mirtazapine
Remeron, Remeron SolTab

Available forms
Available by prescription only
Tablets: 15 mg, 30 mg, 45 mg
Orally disintegrating tablets: 15 mg, 30 mg, 45 mg

Indications and dosages
 Depression. Adults: Initially, 15 mg P.O. h.s. Maintenance dosage ranges from 15 mg to 45 mg daily. Dosage adjustments should be made at intervals no less than 1 to 2 weeks apart.

Pharmacodynamics
Antidepressant action: Mirtazepine is a potent antagonist of 5HT₂ and 5HT₃ receptors. The exact mechanism of action is unknown, but it may enhance central noradrenergic and serotonergic activity.

Pharmacokinetics
Absorption: Rapidly and completely absorbed from the GI tract. Absolute bioavailability of drug is about 50%.
Distribution: About 85% is bound to plasma protein.
Metabolism: Extensively metabolized in the liver.
Excretion: Predominantly eliminated in urine (75%) with 15% excreted in feces. Half-life is between 20 and 40 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug. Coadministration with MAO inhibitors is contraindicated.
  Use cautiously in patients with CV or cerebrovascular disease, seizure disorders, suicidal ideation, impaired hepatic and renal function, or history of mania or hypomania. Also use cautiously in pregnant patients and those with conditions that predispose them to hypotension, such as dehydration, hypovolemia, or antihypertensive treatment. Use cautiously in patients with increased intraocular pressure, history of urine retention, or history of angle-closure glaucoma because of anticholinergic properties.

Interactions
Drug-drug. Diazepam, other CNS depressants: May cause additive CNS effects. Avoid use together.
MAO inhibitors or within 14 days of starting or stopping an MAO inhibitor: May cause serious, and sometimes fatal, reactions. Avoid use together.
Drug-lifestyle. Alcohol use: Causes additive CNS effects. Discourage alcohol use.

Adverse reactions
CNS: somnolence, dizziness, asthenia, abnormal dreams, abnormal thinking, tremor, confusion.
CV: edema, hypertension, orthostatic hypotension.
GI: nausea, increased appetite, dry mouth, constipation, vomiting.
GU: urinary frequency.
Metabolic: weight gain.
Musculoskeletal: back pain, myalgia.
Respiratory: dyspnea.
Skin: pruritus, rash.
Other: flu syndrome, peripheral edema.

Effects on lab test results
• May increase ALT levels.

Overdose and treatment
Overdose may result in disorientation, drowsiness, impaired memory, tachycardia, severe hypotension, convulsions, CNS depression (including coma), and heart failure.
 Treat as for any antidepressant overdose. If patient is unconscious, establish an airway and provide adequate oxygenation. Consider gastric lavage, induced emesis, or both; also consider activated charcoal. Monitor cardiac and vital signs and provide general symptomatic and supportive measures.

Special considerations
• There should be a drug-free interval of at least 2 weeks when switching from MAO-inhibitor therapy to mirtazapine or from mirtazapine to an MAO inhibitor.
• Although risk of agranulocytosis is rare, discontinue drug and monitor patient closely if he develops a sore throat, fever, stomatitis, or other signs of infection with a low WBC count.
• Patient requires close observation because it isn’t known if mirtazapine causes physical or psychological dependence.
Breast-feeding patients
• It isn’t known if drug appears in breast milk. Use cautiously in breast-feeding women.
Pediatric patients
• Safety and efficacy in children haven’t been established.
Geriatric patients
• Weight gain occurs predominantly in elderly patients. May be used as therapeutic advantage in patients who need appetite stimulation.
• Administer mirtazapine cautiously to geriatric patients because pharmacokinetic studies reveal decreased clearance in elderly people.

Patient education
• Instruct patient to remove orally disintegrating tablet from blister pack and immediately place on the tongue. Patient doesn’t need water to swallow tablet.
• Caution patient not to break or split tablet, but to place oral disintegrating tablet on top of tongue for a few seconds and to swallow it after it dissolves.
• Caution patient not to perform hazardous activities if somnolence occurs.
• Instruct patient not to use alcohol or other CNS depressants while taking drug because of additive effect.
• Tell patient to report signs and symptoms of infection, such as fever, chills, sore throat, mucous membrane ulceration, or other possible signs of infection, including flulike complaints.
• Stress importance of compliance with mirtazapine therapy.
• Instruct patient not to take other drugs without medical approval.
• Tell women of childbearing age to report suspected pregnancy immediately.
• Tell patient with phenylketonuria that oral disintegrating tablets contain aspartame.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use