The P-I-E-N-O Parkinsn's List Drug Database
amoxapine / AsendinTM
ANTIDEPRESSANT:
MODERATE RISK
Description: Amoxapine is an antidepressant of the dibenzoxapine type. It is structurally similar to the older tricyclic antidepressants and shares similarities with the phenothiazines. It is used to treat depression. Amoxapine's onset of action appears to be more rapid than that of amitriptyline or imipramine. Amoxapine received FDA approval in 1980.
Mechanism of Action: The concise action of tricyclic antidepressants is not fully understood, but it is believed that the most important effect is the enhancement of the actions of norepinephrine and serotonin by blocking the reuptake of various neurotransmitters at the neuronal membrane. Amoxapine also shares some similarity with antipsychotic drugs in that it blocks dopamine receptors and can cause dyskinesia. Amoxapine blocks the reuptake of norepinephrine, similar to the action of desipramine and maprotiline. The possibility of orthostatic hypotension occurring with amoxapine is low to moderate. Recent evidence suggests that the upset of monoamine output seen in depressed patients may be regulated by antidepressants following long-term treatment due to their action on œ-adrenergic receptors. This action on œ-receptors may be a better explanation than the reuptake theory of their antidepressant effects.
Monoamine oxidase is not inhibited by amoxapine. Varying degrees of sedation can be produced, which is low to moderate for amoxapine, and 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. Changes in sex hormone concentrations and blood glucose can result from the effect of amoxapine on the endocrine system.
Pharmacokinetics: Amoxapine is rapidly absorbed from the gut, and peak plasma concentrations are achieved in about 90 minutes. It is widely distributed throughout the body, with high concentrations appearing in lungs, spleen, kidneys, heart, and brain, and low concentrations in the testes and muscle.
Amoxapine is almost completely metabolized in the liver to produce two active metabolites, 8-hydroxyamoxapine, which has a half- life of 30 hours, and 7-hydroxyamoxapine, with a half-life of about 6.5 hours. The metabolites are excreted in conjugated form in the urine, with about 60% of a dose excreted within 6 days.
CONTRAINDICATIONS/PRECAUTIONS: Anticholinergic effects of tricyclic antidepressants contraindicate their use in patients with decreased GI motility. Tricyclic antidepressants can induce or exacerbate hiatal hernia and can cause paralytic ileus or constipation. Patients who have increased intraocular pressure, angle-closure glaucoma, benign prostatic hypertrophy, GI disease, gastroesophageal reflux disease (GERD), or urinary retention should be treated with caution because of the anticholinergic activity of tricyclic antidepressants. Anticholinergic effects appear most frequently and cause the greatest morbidity in geriatric patients.
Following prolonged therapy in high doses, abrupt discontinuation of the tricyclic antidepressant should be avoided because it could precipitate symptoms of cholinergic rebound such as nausea, vomiting, or diarrhea. This is particularly true for the tertiary amine tricyclic antidepressants: amitriptyline, imipramine, clomipramine, trimipramine, and doxepin.
Tricyclic antidepressants should be used with caution in patients with a history of alcoholism or who may use alcohol or other sedative medications because the depressant effects on the CNS can be potentiated. There can be decreased mental alertness.
Tricyclic antidepressants can exacerbate schizophrenia or manic symptoms of bipolar disorder because of the effects of the drug on the CNS. Bipolar disorder patients not concomitantly treated with an anticyclic medication are likely to switch from depression to mania, and some schizophrenic patients can experience exacerbation of psychosis.
Tricyclic antidepressants should be used with extreme caution in patients with a preexisting seizure disorder because of the seizure threshold can be lowered.
Tricyclic antidepressants should be used with caution in patients with Parkinson's disease. Tricyclic antidepressants rarely can induce or worsen extrapyramidal symptoms. In addition, involuntary movements, which appear to be tardive dyskinesia, can occur.
Patients with respiratory depression should be treated cautiously with tricyclic antidepressants because of additive CNS- depressant effects.
Tricyclic antidepressants should be used with caution in patients (especially children and elderly) with cardiac disease because of the alterations in ECG patterns. Many adverse cardiovascular effects are associated with the use of tricyclic antidepressant drugs, which can lead to complete cardiac collapse and sudden death. Although these events are more likely to occur after acute overdose, patients with cardiovascular disease should be closely monitored and regular ECG tracings made. Tricyclic antidepressants should not be given to patients who are in the acute recovery phase following myocardial infarction; sudden death could occur.
