Class: Tetracyclic compound
- Tablets 7.5 mg
- Tablets 15 mg
- Tablets 30 mg
- Tablets 45 mg
- Tablets, orally disintegrating 15 mg
- Tablets, orally disintegrating 30 mg
- Tablets, orally disintegrating 45 mg
CO Mirtazapine (Canada)
Novo-Mirtazapine OD (Canada)
Remeron RD (Canada)
Sandoz Mirtazapine (Canada)
Sandoz Mirtazapine FC (Canada)
Unknown. May enhance central noradrenergic and serotonergic activity.
Tablets and orally disintegrating tablets are rapidly and completely absorbed; absolute bioavailability is approximately 50%. T max is about 2 h. Food has a minimal effect on rate and extent of absorption. Steady state is achieved in approximately 5 days.
Plasma levels are linearly related to dose (15 to 80 mg). Approximately 85% is protein bound.
Mirtazapine is extensively metabolized by demethylation and hydroxylation followed by glucuronide conjugation. CYP2D6 and CYP1A2 are involved in formation of an 8-hydroxy metabolite. CYP3A is responsible for formation of N-desmethyl and N-oxide metabolites.
Primary route of elimination is urine (75%) and feces (15%). The half-life is about 20 to 40 h. The (−) enantiomer half-life is about twice as long as the (+) enantiomer.
Special PopulationsRenal Function Impairment
Cl is reduced approximately 30% in patients with moderate (CrCl 11 to 39 mL/min) and approximately 50% in patients with severe (CrCl less than 10 mL/min) renal function impairment.Hepatic Function Impairment
Cl is decreased approximately 30% in patients with hepatic function impairment.Elderly
Cl is reduced 40% in elderly men and 10% in elderly women.Gender
Women have a longer elimination half-life (37 h) than men (26 h).Race
The effects of race on pharmacokinetics have not been studied.
Indications and Usage
Treatment of major depressive disorder.
Sensitivity to mirtazapine or any component of the product; concomitant use with MAOIs or within 14 days of initiating or discontinuing use of an MAOI.
Dosage and AdministrationAdults
PO 15 mg/day as single dose, preferably in the evening. Dose may be increased at intervals of 1 to 2 wk to a max of 45 mg/day. Efficacy is maintained for up to 40 wk.
- 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
- Inform patients that orally disintegrating tablets contain phenylalanine.
- Open tablet blister pack with dry hands and immediately place the tablet on the tongue. Instruct patient to allow tablet to disintegrate on tongue and then to swallow with saliva.
- Do not cut or split orally disintegrating tablet.
Store at 59° to 86°F. Protect from light and moisture. Store orally disintegrating tablets in tablet blister and use immediately upon opening tablet blister.
Drug InteractionsAlcohol, CNS depressants (eg, diazepam)
Additive CNS effects. Advise patients to avoid alcohol and other CNS depressants while taking mirtazapine.Clonidine
The antihypertensive effects of clonidine may be reduced. Closely monitor BP when mirtazapine is started or stopped and adjust the clonidine dose as needed.CYP inducers (eg, carbamazepine, hydantoins [eg, phenytoin], rifampin)
In vitro, mirtazapine is a substrate for several CYP-450 enzymes (eg, 2D6, 1A2, 3A4). Mirtazapine plasma concentrations may be reduced by CYP inducers, decreasing the pharmacologic effect. Use with caution. Monitor the clinical response of the patient when starting or stopping a CYP inducer and adjust the mirtazapine dose as needed.CYP inhibitors (eg, azole antifungal agents [eg, ketoconazole], cimetidine, fluvoxamine, macrolide antibiotics [eg, erythromycin], nefazodone, protease inhibitors [eg, atazanavir, indinavir])
In vitro, mirtazapine is a substrate for several CYP-450 enzymes (eg, 2D6, 1A2, 3A4). Mirtazapine plasma concentrations may be elevated by CYP inhibitors, increasing the pharmacologic effects and risk of adverse reactions. Use with caution. Monitor the clinical response of the patient when starting or stopping a CYP inhibitor and adjust the mirtazapine dose as needed.Furazolidone
Furazolidone has MAOI activity. Administration of mirtazapine is contraindicated with furazolidone and other agents exhibiting MAOI activity or within 14 days of initiating or discontinuing therapy with an MAOI.L-tryptophan
The risk of serotonin syndrome may be increased. Avoid coadministration.MAOIs
May precipitate hypertensive crisis and convulsions with possible fatal results. Use is not recommended in combination with MAOIs or within 14 days of starting or stopping therapy with MAOIs.Rasagiline
