additive anticholinergic effects are possible during coadministration of promethazine and amoxapine. Additive drowsiness and sedation are also possible. Anticholinergic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Promethazine; Phenylephrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent. (Moderate) Additive anticholinergic effects are possible during coadministration of promethazine and amoxapine. Additive drowsiness and sedation are also possible. Anticholinergic effects may be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature regulation.
Propafenone: (Major) Because most cyclic antidepressants are partially metabolized by CYP2D6, caution is advisable during co-administration of amoxapine and potent CYP2D6 inhibitors such as quinidine. Elevated plasma concentrations of amoxapine may result in more pronounced anticholinergic effects and the risk of seizures may be increased. Anti-arrhythmics that are less potent inhibitors of CYP2D6, such as propafenone, may similarly interact with amoxapine. CYP2D6 substrates including flecainide may compete with amoxapine for the same metabolic pathway.
Pseudoephedrine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent.
Pseudoephedrine; Triprolidine: (Major) Concomitant use of amoxapine with sympathomimetics should be avoided whenever possible; use with caution when concurrent use cannot be avoided. One drug information reference suggests that cyclic antidepressants potentiate the pharmacologic effects of direct-acting sympathomimetics, but decrease the pressor response to indirect-acting sympathomimetics, however, the data are not consistent. (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Pyridostigmine: (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 pyridostigmine. Consider alternatives if concurrent therapy is needed.
Pyrilamine: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Quazepam: (Moderate) Amoxapine may enhance the response to the effects of benzodiazepines and other CNS depressants. Patients should be warned of the possibility of drowsiness that may impair performance of potentially hazardous tasks such as driving an automobile or operating machinery.
Quetiapine: (Moderate) Use caution during co-administration of amoxapine and quetiapine. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of seizure threshold are potential problems with the combined use of amoxapine and antipsychotics.
Quinidine: (Major) Because most cyclic antidepressants are partially metabolized by CYP2D6, caution is advisable during co-administration of amoxapine and potent CYP2D6 inhibitors such as quinidine. Elevated plasma concentrations of amoxapine may result in more pronounced anticholinergic effects and the risk of seizures may be increased. Anti-arrhythmics that are less potent inhibitors of CYP2D6, such as propafenone, may similarly interact with amoxapine. CYP2D6 substrates including flecainide may compete with amoxapine for the same metabolic pathway.
Quinine: (Moderate) Concentrations of amoxapine may be increased with concomitant use of quinine. Amoxapine is a CYP2D6 substrate and quinine is a CYP2D6 inhibitor.
Rasagiline: (Major) Concurrent use of rasagiline and antidepressants, including amoxapine, should be avoided if possible. Severe CNS toxicity with hyperpyrexia has been reported during concurrent use of antidepressants and selective or non-selective MAOIs. During postmarketing use of rasagiline, non-fatal cases of serotonin syndrome have been reported during concomitant antidepressant administration. At least 2 weeks should elapse between stopping rasagiline treatment and beginning therapy with an antidepressant. Conversely, when discontinuing amoxapine, it is advisable to wait the length of 4 to 5 half-lives of the individual agent being discontinued prior to initiation with rasagiline.
Remifentanil: (Major) Consider alternative therapy or reduce the dose of one or both drugs if remifentanil is used with another CNS depressant, such as amoxapine. The magnitude and duration of CNS and cardiovascular effects may be enhanced. Monitor patients for hypotension or prolonged respiratory depression and sedation. Consider the total dose of all opioid agonists before ordering opioid analgesics during recovery from anesthesia.
Remimazolam: (Moderate) Amoxapine may enhance the response to the effects of benzodiazepines and other CNS depressants. Patients should be warned of the possibility of drowsiness that may impair performance of potentially hazardous tasks such as driving an automobile or operating machinery.
Risperidone: (Moderate) Use caution during co-administration of amoxapine and risperidone. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of seizure threshold are potential problems with the combined use of amoxapine and antipsychotics.
Ritonavir: (Major) Ritonavir potently inhibits CYP2D6, and may inhibit the metabolism of amoxapine. Since the magnitude of the interaction with the amoxapine is difficult to predict but may be significant, monitor patients receiving ritonavir and amoxapine concurrently closely. Adjust the dosage of the coadministered drug based on therapeutic response. Amoxapine serum concentration monitoring may be useful to guide adjustments and prevent toxicity.
