Amitriptyline

Amitriptyline HCl is 3-(10,11-dihydro-5H-dibenzo [a,d] cycloheptene-5-ylidene)-N,N-dimethyl-1- propanamine hydrochloride. Its empirical formula is C20H23N•HCl, and its structural formula is:

Amitriptyline HCl, a dibenzocycloheptadiene derivative, has a molecular weight of 313.87. It is a white, odorless, crystalline compound which is freely soluble in water.

Amitriptyline HCl is supplied as 10 mg, 25 mg, 50 mg, 75 mg, 100 mg or 150 mg tablets. Each tablet contains the following inactive ingredients: colloidal silicon dioxide, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate, sodium starch glycolate and titanium dioxide. The 10 mg tablets also contain FD&C blue #1 lake. The 25 mg tablets also contain D&C yellow #10 lake and FD&C blue #2 lake. The 50 mg tablets also contain synthetic black iron oxide, synthetic red iron oxide and synthetic yellow iron oxide. The 75 mg tablets also contain FD&C yellow #6 lake. The 100 mg tablets also contain D&C red #33 lake and FD&C red #40 lake. The 150 mg tablets also contain FD&C blue #2 lake and FD&C yellow #6 lake.

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of amitriptyline, there are no specific foods that you must exclude from your diet when receiving amitriptyline.

Tell your doctor if you are pregnant or plan to become pregnant.

The FDA categorizes medications based on safety for use during pregnancy. Five categories - A, B, C, D, and X, are used to classify the possible risks to an unborn baby when a medication is taken during pregnancy.

Amitriptyline falls into category C. It is not known if amitriptyline will harm your unborn baby. This medication may be given to a pregnant woman if her healthcare provider believes that its benefits to the pregnant woman outweigh any possible risks to her unborn baby.

Take amitriptyline exactly as prescribed.

This medication comes in tablet form and is taken once or more times per day, with or without food.

Your doctor may suggest taking amitriptyline at bedtime.

If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose and take your next dose at the regular time. Do not take two doses of amitriptyline at the same time.

If you take too much amitriptyline call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If amitriptyline is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

In the U.S.

• Elavil
• Vanatrip

Available Dosage Forms:

• Tablet

Therapeutic Class: Antidepressant

Pharmacologic Class: Antidepressant, Tricyclic

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For amitriptyline, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to amitriptyline or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies have not been performed on the relationship of age to the effects of amitriptyline in children below 12 years of age. Safety and efficacy have not been established.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of amitriptyline in the elderly. However, elderly patients are more likely to have age-related liver problems, which may require an adjustment in the dose for patients receiving amitriptyline.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking amitriptyline, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using amitriptyline with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Amifampridine
• Bepridil
• Bromopride
• Cisapride
• Clorgyline
• Dronedarone
• Furazolidone
• Grepafloxacin
• Iproniazid
• Isocarboxazid
• Levomethadyl
• Linezolid
• Mesoridazine
• Methylene Blue
• Metoclopramide
• Moclobemide
• Nialamide
• Pargyline
• Phenelzine
• Pimozide
• Piperaquine
• Procarbazine
• Ranolazine
• Safinamide
• Saquinavir
• Selegiline
• Sparfloxacin
• Terfenadine
• Thioridazine
• Toloxatone
• Tranylcypromine
• Ziprasidone

Using amitriptyline with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acecainide
• Aceclofenac
• Acemetacin
• Albuterol
• Alfentanil
• Alfuzosin
• Almotriptan
• Amiodarone
• Amisulpride
• Amoxapine
• Amphetamine
• Amtolmetin Guacil
• Anagrelide
• Apomorphine
• Aprindine
• Aripiprazole
• Aripiprazole Lauroxil
• Arsenic Trioxide
• Artemether
• Asenapine
• Aspirin
• Astemizole
• Atazanavir
• Azimilide
• Azithromycin
• Benzphetamine
• Bretylium
• Bromfenac
• Brompheniramine
• Bufexamac
• Buprenorphine
• Bupropion
• Buserelin
• Buspirone
• Butorphanol
• Celecoxib
• Chloral Hydrate
• Chloroquine
• Chlorpheniramine
• Chlorpromazine
• Choline Salicylate
• Ciprofloxacin
• Citalopram
• Clarithromycin
• Clomipramine
• Clonidine
• Clonixin
• Clozapine
• Cocaine
• Codeine
• Crizotinib
• Cyclobenzaprine
• Dabrafenib
• Darunavir
• Dasatinib
• Degarelix
• Delamanid
• Desipramine
• Deslorelin
• Desmopressin
• Desvenlafaxine
• Deutetrabenazine
• Dexibuprofen
• Dexketoprofen
• Dextroamphetamine
• Dextromethorphan
• Diclofenac
• Diflunisal
• Dihydrocodeine
• Dipyrone
• Disopyramide
• Dofetilide
• Dolasetron
• Domperidone
• Donepezil
• Doxepin
• Doxorubicin
• Doxorubicin Hydrochloride Liposome
• Droperidol
• Droxicam
• Efavirenz
• Eletriptan
• Eliglustat
• Enflurane
• Epinephrine
• Erythromycin
• Escitalopram
• Eslicarbazepine Acetate
• Etilefrine
• Etodolac
• Etofenamate
• Etoricoxib
• Felbinac
• Fenoprofen
• Fentanyl
• Fepradinol
• Feprazone
• Fingolimod
• Flecainide
• Floctafenine
• Fluconazole
• Flufenamic Acid
• Fluoxetine
• Flurbiprofen
• Foscarnet
• Frovatriptan
• Gatifloxacin
• Gemifloxacin
• Gonadorelin
• Goserelin
• Granisetron
• Halofantrine
• Haloperidol
• Halothane
• Histrelin
• Hydrocodone
• Hydromorphone
• Hydroxychloroquine
• Hydroxytryptophan
• Hydroxyzine
• Ibuprofen
• Ibutilide
• Iloperidone
• Imipramine
• Indomethacin
• Iobenguane I 123
• Isoflurane
• Isradipine
• Ivabradine
• Ketoconazole
• Ketoprofen
• Ketorolac
• Lacosamide
• Lapatinib
• Leuprolide
• Levalbuterol
• Levofloxacin
• Levomilnacipran
• Levorphanol
• Levothyroxine
• Lidoflazine
• Lisdexamfetamine
• Lithium
• Lopinavir
• Lorcainide
• Lorcaserin
• Lornoxicam
• Loxoprofen
• Lumefantrine
• Lumiracoxib
• Meclofenamate
• Mefenamic Acid
• Mefloquine
• Meloxicam
• Meperidine
• Methadone
• Methamphetamine
• Methoxamine
• Metronidazole
• Midodrine
• Milnacipran
• Mirtazapine
• Moricizine
• Morniflumate
• Morphine
• Morphine Sulfate Liposome
• Moxifloxacin
• Nabumetone
• Nafarelin
• Nalbuphine
• Naproxen
• Naratriptan
• Nefazodone
• Nefopam
• Nepafenac
• Niflumic Acid
• Nilotinib
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Norepinephrine
• Norfloxacin
• Nortriptyline
• Octreotide
• Ofloxacin
• Ondansetron
• Oxaprozin
• Oxilofrine
• Oxycodone
• Oxymetazoline
• Oxymorphone
• Oxyphenbutazone
• Paliperidone
• Palonosetron
• Panobinostat
• Parecoxib
• Paroxetine
• Pasireotide
• Pazopanib
• Peginterferon Alfa-2b
• Pentamidine
• Pentazocine
• Phenylbutazone
• Phenylephrine
• Piketoprofen
• Pimavanserin
• Piroxicam
• Pitolisant
• Pixantrone
• Posaconazole
• Pranoprofen
• Procainamide
• Prochlorperazine
• Proglumetacin
• Promethazine
• Propafenone
• Propoxyphene
• Propyphenazone
• Proquazone
• Protriptyline
• Quetiapine
• Quinidine
• Quinine
• Rasagiline
• Remifentanil
• Ribociclib
• Risperidone
• Rizatriptan
• Rofecoxib
• Salicylic Acid
• Salsalate
• Sematilide
• Sertindole
• Sertraline
• Sevoflurane
• Sibutramine
• Sodium Phosphate
• Sodium Phosphate, Dibasic
• Sodium Phosphate, Monobasic
• Sodium Salicylate
• Solifenacin
• Sorafenib
• Sotalol
• Spiramycin
• Sufentanil
• Sulfamethoxazole
• Sulindac
• Sulpiride
• Sultopride
• Sumatriptan
• Sunitinib
• Tacrolimus
• Tapentadol
• Tedisamil
• Telavancin
• Telithromycin
• Tenoxicam
• Tetrabenazine
• Tiaprofenic Acid
• Tiotropium
• Tolfenamic Acid
• Tolmetin
• Toremifene
• Tramadol
• Trazodone
• Trifluoperazine
• Trimethoprim
• Trimipramine
• Triptorelin
• Tryptophan
• Valdecoxib
• Vandetanib
• Vardenafil
• Vasopressin
• Vemurafenib
• Venlafaxine
• Vilanterol
• Vilazodone
• Vinflunine
• Voriconazole
• Vortioxetine
• Zolmitriptan
• Zotepine
• Zuclopenthixol

