SUICIDALITY AND ANTIDEPRESSANT DRUGS
Antidepressants increased the risk compared to placebo of suicidal
thinking and behavior (suicidality) in children, adolescents, and young adults
in short-term studies of major depressive disorder (MDD) and other psychiatric
disorders. Anyone considering the use of doxepin hydrochloride or any other
antidepressant in a child, adolescent, or young adult must balance this risk
with the clinical need. Short-term studies did not show an increase in the risk
of suicidality with antidepressants compared to placebo in adults beyond age 24;
there was a reduction in risk with antidepressants compared to placebo in adults
aged 65 and older. Depression and certain other psychiatric disorders are
themselves associated with increases in the risk of suicide. Patients of all
ages who are started on antidepressant therapy should be monitored appropriately
and observed closely for clinical worsening, suicidality, or unusual changes in
behavior. Families and caregivers should be advised of the need for close
observation and communication with the prescriber. Doxepin hydrochloride is not
approved for use in pediatric patients. (See WARNINGS: Clinical Worsening and
Suicide Risk, PRECAUTIONS: Information for Patients, and PRECAUTIONS: Pediatric
Use)
SUICIDALITY AND ANTIDEPRESSANT DRUGS Antidepressants increased the risk compared to placebo of suicidal
thinking and behavior (suicidality) in children, adolescents, and young adults
in short-term studies of major depressive disorder (MDD) and other psychiatric
disorders. Anyone considering the use of doxepin hydrochloride or any other
antidepressant in a child, adolescent, or young adult must balance this risk
with the clinical need. Short-term studies did not show an increase in the risk
of suicidality with antidepressants compared to placebo in adults beyond age 24;
there was a reduction in risk with antidepressants compared to placebo in adults
aged 65 and older. Depression and certain other psychiatric disorders are
themselves associated with increases in the risk of suicide. Patients of all
ages who are started on antidepressant therapy should be monitored appropriately
and observed closely for clinical worsening, suicidality, or unusual changes in
behavior. Families and caregivers should be advised of the need for close
observation and communication with the prescriber. Doxepin hydrochloride is not
approved for use in pediatric patients. (See WARNINGS: Clinical Worsening and
Suicide Risk, PRECAUTIONS: Information for Patients, and PRECAUTIONS: Pediatric
Use)
Description
Doxepin hydrochloride is one of a class of psychotherapeutic agents known as
dibenzoxepin tricyclic compounds. The molecular formula of the compound is C
19H21NO•HCl having a molecular
weight of 315.84. It is a white crystalline solid readily soluble in water,
lower alcohols and chloroform. Its structural formula is:
C19H21NO●HCl
MW: 315.84
Chemistry:Doxepin HCl is a dibenzoxepin derivative and is the
first of a family of tricyclic psychotherapeutic agents. Specifically, it is an
isomeric mixture of: 1-Propanamine, 3-dibenz[b,e]oxepin-11(6 H)ylidene-N,N-dimethyl-hydrochloride. Each doxepin hydrochloride
capsule is equivalent to 10 mg, 25 mg, 50 mg, 75 mg or 100 mg of doxepin for
oral administration.
Each capsule contains
the following inactive ingredients: corn starch, D&C Yellow #10, FD&C
Blue #1, FD&C Blue #2, FD&C Red #40, gelatin, magnesium stearate,
pharmaceutical glaze, sodium laurel sulfate, synthetic black iron oxide,
titanium dioxide and other ingredients. In addition, the 10 mg capsule contains
FD&C Yellow #6; the 25 mg and 50 mg capsules contain FD&C Yellow #6 and
propylene glycol; the 75 mg capsule contains FD&C Green #3 and propylene
glycol; and the 100 mg capsule contains FD&C Green #3.
Actions
The mechanism of action
of doxepin HCl is not definitely known. It is not a central nervous system
stimulant nor a monoamine oxidase inhibitor. The current hypothesis is that the
clinical effects are due, at least in part, to influences on the adrenergic
activity at the synapses so that deactivation of norepinephrine by reuptake into
the nerve terminals is prevented. Animal studies suggest that doxepin HCl does
not appreciably antagonize the antihypertensive action of guanethidine. In
animal studies anticholinergic, anti-serotonin and antihistamine effects on
smooth muscle have been demonstrated. At higher than usual clinical doses,
norepinephrine response was potentiated in animals. This effect was not
demonstrated in humans.
