Amoxapine

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• Monoamine oxidase (MAO) inhibitor such as isocarboxazid (Marplan), phenelzine (Nardil), selegiline (Eldepryl, Emsam, Zelapar), and tranylcypromine (Parnate)
• anticoagulants (blood thinners) such as warfarin (Coumadin)
• medications that block a protein in the body (CYP2D6) such as quinidine (Qualaquin), fluoxetine (Prozac,Sarafem), amitriptyline (Elavil), and paroxetine (Paxil)
• antihistamines
• cimetidine (Tagamet)
• flecainide (Tambocor)
• levodopa (Sinemet, Larodopa)
• lithium (Eskalith, Lithobid)
• medications for high blood pressure, seizures, Parkinson's disease, asthma, colds, or allergies
• methylphenidate (Ritalin)
• muscle relaxants
• propafenone (Rhythmol)
• sedatives
• selective serotonin reuptake inhibitors (SSRIs) such as citalopram (Celexa), escitalopram (Lexapro), fluvoxamine (Luvox), and sertraline (Zoloft)
• sleeping pills and tranquilizers
• thyroid medications
• alcohol

This is not a complete list of amoxapine drug interactions. Ask your doctor or pharmacist for more information.

Before taking amoxapine, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• tell your doctor and pharmacist if you are allergic to amoxapine, doxepin (Sinequan), any other medications, or any of the inactive ingredients in amoxapine
• are being treated with electroshock therapy (procedure in which small electric shocks are administered to the brain to treat certain mental illnesses)
• have or have ever had a heart attack, glaucoma (an eye disease)
• have or have ever had an enlarged prostate (a male reproductive organ)
• have or have ever had difficulty urinating
• have or have ever had seizures
• have or have ever had overactive thyroid gland, or liver, kidney, or heart disease
• are pregnant, plan to become pregnant. If you become pregnant while taking amoxapine, call your doctor immediately.
• are breast-feeding
• if you are having surgery, including dental surgery
• drink alcohol. Alcohol can add to the drowsiness caused by this medication.
• have stopped taking an MAO inhibitor within the past 14 days. Your doctor will probably tell you not to take amoxapine. If you stop taking amoxapine, you should wait at least 14 days before you start to take an MAO inhibitor.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Amoxapine falls into category C. There are no well-controlled studies that have been done in pregnant women. Amoxapine should be used during pregnancy only if the possible benefit outweighs the possible risk to the unborn baby.

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.

The dose your doctor recommends may be based on the following:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your age

The recommended dose range of amoxapine (Asendin) is 200 to 300 mg daily.

• In general, lower dosages are recommended for elderly patients.

Some hospitalized patients who have been refractory to antidepressant therapy and who have no history of convulsive seizures may have doses given up to 600 mg daily in divided doses.

If you take too much amoxapine, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

Contraindications

• Concurrent or recent (i.e., within 2 weeks) therapy with an MAO inhibitor.101 a c (See Specific Drugs under Interactions.)

• During the acute recovery phase following MI.101 a c

• Known hypersensitivity to amoxapine or other dibenzoxazepine-derivative TCAs (e.g., doxepin).101 a c

Warnings/Precautions

Warnings

Shares the toxic potentials of other tricyclic antidepressants; observe the usual precautions of tricyclic antidepressant therapy.101 a b c

Possible worsening of depression and/or emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior in both adult and pediatric patients with major depressive disorder, whether or not they are taking antidepressants; may persist until clinically important remission occurs.a d g o p q However, suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide.a o p q

Appropriately monitor and closely observe patients receiving amoxapine for any reason, particularly during initiation of therapy (i.e., the first few months) and during periods of dosage adjustments.a d o p q (See Boxed Warning and also see Pediatric Use under Cautions.)

Anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and/or mania may be precursors to emerging suicidality.p q Consider changing or discontinuing therapy in patients whose depression is persistently worse or in those with emerging suicidality or symptoms that might be precursors to worsening depression or suicidality, particularly if severe, abrupt in onset, or not part of patient’s presenting symptoms.o p q

Prescribe in smallest quantity consistent with good patient management to reduce risk of overdosage.a c d p

Observe these precautions for patients with psychiatric (e.g., major depressive disorder, obsessive-compulsive disorder) or nonpsychiatric disorders.a c p

May unmask bipolar disorder.a p (See Activation of Mania or Hypomania under Cautions.) Amoxapine is not approved for use in treating bipolar depression.a

Screen for risk of bipolar disorder by obtaining detailed psychiatric history (e.g., family history of suicide, bipolar disorder, depression) prior to initiating therapy.a d p

Tardive dyskinesia, a syndrome of potentially irreversible, involuntary, dyskinetic movements, reported rarely in patients receiving amoxapine.101 a b c Consider discontinuance.101 a

Neuroleptic malignant syndrome (NMS), a potentially fatal syndrome requiring immediate discontinuance of the drug and intensive symptomatic treatment, has been reported with amoxapine.101 102 a b c

Possible conduction defects, arrhythmias, acute MI, stroke, and sinus tachycardia, particularly at higher dosages.101 a c f k l

Patients with preexisting cardiac disease and patients with disturbed eating behaviors (e.g., purging) that result in inadequate hydration and/or compromised cardiac status most at risk; monitor closely (e.g., perform ECG at baseline and as appropriate during therapy).101 a c f k l

Use with caution in patients for whom excess anticholinergic activity could be harmful (e.g., history of urinary retention, increased IOP, angle-closure glaucoma).101 a c l

Seizures reported; use with extreme caution in patients with a seizure disorder.101 a c l

Sensitivity Reactions

Possible sensitivity reactions including skin rash and drug fever; most likely during first few days of treatment.a c Discontinue drug if rash and/or fever occur.a

General Precautions

Possible activation of mania and hypomania, particularly in patients with bipolar disorder.101 a c (See Bipolar Disorder under Cautions.)

