A-Z Drug Facts > Mirtazapine

Mirtazapine

Pronouncation: (mer-TAZ-ah-peen)
Class: Tetracyclic compound

Trade Names:
Remeron
- Tablets 15 mg
- Tablets 30 mg
- Tablets 45 mg

Trade Names:
Remeron SolTab
- Tablets, orally disintegrating 15 mg
- Tablets, orally disintegrating 30 mg
- Tablets, orally disintegrating 45 mg

Pharmacology

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Unknown. May enhance central noradrenergic and serotonergic activity.

Pharmacokinetics

Absorption

Tablets and orally disintegrating tablets are rapidly and completely absorbed; absolute bioavailability about 50%. T _max is about 2 h. Food has a minimal effect on rate and extent of absorption. Steady state achieved in about 5 days.

Distribution

Plasma levels linearly related to dose (15 to 80 mg). Approximately 85% is protein bound.

Metabolism

Mirtazapine is extensively metabolized by demethylation and hydroxylation followed by glucuronide conjugation. CYP 2D6 and 1A2 are involved in formation of an 8-hydroxy metabolite. CYP3A is responsible for formation of N-desmethyl and N-oxide metabolites.

Elimination

Primary route of elimination is urine (75%) and feces (15%). The t _½ is about 20 to 40 h. The (−) enantiomer t _½ is about twice as long as the (+) enantiomer.

Onset

1 to 4 wk.

Special Populations

Renal Function Impairment

Cl reduced about 30% in patients with moderate (CrCl 11 to 39 mL/min) and about 50% in patients with severe (CrCl less than 10 mL/min) renal function impairment.

Hepatic Function Impairment

Cl decreased about 30% in patients with hepatic function impairment.

Elderly

Cl reduced 40% in elderly men and 10% in elderly women.

Gender

Women have longer elimination t _½ (37 h) than men (26 h).

Indications and Usage

Treatment of major depressive disorder.

Contraindications

Hypersensitivity to maprotiline or mirtazapine; concomitant use with MAOIs.

Dosage and Administration

Adults

PO 15 mg as single dose. If an inadequate response is noted, may increase dose in 15 mg increments, at intervals of no less than 1 to 2 wk, to max dose of 45 mg/day. For acute episodes, continue therapy for several months or longer.

General Advice

• Tablets and orally disintegrating tablets are interchangeable on a mg-to-mg basis.
• Administer prescribed dose once daily, preferably in the evening prior to sleep.
• Administer without regard to meals. Administer with food if GI upset occurs.

• Orally disintegrating tablets
• Orally disintegrating tablets contain phenylalanine. Do not administer to patient with phenylketonuria without first discussing with health care provider.
• Open tablet blister pack with dry hands and immediately place the tablet on the tongue. Allow tablet to disintegrate on tongue and then have patient swallow with saliva.
• Do not cut or split orally disintegrating tablet.

Storage/Stability

Store at controlled room temperature (59° to 86°F). Protect from light and moisture. Store orally disintegrating tablets in tablet blister and use immediately upon opening tablet blister.

Drug Interactions

Alcohol, CNS depressants

Additive CNS effects.

MAOIs

May precipitate hypertensive crisis and convulsions with possible fatal results. Do not use mirtazapine in combination with MAOIs, or within 14 days of starting or stopping therapy with MAOIs.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypertension, vasodilatation (at least 1%); torsades de pointes, ventricular arrhythmia, (postmarketing).

CNS

Somnolence (54%), increased appetite (17%); asthenia (8%); dizziness (7%); abnormal dreams (4%); abnormal thinking (3%); confusion, tremor (2%); agitation, amnesia, anxiety, apathy, depression, hyperkinesis, hypesthesia, hypokinesia, malaise, paresthesia, twitching, vertigo (at least 1%).

Dermatologic

Pruritus, rash (at least 1%).

GI

Dry mouth (25%); constipation (13%); nausea (2%); abdominal pain, acute abdominal syndrome, anorexia, vomiting (at least 1%).

Genitourinary

Urinary frequency (2%); UTI (at least 1%).

Metabolic-Nutritional

Weight gain (12%); peripheral edema (2%); edema (1%); thirst (at least 1%).

Musculoskeletal

Back pain, myalgia (2%); arthralgia, myasthenia (at least 1%).

Respiratory

Dyspnea (1%); increased cough, sinusitis (at least 1%).

Miscellaneous

Flu syndrome (5%).

Precautions

Warnings Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children and adolescents with major depressive disorder and other psychiatric disorders. When considering the use of any antidepressant in a child or adolescent, balance this risk with clinical need. Closely observe patients who are started on therapy for clinical worsening, suicidality, or unusual changes in behavior during the initial few months of therapy, or at times of dose changes, either increases or decreases. Advise families and caregivers of the need for close observation and communication with the prescriber. Mirtazapine orally disintegrating tablets are not approved for use in children.