At clinical dosages up
to 150 mg per day, doxepin HCl can be given to man concomitantly with
guanethidine and related compounds without blocking the antihypertensive effect.
At dosages above 150 mg per day blocking of the antihypertensive effect of these
compounds has been reported.
Doxepin HCl is virtually
devoid of euphoria as a side effect. Characteristic of this type of compound,
doxepin HCl has not been demonstrated to produce the physical tolerance or
psychological dependence associated with addictive compounds.
Indications
Doxepin HCl is
recommended for the treatment of:
Psychoneurotic patients with depression and/or anxiety.
Depression and/or anxiety associated with alcoholism (not to be taken
concomitantly with alcohol).
Depression and/or anxiety associated with organic disease (the possibility
of drug interaction should be considered if the patient is receiving other drugs
concomitantly).
Psychotic depressive disorders with associated anxiety including
involutional depression and manic-depressive disorders.
The target symptoms of
psychoneurosis that respond particularly well to doxepin HCl include anxiety,
tension, depression, somatic symptoms and concerns, sleep disturbances, guilt,
lack of energy, fear, apprehension and worry.
Clinical experience has
shown that doxepin HCl is safe and well tolerated even in the elderly patient.
Owing to lack of clinical experience in the pediatric population, doxepin HCl is
not recommended for use in children under 12 years of age.
Contraindications
Doxepin HCl is
contraindicated in individuals who have shown hypersensitivity to the drug.
Possibility of cross sensitivity with other dibenzoxepines should be kept in
mind.
Doxepin HCl is
contraindicated in patients with glaucoma or a tendency to urinary retention.
These disorders should be ruled out, particularly in older patients.
Warnings
Clinical Worsening and Suicide Risk
Patients with major
depressive disorder (MDD), both adult and pediatric, may experience worsening of
their depression and/or the emergence of suicidal ideation and behavior
(suicidality) or unusual changes in behavior, whether or not they are taking
antidepressant medications, and this risk may persist until significant
remission occurs. Suicide is a known risk of depression and certain other
psychiatric disorders, and these disorders themselves are the strongest
predictors of suicide. There has been a long-standing concern, however, that
antidepressants may have a role in inducing worsening of depression and the
emergence of suicidality in certain patients during the early phases of
treatment. Pooled analyses of short-term placebo-controlled trials of
antidepressant drugs (SSRIs and others) showed that these drugs increase the
risk of suicidal thinking and behavior (suicidality) in children, adolescents,
and young adults (ages 18-24) with major depressive disorder (MDD) and other
psychiatric disorders. Short-term studies did not show an increase in the risk
of suicidality with antidepressants compared to placebo in adults beyond age 24;
there was a reduction with antidepressants compared to placebo in adults aged 65
and older.
The pooled analyses of
placebo-controlled trials in children and adolescents with MDD, obsessive
compulsive disorder (OCD), or other psychiatric disorders included a total of 24
short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled
analyses of placebo-controlled trials in adults with MDD or other psychiatric
disorders included a total of 295 short-term trials (median duration of 2
months) of 11 antidepressant drugs in over 77,000 patients. There was
considerable variation in risk of suicidality among drugs, but a tendency toward
an increase in the younger patients for almost all drugs studied. There were
differences in absolute risk of suicidality across the different indications,
with the highest incidence in MDD. The risk differences (drug vs placebo),
however, were relatively stable within age strata and across indications. These
risk differences (drug-placebo difference in the number of cases of suicidality
per 1000 patients treated) are provided in Table 1.
Table 1
Age Range
Drug-Placebo Difference in Number of Cases
of Suicidality per 1000 Patients Treated
Increases Compared to Placebo
Less than 18
14 additional cases
18 – 24
5 additional cases
Decreases Compared to Placebo
25 – 64
1 fewer case
Greater than or equal to 65
6 fewer cases
No suicides occurred in
any of the pediatric trials. There were suicides in the adult trials, but the
number was not sufficient to reach any conclusion about drug effect on
suicide.
It is unknown whether
the suicidality risk extends to longer-term use, i.e., beyond several months.
However, there is substantial evidence from placebo-controlled maintenance
trials in adults with depression that the use of antidepressants can delay the
recurrence of depression.