Asthma can be aggravated by administering tricyclic antidepressants to patients with the disease.
Tricyclic antidepressants are known to produce an allergic response in some patients. There appears to be cross- sensitivity, so caution should be used when changing from one tricyclic antidepressant to another. Alternative therapy should be considered. Alternative therapy should be considered. Tricyclic antidepressants can also display cross-sensitivity to carbamazepine, maprotiline, or trazodone.
Tricyclic antidepressant therapy should be discontinued several days before elective surgery because of the risk of hypertensive episodes.
On rare occasions, agranulocytosis, thrombocytopenia, eosinophilia, leukopenia, or purpura has been reported with tricyclic antidepressants. Any patient with symptoms of blood dyscrasia (sore throat, fever, bruising, etc.) should have immediate laboratory studies performed and suitable therapy initiated. Use tricyclic antidepressants cautiously in patients with preexisting hematological disease.
Intramuscular injections should be administered cautiously to patients receiving amoxapine. IM injections may cause bleeding, bruising, or hematomas due to thrombocytopenia secondary to amoxapine therapy.
Tricyclic antidepressants should be used with caution in patients with hepatic disease. Hepatitis and jaundice have resulted from use of tricyclic antidepressants, which are reversible on discontinuation of the drug. Hepatic failure and death have occurred when tricyclic antidepressants were continued. Liver- function tests should be performed and the drug discontinued if there is persistent elevation of enzymes. Metabolism of tricyclic antidepressants may be altered in patients with hepatic impairment.
Patients can be more prone to sunburn during therapy with a tricyclic antidepressant. Suitable precautions should be taken such as wearing long-sleeved clothing and a hat, and routinely applying a sunblock with an SPF +15.
Tricyclic antidepressants should be used with caution in patients with hyperthyroidism or in patients receiving thyroid drugs. Concomitant use with thyroid drugs can produce cardiac arrhythmias. Hypothyroidism that is untreated will prevent adequate response to antidepressant therapy. Thyroid agents also can accelerate the onset of the response to tricyclic antidepressants.
Tricyclic antidepressants affect blood glucose concentrations because of their effect on the endocrine system and should be used with caution in patients with diabetes mellitus.
Tricyclic antidepressants are not recommended for use during pregnancy, unless the possible benefits outweigh the risks. Amoxapine is classified as FDA category C. Patients should be made aware of the risks to the neonate: possible fetal abnormality, delayed development, or withdrawal symptoms. The benefits and risks of breast-feeding should be carefully weighed if tricyclic antidepressants are needed in the mother because the drugs are excreted into breast milk.
All antidepressants should be used with caution in depressed patients because of the possibility of suicidal ideation. Close monitoring of the patient is essential during the initial stages of therapy and amoxapine prescribed in the smallest quantity consistent with good management.
DRUG INTERACTIONS: Monoamine oxidase inhibitors (MAOIs), such as furazolidone, isocarboxazid, phenelzine, procarbazine, selegiline, or tranylcypromine), concurrently used with tricyclic antidepressants can cause hyperpyrexia, hypertension, or seizures. In the rare patients in whom this combination therapy is necessary, the interaction can be minimized by initiating therapy with a tricyclic antidepressant and then beginning MAOI therapy at low doses, followed by a very gradual increase. The tricyclic antidepressant should inhibit the uptake of tyramine from food in the GI tract; the subsequent addition of an MAOI should not lead to high levels of tyramine. Conversely, tricyclic antidepressants should not be added to an existing MAOI regimen because the reuptake blockade will be unopposed due to the existing inhibition of the main elimination pathway. An interval of 14 days is recommended between cessation of an irreversible MAOI agent and initiation of tricyclic antidepressant therapy.
Tricyclic antidepressants (with the exception of doxepin in doses <150 mg/day) block the uptake of guanadrel, guanethidine, and methyldopa into norepinephrine neurons, preventing the expected antihypertensive effects. Reserpine and other rauwolfia alkaloids can have decreased antihypertensive effects when used with tricyclic antidepressants.
Guanabenz can lead to increased circulation of catecholamines. Concomitant use of tricyclic antidepressants can cause hypertension, especially during the second week of tricyclic antidepressant therapy. Occasionally, the hypertension will occur within the first few days of tricyclic antidepressant therapy.