Possible exacerbation of psychosis in patients with schizophrenia, particularly in patients with paranoid symptoms; decrease dosage and/or administer an antipsychotic agent concomitantly.101 a c

Possible increased ECT risks.101 a

Specific Populations

Category C.101 a e

Distributed into milk.100 101 a e l Caution if used in nursing women; carefully assess potential benefits and risks.101 a c e

Safety and efficacy of amoxapine in pediatric patients <16 years of age have not been established.101 a b

FDA warns that a greater risk of suicidal thinking or behavior (suicidality) occurred during first few months of antidepressant treatment (4%) compared with placebo (2%) in children and adolescents with major depressive disorder, obsessive-compulsive disorder (OCD), or other psychiatric disorders based on pooled analyses of 24 short-term, placebo-controlled trials of 9 antidepressant drugs (SSRIs and others).a d p However, a more recent meta-analysis of 27 placebo-controlled trials of 9 antidepressants (SSRIs and others) in patients <19 years of age with major depressive disorder, OCD, or non-OCD anxiety disorders suggests that the benefits of antidepressant therapy in treating these conditions may outweigh the risks of suicidal behavior or suicidal ideation.g No suicides occurred in these pediatric trials.a d g p

Carefully consider these findings when assessing potential benefits and risks of amoxapine in a child or adolescent for any clinical use.a c g o p q (See Worsening of Depression and Suicidality Risk under Cautions.)

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.a

In pooled data analyses, a reduced risk of suicidality was observed in adults ≥65 years of age with antidepressant therapy compared with placebo.o p (See Boxed Warning and also see Worsening of Depression and Suicidality Risk under Cautions.)

Possible increased sensitivity to adverse effects of amoxapine (e.g., tardive dyskinesia, sedation)a c and to anticholinergic (e.g., dry mouth, constipation, vision disturbance), cardiovascular, and orthostatic hypotension effects of TCAs.

Titrate dosage carefully.a (See Geriatric Patients under Dosage and Administration.)

Common Adverse Effects

Anticholinergic effects (e.g., dry mouth, constipation, blurred vision), drowsiness, fatigue or lethargy, dizziness.101 a c k l s

Absorption

Bioavailability

Rapidly and almost completely absorbed from the GI tract following oral administration.101 a b k l r s

Peak plasma concentrations usually occur within 1–2 hours after oral administration.101 a b j k l s

Onset

Antidepressant effects usually occur within 2 weeks in most patients who respond and may occur within 4–7 days.101 a b j

Distribution

Extent

Widely distributed in the body.c k l s

Amoxapine and its active metabolite, 8-hydroxyamoxapine, distribute into milk.100 101 a e l s

Plasma Protein Binding

Approximately 90%.101 a c k s

Elimination

Metabolism

Metabolized in the liver principally by CYP2D6 to 2 active metabolites, 8-hydroxyamoxapine and 7-hydroxyamoxapine.101 a b c h i j k l s Poor metabolizers of CYP2D6 metabolize the drug more slowly than normal metabolizers.a

Elimination Route

Excreted principally in urine as conjugated metabolites (60–69%) within 6 days and 7–18% excreted in feces principally as unconjugated metabolites; <5% excreted unchanged.101 a b c k l s

Half-life

Amoxapine: Approximately 8 hours.101 a b k l s

8-Hydroxyamoxapine: 30 hours.101 a b h j k l s

7-Hydroxyamoxapine: 6.5 hours.b h j k l

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For amoxapine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to amoxapine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of amoxapine in the pediatric population. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of amoxapine in the elderly. However, elderly patients are more likely to have unwanted effects (e.g., movement disorders, unusual drowsiness) or age-related kidney or liver problems, which may require an adjustment in the dose for patients receiving amoxapine.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking amoxapine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using amoxapine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Bromopride
• Clorgyline
• Grepafloxacin
• Isocarboxazid
• Levomethadyl
• Linezolid
• Methylene Blue
• Metoclopramide
• Moclobemide
• Phenelzine
• Ranolazine
• Safinamide
• Selegiline
• Tranylcypromine