Using amitriptyline with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acenocoumarol
• Arbutamine
• Atomoxetine
• Bethanidine
• Carbamazepine
• Cimetidine
• Diazepam
• Dicumarol
• Fluvoxamine
• Fosphenytoin
• Galantamine
• Guanethidine
• Phenprocoumon
• Phenytoin
• Rifapentine
• Ritonavir
• S-Adenosylmethionine
• St John's Wort
• Warfarin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using amitriptyline with any of the following is usually not recommended, but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use amitriptyline, or give you special instructions about the use of food, alcohol, or tobacco.

• Tobacco

Using amitriptyline with any of the following may cause an increased risk of certain side effects but may be unavoidable in some cases. If used together, your doctor may change the dose or how often you use amitriptyline, or give you special instructions about the use of food, alcohol, or tobacco.

• Ethanol

Other Medical Problems

The presence of other medical problems may affect the use of amitriptyline. Make sure you tell your doctor if you have any other medical problems, especially:

• Bipolar disorder (mood disorder with alternating episodes of mania and depression), or risk of or
• Heart attack, recent—Should not be used in patients with these conditions.

• Diabetes or
• Glaucoma or
• Heart disease or
• Overactive thyroid or
• Schizophrenia or
• Seizures, history of or
• Urinary retention (trouble urinating), history of—Use with caution. May make these conditions worse.

• Liver disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Amitriptyline hydrochloride is contraindicated in patients who have shown prior hypersensitivity to it.

It should not be given concomitantly with monoamine oxidase inhibitors. Hyperpyretic crises, severe convulsions, and deaths have occurred in patients receiving tricyclic antidepressant and monoamine oxidase inhibiting drugs simultaneously. When it is desired to replace a monoamine oxidase inhibitor with Amitriptyline hydrochloride, a minimum of 14 days should be allowed to elapse after the former is discontinued. Amitriptyline hydrochloride should then be initiated cautiously with gradual increase in dosage until optimum response is achieved.

Amitriptyline hydrochloride should not be given with cisapride due to the potential for increased QT interval and increased risk for arrhythmia.

This drug is not recommended for use during the acute recovery phase following myocardial infarction.

Oral Dosage

Dosage should be initiated at a low level and increased gradually, noting carefully the clinical response and any evidence of intolerance.

Initial Dosage for Adults

For outpatients 75 mg of Amitriptyline HCl a day in divided doses is usually satisfactory. If necessary, this may be increased to a total of 150 mg per day. Increases are made preferably in the late afternoon and/or bedtime doses. A sedative effect may be apparent before the antidepressant effect is noted, but an adequate therapeutic effect may take as long as 30 days to develop.

An alternate method of initiating therapy in outpatients is to begin with 50 to 100 mg Amitriptyline HCl at bedtime. This may be increased by 25 or 50 mg as necessary in the bedtime dose to a total of 150 mg per day.

Hospitalized patients may require 100 mg a day initially. This can be increased gradually to 200 mg a day if necessary. A small number of hospitalized patients may need as much as 300 mg a day.

Adolescent and Elderly Patients

In general, lower dosages are recommended for these patients. Ten mg 3 times a day with 20 mg at bedtime may be satisfactory in adolescent and elderly patients who do not tolerate higher dosages.

Maintenance

The usual maintenance dosage of Amitriptyline HCl is 50 to 100 mg per day. In some patients 40 mg per day is sufficient. For maintenance therapy the total daily dosage may be given in a single dose preferably at bedtime. When satisfactory improvement has been reached, dosage should be reduced to the lowest amount that will maintain relief of symptoms. It is appropriate to continue maintenance therapy 3 months or longer, to lessen the possibility of relapse.

Usage in Pediatric Patients

In view of the lack of experience with the use of this drug in pediatric patients, it is not recommended at the present time for patients under 12 years of age.