Labetalol, when used with tricyclic antidepressants, has been reported to result in an increased incidence of tremor.
Clonidine's antihypertensive effect can be reduced by tricyclic antidepressants (reported with imipramine and desipramine). Concomitant use of tricyclic antidepressants can lead to hypertension, especially during the second week of tricyclic antidepressant therapy. Occasionally, the hypertension will occur within the first few days of tricyclic antidepressant therapy. In addition, concurrent administration of a tricyclic antidepressant (amitriptyline) and clonidine in rats has produced corneal lesions within 5 days.
Ethanol or other CNS depressants in combination with tricyclic antidepressants should be used with caution because of the additive depressant effects and possible respiratory depression or hypotension. Barbiturates and carbamazepine induce hepatic microsomal enzymes and increase the metabolism of tricyclic antidepressants. The tricyclic antidepressants' plasma concentrations are reduced and may require increased dosage to achieve equivalent therapeutic effects.
Benzodiazepines (alprazolam and diazepam) have been reported to increase the concentrations of tricyclic antidepressants (imipramine and amitriptyline) or metabolites (desipramine and nortriptyline) when coadministered. This is a commonly used drug combination and is considered to be safe, as long as patients are monitored for excessive adverse effects from either agent. Benzodiazepines and tricyclic antidepressants will produce additive CNS depression.
Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, sertraline, paroxetine, and fluvoxamine, are another class of antidepressants that have been reported to cause symptoms of tricyclic antidepressant toxicity when used with a tricyclic antidepressant. The mechanism of this interaction is poorly understood but is believed to involve specific isoenzymes of the cytochrome P-450 mixed-function oxidase system. The most critical and well studied pathway is 2D6. Cytochrome P-450 2D6 is impaired most by fluoxetine and least by sertraline. Patients receiving an SSRI and tricyclic antidepressant should be monitored closely for excessive adverse effects from either agent.
Tricyclic antidepressants can lower the seizure threshold. Concomitant use with anticonvulsants may require increased concentrations of the anticonvulsant to achieve equivalent effects.
Tricyclic antidepressants used concomitantly with disulfiram or ethchlorvynol can produce transient delirium.
Tricyclic antidepressants used concomitantly with strong anticholinergic agents such as anticholinergics; HA-blockers; cyclobenzaprine; antipsychotics (haloperidol, loxapine, molindone, phenothiazines, or thioxanthenes); or metoclopramide, will increase the anticholinergic and sedative effects. Concomitant therapy should be avoided whenever possible. If necessary, doses of both drugs should be started lower and increased cautiously with careful monitoring.
Tricyclic antidepressants can potentiate cardiac arrhythmias if used concurrently with pimozide.
Pressor effects of ophthalmic or nasal vasoconstrictors (naphazoline, oxymetazoline, phenylephrine, or xylometazoline) can be potentiated by tricyclic antidepressants. Concomitant use of tricyclic antidepressants with sympathomimetics (isoproterenol, phenylephrine, norepinephrine, epinephrine, or amphetamines) can result in adverse cardiovascular effects such as arrhythmias, tachycardia, or severe hypertension or hyperpyrexia.
Tricyclic antidepressant metabolism can be inhibited by cimetidine or ranitidine, resulting in increased plasma levels of the tricyclic antidepressant that could lead to toxicity. Patients should be closely observed for toxic effects such as orthostatic hypotension or sedation.
Oral contraceptives, fluoxetine, erythromycin, or methylphenidate can inhibit the hepatic metabolism of tricyclic antidepressants and can increase the risk of tricyclic antidepressant toxicity if used concurrently.
The risk of developing agranulocytosis is increased if tricyclic antidepressant drugs are used concurrently with antithyroid agents.
Amitriptyline can increase the risk of developing cardiac arrhythmias when used in conjunction with cocaine. If local anesthesia with cocaine is essential in a patient receiving amitriptyline, lower doses of cocaine and/or electrocardiographic monitoring may be necessary.
Intrathecal administration of metrizamide to a patient taking amitriptyline can increase the risk of seizures. Tricyclic antidepressant therapy should be discontinued 48 hours before, and not restarted until 24 hours after, myelography.
Tricyclic antidepressants used concomitantly with thyroid hormones can increase therapeutic and toxic effects (such as arrhythmias and CNS stimulation) of both medicines.
The anticholinergic activity of tricyclic antidepressants 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.
ADVERSE REACTIONS: Amoxapine possesses adverse reactions similar to those of the tricyclic antidepressants and also some reactions similar to the phenothiazines. A wide variety of cardiovascular side effects can result from the use of tricyclic antidepressants due to their direct quinidine-like action, their potent anticholinergic properties, and their ability to potentiate norepinephrine. Ventricular tachycardia, palpitations, hypertension, and orthostatic hypotension all can be precipitated, with the possibility of more severe reactions occurring such as myocardial infarction, congestive heart failure, or stroke. Imipramine, and possibly other tricyclic antidepressants, can cause both PR prolongation and QT prolongation. Imipramine and nortriptyline are known to prolong the QRS interval. Other tricyclics would be expected to produce similar ECG changes. The cardiovascular response to tricyclic antidepressants depends on the specific agent and the dose. Although all tricyclic antidepressants are thought to be proarrhythmic after acute overdoses, at therapeutic doses, their actions on the conducting system of the heart may vary. Imipramine has been utilized therapeutically for its antiarrhythmic effect. The cardiovascular response to tricyclic antidepressants is varied, and patients most at risk have preexisting cardiovascular disease.
In common with the antipsychotic drugs, amoxapine has been implicated in producing neuroleptic malignant syndrome (NMS). NMS is characterized by hyperthermia, severe extrapyramidal dysfunction, alterations in consciousness, altered mental status, and autonomic instability. NMS can have a fatal outcome. Several predisposing factors can contribute to the development of NMS including heat stress, physical exhaustion, dehydration, and organic brain disease. NMS occurs more frequently in young men. Amoxapine should be immediately discontinued and appropriate supportive therapy initiated as soon as symptoms of NMS are discovered.
In common with the antipsychotic drugs, amoxapine has been implicated in producing tardive dyskinesia (TD). Although amoxapine is not an antipsychotic, it has substantial neuroleptic activity. Tardive dyskinesia is characterized by involuntary movements of the perioral region (tongue, mouth, jaw, eyelids, or face) or choreoathetoid movements in the extremities. It can develop during long-term therapy or following discontinuation of amoxapine, and it occurs more frequently in elderly women. Some cases are irreversible. While contradictory evidence exists, it has been suggested that the likelihood of developing TD increases with prolonged treatment and cumulative doses. If signs or symptoms of TD develop, amoxapine use should be reevaluated and possibly discontinued.
Amoxapine possesses adverse reactions similar to those of the tricyclic antidepressants and also some reactions similar to the phenothiazines. Drowsiness is the most frequent central nervous system (CNS) adverse effect from therapy with tricyclic antidepressants. Sedation can be a desirable effect if the tricyclic antidepressant is administered at bedtime; this will minimize undesirable drowsiness and sedation during the day. Dizziness usually is due to orthostatic hypotension and can be reduced by having the patient stand more slowly. Some patients exhibit excitation and anxiety. Confusion is most apparent in the elderly.
Amoxapine possesses adverse reactions similar to those of the tricyclic antidepressants and also some reactions similar to the phenothiazines. Peripheral nervous system adverse reactions can occur during therapy with tricyclic antidepressants. Tremor can result from norepinephrine reuptake blockade. Rarely, extrapyramidal symptoms can occur in both young and elderly patients. Parkinsonism is more likely to occur in the elderly, especially if receiving high doses.
Amoxapine possesses adverse reactions similar to those of the tricyclic antidepressants and also some reactions similar to the phenothiazines. Seizure activity is one of the most frequent adverse reactions after overdoses of amoxapine. Patients who have a preexisting seizure disorder may require increased concentrations of their anticonvulsant to maintain seizure control. Seizures and EEG changes have been observed more commonly in children than in adults during therapy with tricyclic antidepressants.
Amoxapine possesses adverse reactions similar to those of the tricyclic antidepressants and also some reactions similar to the phenothiazines. Ocular manifestations of the anticholinergic actions of tricyclic antidepressants may include blurred vision due to cycloplegia, mydriasis, and increased intraocular pressure. Increased intraocular pressure can precipitate a crisis in patients with angle-closure glaucoma. Ophthalmological examination is recommended when patients experience visual changes.
