desipramine (dess-ip-ra-meen) Norpramin

 Indications

Depression. Unlabeled Use: Chronic pain syndromes.

Anxiety. Insomnia.

Action

Potentiates the effect of serotonin and norepinephrine

in the CNS. Has significant anticholinergic properties.

Therapeutic Effects: Antidepressant action (may

develop only over several weeks). 

Pharmacokinetics

Absorption: Well absorbed from the GI tract.

Distribution: Widely distributed.

Protein Binding: 90–92%.

Metabolism and Excretion: Mostly metabolized

by the liver (CYP2D6 isoenzyme); one metabolite is

pharmacologically active (2-hydroxydesipramine);

the CYP2D6 enzyme system exhibits genetic polymorphism;

7% of population may be poor metabolizers

(PMs) and may have significantlyqdesipramine concentrations

and anqrisk of adverse effects. Small

amounts enter breast milk.

Half-life: 12–27 hr.

TIME/ACTION PROFILE (antidepressant effect)

ROUTE ONSET PEAK DURATION

PO 2–3 wk 2–6 wk days–wk

Contraindications/Precautions

Contraindicated in: Angle-closure glaucoma; Recent

MI, heart failure, known history of QTc prolongation.

Use Cautiously in: Patients with pre-existing cardiovascular

disease; Family history of sudden death,

cardiac arrhythmias, or conduction disturbances; Prostatic

hyperplasia (qsusceptibility to urinary retention);

History of seizures (threshold may bepseizures may

precede the development of cardiac arrhythmias or

death); Mayqrisk of suicide attempt/ideation especially

during early treatment or dose adjustment; risk

may be greater in children or adolescents; OB: Use during

pregnancy only if potential maternal benefit outweighs

risks to fetus; use during lactation may result in

neonatal sedation; Pedi: Children 12 yr (safety not established);

Geri:qsensitivity to effects.

Adverse Reactions/Side Effects

CNS: drowsiness, fatigue. EENT: blurred vision, dry

eyes, dry mouth. CV: ARRHYTHMIAS, hypotension, ECG

changes. GI: constipation, drug-induced hepatitis,

paralytic ileus,qappetite, weight gain. GU: urinary retention,

plibido. Derm: photosensitivity. Endo:

changes in blood glucose, gynecomastia. Hemat:

blood dyscrasias.

Interactions

Drug-Drug: Desipramine is metabolized in the liver

by the cytochrome P450 2D6 enzyme and its action may

be affected by drugs which compete for metabolism by

or alter the activity of this enzyme including other antidepressants,

phenothiazines, carbamazepine,

class 1C antiarrthythmics (propafenone or flecainide);

when used concurrently dosepof one or the

other or both may be necessary. Concurrent use of

other drugs that inhibit the activity of the enzyme, including

cimetidine, quinidine, amiodarone, and ritonavir,

may result inqeffects. May cause hypotension,

tachycardia, and potentially fatal reactions when

used with MAO inhibitors (avoid concurrent use—

discontinue 2 wk prior to). Concurrent use with SSRI

antidepressants may result inqtoxicity and should

be avoided (fluoxetine should be stopped 5 wk before).

Concurrent use with clonidine may result in hypertensive

crisis and should be avoided. Phenytoin mayp

levels and effectiveness;qdoses of desipramine may be

required to treat depression. Concurrent use with levodopa

may result in delayed/pabsorption of levodopa

or hypertension. Blood levels and effects may bepby

rifampin, carbamazepine, and barbiturates. Concurrent

use with moxifloxacinqrisk of adverse cardiovascular

reactions.qCNS depression with other

CNS depressants including alcohol, antihistamines,

clonidine, opioid analgesics, and sedative/

hypnotics. Barbiturates may alter blood levels and

effects. Adrenergic and anticholinergic side effects

may beqwith other agents having these properties.

Hormonal contraceptivesqlevels and may cause

toxicity. Cigarette smoking mayqmetabolism and alter

effects.

Drug-Natural Products: Concomitant use of

kava-kava, valerian, or chamomile canqCNS depression.

qanticholinergic effects with jimson weed

and scopolia.

Route/Dosage

PO (Adults): 100–200 mg/day as a single dose or in

divided doses (up to 300 mg/day).

PO (Geriatric Patients): 25–50 mg/day in divided

doses (up to 150 mg/day).

PO (Children 12 yr): 25–50 mg/day in divided

doses, mayqas needed up to 100 mg/day.

PO (Children 6–12 yr): 10–30 mg/day (1–5 mg/

kg/day) in divided doses.

Availability (generic available)

Tablets: 10 mg, 25 mg, 50 mg, 75 mg, 100 mg, 150

mg.