Plasma Levels

Because of the wide variation in the absorption and distribution of tricyclic antidepressants in body fluids, it is difficult to directly correlate plasma levels and therapeutic effect. However, determination of plasma levels may be useful in identifying patients who appear to have toxic effects and may have excessively high levels, or those in whom lack of absorption or noncompliance is suspected. Because of increased intestinal transit time and decreased hepatic metabolism in elderly patients, plasma levels are generally higher for a given oral dose of Amitriptyline hydrochloride than in younger patients. Elderly patients should be monitored carefully and quantitative serum levels obtained as clinically appropriate. Adjustments in dosage should be made according to the patient's clinical response and not on the basis of plasma levels.2

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral, as hydrochloride:

Elavil: 25 mg [contains fd&c blue #2 aluminum lake, fd&c yellow #10 aluminum lake]

Generic: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg

• Elavil

Hypersensitivity to amitriptyline or any component of the formulation; coadministration with or within 14 days of MAOIs; coadministration with cisapride; acute recovery phase following myocardial infarction

Documentation of allergenic cross-reactivity for tricyclic antidepressants is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Depression: Oral: Usual dosage (recommended by the manufacturer): 10 mg 3 times daily and 20 mg at bedtime. In general, lower doses are recommended for elderly patients

Postherpetic neuralgia (off-label use): Oral: Initial: 10 to 12.5 mg, given once daily at bedtime or divided into twice daily doses. Increase dose based on response and tolerability in increments of 10 to 25 mg every 2 to 7 days up to 200 mg/day; one study reported no benefit with doses greater than 100 mg daily (Graff-Radford 2000; Max 1988; Rowbotham 2005; Watson 1982; Watson 1992; Watson 1998).

Discontinuation of therapy: Refer to adult dosing.

MAO inhibitor recommendations: Refer to adult dosing.

Chronic pain management (off-label use): Oral: Initial: 0.1 mg/kg/day at bedtime, may advance as tolerated over 2-3 weeks to 0.5-2 mg/kg/day at bedtime (APS [Miaskowski, 2008]; Freidrichsdorf, 2007; Kliegman, 2011)

Depressive disorders: Adolescents: Usual dosage (recommended by the manufacturer): 10 mg three times daily and 20 mg at bedtime. In general, lower doses are recommended for adolescent patients. Note: Controlled clinical trials have not shown tricyclic antidepressants to be superior to placebo for the treatment of depression in children and adolescents; not recommended as first-line medication; may be beneficial for patient with comorbid conditions (Birmaher, 2007; Dopheide, 2006; Wagner, 2005).

Migraine prophylaxis (off-label use): Oral: Initial: 0.25 mg/kg/day, given at bedtime; increase dose by 0.25 mg/kg/day every 2 weeks to 1 mg/kg/day. Reported dosing range: 0.2-1.7 mg/kg/day (Hershey, 2000).

Discontinuation of therapy: Refer to adult dosing.

MAO inhibitor recommendations: Refer to adult dosing.

Oral: Administer higher doses preferably at late afternoon or as bedtime doses to minimize daytime sedation.

Abiraterone Acetate: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of abiraterone with CYP2D6 substrates that have a narrow therapeutic index whenever possible. When concurrent use is not avoidable, monitor patients closely for signs/symptoms of toxicity. Consider therapy modification

AbobotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of AbobotulinumtoxinA. Monitor therapy

Acetylcholinesterase Inhibitors: Anticholinergic Agents may diminish the therapeutic effect of Acetylcholinesterase Inhibitors. Acetylcholinesterase Inhibitors may diminish the therapeutic effect of Anticholinergic Agents. Monitor therapy

Aclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Alcohol (Ethyl): CNS Depressants may enhance the CNS depressant effect of Alcohol (Ethyl). Monitor therapy

Alpha-/Beta-Agonists (Direct-Acting): Tricyclic Antidepressants may enhance the vasopressor effect of Alpha-/Beta-Agonists (Direct-Acting). Management: Avoid, if possible, the use of direct-acting alpha-/beta-agonists in patients receiving tricyclic antidepressants. If combined, monitor for evidence of increased pressor effects and consider reductions in initial dosages of the alpha-/beta-agonist. Exceptions: Dipivefrin. Consider therapy modification

Alpha1-Agonists: Tricyclic Antidepressants may enhance the vasopressor effect of Alpha1-Agonists. Tricyclic Antidepressants may diminish the vasopressor effect of Alpha1-Agonists. Monitor therapy

Alpha2-Agonists: Tricyclic Antidepressants may diminish the antihypertensive effect of Alpha2-Agonists. Exceptions: Apraclonidine; Brimonidine (Ophthalmic). Consider therapy modification

Alpha2-Agonists (Ophthalmic): Tricyclic Antidepressants may diminish the therapeutic effect of Alpha2-Agonists (Ophthalmic). Monitor therapy

Altretamine: May enhance the orthostatic hypotensive effect of Tricyclic Antidepressants. Monitor therapy

Amantadine: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy

Amifampridine: May diminish the anticholinergic effect of Anticholinergic Agents. Anticholinergic Agents may diminish the therapeutic effect of Amifampridine. Monitor therapy

Amifampridine: May enhance the adverse/toxic effect of Tricyclic Antidepressants. Specifically, both drugs have the potential to decrease the seizure threshold, possibly increasing the risk for seizures. Tricyclic Antidepressants may diminish the therapeutic effect of Amifampridine. Monitor therapy

Amphetamines: Tricyclic Antidepressants may enhance the stimulatory effect of Amphetamines. Tricyclic Antidepressants may also potentiate the cardiovascular effects of Amphetamines. Monitor therapy

Analgesics (Opioid): CNS Depressants may enhance the CNS depressant effect of Analgesics (Opioid). Management: Avoid concomitant use of opioid analgesics and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Anticholinergic Agents: May enhance the adverse/toxic effect of other Anticholinergic Agents. Monitor therapy

Antiemetics (5HT3 Antagonists): May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Antipsychotic Agents: Serotonin Modulators may enhance the adverse/toxic effect of Antipsychotic Agents. Specifically, serotonin modulators may enhance dopamine blockade, possibly increasing the risk for neuroleptic malignant syndrome. Antipsychotic Agents may enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Aspirin: Antidepressants (Tricyclic, Tertiary Amine) may enhance the antiplatelet effect of Aspirin. Monitor therapy

Asunaprevir: May increase the serum concentration of CYP2D6 Substrates. Consider therapy modification

Azelastine (Nasal): CNS Depressants may enhance the CNS depressant effect of Azelastine (Nasal). Avoid combination

Barbiturates: May increase the metabolism of Tricyclic Antidepressants. Consider therapy modification

Beta2-Agonists: Tricyclic Antidepressants may enhance the adverse/toxic effect of Beta2-Agonists. Monitor therapy

Blonanserin: CNS Depressants may enhance the CNS depressant effect of Blonanserin. Consider therapy modification

Brimonidine (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Buprenorphine: CNS Depressants may enhance the CNS depressant effect of Buprenorphine. Management: Consider reduced doses of other CNS depressants, and avoiding such drugs in patients at high risk of buprenorphine overuse/self-injection. Initiate buprenorphine patches (Butrans brand) at 5 mcg/hr in adults when used with other CNS depressants. Consider therapy modification

BuPROPion: May decrease the metabolism of Tricyclic Antidepressants. Management: Seek alternatives when possible. Monitor patients receiving these combinations closely for increased serum concentrations (when testing is available) and toxic effects of the tricyclic antidepressant. Consider therapy modification

Cannabis: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

CarBAMazepine: May decrease the serum concentration of Tricyclic Antidepressants. Monitor therapy