Rivastigmine: (Moderate) Concurrent use of amoxapine and rivastigmine should be avoided if possible. Amoxapine may exhibit significant anticholinergic activity, thereby interfering with the therapeutic effect of rivastigmine.
Ropinirole: (Moderate) Ropinirole may cause additive drowsiness when combined with amoxapine.
Safinamide: (Contraindicated) Safinamide is contraindicated for use with amoxapine due to the risk of serotonin syndrome. At least 14 days should elapse between the discontinuation of safinamide and the initiation of amoxapine.
Secobarbital: (Major) Monitor for excessive sedation and somnolence during coadministration of amoxapine and barbiturates. Concurrent use may result in additive CNS depression.
Sedating H1-blockers: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Selegiline: (Contraindicated) Amoxapine, a heterocyclic antidepressant, is contraindicated for use with selegiline, a selective monoamine oxidase type B inhibitor (MAO-B inhibitor). At least 14 days should elapse between discontinuation of selegiline and initiation of treatment with amoxapine. After stopping treatment with amoxapine, a time period equal to 4 to 5 half-lives of amoxapine or any active metabolite should elapse before starting therapy with selegiline. Hyperpyretic crisis and serotonin syndrome have occurred in patients receiving selective MAO-B inhibitors and cyclic antidepressants simultaneously.
Sertraline: (Moderate) Sertraline is an in vivo inhibitor of CYP2D6, the isoenzyme partially responsible for the metabolism of amoxapine, a tetracyclic antidepressant. In several cases, symptoms of toxicity, including seizures, have been reported when tricyclic antidepressants have been coadministered with an SSRI. At least one case report exists of a death thought to be due to impaired clearance of the tricyclic antidepressant amitriptyline by fluoxetine. Also, this combination may represent duplicative therapy. Patients receiving amoxapine should be monitored closely for toxicity if sertraline is added.
Solifenacin: (Moderate) Additive anticholinergic effects may be seen when solifenacin is used concomitantly with other commonly used drugs with moderate to significant anticholinergic effects such as amoxapine. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
St. John's Wort, Hypericum perforatum: (Minor) It is not known if additive pharmacodynamic effects could occur as a result of coadministration of St. John's wort with amoxapine. Therefore, coadministration of St. John's wort with amoxapine therapy is not usually recommended.
Stiripentol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of stiripentol and amoxapine. CNS depressants can potentiate the effects of stiripentol.
Succinimides: (Moderate) Amoxapine, when used concomitantly with anticonvulsants, can increase CNS depression and may also lower the seizure threshold, leading to pharmacodynamic interactions.
Sufentanil: (Major) The use of sufentanil with CNS depressants may result in decreased pulmonary artery pressure and hypotension. As postoperative analgesia, concomitant use increases the risk for hypotension, respiratory depression, profound sedation, coma, and death.
Tapentadol: (Major) Concomitant use of opioid agonists with amoxapine may cause excessive sedation and somnolence. Limit the use of opioid pain medications with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Temazepam: (Moderate) Amoxapine may enhance the response to the effects of benzodiazepines and other CNS depressants. Patients should be warned of the possibility of drowsiness that may impair performance of potentially hazardous tasks such as driving an automobile or operating machinery.
Terbinafine: (Moderate) In vitro studies have shown systemic terbinafine to inhibit hepatic isoenzyme CYP2D6, and thus may inhibit the clearance of drugs metabolized by this isoenzyme, such as amoxapine.
Thioridazine: (Moderate) Use caution during coadministration of amoxapine and thioridazine. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of the seizure threshold are potential problems with the combined use of amoxapine and many antipsychotics, such as phenothiazines.
Thiothixene: (Moderate) Use caution during co-administration of amoxapine and thiothixene. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of seizure threshold are potential problems with the combined use of amoxapine and antipsychotics.
Thyroid hormones: (Minor) Thyroid hormones may increase receptor sensitivity and enhance the effects of amoxapine. Although this drug combination appears to be safe, clinicians should be aware of the remote possibility of exaggerated cardiovascular side effects such as arrhythmias and CNS stimulation.
Tipranavir: (Major) Because most cyclic antidepressants are partially metabolized by CYP2D6, caution is advisable during co-administration of amoxapine and potent CYP2D6 inhibitors such as tipranavir. Elevated plasma concentrations of amoxapine may result in more pronounced anticholinergic effects and the risk of seizures may be increased.