All
patients being treated with antidepressants for any indication should be
monitored appropriately and observed closely for clinical worsening,
suicidality, and unusual changes in behavior, especially during the initial few
months of a course of drug therapy, or at times of dose changes, either
increases or decreases.
The following symptoms,
anxiety, agitation, panic attacks, insomnia, irritability, hostility,
aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania,
and mania, have been reported in adult and pediatric patients being treated with
antidepressants for major depressive disorder as well as for other indications,
both psychiatric and nonpsychiatric. Although a causal link between the
emergence of such symptoms and either the worsening of depression and/or the
emergence of suicidal impulses has not been established, there is concern that
such symptoms may represent precursors to emerging suicidality.
Consideration should be
given to changing the therapeutic regimen, including possibly discontinuing the
medication, in patients whose depression is persistently worse, or who are
experiencing emergent suicidality or symptoms that might be precursors to
worsening depression or suicidality, especially if these symptoms are severe,
abrupt in onset, or were not part of the patient's presenting symptoms.
Families and caregivers of patients being treated with
antidepressants for major depressive disorder or other indications, both
psychiatric and nonpsychiatric, should be alerted about the need to monitor
patients for the emergence of agitation, irritability, unusual changes in
behavior, and the other symptoms described above, as well as the emergence of
suicidality, and to report such symptoms immediately to health care providers.
Such monitoring should include daily observation by families and caregivers.
Prescriptions for doxepin hydrochloride should be written for the
smallest quantity of tablets consistent with good patient management, in order
to reduce the risk of overdose.
Screening Patients for Bipolar Disorder: A major depressive
episode may be the initial presentation of bipolar disorder. It is generally
believed (though not established in controlled trials) that treating such an
episode with an antidepressant alone may increase the likelihood of
precipitation of a mixed/manic episode in patients at risk for bipolar disorder.
Whether any of the symptoms described above represent such a conversion is
unknown. However, prior to initiating treatment with an antidepressant, patients
with depressive symptoms should be adequately screened to determine if they are
at risk for bipolar disorder; such screening should include a detailed
psychiatric history, including a family history of suicide, bipolar disorder,
and depression. It should be noted that doxepin hydrochloride is not approved
for use in treating bipolar depression.
The once-a-day dosage
regimen of doxepin HCl in patients with intercurrent illness or patients taking
other medications should be carefully adjusted. This is especially important in
patients receiving other medications with anticholinergic effects.
Usage
in Geriatrics
The use of doxepin HCl
on a once-a-day dosage regimen in geriatric patients should be adjusted
carefully based on the patient’s condition (see PRECAUTIONS-Geriatric Use).
Usage
in Pregnancy
Reproduction studies
have been performed in rats, rabbits, monkeys and dogs and there was no evidence
of harm to the animal fetus. The relevance to humans is not known. Since there
is no experience in pregnant women who have received this drug, safety in
pregnancy has not been established. There has been a report of apnea and
drowsiness occurring in a nursing infant whose mother was taking doxepin
hydrochloride.
Usage
in Children
The use of doxepin HCl
in children under 12 years of age is not recommended because safe conditions for
its use have not been established.
Precautions
Information for Patients Prescribers or other
health professionals should inform patients, their families, and their
caregivers about the benefits and risks associated with treatment with doxepin
hydrochloride and should counsel them in its appropriate use. A patient
Medication Guide about “Antidepressant Medicines, Depression and other Serious
Mental Illness, and Suicidal Thoughts or Actions” is available for doxepin
hydrochloride. The prescriber or health professional should instruct patients,
their families, and their caregivers to read the Medication Guide and should
assist them in understanding its contents. Patients should be given the
opportunity to discuss the contents of the Medication Guide and to obtain
answers to any questions they may have. The complete text of the Medication
Guide is reprinted at the end of this document.
Patients should be
advised of the following issues and asked to alert their prescriber if these
occur while taking doxepin hydrochloride.