Monitor Monitor children and adults for clinical worsening, suicidality, and unusual changes in behavior, especially during the first few months of therapy, or at times of dose changes, either increases or decreases. Evaluate children or their parents or caregivers at least weekly with face-to-face contact during the first 4 wk of therapy, then every other week for the next 4 wk, then at 12 wk, and as clinically indicated thereafter. Observe adults similarly for clinical worsening and suicidality, especially during the initial few months of therapy and following an increase or decrease in dose. The following symptoms may represent precursors to suicidality and should be reported to health care provider immediately if noted or suspected: aggressiveness, agitation, anxiety, hostility, hypomania, impulsivity, insomnia, irritability, mania, panic attacks, psychomotor restlessness. Frequently assess patient for response to treatment. Periodically review therapy to determine if therapy needs to be continued without change or if a dose change (eg, increase, decrease, discontinuation) is indicated.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Use with caution.

Renal Function

Use with caution.

Hepatic Function

Use with caution. Transaminase elevations may occur with symptoms of compromised liver function.

Special Risk Patients

Use with caution in patients with known CV or cerebrovascular disease that could be exacerbated by hypotension (eg, angina, history of MI, ischemic stroke) and conditions that would predispose patients to hypotension (eg, dehydration, hypovolemia, treatment with antihypertensive agents).

Hazardous Tasks

May impair judgment, thinking, or motor skills.

Activation of mania/hypomania

Has been reported. Use cautiously in patients with history of mania/hypomania.

Agranulocytosis

Neutropenia, with and without associated infection, has been reported rarely. Discontinue mirtazapine if patient develops neutropenia and a sore throat, fever, stomatitis, or other signs of infection, and closely monitor patient.

Cholesterol/Triglycerides

Increases have been reported.

Concomitant illness

Use with caution in patients with diseases or conditions that could affect metabolism or hemodynamic responses.

Increased appetite/weight gain

Increases in appetite and weight gain have been reported.

Phenylketonuria

Orally disintegrating tablets contain phenylalanine.

Screening for bipolar disorder

A major depressive episode may be the initial presentation of bipolar disorder and treating such an episode with an antidepressant alone may increase the likelihood of precipitating a mixed/manic episode in patients at risk for bipolar disorder. Screen patients with depression for risk of bipolar disorder prior to initiating therapy with an antidepressant.

Seizures

May occur; use with caution in patients with a history of seizures or with conditions that potentially lower the seizure threshold. Discontinue use if seizures occur.

Suicide

Suicidal ideation is inherent in depression and may persist until significant remission occurs. Closely supervise high-risk patients during initial drug therapy. Prescribe smallest quantity of medication consistent with good patient management in order to reduce risk of overdose.

Overdosage

Symptoms

Disorientation, drowsiness, impaired memory, tachycardia.

Patient Information

• Advise patient or caregiver to read patient information leaflet before starting therapy and to read and check for new information each time the medication is refilled.
• If patient is a child or adolescent being treated for depression, advise patient, their family, or caregiver to read the Medication Guide About Using Antidepressants in Children and Teenagers before starting therapy and with each refill. Review face-to-face monitoring schedule required for use of drug in this situation.
• Review dosing schedule with patient. Advise patient to take as a single daily dose in the evening prior to sleep.
• Advise patient that dose will be started low and then increased, if necessary, until max benefit is obtained.
• Advise patient to take each dose without regard to meals but to take with food if stomach upset occurs.
• Advise patient using orally disintegrating tablets to store tablets in blister pack until immediately before use, then open tablet blister pack with dry hands; immediately place the tablet on the tongue, allow tablet to disintegrate on tongue, and then swallow with saliva.
• Caution patient not to cut or split orally disintegrating tablet.
• Advise patient that if a dose is missed to take the missed dose as soon as possible unless it is nearing time for the next dose. If nearing time for the next dose, advise patient to skip the missed dose and take the next dose at the regularly scheduled time. Caution patient not to double the dose to catch up and to never take 2 doses at the same time.
• Instruct patient not to change the dose or stop taking medication unless advised by health care provider.
• Advise patient or caregiver that it may take between 1 and 4 wk of therapy before improvement is noted and not to stop taking the medication when they feel better.
• Instruct patient to contact health care provider if symptoms do not appear to be getting better, are getting worse, or if bothersome adverse reactions (eg, abnormal dreams, constipation, dizziness, excessive drowsiness, increased appetite) occur.
• Advise patient being treated for depression, and family or caregiver of patient, to be alert for abnormal changes in mood or thinking and to immediately report any of the following to health care provider: agitation, akathisia (psychomotor restlessness), anxiety, change in mood, change in personality, hostility or aggressiveness, impulsivity, insomnia, irritability, panic attacks, suicidal thoughts or behavior. Advise families and caregivers of patients to observe for emergence on a day-to-day basis because changes may be abrupt.
• Advise patient to take frequent sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
• Advise patient or caregiver to discontinue mirtazapine and immediately notify health care provider if fever, chills, sore throat, mouth sores, or other signs of infection are noted.
• Advise patient, family, or caregiver to notify health care provider if rash, hives, or other symptoms of an allergic reaction develop.
• Advise patient that if medication needs to be discontinued it will be slowly withdrawn unless safety concerns (eg, rash) require a more rapid withdrawal.
• Instruct patient to avoid alcoholic beverages and sedatives or depressants (eg, diazepam) while taking medication.
• Advise patient that drug may impair judgment, thinking, or motor skills, or cause drowsiness or dizziness, and to use caution while driving or performing other tasks requiring mental alertness or coordination until tolerance is determined.

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