Chloral Betaine: May enhance the adverse/toxic effect of Anticholinergic Agents. Monitor therapy

Chlormethiazole: May enhance the CNS depressant effect of CNS Depressants. Management: Monitor closely for evidence of excessive CNS depression. The chlormethiazole labeling states that an appropriately reduced dose should be used if such a combination must be used. Consider therapy modification

Chlorphenesin Carbamate: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Cimetidine: May decrease the metabolism of Tricyclic Antidepressants. Monitor therapy

Cimetropium: Anticholinergic Agents may enhance the anticholinergic effect of Cimetropium. Avoid combination

Cinacalcet: May increase the serum concentration of Tricyclic Antidepressants. Management: Seek alternatives when possible. If these combinations are used, monitor closely for increased effects/toxicity and/or elevated serum concentrations (when testing is available) of the tricyclic antidepressant. Consider therapy modification

Cisapride: Amitriptyline may enhance the arrhythmogenic effect of Cisapride. Avoid combination

Citalopram: Tricyclic Antidepressants may enhance the adverse/toxic effect of Citalopram. Tricyclic Antidepressants may increase the serum concentration of Citalopram. Citalopram may increase the serum concentration of Tricyclic Antidepressants. Management: Consider alternatives to this combination when possible. Monitor for adverse effects of tricyclic antidepressants (TCAs), including serotonin syndrome and QT-interval prolongation, when a TCA is being used in combination with citalopram. Consider therapy modification

CNS Depressants: May enhance the adverse/toxic effect of other CNS Depressants. Monitor therapy

Cobicistat: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy

CYP2D6 Inhibitors (Moderate): May decrease the metabolism of CYP2D6 Substrates. Monitor therapy

CYP2D6 Inhibitors (Strong): May decrease the metabolism of CYP2D6 Substrates. Consider therapy modification

Dapoxetine: May enhance the adverse/toxic effect of Serotonin Modulators. Avoid combination

Darunavir: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy

Desmopressin: Tricyclic Antidepressants may enhance the adverse/toxic effect of Desmopressin. Monitor therapy

Dexmethylphenidate: May enhance the adverse/toxic effect of Tricyclic Antidepressants. Dexmethylphenidate may increase the serum concentration of Tricyclic Antidepressants. Monitor therapy

Dimethindene (Topical): May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Doxylamine: May enhance the CNS depressant effect of CNS Depressants. Management: The manufacturer of Diclegis (doxylamine/pyridoxine), intended for use in pregnancy, specifically states that use with other CNS depressants is not recommended. Monitor therapy

Dronabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Dronedarone: Tricyclic Antidepressants may enhance the arrhythmogenic effect of Dronedarone. Avoid combination

Droperidol: May enhance the CNS depressant effect of CNS Depressants. Management: Consider dose reductions of droperidol or of other CNS agents (e.g., opioids, barbiturates) with concomitant use. Consider therapy modification

DULoxetine: May enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome. DULoxetine may decrease the metabolism of Tricyclic Antidepressants. Monitor therapy

Eluxadoline: Anticholinergic Agents may enhance the constipating effect of Eluxadoline. Avoid combination

Escitalopram: Tricyclic Antidepressants may enhance the adverse/toxic effect of Escitalopram. Escitalopram may increase the serum concentration of Tricyclic Antidepressants. Management: Consider alternatives to this combination when possible. Monitor for adverse effects of tricyclic antidepressants (TCAs), including serotonin syndrome and QT-interval prolongation, when a TCA is being used in combination with escitalopram. Consider therapy modification

Fluconazole: Amitriptyline may enhance the QTc-prolonging effect of Fluconazole. Fluconazole may increase the serum concentration of Amitriptyline. Monitor therapy

Flunitrazepam: CNS Depressants may enhance the CNS depressant effect of Flunitrazepam. Consider therapy modification

FLUoxetine: May enhance the adverse/toxic effect of Tricyclic Antidepressants. FLUoxetine may increase the serum concentration of Tricyclic Antidepressants. Management: Consider alternatives to this combination when possible. Monitor for adverse effects of tricyclic antidepressants (TCAs), including serotonin syndrome and QT-interval prolongation, when a TCA is being used in combination with fluoxetine. Consider therapy modification

FluvoxaMINE: May enhance the adverse/toxic effect of Tricyclic Antidepressants. FluvoxaMINE may increase the serum concentration of Tricyclic Antidepressants. Management: Consider alternatives to this combination when possible. Monitor for adverse effects of tricyclic antidepressants (TCAs), including serotonin syndrome and QT-interval prolongation, when a TCA is being used in combination with fluvoxamine. Consider therapy modification

Gastrointestinal Agents (Prokinetic): Anticholinergic Agents may diminish the therapeutic effect of Gastrointestinal Agents (Prokinetic). Monitor therapy

Glucagon: Anticholinergic Agents may enhance the adverse/toxic effect of Glucagon. Specifically, the risk of gastrointestinal adverse effects may be increased. Avoid combination

Glycopyrrolate (Oral Inhalation): Anticholinergic Agents may enhance the anticholinergic effect of Glycopyrrolate (Oral Inhalation). Avoid combination

Guanethidine: Tricyclic Antidepressants may diminish the therapeutic effect of Guanethidine. Monitor therapy

Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification

HYDROcodone: CNS Depressants may enhance the CNS depressant effect of HYDROcodone. Management: Avoid concomitant use of hydrocodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

HydrOXYzine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Imatinib: May increase the serum concentration of CYP2D6 Substrates. Monitor therapy

Iobenguane I 123: Tricyclic Antidepressants may diminish the therapeutic effect of Iobenguane I 123. Avoid combination

Iohexol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iohexol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iohexol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification

Iomeprol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iomeprol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iomeprol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification

Iopamidol: Agents With Seizure Threshold Lowering Potential may enhance the adverse/toxic effect of Iopamidol. Specifically, the risk for seizures may be increased. Management: Discontinue agents that may lower the seizure threshold 48 hours prior to intrathecal use of iopamidol. Wait at least 24 hours after the procedure to resume such agents. In nonelective procedures, consider use of prophylactic anticonvulsants. Consider therapy modification

Ipratropium (Oral Inhalation): May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Itopride: Anticholinergic Agents may diminish the therapeutic effect of Itopride. Monitor therapy

Kava Kava: May enhance the adverse/toxic effect of CNS Depressants. Monitor therapy

Levosulpiride: Anticholinergic Agents may diminish the therapeutic effect of Levosulpiride. Avoid combination

Linezolid: May enhance the serotonergic effect of Tricyclic Antidepressants. This could result in serotonin syndrome. Avoid combination

Lithium: May enhance the neurotoxic effect of Tricyclic Antidepressants. Management: This combination should be undertaken with great caution. When combined treatment is clinically indicated, monitor closely for signs of serotonin toxicity/serotonin syndrome. Consider therapy modification