Clinical Worsening and Suicide Risk:
Patients, their
families, and their caregivers should be encouraged to be alert to the emergence
of anxiety, agitation, panic attacks, insomnia, irritability, hostility,
aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania,
mania, other unusual changes in behavior, worsening of depression, and suicidal
ideation, especially early during antidepressant treatment and when the dose is
adjusted up or down. Families and caregivers of patients should be advised to
look for the emergence of such symptoms on a day-to-day basis, since changes may
be abrupt. Such symptoms should be reported to the patient's prescriber or
health professional, especially if they are severe, abrupt in onset, or were not
part of the patient's presenting symptoms. Symptoms such as these may be
associated with an increased risk for suicidal thinking and behavior and
indicate a need for very close monitoring and possibly changes in the
medication.
Pediatric Use: Safety and effectiveness in the pediatric
population have not been established (see BOX WARNING
and WARNINGS – Clinical Worsening and Suicide
Risk). Anyone considering the use of doxepin HCl in a child or adolescent
must balance the potential risks with the clinical need. Drug Interactions Drugs Metabolized by P450 2D6: 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 co-administration 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 co-administered with another drug known to be an inhibitor of P450
2D6.
Doxepin is primarily
metabolized by CYP2D6 (with CYP1A2 & CYP3A4 as minor pathways). Inihibitors
or substrates of CYP2D6 (i.e., quinidine, selective serotonin reuptake
inhibitors [SSRIs]) may increase the plasma concentration of doxepin when
administered concomitantly. The extent of interaction depends on the variability
of effect on CYP2D6. The clinical significance of this interaction with doxepin
has not been systematically evaluated.
MAO
Inhibitors
Serious side effects and
even death have been reported following the concomitant use of certain drugs
with MAO inhibitors. Therefore, MAO inhibitors should be discontinued at least
two weeks prior to the cautious initiation of therapy with doxepin HCl. The
exact length of time may vary and is dependent upon the particular MAO inhibitor
being used, the length of time it has been administered, and the dosage
involved.
Cimetidine
Cimetidine has been
reported to produce clinically significant fluctuations in steady-state serum
concentrations of various tricyclic antidepressants. Serious anticholinergic
symptoms (i.e., severe dry mouth, urinary retention and blurred vision) have
been associated with elevations in the serum levels of tricyclic antidepressants
when cimetidine therapy is initiated. Additionally, higher than expected
tricyclic antidepressant levels have been observed when they are begun in
patients already taking cimetidine. In patients who have been reported to be
well controlled on tricyclic antidepressants receiving concurrent cimetidine
therapy, discontinuation of cimetidine has been reported to decrease established
steady-state serum tricyclic antidepressant levels and compromise their
therapeutic effects.
Alcohol
It should be borne in
mind that alcohol ingestion may increase the danger inherent in any intentional
or unintentional doxepin HCl overdosage. This is especially important in
patients who may use alcohol excessively.
Tolazamide
A case of severe
hypoglycemia has been reported in a type II diabetic patient maintained on
tolazamide (1 gm/day) 11 days after the addition of doxepin (75 mg/day).
Drowsiness
Since drowsiness may
occur with the use of this drug, patients should be warned of the possibility
and cautioned against driving a car or operating dangerous machinery while
taking the drug. Patients should also be cautioned that their response to
alcohol may be potentiated.
Sedating drugs may cause
confusion and over sedation in the elderly; elderly patients generally should be
started on low doses of doxepin HCl and observed closely (see PRECAUTIONS-Geriatric Use).
Suicide
Since suicide is an
inherent risk in any depressed patient and may remain so until significant
improvement has occurred, patients should be closely supervised during the early
course of therapy. Prescriptions should be written for the smallest feasible
amount.
Psychosis
Should increased
symptoms of psychosis or shift to manic symptomatology occur, it may be
necessary to reduce dosage or add a major tranquilizer dosage regimen. Pediatric Use Safety and effectiveness
in the pediatric population have not been established (see BOX
WARNING and WARNINGS- Clinical Worsening and Suicide
Risk). Anyone considering the use of doxepin HCl in a child or adolescent
must balance the potential risks with the clinical need. Geriatric Use A determination has not
been made whether controlled clinical studies of doxepin HCl included sufficient
numbers of subjects aged 65 and over to define a difference in response from
younger subjects. Other reported clinical experience has not identified
differences in responses between the elderly and younger patients. In general,
dose selection for an elderly patient should be cautious, usually starting at
the low end of the dosing range, reflecting the greater frequency of decreased
hepatic, renal or cardiac function, and of concomitant disease or other drug
therapy.