Using amoxapine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acecainide
• Aceclofenac
• Acemetacin
• Albuterol
• Alfentanil
• Alfuzosin
• Almotriptan
• Amitriptyline
• Amphetamine
• Amtolmetin Guacil
• Apomorphine
• Aprindine
• Arsenic Trioxide
• Asenapine
• Aspirin
• Astemizole
• Azimilide
• Azithromycin
• Benzphetamine
• Bretylium
• Bromfenac
• Bromocriptine
• Brompheniramine
• Bufexamac
• Buprenorphine
• Bupropion
• Buspirone
• Butorphanol
• Celecoxib
• Chloral Hydrate
• Chloroquine
• Chlorpheniramine
• Chlorpromazine
• Choline Salicylate
• Ciprofloxacin
• Citalopram
• Clomipramine
• Clonidine
• Clonixin
• Cocaine
• Codeine
• Cyclobenzaprine
• Darunavir
• Dasatinib
• Desipramine
• Desmopressin
• Desvenlafaxine
• Dexibuprofen
• Dexketoprofen
• Dextroamphetamine
• Dextromethorphan
• Diclofenac
• Diflunisal
• Dihydrocodeine
• Dipyrone
• Disopyramide
• Dofetilide
• Dolasetron
• Domperidone
• Donepezil
• Doxepin
• Droperidol
• Droxicam
• Eletriptan
• Enflurane
• Epinephrine
• Erythromycin
• Escitalopram
• Etilefrine
• Etodolac
• Etofenamate
• Etoricoxib
• Felbinac
• Fenoprofen
• Fentanyl
• Fepradinol
• Feprazone
• Fingolimod
• Flecainide
• Floctafenine
• Fluconazole
• Flufenamic Acid
• Fluoxetine
• Flurbiprofen
• Fluvoxamine
• Foscarnet
• Frovatriptan
• Gatifloxacin
• Gemifloxacin
• Granisetron
• Halofantrine
• Halothane
• Hydrocodone
• Hydromorphone
• Hydroxytryptophan
• Ibuprofen
• Ibutilide
• Iloperidone
• Imipramine
• Indomethacin
• Iobenguane I 123
• Iproniazid
• Isoflurane
• Isradipine
• Ketoprofen
• Ketorolac
• Lapatinib
• Levalbuterol
• Levomilnacipran
• Levorphanol
• Levothyroxine
• Lidoflazine
• Lisdexamfetamine
• Lithium
• Lopinavir
• Lorcainide
• Lorcaserin
• Lornoxicam
• Loxoprofen
• Lumefantrine
• Lumiracoxib
• Meclofenamate
• Mefenamic Acid
• Mefloquine
• Meloxicam
• Meperidine
• Methadone
• Methamphetamine
• Methoxamine
• Midodrine
• Milnacipran
• Mirtazapine
• Moricizine
• Morniflumate
• Morphine
• Morphine Sulfate Liposome
• Nabumetone
• Nalbuphine
• Naproxen
• Naratriptan
• Nefazodone
• Nefopam
• Nepafenac
• Niflumic Acid
• Nilotinib
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Norepinephrine
• Norfloxacin
• Nortriptyline
• Octreotide
• Ofloxacin
• Ondansetron
• Oxaprozin
• Oxilofrine
• Oxycodone
• Oxymetazoline
• Oxymorphone
• Oxyphenbutazone
• Paliperidone
• Palonosetron
• Parecoxib
• Pargyline
• Pazopanib
• Pentamidine
• Pentazocine
• Phenylbutazone
• Phenylephrine
• Piketoprofen
• Piroxicam
• Pranoprofen
• Procainamide
• Procarbazine
• Prochlorperazine
• Proglumetacin
• Promethazine
• Propafenone
• Propyphenazone
• Proquazone
• Protriptyline
• Quinidine
• Quinine
• Rasagiline
• Remifentanil
• Rofecoxib
• Salicylic Acid
• Salsalate
• Sematilide
• Sertraline
• Sodium Phosphate
• Sodium Phosphate, Dibasic
• Sodium Phosphate, Monobasic
• Sodium Salicylate
• Solifenacin
• Sorafenib
• Sotalol
• Spiramycin
• Sufentanil
• Sulfamethoxazole
• Sulindac
• Sumatriptan
• Sunitinib
• Tapentadol
• Tedisamil
• Telavancin
• Telithromycin
• Tenoxicam
• Tetrabenazine
• Tiaprofenic Acid
• Tiotropium
• Tolfenamic Acid
• Tolmetin
• Toremifene
• Tramadol
• Trazodone
• Trifluoperazine
• Trimethoprim
• Trimipramine
• Tryptophan
• Valdecoxib
• Vardenafil
• Vasopressin
• Venlafaxine
• Vilanterol
• Vilazodone
• Voriconazole
• Vortioxetine
• Ziprasidone
• Zolmitriptan

Using amoxapine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acenocoumarol
• Arbutamine
• Atomoxetine
• Cannabis
• Carbamazepine
• Dicumarol
• Paroxetine
• Phenprocoumon
• S-Adenosylmethionine

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using amoxapine with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use amoxapine, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Other Medical Problems

The presence of other medical problems may affect the use of amoxapine. Make sure you tell your doctor if you have any other medical problems, especially:

• Bipolar disorder (mood disorder with alternating episodes of mania and depression), or risk of or
• Heart attack, recent—Should not be used in patients with these conditions.

• Glaucoma, history of or
• Heart disease or
• Schizophrenia or
• Seizures, history of or
• Urinary retention (trouble urinating), history of—Use with caution. May make these conditions worse.

It is very important that your doctor check your progress at regular visits to allow for changes in your dose and to check for any unwanted effects.