Magnesium Sulfate: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

MAO Inhibitors: May enhance the serotonergic effect of Tricyclic Antidepressants. This may cause serotonin syndrome. While methylene blue and linezolid are expected to interact via this mechanism, management recommendations differ from other monoamine oxidase inhibitors. Refer to monographs specific to those agents for details. Exceptions: Linezolid; Methylene Blue; Tedizolid. Avoid combination

Metaxalone: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Methotrimeprazine: May enhance the CNS depressant effect of CNS Depressants. CNS Depressants may enhance the CNS depressant effect of Methotrimeprazine. Management: Reduce adult dose of CNS depressant agents by 50% with initiation of concomitant methotrimeprazine therapy. Further CNS depressant dosage adjustments should be initiated only after clinically effective methotrimeprazine dose is established. Consider therapy modification

Methylene Blue: Tricyclic Antidepressants may enhance the serotonergic effect of Methylene Blue. This could result in serotonin syndrome. Avoid combination

Methylene Blue: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Avoid combination

Methylphenidate: May enhance the adverse/toxic effect of Tricyclic Antidepressants. Methylphenidate may increase the serum concentration of Tricyclic Antidepressants. Monitor therapy

Methylphenidate: May enhance the adverse/toxic effect of Serotonin Modulators. Specifically, the risk of serotonin syndrome or serotonin toxicity may be increased. Monitor therapy

Metoclopramide: May enhance the adverse/toxic effect of Tricyclic Antidepressants. Management: Seek alternatives to this combination when possible. Monitor patients receiving metoclopramide with tricyclic antidepressants for signs of extrapyramidal symptoms, neuroleptic malignant syndrome, and serotonin syndrome. Consider therapy modification

MetyroSINE: CNS Depressants may enhance the sedative effect of MetyroSINE. Monitor therapy

MetyroSINE: May enhance the adverse/toxic effect of Tricyclic Antidepressants. Monitor therapy

Mianserin: May enhance the anticholinergic effect of Anticholinergic Agents. Monitor therapy

MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification

Minocycline: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Mirabegron: Anticholinergic Agents may enhance the adverse/toxic effect of Mirabegron. Monitor therapy

Mirtazapine: CNS Depressants may enhance the CNS depressant effect of Mirtazapine. Monitor therapy

Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy

Nabilone: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Nicorandil: Tricyclic Antidepressants may enhance the hypotensive effect of Nicorandil. Monitor therapy

Nitroglycerin: Anticholinergic Agents may decrease the absorption of Nitroglycerin. Specifically, anticholinergic agents may decrease the dissolution of sublingual nitroglycerin tablets, possibly impairing or slowing nitroglycerin absorption. Monitor therapy

NSAID (COX-2 Inhibitor): Antidepressants (Tricyclic, Tertiary Amine) may enhance the antiplatelet effect of NSAID (COX-2 Inhibitor). Monitor therapy

NSAID (Nonselective): Antidepressants (Tricyclic, Tertiary Amine) may enhance the antiplatelet effect of NSAID (Nonselective). Monitor therapy

OnabotulinumtoxinA: Anticholinergic Agents may enhance the anticholinergic effect of OnabotulinumtoxinA. Monitor therapy

Orphenadrine: CNS Depressants may enhance the CNS depressant effect of Orphenadrine. Avoid combination

Oxatomide: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Oxomemazine: May enhance the CNS depressant effect of CNS Depressants. Avoid combination

OxyCODONE: CNS Depressants may enhance the CNS depressant effect of OxyCODONE. Management: Avoid concomitant use of oxycodone and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Panobinostat: May increase the serum concentration of CYP2D6 Substrates. Management: Avoid concurrent use of sensitive CYP2D6 substrates when possible, particularly those substrates with a narrow therapeutic index. Consider therapy modification

Paraldehyde: CNS Depressants may enhance the CNS depressant effect of Paraldehyde. Avoid combination

PARoxetine: May enhance the adverse/toxic effect of Tricyclic Antidepressants. PARoxetine may increase the serum concentration of Tricyclic Antidepressants. Management: Consider alternatives to this combination when possible. Monitor for adverse effects of tricyclic antidepressants (TCAs), including serotonin syndrome and QT-interval prolongation, when a TCA is being used in combination with paroxetine. Consider therapy modification

Peginterferon Alfa-2b: May decrease the serum concentration of CYP2D6 Substrates. Peginterferon Alfa-2b may increase the serum concentration of CYP2D6 Substrates. Monitor therapy

Perampanel: May enhance the CNS depressant effect of CNS Depressants. Management: Patients taking perampanel with any other drug that has CNS depressant activities should avoid complex and high-risk activities, particularly those such as driving that require alertness and coordination, until they have experience using the combination. Consider therapy modification

Perhexiline: CYP2D6 Substrates may increase the serum concentration of Perhexiline. Perhexiline may increase the serum concentration of CYP2D6 Substrates. Monitor therapy

Piribedil: CNS Depressants may enhance the CNS depressant effect of Piribedil. Monitor therapy

Potassium Chloride: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Chloride. Management: Patients on drugs with substantial anticholinergic effects should avoid using any solid oral dosage form of potassium chloride. Avoid combination

Potassium Citrate: Anticholinergic Agents may enhance the ulcerogenic effect of Potassium Citrate. Avoid combination

Pramipexole: CNS Depressants may enhance the sedative effect of Pramipexole. Monitor therapy

Pramlintide: May enhance the anticholinergic effect of Anticholinergic Agents. These effects are specific to the GI tract. Consider therapy modification

Protease Inhibitors: May increase the serum concentration of Tricyclic Antidepressants. Monitor therapy

QuiNIDine: Tricyclic Antidepressants may enhance the QTc-prolonging effect of QuiNIDine. QuiNIDine may increase the serum concentration of Tricyclic Antidepressants. Consider therapy modification

Ramosetron: Anticholinergic Agents may enhance the constipating effect of Ramosetron. Monitor therapy

RimabotulinumtoxinB: Anticholinergic Agents may enhance the anticholinergic effect of RimabotulinumtoxinB. Monitor therapy

ROPINIRole: CNS Depressants may enhance the sedative effect of ROPINIRole. Monitor therapy

Rotigotine: CNS Depressants may enhance the sedative effect of Rotigotine. Monitor therapy

Rufinamide: May enhance the adverse/toxic effect of CNS Depressants. Specifically, sleepiness and dizziness may be enhanced. Monitor therapy

Secretin: Anticholinergic Agents may diminish the therapeutic effect of Secretin. Management: Avoid concomitant use of anticholinergic agents and secretin. Discontinue anticholinergic agents at least 5 half-lives prior to administration of secretin. Consider therapy modification

Selective Serotonin Reuptake Inhibitors: CNS Depressants may enhance the adverse/toxic effect of Selective Serotonin Reuptake Inhibitors. Specifically, the risk of psychomotor impairment may be enhanced. Monitor therapy