The extent of renal
excretion of doxepin HCl has not been determined. Because elderly patients are
more likely to have decreased renal function, care should be taken in dose
selections.
Sedating drugs may cause
confusion and over sedation in the elderly; elderly patients generally should be
started on low doses of doxepin HCl and observed closely. (See WARNINGS.)
Adverse Reactions
NOTE:
Some of the adverse
reactions noted below have not been specifically reported with doxepin HCl use.
However, due to the close pharmacological similarities among the tricyclics, the
reactions should be considered when prescribing doxepin HCl.
Anticholinergic Effects:
Dry mouth, blurred
vision, constipation, and urinary retention have been reported. If they do not
subside with continued therapy, or become severe, it may be necessary to reduce
the dosage.
Central
Nervous System Effects:
Drowsiness is the most
commonly noticed side effect. This tends to disappear as therapy is continued.
Other infrequently reported CNS side effects are confusion, disorientation,
hallucinations, numbness, parethesias, ataxia, extrapyramidal symptoms,
seizures, tardive dyskinesia and tremor.
Cardiovascular:
Cardiovascular effects
including hypotension, hypertension, and tachycardia have been reported
occasionally.
Allergic:
Skin rash, edema,
photosensitization, and pruritus have occasionally occurred.
Hematologic:
Eosinophillia has been
reported in a few patients. There have been occasional reports of bone marrow
depression manifesting as agranulocytosis, leukopenia, thrombocytopenia, and
purpura.
Gastrointestinal:
Nausea, vomiting,
indigestion, taste disturbances, diarrhea, anorexia, and aphthous stomatitis
have been reported. (SeeAnticholinergic
Effects.)
Endocrine:
Raised or lowered
libido, testicular swelling, gynecomastia in males, enlargement of breasts and
galactorrhea in the female, raising or lowering of blood sugar levels and
syndrome of inappropriate antidiuretic hormone secretion have been reported with
tricyclic administration.
Other:
Dizziness, tinnitus,
weight gain, sweating, chills, fatigue, weakness, flushing, jaundice, alopecia,
headache, exacerbation of asthma, and hyperpyrexia (in association with
chlorpromazine) have been occasionally observed as adverse effects.
Withdrawal Symptoms:
The possibility of
development of withdrawal symptoms upon abrupt cessation of treatment after
prolonged doxepin HCl administration should be borne in mind. These are not
indicative of addiction and gradual withdrawal of medication should not cause
these symptoms.
Overdosage
Deaths may occur from
overdosage with this class of drugs. Multiple drug ingestion (including alcohol)
is common in deliberate tricyclic antidepressant overdose. As the management is
complex and changing, it is recommended that the physician contact a poison
control center for current information on treatment. Signs and symptoms of
toxicity develop rapidly after tricyclic antidepressant overdose; therefore,
hospital monitoring is required as soon as possible.
Manifestations
Critical manifestations
of overdose include: cardiac dysrhythmias, severe hypotension, convulsions, and
CNS depression, including coma. Changes in the electrocardiogram, particularly
in QRS axis or width, are clinically significant indicators of tricyclic
antidepressant toxicity.
Other signs of overdose
may include: confusion, disturbed concentration, transient visual
hallucinations, dilated pupils, agitation, hyperactive reflexes, stupor,
drowsiness, muscle rigidity, vomiting, hypothermia, hyperpyrexia, or any of the
symptoms uled under ADVERSE REACTIONS.
General
Recommendations:
General
Obtain an ECG and
immediately initiate cardiac monitoring. Protect the patient’s airway, establish
an intravenous line and initiate gastric decontamination. A minimum of six hours
of observation with cardiac monitoring and observation for signs of CNS or
respiratory depression, hypotension, cardiac dysrhythmias and/or conduction
blocks and seizures is strongly advised. If signs of toxicity occur at any time
during this period, extended monitoring is recommended. There are case reports
of patients succumbing to fatal dysrhythmias late after overdose; these patients
had clinical evidence of significant poisoning prior to death and most received
inadequate gastrointenstinal decontamination. Monitoring of plasma drug levels
should not guide management of the patient.
