Antidepressant, Tricyclic (Secondary Amine)
Treatment of symptoms of depression
Hypersensitivity to this drug and similar chemical class; use of monoamine
oxidase inhibitors within 14 days; use in a patient during the acute recovery
phase of MI
May cause sedation, resulting in impaired performance of tasks requiring
alertness (ie, operating machinery or driving). Sedative effects may be additive
with other CNS depressants and/or ethanol. The degree of sedation is
low-moderate relative to other antidepressants. May worsen psychosis in some
patients or precipitate a shift to mania or hypomania in patients with bipolar
disease. May increase the risks associated with electroconvulsive therapy. This
agent should be discontinued, when possible, prior to elective surgery. Therapy
should not be abruptly discontinued in patients receiving high doses for
prolonged periods. May alter glucose regulation - use caution in patients with
Use caution in patients with depression, particularly if suicidal risk may be
present. Use with caution in patients with a history of cardiovascular disease
(including previous MI, stroke, tachycardia, or conduction abnormalities). The
risk of conduction abnormalities with this agent is moderate relative to other
antidepressants. Use caution in patients with a previous seizure disorder or
condition predisposing to seizures such as brain damage, alcoholism, or
concurrent therapy with other drugs which lower the seizure threshold. Use with
caution in hyperthyroid patients or those receiving thyroid supplementation. Use
with caution in patients with hepatic or renal dysfunction and in elderly
Cardiovascular: Postural hypotension, arrhythmias, hypertension, heart block,
tachycardia, palpitations, myocardial infarction
Central nervous system: Confusion, delirium, hallucinations, restlessness,
insomnia, disorientation, delusions, anxiety, agitation, panic, nightmares,
hypomania, exacerbation of psychosis, incoordination, ataxia, extrapyramidal
Dermatologic: Alopecia, photosensitivity, rash, petechiae, urticaria, itching
Endocrine & metabolic: Sexual dysfunction, gynecomastia, breast
enlargement, galactorrhea, increase or decrease in libido, increase in blood
Gastrointestinal: Xerostomia, constipation, vomiting, anorexia, diarrhea,
abdominal cramps, black tongue, nausea, unpleasant taste, weight gain or loss
Genitourinary: Urinary retention, delayed micturition, impotence, testicular
Hematologic: Rarely agranulocytosis, eosinophilia, purpura, thrombocytopenia
Hepatic: Increased liver enzymes, cholestatic jaundice
Neuromuscular & skeletal: Tremor, numbness, tingling, paresthesias,
Ocular: Blurred vision, eye pain, disturbances in accommodation, mydriasis
Miscellaneous: Diaphoresis (excessive), allergic reactions
Symptoms of overdose include agitation, confusion, hallucinations, urinary
retention, hypothermia, hypotension, seizures, ventricular tachycardia
Following initiation of essential overdose management, toxic symptoms should
be treated. Sodium bicarbonate is indicated when QRS interval is >0.10
seconds or QTc >0.42 seconds. Ventricular arrhythmias and EKG
changes (QRS widening) often respond to phenytoin 15-20 mg/kg (adults) with
concurrent systemic alkalinization (sodium bicarbonate 0.5-2 mEq/kg I.V.).
Arrhythmias unresponsive to this therapy may respond to lidocaine 1 mg/kg I.V.
followed by a titrated infusion. Physostigmine (1-2 mg I.V. slowly for adults or
0.5 mg I.V. slowly for children) may be indicated in reversing cardiac
arrhythmias that are life-threatening. Seizures usually respond to diazepam I.V.
boluses (5-10 mg for adults up to 30 mg or 0.25-0.4 mg/kg/dose for children up
to 10 mg/dose). If seizures are unresponsive or recur, phenytoin or
phenobarbital may be required.
CYP1A2 and 2D6 enzyme substrate
Nortriptyline inhibits the antihypertensive response to bethanidine,
clonidine, debrisoquin, guanadrel, guanethidine, guanabenz, guanfacine; monitor
BP; consider alternate antihypertensive agent
Abrupt discontinuation of clonidine may cause hypertensive crisis,
nortriptyline may enhance the response
Use with altretamine may cause orthostatic hypertension
Nortriptyline may be additive with or may potentiate the action of other CNS
depressants (sedatives, hypnotics, or ethanol); with MAO inhibitors,
hyperpyrexia, hypertension, tachycardia, confusion, seizures, and deaths
have been reported (serotonin syndrome), this combination should be avoided
Nortriptyline may increase the prothrombin time in patients stabilized on
Cimetidine and methylphenidate may decrease the metabolism of nortriptyline
Additive anticholinergic effects seen with other anticholinergic agents
The SSRIs, to varying degrees, inhibit the metabolism of TCAs and clinical
toxicity may result
Use of lithium with a TCA may increase the risk for neurotoxicity
Phenothiazines may increase concentration of some TCAs and TCAs may increase
concentration of phenothiazines; monitor for altered clinical response
TCAs may enhance the hypoglycemic effects of tolazamide, chlorpropamide, or
insulin; monitor for changes in blood glucose levels
Cholestyramine and colestipol may bind TCAs and reduce their absorption;
monitor for altered response
TCAs may enhance the effect of amphetamines; monitor for adverse CV effects
Verapamil and diltiazem appear to decrease the metabolism of imipramine and
potentially other TCAs; monitor for increased TCA concentrations. The pressor
response to I.V. epinephrine, norepinephrine, and phenylephrine may be enhanced
in patients receiving TCAs, this combination is best avoided.
Grapefruit juice, amprenavir, indinavir, ritonavir may inhibit the metabolism
of clomipramine and potentially other TCAs; monitor for altered effects; a
decrease in TCA dosage may be required
Quinidine may inhibit the metabolism of TCAs; monitor for altered effect
Combined use of anticholinergics with TCAs may produce additive
anticholinergic effects; combined use of beta-agonists with TCAs may predispose
patients to cardiac arrhythmias
Protect from light
Traditionally believed to increase the synaptic concentration of serotonin
and/or norepinephrine in the central nervous system by inhibition of their
reuptake by the presynaptic neuronal membrane. However, additional receptor
effects have been found including desensitization of adenyl cyclase, down
regulation of beta-adrenergic receptors, and down regulation of serotonin
Onset of action: 1-3 weeks before therapeutic effects are seen
Distribution: Vd: 21 L/kg
Protein binding: 93% to 95%
Metabolism: Undergoes significant first-pass metabolism; primarily detoxified
in the liver
Half-life: 28-31 hours
Time to peak serum concentration: Oral: Within 7-8.5 hours
Elimination: As metabolites and small amounts of unchanged drug in urine;
small amounts of biliary elimination occur
6-7 years (20-25 kg): 10 mg/day
8-11 years (25-35 kg): 10-20 mg/day
>11 years (35-54 kg): 25-35 mg/day
Adolescents: 30-50 mg/day in divided doses
Adults: 25 mg 3-4 times/day up to 150 mg/day
Elderly ( Note: Nortriptyline is one of the best tolerated TCAs in the
Initial: 10-25 mg at bedtime
Dosage can be increased by 25 mg every 3 days for inpatients and weekly for
outpatients if tolerated
Usual maintenance dose: 75 mg as a single bedtime dose, however, lower or
higher doses may be required to stay within the therapeutic window
Dosing adjustment in hepatic impairment: Lower doses and slower
titration dependent on individualization of dosage is recommended
Alcohol: Additive CNS effect, avoid use
Monitor blood pressure and pulse rate prior to and during initial therapy;
evaluate mental status; monitor weight
Plasma levels do not always correlate with clinical effectiveness
Therapeutic: 50-150 ng/mL (SI: 190-570 nmol/L)
Toxic: >500 ng/mL (SI: >1900 nmol/L)
|Dental Health: Local
Use with caution; epinephrine, norepinephrine and levonordefrin have been
shown to have an increased pressor response in combination with
Effects on Dental Treatment|
>10% of patients experience dry mouth; long-term treatment with TCAs such
as nortriptyline increases the risk of caries by reducing salivation and
salivary buffer capacity
Oral: Take exactly as directed (do not increase dose or frequency); may take
2-3 weeks to achieve desired results; may cause physical and/or psychological
dependence. Take once-a-day dose at bedtime. Avoid excessive alcohol, caffeine,
and other prescription or OTC medications not approved by prescriber. Maintain
adequate hydration (2-3 L/day of fluids unless instructed to restrict fluid
intake). You may experience drowsiness, lightheadedness, impaired coordination,
dizziness, or blurred vision (use caution when driving or engaging in tasks
requiring alertness until response to drug is known); nausea, vomiting, altered
taste, dry mouth (small frequent meals, frequent mouth care, chewing gum,
sucking lozenges may help); constipation (increased exercise, fluids, or dietary
fruit and fiber may help); diarrhea (buttermilk, yogurt, or boiled milk may
help); increased appetite (monitor dietary intake to avoid excess weight gain);
postural hypotension (use caution when climbing stairs or changing position from
lying or sitting to standing); urinary retention (void before taking
medication); or sexual dysfunction (reversible). Report persistent CNS effects
(eg, insomnia, nervousness, restlessness, hallucinations, daytime sedation,
impaired cognitive function); muscle cramping or tremors; chest pain,
palpitations, rapid heartbeat, swelling of extremities, or severe dizziness;
blurred vision or eye pain; yellowing of eyes or skin; pale stools/dark urine;
or worsening of condition. Pregnancy/breast-feeding precautions: Do not
get pregnant while taking this medication; use appropriate barrier contraceptive
measures. Do not breast-feed.
May increase appetite and possibly a craving for sweets
Capsule, as hydrochloride: 10 mg, 25 mg, 50 mg, 75 mg
Solution, as hydrochloride: 10 mg/5 mL (473 mL)
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