Tolterodine: (Moderate) Additive anticholinergic effects may be seen when drugs with antimuscarinic properties like tolterodine are used concomitantly with psychiatric medications with anticholinergic effects such as amoxapine. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function, the CNS, the eye, and temperature regulation. Additive drowsiness may also occur.
Tramadol: (Major) Concomitant use of tramadol with amoxapine may cause excessive sedation and somnolence and increase the risk for seizures. Limit the use of tramadol with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and the potential increased risk for seizures.
Tramadol; Acetaminophen: (Major) Concomitant use of tramadol with amoxapine may cause excessive sedation and somnolence and increase the risk for seizures. Limit the use of tramadol with amoxapine to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression and the potential increased risk for seizures.
Tranylcypromine: (Contraindicated) Amoxapine, a heterocyclic antidepressant, is contraindicated for use with monoamine oxidase inhibitors (MAOIs) intended to treat psychiatric disorders or within 14 days of discontinuing treatment with an MAOI. Conversely, an MAOI should not be initiated within 14 days of stopping amoxapine. Hyperpyretic crisis, severe convulsions, and deaths have occurred in patients receiving other cyclic antidepressants and MAOIs simultaneously.
Trazodone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of amoxapine and trazodone. Concurrent use may result in additive CNS depression.
Triazolam: (Moderate) Amoxapine may enhance the response to the effects of benzodiazepines and other CNS depressants. Patients should be warned of the possibility of drowsiness that may impair performance of potentially hazardous tasks such as driving an automobile or operating machinery.
Tricyclic antidepressants: (Major) The use of a heterocyclic antidepressant, such as amoxapine, with tricyclic antidepressants (TCAs) is not generally recommended due to the duplicative nature of therapy and the risk for side effects. Additive cardiac effects (e.g., tachycardia), CNS effects, or antimuscarinic effects may occur. Additive dry mouth, constipation, drowsiness, bladder difficulties, or changes in heart rate might be possible.
Trifluoperazine: (Moderate) Use caution during coadministration of amoxapine and trifluoperazine. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of seizure threshold are potential problems with the combined use of amoxapine and antipsychotics.
Triprolidine: (Moderate) Additive anticholinergic effects may be seen when amoxapine is used concomitantly with drugs are known to possess relatively significant antimuscarinic properties, including sedating H1-blockers. Antimuscarinic effects might be seen not only on GI smooth muscle, but also on bladder function, the eye, and temperature Additive sedation may also occur.
Triptorelin: (Major) Avoid coadministration of triptorelin with amoxapine due to the risk of reduced efficacy of triptorelin. Amoxapine can cause hyperprolactinemia, which reduces the number of pituitary gonadotropin releasing hormone (GnRH) receptors; triptorelin is a GnRH analog.
Trospium: (Moderate) Additive anticholinergic and CNS effects may be seen when amoxapine is used concomitantly with other antimuscarinics, such as trospium. Clinicians should note that additive antimuscarinic effects may be seen not only on GI smooth muscle, but also on bladder function and temperature regulation. While CNS-related side effects such as drowsiness and blurred vision are not typically noted with trospium, they may occur in some patients. Monitor for anticholinergic effects such as such as confusion, constipation, dizziness, urinary retention, dry mouth and eyes, blurred vision, or rarely, fast, irregular heartbeat.
Viloxazine: (Major) Lower doses of amoxapine may be required during concurrent use of viloxazine due to the potential for increased amoxapine exposure. If viloxazine is discontinued, an increased dose of amoxapine may be necessary. Amoxapine is a CYP2D6 substrate; viloxazine is a CYP2D6 inhibitor.
Zaleplon: (Moderate) CNS depressants should be combined cautiously with amoxapine because they could cause additive depressant effects and possible respiratory depression or hypotension.
Ziconotide: (Moderate) Due to potentially additive effects, dosage adjustments may be necessary if ziconotide is used with a drug that has CNS depressant effects such as amoxapine. Coadministration of CNS depressants may increase drowsiness, dizziness, and confusion that are associated with ziconotide. If altered consciousness occurs, consider discontinuation of either agent.
Ziprasidone: (Moderate) Use caution during co-administration of amoxapine and ziprasidone. Amoxapine exhibits some antipsychotic activity and may increase the risk of tardive dyskinesia or neuroleptic malignant syndrome (NMS) when antipsychotics are given concurrently. CNS effects, orthostatic hypotension, anticholinergic effects, and lowering of seizure threshold are potential problems with the combined use of amoxapine and antipsychotics.
Zolpidem: (Moderate) CNS depressants should be combined cautiously with amoxapine because they could cause additive depressant effects and possible respiratory depression or hypotension.