Amoxapine may cause some people to be agitated, irritable, or display other abnormal behaviors. It may also cause some people to have suicidal thoughts and tendencies or to become more depressed. If you, your child, or your caregiver notice any of these side effects, tell your doctor or your child's doctor right away.

Do not take amoxapine if you have taken a monoamine oxidase (MAO) inhibitor (isocarboxazid [Marplan®], phenelzine [Nardil®], selegiline [Eldepryl®, or tranylcypromine [Parnate®]) in the past two weeks. Do not start taking a MAO inhibitor within two weeks of stopping amoxapine. If you do, you may develop confusion, agitation, restlessness, stomach or intestinal symptoms, sudden high body temperature, extremely high blood pressure, or severe convulsions.

amoxapine may cause tardive dyskinesia (a movement disorder). Check with your doctor right away if you have any of the following symptoms while taking amoxapine: lip smacking or puckering, puffing of the cheeks, rapid or worm-like movements of the tongue, uncontrolled chewing movements, or uncontrolled movements of the arms and legs.

Check with your doctor right away if you are having convulsions (seizures); difficulty with breathing; a fast heartbeat; high fever; high or low blood pressure; increased sweating; loss of bladder control; severe muscle stiffness; unusually pale skin; or tiredness. These could be symptoms of a serious condition called neuroleptic malignant syndrome (NMS).

Do not stop taking amoxapine without first checking with your doctor . Your doctor may want you to gradually reduce the amount you are using before stopping it completely. This may help prevent a possible worsening of your condition and reduce the possibility of withdrawal symptoms such as headache, nausea, or a general feeling of discomfort or illness.

amoxapine will add to the effects of alcohol and other central nervous system (CNS) depressants (medicines that cause drowsiness). Some examples of CNS depressants are antihistamines or medicine for hay fever, other allergies or colds; sedatives, tranquilizers, or sleeping medicines; prescription pain medicine or narcotics; barbiturates; medicine for seizures; muscle relaxants; or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the above while you are using amoxapine.

amoxapine may cause some people to become drowsy or less alert than they are normally. Make sure you know how you react to amoxapine before you drive, use machines, or do anything else that could be dangerous if you are drowsy or not alert.

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

• Excitement
• fast, irregular, pounding, or racing heartbeat or pulse
• fear or nervousness
• mood or mental changes
• nightmares
• restlessness
• shakiness and unsteady walk
• shakiness in legs, arms, hands, or feet
• sleeplessness
• swelling
• trouble sleeping
• unable to sleep
• unsteadiness, trembling, or other problems with muscle control or coordination

• Abdominal or stomach pain
• actions that are out of control
• black, tarry stools
• bleeding gums
• bloating
• blood in urine or stools
• blurred vision
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• chest pain or discomfort
• chills
• clay-colored stools
• confusion
• confusion about identity, place, and time
• constipation
• continuing ringing or buzzing or other unexplained noise in ears
• convulsions
• cough or hoarseness
• dark urine
• decrease in frequency of urination
• decrease in urine volume
• difficulty in breathing
• difficulty in passing urine (dribbling)
• difficulty in speaking
• disturbed concentration
• dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly
• double vision
• drooling
• extremely high fever or body temperature
• false beliefs that cannot be changed by facts
• fast, weak heartbeat
• fever with or without chills
• general feeling of tiredness or weakness
• headache
• hearing loss
• high fever
• high or low blood pressure
• hives or welts
• inability to move arms, legs, or facial muscles
• inability to speak
• increased need to urinate
• increased sweating
• indigestion
• irritability
• itching
• lack of coordination
• light-colored stools
• lip smacking or puckering
• loss of appetite
• loss of bladder control
• lower back or side pain
• muscle cramps
• muscle spasm or jerking of all extremities
• muscle trembling, jerking, or stiffness
• nausea and vomiting
• nervousness
• numbness
• pain or discomfort in arms, jaw, back, or neck
• painful or difficult urination
• pains in stomach, side, or abdomen, possibly radiating to the back
• pale, clammy skin
• passing urine more often
• pinpoint red spots on skin
• pounding in the ears
• puffing of cheeks
• rapid or worm-like movements of tongue
• redness of skin
• seeing, hearing, or feeling things that are not there
• severe muscle stiffness
• shortness of breath
• shuffling walk
• skin rash
• slow speech
• sore throat
• sores, ulcers, or white spots on lips or in mouth
• stiffness of limbs
• sudden loss of consciousness
• sweating
• swollen glands
• talking, feeling, and acting with excitement
• testicular swelling
• thirst
• trouble in holding or releasing urine
• twisting movements of body
• uncontrolled chewing movements
• uncontrolled movements, especially of face, neck, and back
• unpleasant breath odor
• unusual bleeding or bruising
• unusually pale skin
• upper right abdominal pain
• vomiting of blood
• yellow eyes and skin

Get emergency help immediately if any of the following symptoms of overdose occur:

• Change in consciousness
• drowsiness
• epileptic seizure that will not stop
• fatigue
• increased blood pressure
• increased thirst
• loss of consciousness
• swelling of face, fingers, or lower legs
• total body jerking
• troubled breathing
• weight gain

