Hepatitis amitriptyline

Dose Initial 0.25 mg PO tid, wkly 10.25 mg/dose, to 3 mg max max 4 mg for RLS Caution [C, /-] Sev e CV, renal, or hepatic impair Contra Component allergy Disp Tabs SE Syncope, postural X BP, NA, HA, somnolence, dosed-related hallucinations, dyskinesias, dizziness Interactions t Risk of bleeding W/ ASA, NSAIDs, fevCTfew, garlic, ginger, horse chestnut, red clover, EtOH, tobacco t effects OF amitriptyline, Li, MTX, theophylline, warfarin t risk of photosensitivity W/ dong quai— use sunscreen, St. John s wort X effects W/ antacids, rifampin X effects OF ACEIs, diuretics EMS t Bleeding risk w/ concurrent EtOH, tobacco, ASA, and NSAID use t effects of warfarin OD May cause N/V, drowsiness, hypotension, and CP symptomatic and supportive... 

Thus, the patient with a toxic TCA concentration (see the case at the start of the Metabolism section) developed excessively high amitriptyline plasma levels due to the additive effects of diminished left ventricular function leading to decreased hepatic arterial blood flow alcohol and age-related decline in liver function and, finally. 

Oral contraceptives reduce the clearance of imipramine, probably by reducing hepatic oxidation, and thus increase its half-life. Hydroxylation of amitriptyline is inhibited by contraceptive steroids. The clinical significance is uncertain, but there is at least anecdotal evidence of an increase in antidepressant adverse effects (360). Caution should be exercised when tricyclic antidepressants are used long term in women taking oral contraceptives. 

St John s wort can cause drug interactions by inducing hepatic microsomal drug-metabolizing enzymes or the drug transporter P-glycoprotein, which causes a net efflux of substrates, such as amitriptyline, from intestinal epithelial cells into the gut lumen (SEDA-24,12). In 12 patients (9 women, 3 men) the addition of St John s wort 900 mg/ day to amitriptyline 150 mg/day led to a 20% reduction in plasma amitriptyline concentrations, while nortriptyline concentrations were almost halved (210). 

TCAs DRUG DEPENDENCE THERAPIES-BUPROPION 1. t risk of seizures This risk is marked in elderly people, in patients with a history of seizures, addiction to opiates/cocaine/ stimulants, and in diabetics treated with oral hypoglycaemics or insulin 2. t plasma concentrations of amitriptyline, clomipramine, desipramine, doxepin and imipramine, with risk of toxic effects 1. Bupropion is associated with a dose-related risk of seizures. TCAs lower the seizure threshold. Additive effects when combined 2. Bupropion and its metabolite hydroxybupropion inhibit CYP2D6 1. Extreme caution. The dose of bupropion should not exceed 450 mg/day (or 150 mg/day in those with severe hepatic cirrhosis) 2. Initiate therapy of these drugs at the lowest effective dose... 

Prototypical agent amitriptyline Inhibits norepinephrine and serotonin reuptake Hepatic metabolism with renal elimination High anticholinergic and antihistamine effects imipramine has high orthostasis profile 2nd degree amines (nortriptyline, desipramine) and doxepin have moderate anticholinergic effects... 

Drug-Drug and Drug-Food Interactions. Since cinacalcet is metabolized by multiple hepatic enzymes there is potential for drug interactions. Cinacalcet is also a potent inhibitor of the enzyme CYP2D6. As a result, dose adjustments of concomitant medications that are predominantly metabolized by this enzyme and have a narrow therapeutic index such as flecainide, thioridazine, vinblastine, and most tricyclic antidepressants (i.e., amitriptyline) may be required. ... 

Carbamazepine induces hepatic catabolic enzymes, with a consequent reduction in serum levels of antidepressants (mainly described with amitriptyline, desipramine, doxepin, imipramine, mianserin, and nortriptyline). A decrease in bupropion serum levels was also reported with carbamazepine. These effects were not observed with clomipramine. Fluoxetine and fluvoxamine inhibit the metabolism of carbamazepine and valproate (up to 30% and 50% increases in serum levels, respectively). No significant interaction has yet been found between paroxetine and carbamazepine or valproate. 

An isolated report describes a woman who developed marked and acute hypotension and weakness when desipramine, fluoxetine and venlafaxine were replaced by nefazodone. Isolated cases describe the serotonin syndrome in patients given nefazodone together, or sequentially, with another serotonei c drug (amitriptyline, paroxetine, St John s wort, or trazodone). The manufacturer recommended that nefazodone should not be used with an MAOI or within 14 days of discontinuing an MAOL Note that, due to adverse hepatic effects nefazodone was widely withdrawn from the market. 

A case series describes 10 incidences of acute hepatitis that were observed over a 2-year period. Cholestasis was observed in 5 of the 10 patients, and in 7 of the 10 cases, the hepatitis was characterized as drug-induced. No liver failure occurred in any of the patients, and cessation of celandine resulted in resolution of hepatitis. Use of celandine was from 1 to 9 months. Prescription and nonprescription drugs and herbal supplements were also being used in some cases, including thyroxine (2 patients), iodide (2 patients), estradiol (2 patients), and amitriptyline (1 patient) (Benninger et al. 1999). Cholestatic hepatitis has been... 

A 48-year-old man developed cholestatic hepatitis, complicated by portal hypertension, after having taken single 425 mg capsules of aged cascara sagrada three times daily for 3 days. Other medications included amitriptyline, cimeti-dine, and baclofen (Nadir et al. 2000). Amitriptyline has been associated with rare but severe incidences of hepatotoxicity, notably, cholestatic injury (Saeian and Rajender-Reddy 2003 Wen et al. 2008). 

A case of hepatitis associated with amitriptyline was reported (33 ) in a 23-year-old man who had taken amitriptyline 150 mg daily for 4 months and was discovered to have raised liver transaminases and alkaline phosphatase. The report is unusual because of the care taken to establish the absence of other toxic agents and because a subsequent challenge with the same drug produced a recurrence of the abnormalities. At that time a liver biopsy revealed an inflammatory picture with infiltration by mononuclear cells and eosinophils cholestasis and clinical jaundice were absent. Elevation of liver enzymes is not infrequent in patients on tricyclic drugs and this report raises the question of whether these changes and their underlying pathology may be quite different from cases in which cholestasis and jaundice occur. 

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