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Apo-Doxepin (CA), Novo-Doxepin (CA), Prudoxin, Silenor, Sinepin (UK), Xepin (UK), Zonalon
Pharmacologic class: Tricyclic antidepressant
Therapeutic class: Antidepressant, anxiolytic, antipruritic
Pregnancy risk category C
FDA Box Warning
• Drug may increase risk of suicidal thinking and behavior in children and adolescents with major depressive disorder and other psychiatric disorders. Risk must be balanced with clinical need, as depression itself increases suicide risk. With patient of any age, observe closely for clinical worsening, suicidality, and unusual behavior changes when therapy begins. Advise family and caregivers to observe patient closely and communicate with prescriber as needed.
• Drug isn't approved for use in pediatric patients.
Unknown. May prevent reuptake of norepinephrine, serotonin, or both at presynaptic neurons, increasing levels of these neurotransmitters in CNS. Exact mechanism in pruritus also unknown, but drug is a potent histamine1- and histamine2-blocker.
Capsules: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150 mg
Cream (topical): 5% in 30-g tube
Oral concentrate: 10 mg/ml
Tablets: 3 mg, 6 mg
⊘Indications and dosages
➣ Endogenous depression; anxiety
Adults: Initially, 25 mg P.O. t.i.d., increased as needed up to 150 mg daily in outpatients and 300 mg daily in hospitalized patients
Elderly adults: Initially, 25 to 50 mg P.O. daily; may be increased as needed
➣ Short-term relief of histamine-mediated pruritus of moderate severity accompanying such conditions as eczematous dermatitis
Adults: Apply a thin film of cream to skin q.i.d., with 3 to 4 hours between applications, for a maximum of 8 days.
Adults: 6 mg P.O. daily 30 minutes before bedtime
• Elderly patients
• Hypersensitivity to drug or other dibenzoxepins
• Predisposition to urinary retention
• MAO inhibitor use within past 14 days
Use cautiously in:
• cardiovascular disease, prostatic enlargement, seizures
• severe sleep apnea (use not recommended)
• elderly patients
• pregnant or breastfeeding patients.
• If desired, mix contents of capsule with food.
• Dilute oral concentrate with 120 ml of water, milk, or juice. Be aware that drug is incompatible with carbonated beverages.
• Know that drug may be given at bedtime to prevent daytime sleepiness. If given for insomnia, avoid giving within 3 hours of a meal.
☞ Don't give within 14 days of MAO inhibitor, because drug interaction may cause cardiovascular instability.
☞ Avoid concurrent use of other CNS depressants, because inadvertent overdose may occur.
• With topical cream, don't apply to broken skin or use occlusive dressings, because doing so increases dermal absorption.
• Be aware that drug is usually given in conjunction with psychotherapy when used for depression.
CNS: fatigue, sedation, agitation, confusion, hallucinations, drowsiness, dizziness, extrapyramidal reactions, poor concentration, syncope, seizures, cerebrovascular accident, increased risk of suicide or suicidal ideation (especially in child or adolescent)
CV: hypotension, orthostatic hypotension, hypertension, vasculitis, ECG changes, tachycardia, palpitations, arrhythmias, myocardial infarction, heart block
EENT: blurred vision, increased intraocular pressure, lacrimation, tinnitus, nasal congestion
GI: nausea, constipation, dry mouth, paralytic ileus
GU: urinary retention, delayed voiding, urinary tract dilation, gynecomastia, galactorrhea, menstrual irregularities, testicular swelling, libido changes
Hematologic: purpura, bone marrow depression, eosinophilia, agranulocytosis, thrombocytopenia, leukopenia
Metabolic: hyperglycemia, hypoglycemia
Skin: photosensitivity, rash, urticaria, pruritus, diaphoresis, flushing, petechiae, alopecia, local burning, stinging, tingling, irritation, or rash (with topical use)
Other: increased appetite, weight gain or loss, hyperthermia, chills, edema, drug-induced fever, hypersensitivity reactions
Drug-drug.Barbiturates, CNS depressants (including antihistamines, clonidine, opioids, sedative-hypnotics): additive CNS depression
Carbamazepine, class IC antiarrhythmics (flecainide, propafenone), other antidepressants, other CYP450-2D6 inhibitors (amiodarone, cimetidine, quinidine, ritonavir), phenothiazines: increased doxepin blood level and effects
Clonidine: hypertensive crisis
Guanethidine: antagonism of antihypertensive effects
Levodopa: delayed or decreased levodopa absorption, hypertension
MAO inhibitors: tachycardia, seizures, potentially fatal reactions
Rifamycin: decreased doxepin effects
Selective serotonin reuptake inhibitors: increased risk of toxicity
Drug-diagnostic tests.Bilirubin, hepatic enzymes: increased levels
Glucose: increased or decreased level
Liver function tests: altered results
Drug-herbs.Angel's trumpet, jimsonweed, scopolia: increased anticholinergic effects
Chamomile, hops, kava, skullcap, valerian: increased CNS depression
Evening primrose oil: additive or synergistic effects
S-adenosylmethionine (SAM-e), St. John's wort, yohimbe: serotonin syndrome
Drug-behaviors.Alcohol use: increased CNS depression
Smoking: increased drug metabolism and altered effects
Sun exposure: increased risk of photosensitivity reactions
☞ Record mood changes and watch for suicidal tendencies, especially in child or adolescent.
