mirtazapine (Remeron, Remeron SolTab)

Dosing and uses of Remeron, Remeron SolTab (mirtazapine)

• Adult
• Pediatric
• Geriatric

 

Adult dosage forms and strengths

tablet

• 7.5mg
• 15mg
• 30mg
• 45mg

disintegrating tablet

• 15mg
• 30mg
• 45mg

 

Depression

15 mg PO qHS; may increase no more frequently than q1-2Weeks; not to exceed 45 mg qHs

 

Post-traumatic Stress Disorder (Off-label)

15 mg PO qHS; may increase no more frequently than q1-2Weeks; not to exceed 60 mg qHs

 

Hot Flashes (Off-label)

7.5-60 mg PO qDay

 

Insomnia (Off-label)

15-45 mg PO qHs

 

Dosing Modifications

Renal impairment (CrCl <39 mL/min): Clearance is reduced; monitor closely

Hepatic impairment: Clearance is reduced; monitor closely

 

Pediatric dosage forms and strengths

Safety and efficacy not established

 

Geriatric dosage forms and strengths

 

Depression

7.5 mg/day PO qHS; increase by 7.5-15 mg/day no more frequently than q1-2Weeks; not to exceed 45 mg/day

 

Alzheimer Dementia-related Depression

7.5 mg/day PO qHS; increase by 7.5-15 mg/day no more frequently than q1-2Weeks; not to exceed 60 mg/day

 

Dosing Considerations

The elderly have reduced clearance of mirtazapine and, as a result, may have increased plasma levels of the drug

Use with caution

 

Remeron, Remeron SolTab (mirtazapine) adverse (side) effects

>10%

Somnolence (54%)

Weight gain (>7% increase in <49% of pediatric patients)

Xerostomia (25%)

Increased appetite (17%)

Constipation (13%)

 

1-10%

Asthenia (8%)

Weakness (8%)

Weight gain (>7% increase in 8% of adults)

Dizziness (7%)

Serum TGs increased (6%)

Dream disorder (4%)

Disturbance in thinking (3%)

ALT increased (2%)

Peripheral edema (2%)

Myalgia (2%)

Confusion (2%)

Urinary frequency (2%)

Tremor (2%)

Back pain (2%)

Dyspnea (1%)

 

<1%

Mania (0.2%)

Grand mal seizure (less than 0.1%)

 

Frequency not defined

Depression exacerbation

Status epilepticus

Suicidal thoughts, suicide (rare)

Agranulocytosis

Neutropenia

 

Postmarketing Reports

Severe skin reactions

• Stevens-Johnson syndrome
• Bullous dermatitis
• Erythema multiforme
• Toxic epidermal necrolysis
• Increased creatine kinase blood levels
• Rhabdomyolysis

 

Warnings

Black box warnings

In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (<24 years) taking antidepressants for major depressive disorders and other psychiatric illnesses

This increase was not seen in patients >24 years

A slight decrease in suicidal thinking was seen in adults >65 years

In children and young adults, risks must be weighed against the benefits of taking antidepressants

Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies

This should be done during the initial 1-2 months of therapy and dosage adjustments; the patient’s family should communicate any abrupt changes in behavior to the healthcare provider

Worsening behavior and suicidal tendencies that are not part of the presenting symptoms may require discontinuation of therapy

This drug is not approved for use in pediatric patients

 

Contraindications

Hypersensitivity

Within 14 days of administration of MAOIs (serotonin syndrome)

Patients receiving linezolid or methylene blue IV

 

Cautions

Start slowly in hepatic or renal dysfunction and in the elderly

Clinical worsening and suicidal ideation may occur despite medication

Rare reports of serotonin syndrome, particularly when coadministered with other serotonergic drugs

Abrupt discontinuation may cause dizziness, abnormal dreams, sensory disturbances (including paresthesia and electric shock sensations), agitation, anxiety, fatigue, confusion, headache, tremor, nausea, vomiting, and sweating

Bone fractures reported with therapy; consider possibility of fragility fracture if patient complains of bone pain, swelling, or bruising

Akathisia and psychomotor restlessness associated with antidepressant use

Rare reports of hyponatremia; caution in elderly or if coadministered with other drug known to cause hyponatremia

Risk for potentially life-threatening serotonin syndrome and neuroleptic malignant syndrome-like reactions has been reported with SSRIs, SNRIs, MAOIs, and other serotonergic drugs used as monotherapy, but particularly with concomitant use of the following agents: serotonergic drugs (including triptans), drugs that impair metabolism of serotonin (including MAOIs), antipsychotics, dopamine antagonists, and nonpsychiatric MAOIs (eg, linezolid, IV methylene blue)

May cause anticholinergic effects; use with caution in patients with xerostomia, BPH, paralytic ileus, or decreased intestinal motility

Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy

May increase serum triglycerides and cholesterol levels

May cause orthostatic hypotension (low risk); use with caution in patients at risk

Sexual dysfunction may occur (incidence lower compared to SSRIs)

May worsen psychosis in some patients or precipitate mania or hypomania in patients with bipolar disorder

Use with caution in patients with history of seizures, head trauma, alcoholism, brain damage, and patients on medictions that may lower seizure treshold

QTc prolongation, ventricular fibrillation, and torsade de pointes rarely reported; use caution in patients with history of QTc prolongation, receiving QTc prolongent agents concomitantly, or with cardiovascular disease

Discontinue therapy if neutropenia/agrunolocytosis occur

May cause CNS depression, which may impair abilities to perform hazardous tasks that require mental alertness

May increase serum cholesterol and triglyceride levels

May increase appetite and cause weight gain

 

Pregnancy and lactation

Pregnancy category: C

Lactation: Avoid

 

Pregnancy categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

 

Pharmacology of Remeron, Remeron SolTab (mirtazapine)

Mechanism of action

Tetracyclic structure different from SSRIs, TCAs and MAOIs; through its central presynaptic alpha2-adrenergic antagonist effects, stimulates norepinephrine and serotonin release; potent antagonist of 5-HT2 and 5-HT3 serotonin and histamine receptors; is a moderate alpha1 adrenergic and muscarinic antagonist

 

Absorption

Bioavailability: 50%

Peak serum time: 2 hr

 

Distribution

Protein bound: 85%

Vd: 4.5 L/kg

 

Metabolism

Hepatic CYP450 enzymes CYP1A2, CYP2D6, CYP3A4

Metabolites: Inactive

 

Elimination

Half-life: 20-40 hr

Excretion: Urine (75%); feces (15%)