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Amitriptyline; nortriptyline (amitriptyline metabolite)
Evaluate toxicity; monitor therapeutic levels
Liquid chromatography/tandem mass spectrometry (LC/MS-MS)
Therapeutic: amitriptyline + nortriptyline: 80−200 ng/mL
Amitriptyline is a tricyclic antidepressant that blocks the reuptake of serotonin at nerve endings and possesses high anticholinergic activity and cardiovascular toxicity. The drug is extensively metabolized to many polar compounds, the chief of which is nortriptyline. It is also an antidepressant. Both drugs are prescribed for depression and a range of other disorders.
Amitriptyline has a peak serum concentration two to six hours postoral dose, and steady-state is achieved after three to eight days of chronic oral dosing. The half-life is 17 to 40 hours and the usual therapeutic range (predose sample at steady-state) includes nortriptyline and is 80−200 ng/mL. Nortriptyline is administered orally, has a half-life of 15 to 90 hours, and peak serum values two to six hours postoral dose. Steady-state is achieved after 4 to 20 days of chronic dosing. Therapeutic levels of nortriptyline alone are 50−150 ng/mL.
All the tricyclic antidepressants have significant drug interactions. Being potent inducers of hepatic drug-metabolizing enzymes, particularly CYP3A4, CYP1A2, and CYP2C9, the antiepileptic drugs, carbamazepine, phenytoin, phenobarbital, and primidone stimulate the oxidative transformation of concurrently prescribed antidepressants.1 This results in decreased drug levels of the antidepressant. To a lesser extent, co-administration of oxcarbazepine, topiramate, and felbamate can also result in decreased antidepressant levels. Other tricyclic antidepressant drug interactions: hydrocortisone, methylphenidate, and phenothiazines increase tricyclic levels; tricyclics impair the antihypertensive effectiveness of clonidine and guanethidine; tricyclics and alcohol produce additive sedative effects, tricyclics and antiparkinsonism agents have potent anticholinergic side effects, and tricyclics and MAO inhibitors should not be co-administered because of the potential for antihypertensive and CNS crises.
Tricyclics should be avoided in pregnant and lactating women because these drugs have not been established as safe. Geriatric patients are especially prone to postural hypotension, urinary retention, and sedation.2 In general, it has been reported that, “Therapeutic drug monitoring of antidepressants allows us to take into account the influence of factors such as co-medications, diet, smoking habit, impaired organ function, and compliance. Therapeutic drug monitoring and genotyping are thus complementary, and their combined use contributes to improve pharmacotherapy with antidepressants and other drugs.”3
Serum or plasma
Transfer separated serum or plasma to a plastic transport tube. For therapeutic monitoring, collect specimen immediately prior to next dose unless specified otherwise.
Causes for Rejection
|Order Code||Order Code Name||Order Loinc||Result Code||Result Code Name||UofM||Result LOINC|
|007476||Amitriptyline (Elavil), Serum||017475||Amitriptyline, Serum||ng/mL||3333-2|
|007476||Amitriptyline (Elavil), Serum||017483||Nortriptyline, Serum||ng/mL||3872-9|
|007476||Amitriptyline (Elavil), Serum||017485||Total (Ami+Nor)||ng/mL||3335-7|