Serotonin Modulators: May enhance the adverse/toxic effect of other Serotonin Modulators. The development of serotonin syndrome may occur. Exceptions: Nicergoline; Tedizolid. Monitor therapy

Sertraline: May enhance the adverse/toxic effect of Tricyclic Antidepressants. Sertraline may increase the serum concentration of Tricyclic Antidepressants. Management: Consider alternatives to this combination when possible. Monitor for adverse effects of tricyclic antidepressants (TCAs), including serotonin syndrome and QT-interval prolongation, when a TCA is being used in combination with sertraline. Consider therapy modification

Sodium Oxybate: May enhance the CNS depressant effect of CNS Depressants. Management: Consider alternatives to combined use. When combined use is needed, consider minimizing doses of one or more drugs. Use of sodium oxybate with alcohol or sedative hypnotics is contraindicated. Consider therapy modification

Sodium Phosphates: Tricyclic Antidepressants may enhance the adverse/toxic effect of Sodium Phosphates. Specifically, the risk of seizure and/or loss of consciousness may be increased in patients with significant sodium phosphate induced fluid/electrolyte abnormalities. Monitor therapy

St John's Wort: May increase the metabolism of Tricyclic Antidepressants. The risk of serotonin syndrome may theoretically be increased. Consider therapy modification

Sulfonylureas: Cyclic Antidepressants may enhance the hypoglycemic effect of Sulfonylureas. Monitor therapy

Suvorexant: CNS Depressants may enhance the CNS depressant effect of Suvorexant. Management: Dose reduction of suvorexant and/or any other CNS depressant may be necessary. Use of suvorexant with alcohol is not recommended, and the use of suvorexant with any other drug to treat insomnia is not recommended. Consider therapy modification

Tapentadol: May enhance the CNS depressant effect of CNS Depressants. Management: Avoid concomitant use of tapentadol and benzodiazepines or other CNS depressants when possible. These agents should only be combined if alternative treatment options are inadequate. If combined, limit the dosages and duration of each drug. Consider therapy modification

Tedizolid: May enhance the serotonergic effect of Serotonin Modulators. This could result in serotonin syndrome. Monitor therapy

Terbinafine (Systemic): May increase the serum concentration of Amitriptyline. Management: Monitor for increased effects/toxicity of amitriptyline during concomitant administration with terbinafine. Reduced dosages of amitriptyline may be needed. Consider therapy modification

Tetrahydrocannabinol: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Thalidomide: CNS Depressants may enhance the CNS depressant effect of Thalidomide. Avoid combination

Thiazide and Thiazide-Like Diuretics: Anticholinergic Agents may increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Monitor therapy

Thyroid Products: May enhance the arrhythmogenic effect of Tricyclic Antidepressants. Thyroid Products may enhance the stimulatory effect of Tricyclic Antidepressants. Monitor therapy

Tiotropium: Anticholinergic Agents may enhance the anticholinergic effect of Tiotropium. Avoid combination

Topiramate: May enhance the CNS depressant effect of Amitriptyline. Topiramate may increase serum concentrations of the active metabolite(s) of Amitriptyline. Topiramate may increase the serum concentration of Amitriptyline. Monitor therapy

Trimeprazine: May enhance the CNS depressant effect of CNS Depressants. Monitor therapy

Umeclidinium: May enhance the anticholinergic effect of Anticholinergic Agents. Avoid combination

Valproate Products: May increase the serum concentration of Tricyclic Antidepressants. Monitor therapy

Vitamin K Antagonists (eg, warfarin): Tricyclic Antidepressants may enhance the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Yohimbine: Tricyclic Antidepressants may increase the serum concentration of Yohimbine. Monitor therapy

Zolpidem: CNS Depressants may enhance the CNS depressant effect of Zolpidem. Management: Reduce the Intermezzo brand sublingual zolpidem adult dose to 1.75 mg for men who are also receiving other CNS depressants. No such dose change is recommended for women. Avoid use with other CNS depressants at bedtime; avoid use with alcohol. Consider therapy modification

Applies to amitriptyline: oral tablet

Along with its needed effects, amitriptyline may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur while taking amitriptyline:

• Abdominal or stomach pain
• agitation
• black, tarry stools
• bleeding gums
• blood in urine or stools
• blurred vision
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• change in consciousness
• changes in patterns and rhythms of speech
• chest pain or discomfort
• chills
• cold sweats
• coma
• confusion
• confusion about identity, place, and time
• continuing ringing, buzzing, or other unexplained noise in ears
• convulsions
• cool, pale skin
• cough or hoarseness
• dark urine
• decrease in frequency of urination
• decrease in urine volume
• decreased urine output
• difficulty in breathing
• difficulty in passing urine (dribbling)
• difficulty in speaking
• disturbance of accommodation
• disturbed concentration
• dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly
• double vision
• drooling
• dry mouth
• excitement
• fainting
• false beliefs that cannot be changed by facts
• fast, slow, or irregular heartbeat
• fear or nervousness
• fever with or without chills
• flushed, dry skin
• fruit-like breath odor
• general feeling of tiredness or weakness
• headache
• hearing loss
• high fever
• high or low blood pressure
• hostility
• inability to move arms, legs, or facial muscles
• inability to speak
• increased hunger
• increased need to urinate
• increased ocular pressure
• increased sweating
• increased thirst
• increased urination
• irritability
• lack of coordination
• lethargy
• light-colored stools
• lip smacking or puckering
• loss of appetite
• loss of balance control
• loss of bladder control
• loss of consciousness
• lower back or side pain
• mental depression or anxiety
• muscle spasm or jerking of all extremities
• muscle tightness
• muscle trembling, jerking, or stiffness
• muscle twitching
• nausea and vomiting
• nightmares or unusually vivid dreams
• overactive reflexes
• painful or difficult urination
• passing urine more often
• pinpoint red spots on skin
• poor coordination
• pounding in the ears
• puffing of cheeks
• rapid or worm-like movements of tongue
• rapid weight gain
• restlessness
• seeing, hearing, or feeling things that are not there
• seizures
• severe muscle stiffness
• shakiness and unsteady walk
• shivering
• shortness of breath
• shuffling walk
• sleeplessness
• slow speech
• slurred speech
• sore throat
• sores, ulcers, or white spots on lips or in mouth
• stiffness of limbs
• stupor
• sudden loss of consciousness
• sweating
• swelling of face, ankles, or hands
• swelling or puffiness of face
• swollen glands
• talking or acting with excitement you cannot control
• trouble in speaking
• trouble sleeping
• troubled breathing
• twisting movements of body pain or discomfort in arms, jaw, back, or neck
• unable to sleep
• uncontrolled chewing movements
• uncontrolled movements, especially of arms, face, neck, back, and legs
• unexplained weight loss
• unpleasant breath odor
• unsteadiness, trembling, or other problems with muscle control or coordination
• unusual bleeding or bruising
• unusual tiredness or weakness
• unusually pale skin
• upper right abdominal pain
• vomiting of blood
• weakness in arms, hands, legs, or feet
• weight gain or loss
• yellow eyes and skin

