trazodone

Absorption: Well absorbed after oral administration.

Distribution: Widely distributed to tissues.

Protein Binding: 89–95%.

Metabolism/Excretion: Extensively metabolized by the liver via the CYP3A4 isoenzyme; minimal excretion of unchanged drug by the kidneys.

Half-Life: 5–9 hr.

Time/Action Profile ⬆ ⬇

(antidepressant effect)

ROUTE	ONSET	PEAK	DURATION
PO	1–2 wk	2–4 wk	wk

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Recovery period after MI;
Concurrent electroconvulsive therapy;
Concurrent use of MAO inhibitors or MAO-inhibitor-like drugs (linezolid or methylene blue);
Angle-closure glaucoma;
Lactation: Lactation.

Use Cautiously in:

May ↑ risk of suicide attempt/ideation especially during early treatment or dose adjustment; this risk appears to be greater in adolescents or children
;
Cardiovascular disease;
Hypovolemia or dehydration (↑ risk of syndrome of inappropriate antidiuretic hormone secretion [SIADH]);
Severe renal impairment (↓ dose);
Severe hepatic impairment (↓ dose);
OB: Other agents preferred for treatment of depression or insomnia in pregnancy;
Pedi: Safety and effectiveness not established in children;
Geri: ↑risk of SIADH in older adults. Initial dose ↓ recommended in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension, arrhythmias, chest pain, hypertension, palpitations, QT interval prolongation, tachycardia

Derm: rash

EENT: blurred vision, tinnitus

F and E: hyponatremia, SIADH

GI: dry mouth, constipation, diarrhea, excess salivation, flatulence, nausea, vomiting

GU: erectile dysfunction, hematuria, priapism, urinary frequency

Hemat: anemia, leukopenia

MS: myalgia

Neuro: drowsiness, confusion, dizziness, dysgeusia, fatigue, hallucinations, headache, insomnia, nightmares, slurred speech, SUICIDAL THOUGHTS/BEHAVIORS, syncope, tremor, weakness

Interactions ⬆ ⬇

Drug-drug:

Serious, potentially fatal reactions (hyperthermia, rigidity, myoclonus, autonomic instability, with fluctuating vital signs and extreme agitation, which may proceed to delirium and coma) may occur with concurrent MAO inhibitors. MAO inhibitors should be stopped ≥14 days before trazodone therapy. Trazodone should be stopped ≥14 days before MAO inhibitor therapy.
MAO-inhibitor-like drugs, such as linezolid or methylene blue, may ↑ risk of serotonin syndrome; concurrent use contraindicated; do not start therapy in patients receiving linezolid or methylene blue; if linezolid or methylene blue need to be started in a patient receiving trazodone, immediately discontinue trazodone and monitor for signs/symptoms of serotonin syndrome for 2 wk or until 24 hr after last dose of linezolid or methylene blue, whichever comes first (may resume trazodone therapy 24 hr after last dose of linezolid or methylene blue).
May ↑ digoxin or phenytoin levels and the risk of toxicity.
↑CNS depression with other CNS depressants, including alcohol, opioid analgesics, and sedative/hypnotics.
↑risk of hypotension with antihypertensives, acute ingestion of alcohol, or nitrates.
Fluoxetine may ↑ levels and risk of toxicity.
CYP3A4 inhibitors, including ritonavir and ketoconazole, may ↑ levels and risk of toxicity.
CYP3A4 inducers, including carbamazepine, may ↓ levels and effectiveness.
Drugs that affect serotonergic neurotransmitter systems, including tricyclic antidepressants, fentanyl, buspirone, tramadol and triptans, may ↑ the risk of serotonin syndrome.
↑risk of bleeding with NSAIDs, aspirin, clopidogrel, prasugrel, ticagrelor, or warfarin.
Diuretics may ↑ risk of SIADH.

