doxepin (systemic)

Contraindicated in:

Hypersensitivity;
Concurrent use of MAO inhibitors;
Some products contain bisulfites and should be avoided in patients with known intolerance;
Untreated angle-closure glaucoma;
Severe urinary retention;
QT interval prolongation, HF, cardiac arrhythmia or recent history of MI;
Lactation: Lactation.

Use Cautiously in:

Pre-existing cardiovascular disease (↑ risk of adverse reactions);
Prostatic enlargement (more susceptible to urinary retention);
Seizures;
OB: Neonates exposed during late third trimester at ↑ risk for complications at birth (prolonged hospitalization, respiratory support, and tube feeding); use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Pedi: May ↑ risk of suicide attempt/ideation especially during dose early treatment or dose adjustment; risk may be greater in children or adolescents; safety not established;
Geri: Appears on Beers list. ↑ risk of adverse reactions in older adults, including falls secondary to sedative and anticholinergic effects and orthostatic hypotension. Avoid use of dose >6 mg/day in older adults. .

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension, arrhythmias

Derm: photosensitivity, rash

EENT: blurred vision, ↑intraocular pressure

GI: constipation, dry mouth, hepatitis, nausea, paralytic ileus

GU: ↓libido, urinary retention

Hemat: blood dyscrasias

Metab: ↑appetite, weight gain

Neuro: fatigue, sedation, agitation, confusion, hallucinations

Misc: hypersensitivity reactions

Interactions ⬆ ⬇

Drug-drug:

CYP2D6 inhibitors, including cimetidine, quinidine, amiodarone, and ritonavir, may ↑ levels and risk of toxicity.
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 SSRIs 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.

Drug-Natural Products:

Concomitant use of kava-kava, valerian, or chamomile can ↑ CNS depression.
↑anticholinergic effects with jimson weed and scopolia.

Availability ⬆ ⬇

(Generic available)

Tablets (Silenor): 3 mg; 6 mg
Capsules: 10 mg; 25 mg; 50 mg; 75 mg; 100 mg; 150 mg
Oral concentrate: 10 mg/mL

Route/Dosage ⬆ ⬇

PO (Adults ): Antidepressant/antianxiety: 25 mg 3 times daily, may ↑ as needed (up to 150 mg/day in outpatients or 300 mg/day in inpatients; some patients may require only 25–50 mg/day). Once stabilized, entire daily dose may be given at bedtime. Antipruritic: 10 mg at bedtime initially, may ↑ up to 25 mg at bedtime. Insomnia: 6 mg at bedtime (should not exceed 3 mg/day if concurrently taking cimetidine).
PO Geriatric Patients ): Antidepressant: 25–50 mg/day initially, may ↑ as needed. Insomnia: 3 mg at bedtime, may ↑ as needed to 6 mg at bedtime (should not exceed 3 mg/day if concurrently taking cimetidine).

US Brand Names ⬆ ⬇

Action ⬆ ⬇

Prevents the reuptake of norepinephrine and serotonin by presynaptic neurons; resultant accumulation of neurotransmitters potentiates their activity.
Also possesses significant anticholinergic properties.

Therapeutic effects:

Relief of depression.
Decreased anxiety.
Sedation and improved sleep maintenance.

Classifications ⬆ ⬇

Therapeutic Classification: antianxiety agents, antidepressants, sedative/hypnotics

Pharmacologic Classification: tricyclic antidepressants

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed from the GI tract, although much is metabolized on first pass through the liver.

Distribution: Widely distributed to tissues.

Metabolism/Excretion: Metabolized by the liver by the CYP2C19 and CYP2D6 isoenzymes; the CYP2C19 isoenzyme exhibits genetic polymorphism; 15–20% of Asian patients and 3–5% of Caucasian and Black patients may be poor metabolizers of CYP2C19 and may have significantly ↑ doxepin concentrations and an ↑ risk of adverse effects; the CYP2D6 isoenzyme also exhibits genetic polymorphism; ∼7% of population may be poor metabolizers of CYP2D6 and may have significantly ↑ doxepin concentrations and an ↑ risk of adverse effects. Some conversion to active antidepressant compound. May re-enter gastric juice via secretion from enterohepatic circulation, where more absorption may occur.

Half-Life: 8–25 hr.

Canadian Brand Names ⬆ ⬇

Time/Action Profile ⬆ ⬇

(antidepressant activity)

ROUTE	ONSET	PEAK	DURATION
PO	2–3 wk	up to 6 wk	days–weeks

Patient/Family Teaching ⬆ ⬇

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, including opioids, 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.
- May be harmful to fetus. Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected and to avoid breastfeeding during therapy. Monitor neonates who were exposed to doxepin in the third trimester of pregnancy for poor neonatal adaptation syndrome. Monitor infants exposed to doxepin through breast milk for excess sedation, respiratory depression and hypotonia. May reduce fertility in males and females.
PO: 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.

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Indications ⬇

Contraind./Precautions ⬆ ⬇