Get emergency help immediately if any of the following symptoms of overdose occur while taking amitriptyline:

• Clumsiness
• drowsiness
• low body temperature
• muscle aches
• muscle weakness
• sleepiness
• tiredness
• weak or feeble pulse

Some side effects of amitriptyline may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Bigger, dilated, or enlarged pupils (black part of eye)
• black tongue
• bloating
• breast enlargement in females
• constipation
• decreased interest in sexual intercourse
• diarrhea
• hair loss, thinning of hair
• hives or welts
• inability to have or keep an erection
• increased in sexual ability, desire, drive, or performance
• increased interest in sexual intercourse
• increased sensitivity of eyes to light
• loss in sexual ability, desire, drive, or performance
• loss of sense of taste
• redness or other discoloration of skin
• severe sunburn
• skin rash
• swelling of testicles
• swelling of the breasts or breast soreness in males
• swelling of the parotid glands
• swelling or inflammation of the mouth
• unexpected or excess milk flow from breasts

-When this drug is coadministered with anticholinergic drugs or sympathomimetic drugs, including epinephrine combined with local anesthetics, dose adjustments are required.

• Amitriptyline is used to treat depression and is thought to work by increasing levels of serotonin and/or norepinephrine in the brain.
• Amitriptyline belongs to a group of medicines known as tricyclic antidepressants.

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• Dry mouth, headache, constipation, diarrhea, and sexual dysfunction.
• May increase the risk of suicidal thoughts or behavior in young adults (similar to other antidepressants).
• May cause drowsiness and affect a person's ability to drive or operate machinery; some people may develop tolerance to this effect.
• Risk of heart-related effects, muscle rigidity, tremor, seizures, increased sensitivity to light, weight gain or loss, hair loss, skin rash, and edema.
• Interaction or overdosage may cause serotonin syndrome (symptoms include agitation, hallucinations, fast heart rate, dizziness, muscle tremor, nausea, vomiting, diarrhea).
• May cause withdrawal symptoms with abrupt discontinuation (symptoms include nausea, headache, sleep disturbance, and generalized tiredness).These are not indicative of addiction. Taper dosage off slowly under medical supervision.
• May interact with a number of other drugs including those that are metabolized by hepatic enzymes CYP2D6, other drugs that cause sedation or have anticholinergic side effects (such as dry mouth, urinary retention, blurred vision, constipation). Extremely high fever (hyperpyrexia) has been reported when amitriptyline has been administered with antipsychotics or anticholinergic drugs.

Notes: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. For a complete list of all side effects, click here.

Summary of Use during Lactation

Milk levels of amitriptyline and its metabolites are low. Immediate side effects have not been reported and a limited amount of follow-up has found no adverse effects on infant growth and development. Amitriptyline use during breastfeeding would usually not be expected to cause any adverse effects in breastfed infants, especially if the infant is older than 2 months. However, rare sedation has been reported in a neonate. Other agents with fewer active metabolites may be preferred when large doses are required or while nursing a newborn or preterm infant.

Drug Levels

Maternal Levels Amitriptyline is metabolized to nortriptyline which has antidepressant activity equal to amitriptyline's.[1]

A mother who had been taking amitriptyline 100 mg daily for 6 weeks postpartum had breastmilk levels of amitriptyline and nortriptyline of 151 and 59 mcg/L, respectively, 16 hours after a dose. Eleven days later, breastmilk levels of amitriptyline and nortriptyline were 135 and 52 mcg/L, respectively, 14 hours after the dose.[2] The amounts in milk represent an infant dosage of about 1.8% of the maternal weight-adjusted dosage.

Amitriptyline and nortriptyline were measured in breastmilk in a mother who was taking amitriptyline 75 mg daily. Her milk amitriptyline levels were 104 and 72 mcg/L and her nortriptyline levels were 75 and 63 mcg/L at 2 and 10 weeks, respectively, after starting treatment (time after dose not specified). After 19 weeks of therapy, an amitriptyline dose of 25 mg daily produced milk amitriptyline levels of 30 mcg/L; nortriptyline levels were not detectable (<30 mcg/L). The authors estimated that this infant would receive 1% of the maternal weight-adjusted dosage.[3]

Another mother who was taking amitriptyline 175 mg daily had amitriptyline and nortriptyline milk levels of 13 and 15 mcg/L each on the morning and evening of the first day of therapy. On days 2 to 26 of therapy, milk amitriptyline ranged from 23 to 38 mcg/L. On day 26 milk nortriptyline was about 64 mcg/L. E-10-hydroxynortriptyline was found in milk in levels averaging 89 mcg/L over this 26-day time period.[4]

A 2-week postpartum mother of a preterm infant had been taking amitriptyline 100 mg daily for 4 days when milk was analyzed. Milk amitriptyline levels were highest at 1.5 and 6 hours after the dose at 103 and 100 mcg/L, respectively. They fell to 29 mcg/L 24 hours after the dose. Milk nortriptyline levels were highest at 18 hours after the dose at 58 mcg/L.[5] Using the peak milk level data from this study, an exclusively breastfed infant would receive an estimated maximum of 0.9% of the maternal weight-adjusted dosage.

Two mothers who were taking amitriptyline had milk samples taken 12 to 15 hours after their daily dose. The mother taking 100 mg daily had a foremilk level of 30 mcg/L and a hindmilk level of 113 mcg/L. The mother taking 175 mg daily had a hindmilk level of 197 mcg/L.[6] Using the hindmilk data from this study, an exclusively breastfed infant would receive an estimated maximum of 1% of the maternal weight-adjusted dosage.

Infant Levels. A mother who had been taking amitriptyline 150 mg daily for 3 weeks was nursing her infant (extent not stated). Amitriptyline and nortriptyline were undetectable (<28 mcg/L) in the infant's serum.[7]

A mother who had been taking amitriptyline 100 mg daily for 7.5 weeks postpartum was nursing her infant. Amitriptyline and nortriptyline were undetectable (<10 mcg/L) 14 hours after a dose.[2]

A 3-week-old breastfed had undetectable serum amitriptyline (<5 mcg/L) and nortriptyline (<15 mcg/L) during maternal amitriptyline use of 75 mg daily.[3]

After 26 days of breastfeeding (4 of 6 daily feedings; 500 to 600 mL daily) during maternal use of amitriptyline 175 mg daily, amitriptyline and its metabolites were undetectable in the serum of one infant.[4]

One infant whose mother was taking amitriptyline 100 mg daily, had a plasma level of 7.5 mcg/L at an unspecified time after the maternal dosage.[8]

Effects in Breastfed Infants

At least 23 infants have been reported to have been exposed to amitriptyline in breastmilk with no reports of adverse reactions with maternal dosages from 75 to 175 mg daily.[3][6][9][10]