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Dry mouth

• Increased appetite
• increased flow of breast milk

• Agitation
• breast enlargement
• change in taste bad unusual or unpleasant (after)taste
• decreased interest in sexual intercourse
• depression
• excess air or gas in stomach or intestines
• full feeling
• hair loss, thinning of hair
• heartburn
• inability to have or keep an erection
• increased in sexual ability, desire, drive, or performance
• increased interest in sexual intercourse
• increased sensitivity of skin to sunlight
• loss in sexual ability, desire, drive, or performance
• menstrual changes
• nasal stuffiness
• painful ejaculation
• passing gas
• rapid weight gain
• redness or other discoloration of skin
• seizures
• severe sunburn
• stupor
• swollen, painful, or tender lymph glands on side of face or neck
• tearing of the eyes
• unexpected or excess milk flow from breasts

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Use amoxapine as ordered by your doctor. Read all information given to you. Follow all instructions closely.

• Take at bedtime if you are taking once a day.
• To gain the most benefit, do not miss doses.
• Keep taking this medicine as you have been told by your doctor or other health care provider, even if you feel well.

What do I do if I miss a dose?

• Take a missed dose as soon as you think about it.
• If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
• Do not take 2 doses at the same time or extra doses.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Dizziness.
• Dry mouth.
• Feeling sleepy.
• Hard stools (constipation).
• Not able to sleep.
• Bad dreams.
• Upset stomach.
• Headache.
• Feeling tired or weak.
• More hungry.
• Sweating a lot.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Adverse reactions reported in controlled studies in the United States are categorized with respect to incidence below. Following this is a listing of reactions known to occur with other antidepressant drugs of this class.

Incidence Greater Than 1%

The most frequent types of adverse reactions occurring with Amoxapine in controlled clinical trials were sedative and anticholinergic: these included drowsiness (14%), dry mouth (14%), constipation (12%), and blurred vision (7%).

Less frequently reported reactions are:

CNS and Neuromuscular: anxiety, insomnia, restlessness, nervousness, palpitations, tremors, confusion, excitement, nightmares, ataxia, alterations in EEG patterns.

Allergic: edema, skin rash.

Endocrine: elevation of prolactin levels.

Gastrointestinal: nausea.

Other: dizziness, headache, fatigue, weakness, excessive appetite, increased perspiration.

Incidence Less Than 1%

Anticholinergic: disturbances of accommodation, mydriasis, delayed micturition, urinary retention, nasal stuffiness.

Cardiovascular: hypotension, hypertension, syncope, tachycardia.

Allergic: drug fever, urticaria, photosensitization, pruritus, vasculitis, hepatitis.

CNS and Neuromuscular: tingling, paresthesias of the extremities, tinnitus, disorientation, seizures, hypomania, numbness, incoordination, disturbed concentration, hyperthermia, extrapyramidal symptoms, including, tardive dyskinesia. Neuroleptic malignant syndrome has been reported. (See WARNINGS.)

Hematologic: leukopenia, agranulocytosis.

Gastrointestinal: epigastric distress, vomiting, flatulence, abdominal pain, peculiar taste, diarrhea.

Endocrine: increased or decreased libido, impotence, menstrual irregularity, breast enlargement and galactorrhea in the female, syndrome of inappropriate antidiuretic hormone secretion.

Other: lacrimation, weight gain or loss, altered liver function, painful ejaculation.

Drug Relationship Unknown

The following reactions have been reported rarely, and occurred under uncontrolled circumstances where a drug relationship was difficult to assess. These observations are listed to serve as alerting information to physicians.

Anticholinergic: paralytic ileus.

Cardiovascular: atrial arrhythmias (including atrial fibrillation), myocardial infarction, stroke, heart block.

CNS and Neuromuscular: hallucinations.

Hematologic: thrombocytopenia, eosinophilia, purpura, petechiae.

Gastrointestinal: parotid swelling.

Endocrine: change in blood glucose levels.

Other: pancreatitis, hepatitis, jaundice, urinary frequency, testicular swelling, anorexia, alopecia.

Additional Adverse Reactions

The following reactions have been reported with other antidepressant drugs.

Anticholinergic: sublingual adenitis, dilation of the urinary tract.

CNS and Neuromuscular: delusions.

Gastrointestinal: stomatitis, black tongue.

Endocrine: gynecomastia.

To report SUSPECTED ADVERSE EVENTS, contact Actavis at 1-800-272-5525 or FDA at 1-800- FDA-1088 or http://www.fda.gov/for voluntary reporting of adverse reactions.

Signs and Symptoms

Toxic manifestations of Amoxapine overdosage differ significantly from those of other tricyclic antidepressants. Serious cardiovascular effects are seldom if ever observed. However, CNS effects - particularly grand mal convulsions - occur frequently, and treatment should be directed primarily toward prevention or control of seizures. Status epilepticus may develop and constitutes a neurologic emergency. Coma and acidosis are other serious complications of substantial Amoxapine overdosage in some cases. Fatal overdoses with Amoxapine have occurred.

Renal failure may develop two to five days after toxic overdosage in patients who may appear otherwise recovered. Acute tubular necrosis with rhabdomyolysis and myoglobinuria is the most common renal complication in such cases. This reaction probably occurs in less than 5% of overdose cases, and typically in those who have experienced multiple seizures.