• Assess bowel elimination pattern. Increase fluids and administer stool softeners as ordered to ease constipation.
• Monitor fluid intake and output. Report changes in voiding pattern.
• Monitor liver function test results, CBC with white cell differential, and glucose level.
• Tell patient to take drug 30 minutes before bedtime and not within 3 hours of a meal when taking for insomnia.
• Advise patient on long-term therapy not to stop taking drug abruptly because this may lead to nausea, headache, and malaise.
☞ Instruct patient and significant other, as appropriate, to monitor mental status carefully and to immediately report increased depression or suicidal thoughts or behavior (especially when used in child or adolescent).
☞ Tell patient to promptly report easy bruising or bleeding.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
• Instruct patient to move slowly when sitting up or standing, to avoid dizziness or light-headedness from sudden blood pressure decrease.
• Explain that drowsiness and dizziness usually subside after several weeks.
• Tell patient that using topical cream on more than 10% of body surface area may cause drowsiness.
• Caution patient using topical cream not to apply it to broken skin and not to use occlusive dressings. Also tell him to avoid contact with eyes and to rinse eyes thoroughly with warm water if contact occurs.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, herbs, and behaviors mentioned above.
ClassificationTherapeutic: antianxiety agents
Pharmacologic: tricyclic antidepressants
- Eczematous dermatitis,
- Lichen simplex chronicus.
- Chronic pain syndromes,
Time/action profile (antidepressant activity)
|PO||2–3 wk||up to 6 wk||days–weeks|
Adverse Reactions/Side Effects
Central nervous system
- fatigue (most frequent)
- sedation (most frequent)
Ear, Eye, Nose, Throat
- blurred vision (most frequent)
- ↑ intraocular pressure
- hypotension (most frequent)
- ECG abnormalities
- constipation (most frequent)
- dry mouth (most frequent)
- ↑ appetite
- paralytic ileus
- weight gain
- ↓ libido
- urinary retention
- blood dyscrasias
- hypersensitivity reactions
InteractionsApply to both topical and oral use
Drug-Drug interactionDoxepin is metabolized in the liver by the cytochrome P450 2D6 enzyme and its action may be affected by drugs that compete for metabolism by this enzyme including other antidepressants, phenothiazines, carbamazepine, propafenone, flecainide ; when used concurrently, dosage ↓ of one or the other or both may be necessary. Concurrent use of other drugs that inhibit the activity of the enzyme, including cimetidine, quinidine, amiodarone, and ritonavir, may result in ↑ effects of doxepin.May cause hypotension, tachycardia, and potentially fatal reactions when used with MAO inhibitors (avoid concurrent use—discontinue 2 wk prior to doxepin).Concurrent use with SSRIantidepressants may result in ↑ serotonin syndrome and should be avoided (fluoxetine should be stopped 5 wk before).Concurrent use with clonidine may result in hypertensive crisis and should be avoided.Concurrent use with levodopa may result in delayed/↓ absorption of levodopa or hypertension.Blood levels and effects may be ↓ by rifamycins.↑ CNS depression with other CNS depressants including alcohol, antihistamines, clonidine, opioid analgesics, and sedative/hypnotics.Barbiturates may alter blood levels and effects.Adrenergic and anticholinergic side effects may be ↑ with other agents having these properties.Phenothiazines or hormonal contraceptives ↑ levels and may cause toxicity.Smoking may ↑ metabolism and alter effects.Concomitant use of kava-kava, valerian, or chamomile can ↑ CNS depression.↑ anticholinergic effects with jimson weed and scopolia.
Availability (generic available)
- Monitor BP and pulse rate prior to and during initial therapy. Patients taking high doses or with a history of cardiovascular disease should have ECG monitored prior to and periodically during therapy.
- Assess for sexual dysfunction (decreased libido; erectile dysfunction).
- Assess weight and BMI initially and throughout treatment. Obtain FBS and cholesterol levels in overweight/obese individuals.
- Geriatric: Assess falls risk and institute fall prevention strategies. Assess for anticholinergic effects.
- Depression: Assess mental status and mood changes (orientation, mood, behavior) frequently, especially during initial few months of therapy and during dose changes. Confusion, agitation, and hallucinations may occur during initiation of therapy and may require dose reduction. Assess for suicidal tendencies, especially during early therapy. Restrict amount of drug available to patient. Risk may be increased in children, adolescents, and adults ≤24 yr. Inform health care professional if patient demonstrates significant increase in signs of depression (depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, suicide attempt or suicidal ideation). Restrict amount of drug available to patient.