Gastrointestinal Decontamination
All patients suspected
of tricyclic antidepressant overdose should receive gastrointestinal
decontamination. This should include large volume gastric lavage followed by
activated charcoal. If consciousness is impaired, the airway should be secured
prior to lavage. Emesis is contraindicated.
Cardiovascular
A maximal limb-lead QRS
duration of ³0.10 seconds may be the best indication of the severity of the
overdose. Intravenous sodium bicarbonate should be used to maintain the serum pH
in the range of 7.45 to 7.55. If the pH response is inadequate, hyperventilation
may also be used. Concomitant use of hyperventilation and sodium bicarbonate
should be done with extreme caution, with frequent pH monitoring. A pH greaer than 7.60
or a pCO 2 less than 20mm Hg is undesirable. Dysrhythmias
unresponsive to sodium bicarbonate therapy/hyperventilation may respond to
lidocaine, bretylium or phenytoin. Type 1A and 1C antiarrhythmias are generally
contraindicated (e.g., quinidine, disopyramide, and procainamide).
In rare instances,
hemoperfusion may be beneficial in acute refractory cardiovascular instability
in patients with acute toxicity. However, Hemodialysis, peritoneal dialysis,
exchange tranfusions, and forced diuresis generally have been reported as
ineffective in tricyclic antidepressant poisoning.
CNS
In patients with CNS
depression, early intubation is advised because of the potential for abrupt
deterioration. Seizures should be controlled with benzodiazepines, or if these
are ineffective, other anticonvulsants (e.g., phenobarbitol and phenytoin).
Physostigmine is not recommended except to treat life-threatening symptoms that
have been unresponsive to other therapies and only in consultation with a poison
control center.
Psychiatric Follow-up
Since overdosage is
often deliberate, patients may attempt suicide by other means during the
recovery phase. Psychiatric referral may be appropriate.
Pediatric Management
The principles of
management of child and adult overdosages are similar. It is strongly
recommended that the physician contact the local poison control center for
specific pediatric treatment.
Dosage And Administration
For most patients with
illness of mild to moderate severity, a starting daily dose of 75 mg is
recommended. Dosage may subsequently be increased or decreased at appropriate
intervals and according to individual response. The usual optimum dose range is
75 mg/day to 150 mg/day.
In more severely ill
patients higher doses may be required with subsequent gradual increase to 300
mg/day if necessary. Additional therapeutic effect is rarely to be obtained by
exceeding a dose of 300 mg/day.
In patients with very
mild symptomatology or emotional symptoms accompanying organic disease, lower
doses may suffice. Some of these patients have been controlled on doses as low
as 25 to 50 mg/day.
The total daily dosage
of doxepin HCl may be given on a divided or once-a-day dosage schedule. If the
once-a-day schedule is employed, the maximum recommended dose is 150 mg/day.
This dose may be given at bedtime. The 150 mg capsule strength
is intended for maintenance therapy only and is not recommended for initiation
of treatment.
Anti-anxiety effect is
apparent before the antidepressant effect. Optimal antidepressant effect may not
be evident for two to three weeks.
How Supplied
Doxepin HCl capsules
USP, equivalent to 10 mg of doxepin are buff opaque/buff opaque capsules,
imprinted “Par 217” on both body and cap. They are supplied in
Bottles of 10
NDC 54868-2317-0
Bottles of 30
NDC 54868-2317-3
Bottles of 60
NDC 54868-2317-2
Bottles of 100
NDC 54868-2317-4
Doxepin HCl capsules
USP, equivalent to 25 mg of doxepin are white opaque/ivory opaque capsules,
imprinted “Par 218” on both body and cap. They are supplied in
Bottles of 15
NDC 54868-0062-4
Bottles of 30
NDC 54868-0062-2
Bottles of 100
NDC 54868-0062-0
Doxepin HCl capsules
USP, equivalent to 50 mg of doxepin are ivory opaque/ivory opaque capsules,
imprinted “Par 219” on both body and cap. They are supplied in
Bottles of 30
NDC 54868-1964-2
Bottles of 100
NDC 54868-1964-3
Doxepin HCl capsules
USP, equivalent to 75 mg of doxepin are bright light green opaque/bright light
green opaque capsules, imprinted “Par 220” on both body and cap. They are
supplied in
Bottles of 30
NDC 54868-2552-2
Bottles of 100
NDC 54868-2552-0
Doxepin HCl capsules
USP, equivalent to 100 mg of doxepin are white opaque/bright light green opaque
capsules, imprinted “Par 221” on both body and cap. They are supplied in
Bottles of 30
NDC 54868-2284-6
Bottles of 100
NDC 54868-2284-2
Doxepin HCl capsules
USP, equivalent to 150 mg of doxepin are buff opaque/buff opaque capsules,
imprinted “Par 222” on both body and cap. They are supplied in
Bottles of 30
NDC 54868-3533-0
Bottles of 100
NDC 54868-3533-1
Store at 20°-25°C
(68°-77°F) [see USP Controlled Room Temperature]
Medication Guide
Antidepressant Medicines, Depression and other Serious Mental
Illnesses,
and
Suicidal Thoughts or Actions
Read the Medication
Guide that comes with you or your family member’s antidepressant medicine. This
Medication Guide is only about the risk of suicidal thoughts and actions with
antidepressant medicines. Talk to your family member’s, or your
healthcare provider about:
all risks and benefits of treatment with antidepressant medicines
all treatment choices for depression or other serious mental illness
What is
the most important information I should know about antidepressant medicines,
depression and other serious mental illnesses, and suicidal thoughts or actions?