Treatment

Treatment of Amoxapine overdosage should be symptomatic and supportive, but with special attention to prevention or control of seizures. If the patient is conscious, induced emesis followed by gastric lavage with appropriate precautions to prevent pulmonary aspiration should be accomplished as soon as possible. Following lavage, activated charcoal may be administered to reduce absorption, and repeated administrations may facilitate drug elimination. An adequate airway should be established in comatose patients and assisted ventilation instituted if necessary. Seizures may respond to standard anticonvulsant therapy such as intravenous diazepam and/or phenytoin. The value of physostigmine appears less certain. Status epilepticus, should it develop, requires vigorous treatment such as that described by Delgado-Escueta et al (N Engl J Med 1982; 306:1337-1340).

Convulsions, when they occur, typically begin within 12 hours after ingestion. Because seizures may occur precipitously in some overdosage patients who appear otherwise relatively asymptomatic, the treating physician may wish to consider prophylactic administration of anticonvulsant medication during this period.

Treatment of renal impairment, should it occur, is the same as that for nondrug-induced renal dysfunction.

Serious cardiovascular effects are rare following Amoxapine overdosage, and the ECG typically remains within normal limits except for sinus tachycardia. Hence, prolongation of the QRS interval beyond 100 milliseconds within the first 24 hours is not a useful guide to the severity of overdosage with this drug.

Fatalities and neurologic sequelae have resulted from prolonged status epilepticus in Amoxapine overdosage patients. While the lethal dose appears higher than that of other tricyclic antidepressants (80% of lethal Amoxapine overdosages have involved ingestion of 3 grams or more), many factors other than amount ingested are important in assessing probability of survival. These include age and physical condition of the patient, concomitant ingestion of other drugs, and especially the interval between drug ingestion and initiation of emergency treatment.

• Antidepressant, Tricyclic (Secondary Amine)

Hypersensitivity to amoxapine, any component of the formulation, or dibenzoxazepine compounds; use with or within 14 days of MAO inhibitors; acute recovery phase following myocardial infarction

Depression: Oral: Initial: 50 mg once to 3 times daily. Doses may be increased to 100 mg 2 to 3 times daily by the end of the first week based on response and tolerability; if 300 mg daily has been reached and maintained for at least 2 weeks and no response is observed, may further increase to 400 mg daily. Hospitalized patients refractory to antidepressant therapy (and no history of seizures) may be cautiously titrated to 600 mg daily in divided doses. Usual dosage: 100 to 400 mg daily (Bauer, 2013). Once an effective dose is reached, doses ≤300 mg may be given once daily at bedtime and doses >300 mg daily should be divided. Maximum daily dose: 400 mg outpatient; 600 mg hospitalized patients.

Discontinuation of therapy: Upon discontinuation of antidepressant therapy, gradually taper the dose to minimize the incidence of withdrawal symptoms and allow for the detection of re-emerging symptoms. Evidence supporting ideal taper rates is limited. APA and NICE guidelines suggest tapering therapy over at least several weeks with consideration to the half-life of the antidepressant; antidepressants with a shorter half-life may need to be tapered more conservatively. In addition for long-term treated patients, WFSBP guidelines recommend tapering over 4 to 6 months. If intolerable withdrawal symptoms occur following a dose reduction, consider resuming the previously prescribed dose and/or decrease dose at a more gradual rate (APA, 2010; Bauer, 2002; Haddad, 2001; NCCMH, 2010; Schatzberg, 2006; Shelton, 2001; Warner 2006).

MAO inhibitor recommendations:

Switching to or from an MAO inhibitor intended to treat psychiatric disorders:

Allow 14 days to elapse between discontinuing an MAO inhibitor intended to treat psychiatric disorders and initiation of amoxapine.

Allow 14 days to elapse between discontinuing amoxapine and initiation of an MAO inhibitor intended to treat psychiatric disorders.

Use with reversible MAO inhibitors (such as linezolid or IV methylene blue):

Do not initiate amoxapine in patients receiving linezolid or IV methylene blue; consider other interventions for psychiatric condition.

If urgent treatment with linezolid or IV methylene blue is required in a patient already receiving amoxapine and potential benefits outweigh potential risks, discontinue amoxapine promptly and administer linezolid or IV methylene blue. Monitor for serotonin syndrome for 2 weeks or until 24 hours after the last dose of linezolid or IV methylene blue, whichever comes first. May resume amoxapine 24 hours after the last dose of linezolid or IV methylene blue.

Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Consider therapy modification

AbobotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of AbobotulinumtoxinA. Monitor therapy

Acetylcholinesterase Inhibitors: Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Acetylcholinesterase Inhibitors may diminish the therapeutic effect of Anticholinergic Agents. Monitor therapy

Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Alpha-/Beta-Agonists (Direct-Acting): Tricyclic Antidepressants may enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Management: Avoid, if possible, the use of direct-acting alpha-/beta-agonists in patients receiving tricyclic antidepressants. If combined, monitor for evidence of increased pressor effects and consider reductions in initial dosages of the alpha-/beta-agonist. Exceptions: Dipivefrin. Consider therapy modification

Alpha1-Agonists: Tricyclic Antidepressants may enhance the vasopressor effect of Alpha1-Agonists. Tricyclic Antidepressants may diminish the vasopressor effect of Alpha1-Agonists. Monitor therapy

Alpha2-Agonists: Tricyclic Antidepressants may diminish the antihypertensive effect of Alpha2-Agonists. Exceptions: Apraclonidine; Brimonidine (Ophthalmic). Consider therapy modification

Alpha2-Agonists (Ophthalmic): Tricyclic Antidepressants may diminish the therapeutic effect of Alpha2-Agonists (Ophthalmic). Monitor therapy

Altretamine: May enhance the orthostatic hypotensive effect of Tricyclic Antidepressants. Monitor therapy

Amantadine: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy

Amifampridine: May diminish the anticholinergic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Amifampridine. Monitor therapy

Amifampridine: May enhance the adverse/toxic effect of Tricyclic Antidepressants. Specifically, both drugs have the potential to decrease the seizure threshold, possibly increasing the risk for seizures. Tricyclic Antidepressants may diminish the therapeutic effect of Amifampridine. Monitor therapy

Amphetamines: Tricyclic Antidepressants may enhance the stimulatory effect of Amphetamines. Tricyclic Antidepressants may also potentiate the cardiovascular effects of Amphetamines. Monitor therapy

Analgesics (Opioid): CNS Depressants may enhance the CNS depressant effect of Analgesics (Opioid). Management: Avoid concomitant use of opioid analgesics and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Monitor therapy

Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Antipsychotic Agents: Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Asunaprevir: May increase the serum concentration of CYP2D6 Substrates. Consider therapy modification

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Barbiturates: May increase the metabolism of Tricyclic Antidepressants. Consider therapy modification

Beta2-Agonists: Tricyclic Antidepressants may enhance the adverse/toxic effect of Beta2-Agonists. Monitor therapy

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

CarBAMazepine: May decrease the serum concentration of Tricyclic Antidepressants. Monitor therapy

Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Cimetidine: May decrease the metabolism of Tricyclic Antidepressants. Monitor therapy

Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Avoid combination

Cinacalcet: May increase the serum concentration of Tricyclic Antidepressants. Management: Seek alternatives when possible. If these combinations are used, monitor closely for increased effects/toxicity and/or elevated serum concentrations (when testing is available) of the tricyclic antidepressant. Consider therapy modification

Citalopram: Tricyclic Antidepressants may enhance the adverse/toxic effect of Citalopram. Tricyclic Antidepressants may increase the serum concentration of Citalopram. Citalopram may increase the serum concentration of Tricyclic Antidepressants. Management: Consider alternatives to this combination when possible. Monitor for adverse effects of tricyclic antidepressants (TCAs), including serotonin syndrome and QT-interval prolongation, when a TCA is being used in combination with citalopram. Consider therapy modification

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

Cobicistat: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy

CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Monitor therapy

CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Consider therapy modification

Dapoxetine: May enhance the adverse/toxic effect of Serotonin Modulators. Avoid combination

Darunavir: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy

Desmopressin: Tricyclic Antidepressants may enhance the adverse/toxic effect of Desmopressin. Monitor therapy

Dexmethylphenidate: May enhance the adverse/toxic effect of Tricyclic Antidepressants. Dexmethylphenidate may increase the serum concentration of Tricyclic Antidepressants. Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Dronedarone: Tricyclic Antidepressants may enhance the arrhythmogenic effect of Dronedarone. Avoid combination

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification

DULoxetine: May enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome. DULoxetine may decrease the metabolism of Tricyclic Antidepressants. Monitor therapy

Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Avoid combination

Escitalopram: Tricyclic Antidepressants may enhance the adverse/toxic effect of Escitalopram. Escitalopram may increase the serum concentration of Tricyclic Antidepressants. Management: Consider alternatives to this combination when possible. Monitor for adverse effects of tricyclic antidepressants (TCAs), including serotonin syndrome and QT-interval prolongation, when a TCA is being used in combination with escitalopram. Consider therapy modification

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

FLUoxetine: May enhance the adverse/toxic effect of Tricyclic Antidepressants. FLUoxetine may increase the serum concentration of Tricyclic Antidepressants. Management: Consider alternatives to this combination when possible. Monitor for adverse effects of tricyclic antidepressants (TCAs), including serotonin syndrome and QT-interval prolongation, when a TCA is being used in combination with fluoxetine. Consider therapy modification

FluvoxaMINE: May enhance the adverse/toxic effect of Tricyclic Antidepressants. FluvoxaMINE may increase the serum concentration of Tricyclic Antidepressants. Management: Consider alternatives to this combination when possible. Monitor for adverse effects of tricyclic antidepressants (TCAs), including serotonin syndrome and QT-interval prolongation, when a TCA is being used in combination with fluvoxamine. Consider therapy modification

Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy

Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Avoid combination

Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Avoid combination

Guanethidine: Tricyclic Antidepressants may diminish the therapeutic effect of Guanethidine. Monitor therapy

Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Imatinib: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy

Iobenguane I 123: Tricyclic Antidepressants may diminish the therapeutic effect of Iobenguane I 123. Avoid combination

