mirtazapine

Absorption: Well absorbed but rapidly metabolized, resulting in 50% bioavailability.

Distribution: Unknown.

Protein Binding: 85%.

Metabolism/Excretion: Extensively metabolized by the liver by the CYP1A2, CYP2D6, and CYP3A isoenzymes; metabolites excreted in urine (75%) and feces (15%).

Half-Life: 20–40 hr.

Time/Action Profile ⬆ ⬇

(antidepressant effect)

ROUTE	ONSET	PEAK	DURATION
PO	1–2 wk	6 wk or more	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Concurrent use of MAO inhibitors or MAO-like drugs (linezolid or methylene blue).

Use Cautiously in:

History of seizures;
History of suicide attempt;
May ↑ risk of suicide attempt/ideation especially during early treatment or dose adjustment;
History of mania/hypomania;
Patients with hepatic or renal impairment;
Angle-closure glaucoma;
OB: Other antidepressants are preferred in pregnancy;
Lactation: Other antidepressants are preferred when breastfeeding;
Pedi: Safety and effectiveness in children not established. Suicide risk may be greater in children or adolescents;
Geri: Appears on Beers list. May worsen or cause syndrome of inappropriate antidiuretic hormone (SIADH) secretion and/or hyponatremia in older adults. Use with caution in older adults and closely monitor sodium concentrations when starting therapy or dose.

Adv. Reactions/Side Effects ⬆ ⬇

CV: edema, hypotension

Derm: BULLOUS DERMATITIS, DRUG REACTION WITH EOSINOPHILIA AND SYSTEMIC SYMPTOMS (DRESS), ERYTHEMA MULTIFORME, pruritus, rash, STEVENS-JOHNSON SYNDROME, TOXIC EPIDERMAL NECROLYSIS

EENT: sinusitis

Endo: SIADH

F and E: ↑thirst, hyponatremia

GI: ↑appetite, constipation, dry mouth, ↑liver enzymes, abdominal pain, anorexia, nausea, vomiting

GU: urinary frequency

Hemat: AGRANULOCYTOSIS

Metab: weight gain, hypercholesterolemia, hypertriglyceridemia

MS: arthralgia, back pain, myalgia

Neuro: drowsiness, abnormal dreams, abnormal thinking, agitation, akathisia, anxiety, apathy, confusion, dizziness, hyperkinesia, hypoesthesia, malaise, NEUROLEPTIC MALIGNANT SYNDROME, SUICIDAL THOUGHTS, twitching, weakness

Resp: cough, dyspnea

Misc: flu-like syndrome, SEROTONIN SYNDROME

Interactions ⬆ ⬇

Drug-drug:

May cause hypertension, seizures, and death when used with MAO inhibitors; do not use within 14 days of MAO inhibitor therapy.
Concurrent use with 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 mirtazapine, immediately discontinue mirtazapine 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 mirtazapine therapy 24 hr after last dose of linezolid or methylene blue)
Drugs that affect serotonergic neurotransmitter systems, including tricyclic antidepressants, SNRIs, fentanyl, buspirone, tramadol, and triptans↑ risk of serotonin syndrome
↑CNS depression with other CNS depressants, including alcohol and benzodiazepines.
Ketoconazole, cimetidine, clarithromycin, erythromycin, itraconazole, nefazodone, nelfinavir, or ritonavir may ↑ levels.
Phenobarbital, phenytoin, carbamazepine, rifampin, or rifabutin may ↓ levels; may need to ↑ mirtazapine dose.
May ↑ the effects and risk of bleeding from warfarin.

Drug-Natural Products:

Concomitant use of kava-kava, valerian, skullcap, chamomile, or hops can ↑ CNS depression.
↑risk of serotonin syndrome with St. John’s wort and SAMe.

Route/Dosage ⬆ ⬇

PO (Adults ): 15 mg/day as a single bedtime dose initially; may be ↑ every 1–2 wk up to 45 mg/day.