Antidepressant medicines may increase suicidal thoughts or
actions in some children, teenagers, and young adults within the first few
months of treatment.
Depression and other serious mental illnesses are the most
important causes of suicidal thoughts and actions.Somepeople may have a particularly high risk
of having suicidal thoughts or actions. These
include people who have (or have a family history of) bipolar illness also
called manic-depressive illness or suicidal thoughts or actions.
How can I watch for and try to prevent suicidal thoughts
and actions in myself or a family member?
Pay close attention to any changes, especially sudden changes, in mood,
behaviors, thoughts, or feelings. This is very important when an antidepressant
medicine is started or when the dose is changed.
Call the healthcare provider right away to report new or sudden changes in
mood, behavior, thoughts, or feelings.
Keep all follow-up visits with the healthcare provider as scheduled. Call
the healthcare provider between visits as needed, especially if you have
concerns about symptoms.
Call a
healthcare provider right away if you or your family member has any of the
following symptoms, especially if they are new, worse, or worry you:
· thoughts about suicide or dying
· attempts to commit suicide
· new or worse depression
· new or worse anxiety
· feeling very agitated or restless
· panic attacks
· trouble sleeping (insomnia)
· new or worse irritability
· acting aggressive, being angry, or violent
· acting on dangerous impulses
· an extreme increase in activity and talking
(mania)
· other unusual changes in behavior or mood
What
else do I need to know about antidepressant medicines?
Never stop an antidepressant medicine without first talking
to a healthcare provider. Stopping an antidepressant medicine suddenly
can cause other symptoms.
Antidepressants are medicines used to treat depression and
other illnesses. It is important to discuss all the risks of treating
depression and also the risks of not treating it. Patients and their families or
other caregivers should discuss all treatment choices with the healthcare
provider, not just the use of antidepressants.
Antidepressant medicines have other side effects.
Talk to the healthcare provider about the side effects of the medicine
prescribed for you or your family member.
Antidepressant medicines can interact with other
medicines. Know all of the medicines that you or your family member
takes. Keep a ul of all medicines to show the healthcare provider. Do not
start new medicines without first checking with your healthcare provider.
Not all antidepressant medicines prescribed for children
are FDA approved for use in children. Talk to your child’s healthcare
provider for more information.
Call you doctor for
medical advice about side effects. You may report side effects to FDA at
1-800-FDA-1088.
This Medication Guide
has been approved by the U.S. Food and Drug Administration for all
antidepressants.
"This tool does not provide medical advice, and is for informational and educational purposes only, and is not a substitute for professional medical advice, treatment or diagnosis. Call your doctor to receive medical advice. If you think you may have a medical emergency, please dial 911."
"Do not rely on openFDA to make decisions regarding medical care. While we make every effort to ensure that data is accurate, you should assume all results are unvalidated. We may limit or otherwise restrict your access to the API in line with our Terms of Service."
"This product uses publicly available data from the U.S. National Library of Medicine (NLM), National Institutes of Health, Department of Health and Human Services; NLM is not responsible for the product and does not endorse or recommend this or any other product."
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