Elavil (Amitriptyline) - Side Effects and Adverse Reactions

SIDE EFFECTS

Within each category the following adverse reactions are listed in order of decreasing severity. Included in the listing are a few adverse reactions which have not been reported with this specific drug. However, pharmacological similarities among the tricyclic antidepressant drugs require that each of the reactions be considered when amitriptyline is administered.

Cardiovascular:

CNS and Neuromuscular:

Anticholinergic:

Allergic:

Hematologic:

Gastrointestinal:

Endocrine:

Other:

Withdrawal Symptoms:

Causal Relationship Unknown:

Body as a Whole:

Digestive:

Postmarketing Adverse Events:

DRUG INTERACTIONS

Drugs Metabolized by P450 2D6 ¾ The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the caucasian population (about 7-10% of caucasians are so called "poor metabolizers"); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8-fold increase in plasma AUC of the TCA).

In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline, and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).

Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be coadministered with another drug known to be an inhibitor of P450 2D6.

Monoamine Oxidase Inhibitors: (See CONTRAINDICATIONS.) Guanethidine or similarly acting compounds; thyroid medication; alcohol, barbiturates and other CNS depressants; and disulfiram (see WARNINGS.)

When amitriptyline HCl is given with anticholinergic agents or sympathomimetic drugs, including epinephrine combined with local anesthetics, close supervision and careful adjustment of dosages are required.

Hyperpyrexia has been reported when amitriptyline HCl is administered with anticholinergic agents or with neuroleptic drugs, particularly during hot weather.

Paralytic ileus may occur in patients taking tricyclic antidepressants in combination with anticholinergic-type drugs.

Cimetidine is reported to reduce hepatic metabolism of certain tricyclic antidepressants, thereby delaying elimination and increasing steady-state concentrations of these drugs. Clinically significant effects have been reported with the tricyclic antidepressants when used concomitantly with cimetidine. Increases in plasma levels of tricyclic antidepressants, and in the frequency and severity of side effects, particularly anticholinergic, have been reported when cimetidine was added to the drug regimen. Discontinuation of cimetidine in well-controlled patients receiving tricyclic antidepressants and cimetidine may decrease the plasma levels and efficacy of the antidepressants.

Caution is advised if patients receive large doses of ethchlorvynol concurrently. Transient delirium has been reported in patients who were treated with one gram of ethchlorvynol and 75 - 150 mg of amitriptyline HCl.

REPORTS OF SIDE EFFECTS / ADVERSE REACTIONS RELATED TO ELAVIL

Possible Elavil side effects / adverse reactions in 71 year old male

Reported by a physician from Japan on 2009-04-15

Patient: 71 year old male

Reactions: Agitation, Hyperkalaemia, Restlessness, Terminal Insomnia, Pyrexia, Constipation, Anxiety, Renal Failure, Dialysis, Blood Uric Acid Increased, Major Depression, Vertigo, Urinary Retention, Feeling Abnormal, Hypochondriasis

Adverse event resulted in: life threatening event

Suspect drug(s):
Enalapril Maleate
    Dosage: (5 mg qd oral)
    Administration route: Oral
    Indication: Hypertension
    End date: 2009-02-04

Elavil
    Dosage: (10 mg qd oral), (55 mg qd oral), (100 mg qd oral)
    Administration route: Oral
    Indication: Depression
    Start date: 2008-12-25
    End date: 2009-01-04

Elavil
    Dosage: (10 mg qd oral), (55 mg qd oral), (100 mg qd oral)
    Administration route: Oral
    Indication: Depression
    Start date: 2009-01-05
    End date: 2009-01-06

Elavil
    Dosage: (10 mg qd oral), (55 mg qd oral), (100 mg qd oral)
    Administration route: Oral
    Indication: Depression
    Start date: 2009-01-07
    End date: 2009-02-04

Other drugs received by patient: Adalat L (Unknown); Benzalin (Unknown); Cephadol (Unknown); Coniel (Unknown); Dogmatyl; Lendodrmin; Rohypnol; Urinorm (Unknown); Constan / 00595201/ (Unknown); Hirnamin /00038601/ (Unknown)

Possible Elavil side effects / adverse reactions in 51 year old female

Reported by a individual with unspecified qualification from United States on 2009-04-17

Patient: 51 year old female weighing 58.1 kg (127.7 pounds)

Reactions: Thinking Abnormal, Amnesia

Adverse event resulted in: disablity

Suspect drug(s):
Elavil
    Dosage: 10 mg - 50 mg 1 daily
    Indication: Migraine
    Start date: 1999-01-01
    End date: 2005-01-01

Amitriptline Hydrochloride TAB
    Dosage: 10 mg - 50 mg 1 daily
    Indication: Migraine
    End date: 2009-01-01

Possible Elavil side effects / adverse reactions in 71 year old male

Reported by a physician from Japan on 2009-04-23

Patient: 71 year old male

Reactions: Agitation, Hyperkalaemia, Pyrexia, Constipation, Dialysis, Blood Uric Acid Increased, Urinary Retention, Terminal Insomnia, Restlessness, Renal Failure Chronic, Decreased Interest, Irritability, Anxiety, Hyperphagia, Major Depression, Disturbance in Attention, Vertigo, Feeling Abnormal

Adverse event resulted in: life threatening event, hospitalization

Suspect drug(s):
Enalapril Maleate
    Dosage: (5 mg qd oral)
    Administration route: Oral
    Indication: Hypertension
    End date: 2009-02-04

Elavil
    Dosage: (10 mg qd oral), (55 mg qd oral), (100 mg qd oral)
    Administration route: Oral
    Indication: Depression
    Start date: 2008-12-25
    End date: 2009-01-04

Elavil
    Dosage: (10 mg qd oral), (55 mg qd oral), (100 mg qd oral)
    Administration route: Oral
    Indication: Depression
    Start date: 2009-01-05
    End date: 2009-01-06

Elavil
    Dosage: (10 mg qd oral), (55 mg qd oral), (100 mg qd oral)
    Administration route: Oral
    Indication: Depression
    Start date: 2009-01-07
    End date: 2009-02-04

Other drugs received by patient: Adalat; Benzalin; Cephadol; Coniel; Dogmatyl; Lendormin; Rohypnol; Urinorm; Alprazolam; Hirnamin