Ioflupane I 123: Amoxapine may diminish the diagnostic effect of Ioflupane I 123. Monitor therapy

Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification

Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification

Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification

Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Avoid combination

Linezolid: May enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome. Avoid combination

Lithium: May enhance the neurotoxic effect of Tricyclic Antidepressants. Management: This combination should be undertaken with great caution. When combined treatment is clinically indicated, monitor closely for signs of serotonin toxicity/serotonin syndrome. Consider therapy modification

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

MAO Inhibitors: May enhance the serotonergic effect of Tricyclic Antidepressants. This may cause serotonin syndrome. While methylene blue and linezolid are expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Exceptions: Linezolid; Methylene Blue; Tedizolid. Avoid combination

Metaxalone: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Methotrimeprazine: May enhance the CNS depressant effect of CNS Depressants. CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

Methylene Blue: Tricyclic Antidepressants may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Avoid combination

Methylene Blue: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Avoid combination

Methylphenidate: May enhance the adverse/toxic effect of Tricyclic Antidepressants. Methylphenidate may increase the serum concentration of Tricyclic Antidepressants. Monitor therapy

Methylphenidate: May enhance the adverse/toxic effect of Serotonin Modulators. Specifically, the risk of serotonin syndrome or serotonin toxicity may be increased. Monitor therapy

Metoclopramide: May enhance the adverse/toxic effect of Tricyclic Antidepressants. Management: Seek alternatives to this combination when possible. Monitor patients receiving metoclopramide with tricyclic antidepressants for signs of extrapyramidal symptoms, neuroleptic malignant syndrome, and serotonin syndrome. Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

MetyroSINE: May enhance the adverse/toxic effect of Tricyclic Antidepressants. Monitor therapy

Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy

MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy

Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Nicorandil: Tricyclic Antidepressants may enhance the hypotensive effect of Nicorandil. Monitor therapy

Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Monitor therapy

OnabotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of OnabotulinumtoxinA. Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Panobinostat: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of sensitive CYP2D6 substrates when possible, particularly those substrates with a narrow therapeutic index. Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

PARoxetine: May enhance the adverse/toxic effect of Tricyclic Antidepressants. PARoxetine may increase the serum concentration of Tricyclic Antidepressants. Management: Consider alternatives to this combination when possible. Monitor for adverse effects of tricyclic antidepressants (TCAs), including serotonin syndrome and QT-interval prolongation, when a TCA is being used in combination with paroxetine. Consider therapy modification

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates. Monitor therapy

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Perhexiline: CYP2D6 Substrates may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates. Monitor therapy

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy

Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Avoid combination

Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Avoid combination

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Consider therapy modification

Protease Inhibitors: May increase the serum concentration of Tricyclic Antidepressants. Monitor therapy

QuiNIDine: Tricyclic Antidepressants may enhance the QTc-prolonging effect of QuiNIDine. QuiNIDine may increase the serum concentration of Tricyclic Antidepressants. Consider therapy modification

Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Monitor therapy

RimabotulinumtoxinB: Anticholinergic Agents may enhance the anticholinergic effect of RimabotulinumtoxinB. Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Consider therapy modification

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid. Monitor therapy

Sertraline: May enhance the adverse/toxic effect of Tricyclic Antidepressants. Sertraline may increase the serum concentration of Tricyclic Antidepressants. Management: Consider alternatives to this combination when possible. Monitor for adverse effects of tricyclic antidepressants (TCAs), including serotonin syndrome and QT-interval prolongation, when a TCA is being used in combination with sertraline. Consider therapy modification

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

Sodium Phosphates: Tricyclic Antidepressants may enhance the adverse/toxic effect of Sodium Phosphates. Specifically, the risk of seizure and/or loss of consciousness may be increased in patients with significant sodium phosphate induced fluid/electrolyte abnormalities. Monitor therapy

St John's Wort: May increase the metabolism of Tricyclic Antidepressants. The risk of serotonin syndrome may theoretically be increased. Consider therapy modification

Sulfonylureas: Cyclic Antidepressants may enhance the hypoglycemic effect of Sulfonylureas. Monitor therapy

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Tedizolid: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Thyroid Products: May enhance the arrhythmogenic effect of Tricyclic Antidepressants. Thyroid Products may enhance the stimulatory effect of Tricyclic Antidepressants. Monitor therapy

Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Avoid combination

Topiramate: Anticholinergic Agents may enhance the adverse/toxic effect of Topiramate. Monitor therapy

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Valproate Products: May increase the serum concentration of Tricyclic Antidepressants. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Tricyclic Antidepressants may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Yohimbine: Tricyclic Antidepressants may increase the serum concentration of Yohimbine. Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

Antidepressants increased the risk compared with placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. Anyone considering the use of amoxapine or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared with placebo in adults older than 24 years; there was a reduction in risk with antidepressants compared with placebo in adults 65 years and older. Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Monitor patients of all ages who are started on antidepressant therapy appropriately and closely observe them for clinical worsening, suicidality, or unusual changes in behavior. Advise families and caregivers of the need for close observation and communication with the health care provider. Amoxapine is not approved for use in pediatric patients.

Commonly reported side effects of amoxapine include: drowsiness. Other side effects include: blurred vision. See below for a comprehensive list of adverse effects.

Data not available