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ชื่อยา
ชื่อยา
ชื่อยา
Hydrochloride
Tablets 10,25 mg
CONTRAIND concomitantly with
ICATIONS a MAO inhibiting,
Hyperpyretic crises,
severe convulsions,
acute recovery phase
following myocardial
infarction, presence of
acute congestive heart
failure
Outpatients, 75 mg 25 mg ORALLY 3
orally (divided into to 4 times daily;
1 to 3 doses per alternatively,
day); may increase administer as a
to MAX, 150 mg/day single daily dose;
[2] MAX 150 mg/day
Antidepressa Suggested
nt Therapeutic Plasma
Concentration
(ng/mL)
Initial
Dose
(mg/day)
Usual
Dosage
Range
(mg/day)
120250b 50150
25 25
100300 50200
Postherpetic neuralgia
Both amitriptyline and nortriptyline have a similar analgesic action
in postherpetic neuralgia34. Nortriptyline causes fewer side
effects and may be better tolerated than amitriptyline.
Depression
Which antidepressant is more effective? Amitriptyline may be
more effective in the treatment of endogenous depressive illness.
depression
[50-150 mg PO qhs]
Start: 25-75 mg PO qhs, may incr. by 25-50 mg/day q2-3
days; Max: 300 mg/day; Info: start 10-25 mg PO qhs in elderly
pts, may incr. by 10-25 mg/day q2-3 days; may give in divided
doses; taper dose gradually to D/C
[25-100 mg PO qhs]
Start: 25 mg PO qhs, titrate slowly; Max: 150 mg/day; Info:
taper dose gradually to D/C
*post-herpetic neuralgia
[75-150 mg PO qhs]
Start: 10-25 mg PO qhs, may incr. by 10-25 mg/day qwk; Max:
150 mg/day; Info: taper dose gradually to D/C
[10-100 mg PO qhs]
Start: 10-25 mg PO qhs, titrate slowly; Max: 150 mg/day; Info:
taper dose gradually to D/C
*fibromyalgia
[25-50 mg PO qhs]
Start: 10 mg PO qhs, may incr. by 10-25 mg/day qwk; Max: 75
mg/day; Info: taper dose gradually to D/C
renal dosing
[no adjustment]
hepatic dosing
[not defined]
hepatic impairment: caution advised
Peds Dosing .
*depression
[9-12 yo]
Dose: 1-3 mg/kg/day PO divided tid; Start: 1 mg/kg/day PO
divided tid x3 days, may incr. by 0.5 mg/kg/day q2-3 days;
Max: 5 mg/kg/day up to 200 mg/day; Info: taper dose
gradually to D/C
[13 yo and older]
Dose: 50-100 mg/day PO divided qd-tid; Start: 10 mg PO tid
and 20 mg qhs, may incr. by 10-25 mg/day q2-3 days; Max:
200 mg/day; Info: taper dose gradually to D/C
*neuropathic pain
renal dosing
[no adjustment]
hepatic dosing
[not defined]
hepatic impairment: caution advised
Contraindications / Cautions .
hypersens. to drug/class/compon.
caution if thyroid dz
caution if asthma
caution if Parkinson dz
caution if schizophrenia
caution if electroconvulsive tx
Interaction Characteristics:
CYP2C19 substrate
CYP2D6 substrate
anticholinergic effects
CNS depression
hypertensive effects
hyponatremia
hypotensive effects
Serious Reactions
hypotension, orthostatic
HTN
syncope
ventricular arrhythmias
QT prolongation
torsades de pointes
AV block
MI
stroke
seizures
extrapyramidal sx
ataxia
tardive dyskinesia
paralytic ileus
glaucoma, angle-closure
IOP incr.
agranulocytosis
leukopenia
thrombocytopenia
hallucinations
psychosis exacerbation
hypomania/mania
depression exacerbation
suicidality
SIADH
hepatitis
angioedema
psychosis, anticholinergic
hyperthermia
heat stroke
Common Reactions
drowsiness
xerostomia
dizziness
constipation
blurred vision
palpitations
tachycardia
impaired coordination
appetite incr.
nausea/vomiting
diaphoresis
weakness
disorientation
confusion
restlessness
insomnia
anxiety/agitation
urinary retention
urinary frequency
rash/urticaria
pruritus
weight gain
libido changes
impotence
gynecomastia
galactorrhea
tremor
hypo/hyperglycemia
paresthesia
photosensitivity
Safety/Monitoring .