Amoxapine/Asendin Oral Tab: 25mg, 50mg, 100mg, 150mg

Adults

400 mg/day PO outpatients; 600 mg/day PO inpatients.

Geriatric

300 mg/day PO, but lower doses (i.e., 150 mg/day PO) often adequate.

Adolescents

Safety and efficacy have not been established.

Children

Safety and efficacy have not been established.

Infants

Not indicated.

The exact action of amoxapine is not fully understood, but the primary therapeutic effect appears to occur from norepinephrine reuptake inhibition at the neuronal membrane. In vitro data suggest that serotonin reuptake inhibition by amoxapine is relatively low compared to the effect on norepinephrine. Changes in postsynaptic neurotransmitter receptor characteristics with chronic administration may contribute to the efficacy of some antidepressants. Norepinephrine is an adrenergic neurotransmitter that appears to be involved in a range of psychological processes, including mood stabilization, sleep regulation, overall alertness and arousal, and in regulating response to stressors that might initiate or exacerbate depressive symptomatology. Similar to antipsychotics, amoxapine blocks dopamine receptors. One of the major metabolites of amoxapine, 7-hydroxy-amoxapine, has significant dopamine antagonist activity and may play an important role in the antidopaminergic effects of the drug. Amoxapine is not a monoamine oxidase inhibitor. The possibility of orthostatic hypotension is low. Varying degrees of sedation can occur based on individual response. The seizure threshold can be lowered. Anticholinergic activity is moderate. Cardiac dysrhythmias can result from the direct quinidine-like effect on cardiac function in combination with anticholinergic activity and the potentiation of norepinephrine. Elevations in prolactin and changes in blood glucose can result from the effect of amoxapine on the endocrine system.[28558] [43230]

Amoxapine is administered orally. The drug is approximately 90% protein bound. Amoxapine is rapidly and widely distributed throughout the body, including the lungs, spleen, kidneys, heart, and brain, with concentrations in the brain that are up to 10-fold more than in plasma. The initial clinical effect may occur within 4 to 7 days and occurs within two weeks in over 80% of responders. Amoxapine has a half-life of about 8 hours and is almost completely metabolized in the liver to produce two active metabolites, 8-hydroxy-amoxapine, which has a half-life of 30 hours, and 7-hydroxy-amoxapine, with a half-life of about 4 hours. The 7-hydroxy-amoxapine metabolite has significant dopamine antagonist activity and may play an important role in the antidopaminergic effects of the drug. The metabolites are excreted in conjugated form in the urine. Unchanged amoxapine accounts for 3% of a dose excreted in the urine, while 36% of a dose is excreted renally as 8-hydroxy-amoxapine, and 27% as 7-hydroxy-amoxapine.
 
Affected Cytochrome P450 isoenzymes and drug transporters: CYP2D6
Amoxapine is similar to the tricyclic antidepressantts and appears to be dependent on CYP2D6 for metabolism. Concomitant use of drugs that can inhibit CYP2D6 may result in a need to decrease amoxapine dosage.

Oral Route

Following oral administration, amoxapine is rapidly absorbed from the intestinal tract, and peak plasma concentrations are achieved in about 1 to 2 hours. Amoxapine may be administered without regard to meals.

Pregnancy

There are no adequate and well controlled studies in pregnant women; amoxapine should only be used in pregnancy if the benefits to the mother clearly outweigh the possible risks to the fetus. Teratogenic effects in animals have not been observed; however, non-teratogenic effects including intrauterine death, stillbirth, decreased birth weight, and decreased postnatal survival have been observed in animals given doses up to 10 times the human dose. Embryotoxicity has been observed in animals during administration of doses approximating human doses. Amoxapine is structurally related to tricyclic antidepressants (TCAs); use of TCAs during pregnancy has been associated with neonatal complications including hypoglycemia, respiratory diagnoses, developmental delays, urinary retention, and jaundice. Neonatal withdrawal symptoms have been reported following in utero exposure to some antidepressants. The effects of amoxapine during labor and delivery are unknown. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to amoxapine; information about the registry can be obtained at womensmentalhealth.org/research/pregnancyregistry or by calling 1-866-961-2388.

Amoxapine is excreted into human breast milk and caution is recommended when administering the drug during breast-feeding. The potential for adverse effects in nursing infants is unknown. Because there is no published experience with amoxapine during breastfeeding, other agents may be preferred, especially while nursing a newborn or preterm infant. For example, nortriptyline, sertraline, or paroxetine have been reported to be preferred antidepressant agents for the breast-feeding mother. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition.