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Additional information about the drug Amoxapine
Amoxapine, sold under the brand name Asendin among others, is a tricyclic antidepressant (TCA). It is the N- demethylated metabolite of loxapine. Amoxapine first received marketing approval in the United States in 1992 (approximately 30 to 40 years after most of the other TCAs were introduced in the United States).
Contents
1 Medical uses
2 Contraindications
2.1 Lactation
3 Side effects
4 Overdose
5 Pharmacology
5.1 Pharmacodynamics
5.2 Pharmacokinetics
6 Society and culture
6.1 Brand names
7 See also
8 References
Medical uses
Amoxapine is used in the treatment of major depressive disorder. Compared to other antidepressants it is believed to have a faster onset of action, with therapeutic effects seen within four to seven days.
Contraindications
As with all FDA -approved antidepressants it carries a black-box warning about the potential of an increase in suicidal thoughts or behaviour in children, adolescents and young adults under the age of 25.
Severe cardiovascular disorders (potential of cardiotoxic adverse effects such as QT interval prolongation)
Uncorrected narrow angle glaucoma
Acute recovery post- myocardial infarction
Its use is also advised against in individuals concurrently on monoamine oxidase inhibitors or if they have been on one in the past 14 days and in individuals on drugs that are known to prolong the QT interval (e.g. ondansetron, citalopram, pimozide, sertindole, ziprasidone, haloperidol, chlorpromazine, thioridazine, etc.).
Lactation
Its use in breastfeeding mothers not recommended as it is excreted in breast milk and the concentration found in breast milk is approximately a quarter that of the maternal serum level.
Side effects
Adverse effects by incidence:
Note: Serious (that is, those that can either result in permanent injury or are irreversible or are potentially life-threatening) are written in bold text.
Very common (>10% incidence) adverse effects include:
Constipation
Dry mouth
Sedation
Common (1–10% incidence) adverse effects include:
Anxiety
Ataxia
Blurred vision
Confusion
Dizziness
Headache
Fatigue
Nausea
Nervousness/restlessness
Excessive appetite
Rash
Increased perspiration (sweating)
Tremor
Palpitations
Nightmares
Excitement
Weakness
ECG changes
Oedema. An abnormal accumulation of fluids in the tissues of the body leading to swelling.
Prolactin levels increased. Prolactin is a hormone that regulates the generation of breast milk. Prolactin elevation is not as significant as with risperidone or haloperidol.
Uncommon/Rare (<1% incidence) adverse effects include: Diarrhoea Flatulence Hypertension (high blood pressure) Hypotension (low blood pressure) Syncope (fainting) Tachycardia (high heart rate) Menstrual irregularity Disturbance of accommodation Mydriasis (pupil dilation) Orthostatic hypotension (a drop in blood pressure that occurs upon standing up) Seizure Urinary retention (being unable to pass urine) Urticaria (hives) Vomiting Nasal congestion Photosensitization Hypomania (a dangerously elated/irritable mood) Tingling Paresthesias of the extremities Tinnitus Disorientation Numbness Incoordination Disturbed concentration Epigastric distress Peculiar taste in the mouth Increased or decreased libido Impotence (difficulty achieving an erection) Painful ejaculation Lacrimation (crying without an emotional cause) Weight gain Altered liver function Breast enlargement Drug fever Pruritus (itchiness) Vasculitis a disorder where blood vessels are destroyed by inflammation. Can be life-threatening if it affects the right blood vessels. Galactorrhoea (lactation that is not associated with pregnancy or breast feeding) Delayed micturition (that is, delays in urination from when a conscious effort to urinate is made) Hyperthermia (elevation of body temperature; its seriousness depends on the extent of the hyperthermia) Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) this is basically when the body's level of the hormone, antidiuretic hormone, which regulates the conservation of water and the restriction of blood vessels, is elevated. This is potentially fatal as it can cause electrolyte abnormalities including hyponatraemia (low blood sodium), hypokalaemia (low blood potassium) and hypocalcaemia (low blood calcium) which can be life-threatening. Agranulocytosis a drop in white blood cell counts. The white blood cells are the cells of the immune system that fight off foreign invaders. Hence agranulocytosis leaves an individual open to life-threatening infections. Leukopaenia the same as agranulocytosis but less severe. Neuroleptic malignant syndrome (a potentially fatal reaction to antidopaminergic agents, most often antipsychotics. It is characterised by hyperthermia, diarrhoea, tachycardia, mental status changes [e.g. confusion], rigidity, extrapyramidal side effects) Tardive dyskinesia a most often irreversible neurologic reaction to antidopaminergic treatment, characterised by involuntary movements of facial muscles, tongue, lips, and other muscles. It develops most often only after prolonged (months, years or even decades) exposure to antidopaminergics. Extrapyramidal side effects. Motor symptoms such as tremor, parkinsonism, involuntary movements, reduced ability to move one's voluntary muscles, etc. Unknown incidence or relationship to drug treatment adverse effects include: Paralytic ileus (paralysed bowel) Atrial arrhythmias including atrial fibrillation Myocardial infarction (heart attack) Stroke Heart block Hallucinations Purpura Petechiae Parotid swelling Changes in blood glucose levels Pancreatitis swelling of the pancreas Hepatitis swelling of the liver Urinary frequency Testicular swelling Anorexia (weight loss) Alopecia (hair loss) Thrombocytopenia a significant drop in platelet count that leaves one open to life-threatening bleeds. Eosinophilia an elevated level of the eosinophils of the body. Eosinophils are the type of immune cell that's job is to fight off parasitic invaders. Jaundice yellowing of the skin, eyes and mucous membranes due to an impaired ability of the body to clear the by product of haem breakdown, bilirubin, most often the result of liver damage as it is the liver's responsibility to clear bilirubin. It tends to produce less anticholinergic effects, sedation and weight gain than some of the earlier TCAs (e.g. amitriptyline, clomipramine, doxepin, imipramine, trimipramine ). Overdose Main article: Tricyclic antidepressant overdose It is considered particularly toxic in overdose, Pharmacology Pharmacodynamics See also: Pharmacology of antidepressants and Tricyclic antidepressant § Binding profiles Amoxapine Site K i (nM) Species Ref SERT 58 Human NET 16 Human DAT 4,310 Human 5-HT 2A 0.5 Human 5-HT 2C 2.0 Monkey 5-HT 6 6.0–50 Human 5-HT 7 41 Monkey α 1 50 Human α 2 2,600 Human D 2 3.6–160 Human D 3 11 Human D 4 2.0–40 Human H 1 7.9–25 Human H 2 ND ND ND H 3 >100,000
Human
H 4
6,310
Human
mACh
1,000
Human
Values are K i (nM). The smaller the value, the more strongly the drug binds to the site.
Amoxapine possesses a wide array of pharmacological effects. It is a moderate and strong reuptake inhibitor of serotonin and norepinephrine, respectively,
7-Hydroxyamoxapine, a major active metabolite of amoxapine, is a more potent dopamine receptor antagonist and contributes to its neuroleptic efficacy,
Pharmacokinetics
Amoxapine is metabolised into two main active metabolites: 7-hydroxyamoxapine and 8-hydroxyamoxapine.
Amoxapine
7-hydroxyamoxapine
8-hydroxyamoxapine
Compound
t 1/2 (hr)
t max (hr)
C SS (ng/mL)
Protein binding
V d
Excretion
Amoxapine
8
1-2
17-93 ng/mL (divided dosing), 13-209 ng/mL (single daily dosing)
90%
0.9-1.2 L/kg
Urine (60%), feces (18%)
8-hydroxyamoxapine
30
5.3 (single dosing)
158-512 ng/mL (divided dosing), 143-593 ng/mL (single dose)
?
?
?
7-hydroxyamoxapine
6.5
2.6-5.4 (single dosing)
?
?
?
?
Where:
– t 1/2 is the elimination half life of the compound.
– t max is the time to peak plasma levels after oral administration of amoxapine.
– C SS is the steady state plasma concentration.
– protein binding is the extent of plasma protein binding.
– V d is the volume of distribution of the compound.
Society and culture
Brand names
Brand names for amoxapine include (where † denotes discontinued brands):
Adisen ( KR )
Amolife ( IN )
Amoxan ( JP )
Asendin† (previously marketed in CA, NZ, US )
Asendis† (previously marketed in IE, UK )
Défanyl ( FR )
Demolox ( DK †, IN, ES †)
Oxamine ( IN )
Oxcap ( IN )
See also
Loxapine
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