Therapeutic Drug Levels
120-250 ng/mL (amitriptyline + nortriptyline); Toxic Levels: >500
ng/mL; Timing: just before next dose; Time to Steady State: 2-10
days; Info: max efficacy may take 6wk, not well-correlated w/
levels
Monitoring Parameters
serum drug levels; ECG if cardiovascular dz; BP, HR in peds pts if
dose >3 mg/kg/24h; sx suicidality, clinical worsening, and/or
unusual behavior changes, especially during initial tx or after dose
changes
Pregnancy/Lactation
Pregnancy
Clinical Considerations
Lactation
Clinical Considerations
Pharmacology .
Metabolism: liver extensively; CYP450: 1A2, 2D6 (primary), 3A4
substrate; Info: active metabolites incl. nortriptyline
Mechanism of Action
exact mechanism of action unknown; inhibits norepinephrine and
serotonin reuptake
Depression
a) SUMMARY: Most studies have indicated that there are no
significant differences between nortriptyline and other
antidepressant drugs of the tricyclic category such as
amitriptyline [1051][1052][1053][1054][1055]
b) Oral nortriptyline 50 to 150 mg/day was as effective as
amitriptyline 100 to 200 mg/day in the treatment of 22
hospitalized unipolar depressed patients [1061]. Of the 22
patients entered in the study, 10 were randomized to receive
amitriptyline and 12 received nortriptyline in a double-blind
manner. Both treatment groups were similar in terms of age, sex
distribution and mean baseline Hamilton Rating Scale (HRS) scores
which were approximately 35. Treatment was initiated with 100
mg nortriptyline or 150 mg amitriptyline. Doses of each drug were
adjusted to achieve plasma concentrations of 60 to 180 ng/mL.
The mean doses at the end of the 4-week study were 131 mg of
amitriptyline and 95 mg of nortriptyline. Four patients (2 from
each group) withdrew from the study because of side effects or
worsening of symptoms. Reductions in HRS scores after 1 week of
treatment were significantly greater in the nortriptyline group than
in the amitriptyline group (55% vs 25%, respectively). There were
no significant differences between groups at weeks 2, 3 and 4;
however, a better outcome was noted for patients in the
nortriptyline group. Patient self-rating global assessments also
reported greater improvement with nortriptyline at 1 week but not
at weeks 2, 3, or 4. Side effects were similar with both drugs. Both
drugs were also unsuccessful in treating unipolar patients who
were delusional.
Postherpetic neuralgia
a) The analgesic action of nortriptyline was as effective as
amitriptyline for the treatment of postherpetic neuralgia in a
double-blind, cross-over trial. Patients (n=31) with
postherpetic neuralgia with at least moderate pain of more
than 3 months' duration received 5 weeks of nortriptyline and
amitriptyline therapy with a 2-week washout period between
treatments. Initial doses of both medications were 10
milligrams (mg) for patients 65 years or older and 20 mg if
younger than 65 years. The dose was increased every 3 to 5
days in 10-mg increments until satisfactory pain relief
occurred or distressing side effects occurred. Patients rated
their pain using a visual analog scale. Pain scores declined
from baseline as time increased with both therapies (p less
than 0.0001). Values for the fifth week showed no significant
differences between the two therapies. Based on pain,
disability, sleep, depression, and satisfaction, similar results
occurred in 21 patients regardless of therapy. Substantial
improvement occurred in 16 patients, and 13 had a good
response on both drugs. Five patients receiving amitriptyline
and 4 receiving nortriptyline had a good response to that drug
but failed to respond to the other drug. Intolerable side effects
(i.e. dry mouth, constipation, and drowsiness) occurred more
often with amitriptyline than with nortriptyline (p=0.05)
[1062].
[1051] Rose JT, Leahy MR, Martin ICA, et al: A comparison of
nortriptyline and amitriptyline in depression. Br J Psychiatry 1965;
111:1101.