- Assess for serotonin syndrome (mental changes [agitation, hallucinations, coma], autonomic instability [tachycardia, labile BP, hyperthermia], neuromuscular aberrations [hyperreflexia, incoordination], and/or GI symptoms [nausea, vomiting, diarrhea]), especially in patients taking other serotonergic drugs (SSRIs, SNRIs, triptans).
- Anxiety: Assess degree and manifestations of anxiety prior to and during therapy.
- Pain: Assess the type, location, and severity of pain prior to and periodically during therapy. Use pain scale to assess effectiveness of therapy.
- Topical: Assess pruritic area prior to and periodically during therapy.
- Lab Test Considerations: Monitor WBC and differential blood counts, hepatic function, and serum glucose periodically. May cause ↑ serum bilirubin and alkaline phosphatase levels. May cause bone marrow depression. Serum glucose may be ↑ or ↓.
Potential Nursing DiagnosesIneffective coping (Indications)
Risk for injury (Side Effects)
Sexual dysfunction (Side Effects)
- Do not confuse Sinequan with Seroquel, saquinavir, Singulair, or Zonegran.
- May be given as a single dose 30 min before bedtime to minimize sedation during the day. Dose increases should be made at bedtime because of sedation. Dose titration is a slow process; may take weeks to months.
- To avoid withdrawal, taper by 50% for 3 days, then 50% again for 3 days, then discontinue.
- Oral: Administer medication with or immediately following a meal to minimize gastric irritation. Capsules may be opened and mixed with foods or fluids if patient has difficulty swallowing.
- Oral concentrate must be diluted in at least 120 mL of water, milk, or fruit juice. Do not mix with carbonated beverages or grape juice. Use calibrated measuring device to ensure accurate amount.
- Topical: Apply thin film of doxepin cream only to affected areas, and rub in gently. Apply only to affected skin; not for ophthalmic, oral, or intravaginal use.
- Inform patient that systemic side effects may occur with oral or topical use.
- May cause drowsiness and blurred vision. Caution patient to avoid driving and other activities requiring alertness until response to the medication is known.
- Orthostatic hypotension, sedation, and confusion are common during early therapy, especially in geriatric patients. Protect patient from falls. Institute fall precautions. Advise patient to change positions slowly.
- Advise patient to avoid alcohol or other CNS depressant drugs during and for at least 3–7 days after therapy has been discontinued.
- Inform patient that doxepin may cause getting up out of bed while not being fully awake and doing an activity that patient does not know he is doing. The next morning, he may not remember that he did anything during the night. May occur more frequently with alcohol or other sedatives. Advise patient to notify health care professional if this occurs.
- Instruct patient to notify health care professional if urinary retention occurs or if dry mouth or constipation persists. Sugarless candy or gum may diminish dry mouth, and an increase in fluid intake or bulk may prevent constipation. If symptoms persist, dose reduction or discontinuation may be necessary. Consult health care professional if dry mouth persists for more than 2 wk.
- Advise patient to notify health care professional of medication regimen prior to treatment or surgery.
- Oral: Instruct patient to take medication as directed. Take missed doses as soon as possible unless almost time for next dose; if regimen is a single dose at bedtime, do not take in the morning because of side effects. Advise patient that drug effects may not be noticed for at least 2 wk. Abrupt discontinuation may cause nausea, vomiting, diarrhea, headache, trouble sleeping with vivid dreams, and irritability. Advise patient, family, and caregivers to look for suicidality, especially during early therapy or dose changes. Notify health care professional immediately if thoughts about suicide or dying, attempts to commit suicide, new or worse depression or anxiety, agitation or restlessness, panic attacks, insomnia, new or worse irritability, aggressiveness, acting on dangerous impulses, mania, or other changes in mood or behavior or if symptoms of serotonin syndrome occur.
- Caution patient to use sunscreen and protective clothing to prevent photosensitivity reactions.
- Inform patient that urine may turn blue-green in color.
- Inform patient of need to monitor dietary intake. Increase in appetite is possible and may lead to undesired weight gain.
- Therapy for depression is usually prolonged. Emphasize the importance of follow-up exams to monitor effectiveness and side effects.
- Topical: Instruct patient to apply a thin film of medication exactly as directed; do not use more medication than directed, apply to a larger area than directed, use more often than directed, or use longer than 8 days.
- Inform patient that topical preparation may cause burning, stinging, swelling, increased itching, or worsening of eczema. Notify health care professional if these symptoms become bothersome.
- Caution patient not to use occlusive dressings; may increase systemic absorption.
- Advise patient to notify health care professional if excessive drowsiness occurs with topical application. Number of applications per day, amount of cream applied, or area of application may be reduced. May require discontinuation of therapy.
- Increased sense of well-being.
- Renewed interest in surroundings.
- Increased appetite.
- Improved energy level.
- Improved sleep.
- Decrease in anxiety.
- Decrease in chronic pain. Patients may require 2–6 wk of oral therapy before full therapeutic effects of medication are evident.
- Decrease in pruritus associated with eczema.