Follow-up for 1 to 3 years in a group of 20 breastfed infants whose mothers were taking a tricyclic antidepressant found no adverse effects on growth and development. One of the mothers whose infant was followed up at 18 months of age was taking amitriptyline 150 mg daily.[9] Two small controlled studies indicate that other tricyclic antidepressants have no adverse effect on infant development.[8][11] In one of the studies, 2 mothers were taking amitriptyine 100 and 175 mg daily. One of the infants tested in the low normal range from birth and on repeat testing.[8]

In another study, 25 infants whose mothers took a tricyclic antidepressant during pregnancy and lactation were tested formally between 15 to 71 months and found to have normal growth and development. Some of the mothers were taking amitriptyline.[10]

A nursing mother was prescribed amitriptyline 10 mg daily for insomnia. After 3 days of the medication, her 15-day-old infant developed severe sedation and an estimated 80% decrease in breastfeeding because of the sedation. The infant was otherwise normal on examination. The drug was discontinued and symptoms decreased within 24 hours and were absent after 48 hours. Amitriptyline was restarted at 10 mg daily. The same effects reappeared in the infant and again disappeared by 48 hours after discontinuation of the drug.[12]

Effects on Lactation and Breastmilk

Amitriptyline has caused increased prolactin levels in nonpregnant, nonnursing patients.[13][14] The clinical relevance of these findings in nursing mothers is not known. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

An observational study looked at outcomes of 2859 women who took an antidepressant during the 2 years prior to pregnancy. Compared to women who did not take an antidepressant during pregnancy, mothers who took an antidepressant during all 3 trimesters of pregnancy were 30% less likely to be breastfeeding upon hospital discharge. Mothers who took an antidepressant only during the third trimester were 75% less likely to be breastfeeding at discharge. Those who took an antidepressant only during the first and second trimesters did not have a reduced likelihood of breastfeeding at discharge.[15] The antidepressants used by the mothers were not specified.

Alternate Drugs to Consider

Nortriptyline, Paroxetine, Sertraline

References

1. Weissman AM, Levy BT, Hartz AJ et al. Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants. Am J Psychiatry. 2004;161:1066-78. PMID: 15169695

2. Bader TF, Newman K. Amitriptyline in human breast milk and the nursing infant's serum. Am J Psychiatry. 1980;137:855-6. PMID: 7386673

3. Brixen-Rasmussen L, Halgrener J, Jorgensen A. Amitriptyline and nortriptyline excretion in human breast milk. Psychopharmacology. 1982;76:94-5. PMID: 6805016

4. Breyer-Pfaff U, Nill K, Entenmann A et al. Secretion of amitriptyline and metabolites into breast milk. Am J Psychiatry. 1995;152:812-3. Letter. PMID: 7726331

5. Pittard WB III, O'Neal W Jr. Amitriptyline excretion in human milk. J Clin Psychopharmacol. 1986;6:383-4. Letter. PMID: 3805339

6. Yoshida K, Smith B, Kumar R. Psychotropic drugs in mothers' milk: a comprehensive review of assay methods, pharmacokinetics and safety of breast-feeding. J Psychopharmacol. 1999;13:64-80. PMID: 10221361

7. Erickson SH, Smith GH, Heidrich F. Tricyclics and breast feeding. Am J Psychiatry. 1979;136:1483. Letter. PMID: 495815

8. Yoshida K, Smith B, Craggs M et al. Investigation of pharmacokinetics and possible adverse effects in infants exposed to tricyclic antidepressants in breast-milk. J Affective Disord. 1997;43:225-37. PMID: 9186793

9. Misri S, Sivertz K. Tricyclic drugs in pregnancy and lactation: a preliminary report. Int J Psychiatry Med. 1991;21:157-71. PMID: 1894455

10. Nulman I, Rovet J, Stewart DE et al. Child development following exposure to tricyclic antidepressants or fluoxetine throughout fetal life: a prospective, controlled study. Am J Psychiatry. 2002;159:1889-95. PMID: 12411224

11. Buist A, Janson H. Effect of exposure to dothiepin and northiaden in breast milk on child development. Br J Psychiatry. 1995;167:370-3. PMID: 7496646

12. Uguz F. Poor feeding and severe sedation in a newborn nursed by a mother on a low dose of amitriptyline. Breastfeed Med. 2017;12:67-8. PMID: 27870551

13. Turkington RW. Prolactin secretion in patients treated with various drugs: phenothiazines, tricyclic antidepressants, reserpine, and methyldopa. Arch Intern Med. 1972;130:349-54. PMID: 4560178

14. Coker F, Taylor D. Antidepressant-induced hyperprolactinaemia: incidence, mechanisms and management. CNS Drugs. 2010;24:563-74. PMID: 20527996

15. Venkatesh KK, Castro VM, Perlis RH et al. Impact of antidepressant treatment during pregnancy on obstetric outcomes among women previously treated for depression. Am J Obstet Gynecol. 2017;216:S466-S467.

Substance Name

Amitriptyline

CAS Registry Number

50-48-6

Drug Class

Antidepressants

Tricyclic Antidepressants

Amitriptyline is a tricyclic antidepressant. Amitriptyline affects chemicals in the brain that may be unbalanced in people with depression.

Amitriptyline is used to treat symptoms of depression.

Amitriptyline may also be used for purposes not listed in this medication guide.

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of amitriptyline can be fatal.

Overdose symptoms may include uneven heartbeats, extreme drowsiness, confusion, agitation, vomiting, hallucinations, feeling hot or cold, muscle stiffness, seizure (convulsions), or fainting.

Do not drink alcohol. Dangerous side effects or death can occur when alcohol is combined with amitriptyline.

This medication may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert.

Avoid exposure to sunlight or tanning beds. Amitriptyline can make you sunburn more easily. Wear protective clothing and use sunscreen (SPF 30 or higher) when you are outdoors.

Get emergency medical help if you have signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Report any new or worsening symptoms to your doctor, such as: mood or behavior changes, anxiety, panic attacks, trouble sleeping, or if you feel impulsive, irritable, agitated, hostile, aggressive, restless, hyperactive (mentally or physically), more depressed, or have thoughts about suicide or hurting yourself.

Call your doctor at once if you have:

• unusual thoughts or behavior;

• a light-headed feeling, like you might pass out;

• chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating;

• pounding heartbeats or fluttering in your chest;

• confusion, hallucinations;

• a seizure (convulsions);

• painful or difficult urination;

• severe constipation;

• easy bruising, unusual bleeding; or

• sudden weakness or ill feeling, fever, chills, sore throat, mouth sores, red or swollen gums, trouble swallowing.

Common side effects may include:

• constipation, diarrhea;

• nausea, vomiting, upset stomach;

• mouth pain, unusual taste, black tongue;

• appetite or weight changes;

• urinating less than usual;

• itching or rash;

• breast swelling (in men or women); or

• decreased sex drive, impotence, or difficulty having an orgasm.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.