Rasagiline and mirtazapine increase CNS serotonin activity, and may increase the risk of serotonin syndrome. Closely monitor patients for signs and symptoms of serotonin syndrome. Serotonin syndrome requires immediate medical attention, including discontinuation of the serotonergic agent and supportive care.Serotonergic drugs (eg, lithium, serotonin reuptake inhibitors [eg, fluoxetine, fluvoxamine, venlafaxine], St. John's wort, tramadol, tricyclic antidepressants [eg, amitriptyline], triptans [eg, almotriptan])
These agents may affect serotonergic neurotransmission, increasing the risk of serotonin syndrome when administered with mirtazapine. Coadminister with caution. Closely monitor patients for adverse reactions. Serotonin syndrome requires immediate medical attention, including discontinuation of the serotonergic agent and supportive care.Serotonin reuptake inhibitors (eg, fluoxetine, fluvoxamine)
Mirtazapine plasma levels may be elevated, increasing the pharmacologic effects and adverse reactions.Warfarin
The anticoagulant effect of warfarin may be increased. Closely monitor the INR when mirtazapine is started or stopped and adjust the warfarin dose as needed.
Hypertension, palpitation, postural hypotension, tachycardia, vasodilatation (at least 1%); torsades de pointes, ventricular arrhythmia (postmarketing).
Somnolence (54%), asthenia (8%); dizziness (7%); abnormal dreams (4%); abnormal thinking (3%); confusion, tremor (2%); agitation, amnesia, anxiety, apathy, depression, headache, hyperkinesis, hypertonia, hypesthesia, hypokinesia, insomnia, malaise, paresthesia, twitching, vertigo (at least 1%).
Pruritus, rash (at least 1%).
Dry mouth (25%); constipation (13%); nausea (2%); abdominal pain, acute abdominal syndrome, anorexia, diarrhea, dyspepsia, flatulence, vomiting (at least 1%).
Urinary frequency (2%); decreased libido, UTI (at least 1%).
Increased appetite, weight gain (12%); peripheral edema (2%); thirst (at least 1%); edema (1%) .
Back pain, myalgia (2%); arthralgia, myasthenia (at least 1%).
Increased cough, sinusitis (at least 1%); dyspnea (1%).
Flu syndrome (5%); amblyopia, pharyngitis, rhinitis, taste perversion, tinnitus (at least 1%).
Antidepressants increased the risk of suicidal thinking and behavior (suicidality) in short-term studies in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders. When considering the use of any antidepressant, 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 health care provider. Mirtazapine tablets and orally disintegrating tablets are not approved for use in children.
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 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. Similarly, observe adults 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 a 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.
Category C .
Safety and efficacy not established.
Use with caution.
Use with caution.
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).
May impair judgment, thinking, or motor skills.
Activation of mania/hypomania
Has been reported. Use cautiously in patients with history of mania/hypomania.
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 the patient.
Increases have been reported.
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.
Orally disintegrating tablets contain phenylalanine.
Screening for bipolar disorder
A major depressive episode may be the initial presentation of bipolar disorder; 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.
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.
Suicidal ideation is inherent in depression and may persist until significant remission occurs. Closely supervise high-risk patients during initial drug therapy. Prescribe the smallest quantity of medication consistent with good patient management in order to reduce risk of overdose.
Disorientation, drowsiness, impaired memory, tachycardia.
- Advise patient or caregiver to read patient information leaflet before starting therapy and to reread and check for new information each time the medication is refilled.
- If patient is a child or adolescent being treated for depression, advise patient, 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 it is 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, or 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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