Amoxapine possesses adverse reactions similar to those of the tricyclic antidepressants and also some reactions similar to the phenothiazines. Gastrointestinal manifestations of tricyclic antidepressants' anticholinergic activity include dry mouth (xerostomia), constipation, urinary retention, adynamic ileus, abdominal pain or cramps, nausea/vomiting, anorexia, diarrhea, and jaundice. Constipation is more commonly observed in elderly patients. If these symptoms become severe, withdrawal of the drug may be necessary.
Amoxapine possesses adverse reactions similar to those of the tricyclic antidepressants and also some reactions similar to the phenothiazines. Allergic reactions to tricyclic antidepressants can include photosensitivity, vasculitis, erythema, urticaria, fever, and/or pruritus. Fever also can indicate a blood dyscrasia.
Amoxapine possesses adverse reactions similar to those of the tricyclic antidepressants and also some reactions similar to the phenothiazines. The effects of tricyclic antidepressants on the endocrine system can result in sexual dysfunction including libido decrease or loss, impotence, testicular swelling, ejaculation dysfunction, breast enlargement and galactorrhea in females, or gynecomastia in males. The syndrome of inappropriate secretion of antidiuretic hormone (SIADH) has been reported. Glucose metabolism can be altered and should be monitored in patients with diabetes mellitus.
Tricyclic antidepressants are associated with hematologic adverse reactions. These effects inclue agranulocytosis, eosinophilia, purpura, thrombocytopenia, and leukopenia.
PATIENT INFORMATION:
What do amoxapine tablets do?
Amoxapine (AsendinTM ) is an antidepressant, a medicine that helps to lift mental depression. Generic amoxapine tablets are not yet available.
What should my doctor, dentist, or pharmacist know before I take amoxapine?
They need to know if you have any of these conditions:
How should I take this medicine?
Take maprotiline tablets by mouth. Follow the directions on the prescription label. Swallow the tablets with a drink of water. Take your doses at regular intervals. Do not take your medicine more often than directed. Do not stop taking the tablets except on your doctor's advice.
Special precautions for use in children:
This medication is not for children under 16 years old.
Elderly patients over 65 years old may have a stronger reaction to this medicine and need smaller doses.
What if I miss a dose?
If you miss a dose, take it as soon as you can. If it is less than four hours to your next dose, take only that dose and skip the missed dose. If you only take a single dose at bedtime and forget, do not take it the next morning without checking with your doctor. Do not take double or extra doses.
What other medicines can interact with amoxapine?
Amoxapine can interact with many other medicines. An interaction can be very important or fairly insignificant. Make sure your doctor knows about all other medicines you are taking; the most important are listed below:
Tell your doctor or pharmacist: about all other medicines you are taking, including non-prescription medicines; if you are a frequent user of drinks with caffeine or alcohol; if you smoke; or if you use illegal drugs. These may affect the way your medicine works. Check before stopping or starting any of your medicines.
What side effects may I notice from taking amoxapine?
Serious side effects with amoxapine include:
Call your doctor as soon as you can if you get any of these side effects.
Minor side effects with amoxapine include:
Let your doctor know about these side effects if they do not go away or if they annoy you.
What do I need to watch for while I take amoxapine?
Visit your doctor for regular checks on your progress. You may have to take amoxapine for several weeks before you feel better. If you have been taking amoxapine for some time, do not suddenly stop taking it. Your doctor may want you to gradually reduce the dose; ask for advice.
You may get drowsy, dizzy or have blurred vision. Do not drive, use machinery, or do anything that needs mental alertness until you know how amoxapine affects you. Do not stand or sit up quickly, especially if you are an older patient. This reduces the risk of dizzy or fainting spells. Alcohol may increase dizziness or drowsiness; avoid alcoholic drinks.
Amoxapine can make your mouth dry. Chewing sugarless gum, sucking hard candy and drinking plenty of water will help.
Amoxapine may make your skin more sensitive to sun or ultraviolet light. Keep out of the sun, or wear protective clothing outdoors and use a sunscreen (at least SPF15). Do not use sun lamps or sun tanning beds or booths.
Do not treat yourself for coughs, colds, or allergies without asking your doctor or pharmacist for advice. Some ingredients may increase possible side effects.
If you are going to have surgery, tell your doctor or dentist well before your scheduled surgery that you are taking amoxapine.
Where can I keep my medicine?
Keep out of the reach of children in a container that small children cannot open.
Store at room temperature between 15 and 30C (59 and 86F). Throw away any unused medicine after the expiration date.
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