Availability ⬆ ⬇

(Generic available)

Tablets: 7.5 mg; 15 mg; 30 mg; 45 mg
Orally disintegrating tabletsorange flavor: 15 mg; 30 mg; 45 mg

Assessment ⬆ ⬇

Assess mental status (orientation, mood, behavior) frequently. Assess for suicidal tendencies, especially during early therapy. Restrict amount of drug available to patient.
Monitor closely for changes in behavior that could indicate the emergence or worsening of suicidal thoughts or behavior or depression.
Assess weight and BMI initially and throughout therapy. For overweight/obese individuals, obtain fasting blood glucose and cholesterol levels. Refer as appropriate for nutritional/weight management and medical management.
Monitor BP and pulse rate periodically during initial therapy. Report significant changes.
Monitor for seizure activity in patients with a history of seizures or alcohol abuse. Institute seizure precautions.
Assess skin periodically during therapy. Severe skin reactions, including drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens-Johnson syndrome, bullous dermatitis, erythema multiforme and toxic epidermal necrolysis may occur. Discontinue mirtazapine immediately if signs of severe skin reactions occur.
Assess for serotonin syndrome (mental changes [agitation, hallucinations, coma], autonomic instability [tachycardia, labile BP, hyperthermia], neuromuscular aberrations [hyper reflexia, incoordination], and/or GI symptoms [nausea, vomiting, diarrhea]), especially in patients taking other serotonergic drugs (SSRIs, SNRIs, triptans).
Monitor for development of neuroleptic malignant syndrome (fever, respiratory distress, tachycardia, seizures, diaphoresis, hypertension or hypotension, pallor, tiredness). Discontinue mirtazapine and notify health care professional immediately if these symptoms occur.

Lab Test Considerations:

Assess CBC and hepatic function before and periodically during therapy.

Implementation ⬆ ⬇

Do not confuse Remeron with Rozerem.
May be given as a single dose at bedtime to minimize excessive drowsiness or dizziness.
- May be taken without regard to food.
For orally disintegrating tablets, do not attempt to push through foil backing; with dry hands, peal back backing and remove tablet. Immediately place tablet on tongue; tablet will dissolve in sec, then swallow with saliva. Administration with liquid is not necessary.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take mirtazapine as directed. Take missed doses as soon as remembered; if almost time for next dose, skip missed dose and return to regular schedule. If single bedtime dose regimen is used, do not take missed dose in morning, but consult health care professional. Do not discontinue abruptly; gradual dose reduction may be required. Advise patient to read Medication Guide before starting therapy and with each Rx refill in case of changes.
May cause drowsiness and dizziness. Caution patient to avoid driving and other activities requiring alertness until response to drug is known.
Encourage patient and family to be alert for emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, mania, worsening of depression and suicidal ideation, especially during early antidepressant therapy. Assess symptoms on a day-to-day basis as changes may be abrupt. If these symptoms occur, notify health care professional.
Caution patient to change positions slowly to minimize orthostatic hypotension.
Advise patient to avoid alcohol or other CNS depressant drugs during and for at least 3–7 days after therapy has been discontinued.
Instruct patient to notify health care professional of signs and symptoms of serotonin syndrome (mental status changes: agitation, hallucinations, coma; autonomic instability: tachycardia, labile BP, hyperthermia; neuromuscular aberrations: hyperreflexia, incoordination; and/or gastrointestinal symptoms: nausea, vomiting, diarrhea) or rash occur.
Advise patient to notify health care professional if dry mouth, urinary retention, or constipation occurs. Frequent rinses, good oral hygiene, and sugarless candy or gum may diminish dry mouth. An increase in fluid intake, fiber, and exercise may prevent constipation.
Inform patient of need to monitor dietary intake. Increase in appetite may lead to undesired weight gain.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications, especially St. John's wort.
Advise patient to notify health care professional of medication regimen before treatment or surgery.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Inform patient of National Pregnancy Registry for Antidepressants that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. Register patients by calling 1-844-405-6185 or visiting online at https://womensmentalhealth.org/clinical-and-research-programs/pregnancyregistry/antidepressants/.
Therapy for depression may be prolonged. Emphasize the importance of follow-up exam to monitor effectiveness and side effects.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