Drug-Natural Products:

Kava-kava, valerian, or chamomile can ↑ CNS depression.
↑risk of serotonergic side effects including serotonin syndrome with St. John’s wort and SAMe.

Route/Dosage ⬆ ⬇

Depression

PO (Adults ): 150 mg/day in 3 divided doses; ↑ by 50 mg/day every 3–4 days until desired response (not to exceed 400 mg/day in outpatients or 600 mg/day in hospitalized patients).
PO Geriatric Patients ): 75 mg/day in divided doses initially; may be ↑ every 3–4 days.

Insomnia

PO (Adults ): 25–100 mg at bedtime.

Availability ⬆ ⬇

(Generic available)

Tablets: 50 mg; 100 mg; 150 mg; 300 mg
Oral solution: 10 mg/mL

Assessment ⬆ ⬇

Monitor BP and HR before and during initial therapy. Monitor ECGs in patients with pre-existing cardiac disease before and periodically during therapy to detect arrhythmias.
Assess for possible sexual dysfunction.
Assess for serotonin syndrome (mental changes [agitation, hallucinations, coma], autonomic instability [tachycardia, labile BP, hyperthermia], neuromuscular aberrations [hyperreflexia, incoordination], GI symptoms [nausea, vomiting, diarrhea]), especially in patients taking other serotonergic drugs (SSRIs, SNRIs, triptans).
Depression: Assess mental status (orientation, mood, and behavior) frequently.
- Assess for suicidal tendencies, especially during early therapy. Restrict amount of drug available to patient. Risk may be ↑ in patients ≤24 yr. After starting therapy, young adults should be seen by health care provider at least weekly for 4 wk, every 3 wk for next 4 wk, and on advice of health care provider thereafter.

Lab Test Considerations:

Assess CBC and renal and hepatic function before starting and periodically during therapy. Slight, clinically insignificant ↓ in leukocyte and neutrophil counts may occur.
May cause hyponatremia, especially in older adults, those on diuretics, and those who are hypovolemic. If symptomatic hyponatremia occurs, discontinue trazodone and treat as indicated.

Implementation ⬆ ⬇

Do not confuse trazodone with tramadol.
PO: Administer with or immediately after meals to minimize side effects (nausea, dizziness) and allow maximum absorption. A larger portion of the total daily dose may be given at bedtime to ↓ daytime drowsiness and dizziness.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
Instruct patient to take missed dose as soon as remembered. Do not take if within 4 hr of next scheduled dose; do not double dose.
Advise patient to consult health care provider before discontinuing medication; gradual dose reduction is necessary to prevent discontinuation syndrome.
May cause drowsiness and blurred vision. Caution patient to avoid driving and other activities requiring alertness until response to drug is known.
Caution patient to change positions slowly to minimize orthostatic hypotension.
Advise patient to avoid concurrent use of alcohol or other CNS depressant drugs.
Advise patient family, and caregivers to look for suicidality, especially during early therapy or dose changes. Notify health care provider 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 occur.
Advise patient and caregivers to immediately notify health care provider if symptoms of serotonin syndrome (mental changes [agitation, hallucinations, coma], autonomic instability [tachycardia, labile BP, hyperthermia], neuromuscular aberrations [hyperreflexia, incoordination], GI symptoms [nausea, vomiting, diarrhea]) occur.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care provider before taking other medications, especially aspirin and NSAIDs.
Inform patient that frequent rinses, good oral hygiene, and sugarless candy or gum may diminish dry mouth. Health care provider should be notified if this persists >2 wk. An ↑ in fluid intake, fiber, and exercise may prevent constipation.
Advise patient to notify health care provider of medication regimen before treatment or surgery.
Instruct patient to notify health care provider if priapism, irregular heartbeat, fainting, confusion, skin rash, or tremors occur or if dry mouth, nausea and vomiting, dizziness, headache, muscle aches, constipation, or diarrhea becomes pronounced.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned and to avoid breastfeeding during therapy.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