Tuesday, July 18, 2023

buPROPion, Aplenzin, Forfivo XL, Wellbutrin,Wellbutrin SR, Wellbutrin XL, Zyban

 Indications

Treatment of depression (with psychotherapy). Depression

with seasonal affective disorder (Aplenzin and

Wellbutrin XL only). Smoking cessation (Zyban only).

Unlabeled Use: Treatment of ADHD in adults (SR

only). To increase sexual desire in women.

Action

Decreases neuronal reuptake of dopamine in the CNS.

Diminished neuronal uptake of serotonin and norepinephrine

(less than tricyclic antidepressants). Therapeutic

Effects: Diminished depression. Decreased

craving for cigarettes.

Pharmacokinetics

Absorption: Although well absorbed, rapidly and extensively

metabolized by the liver.

Distribution: Unknown.

Metabolism and Excretion: Extensively metabolized

by the liver into 3 active metabolites (CYP2B6 involved

in formation of one of the active metabolites).

Half-life: 14 hr (active metabolites may have longer

half-lives).

TIME/ACTION PROFILE (antidepressant effect)

ROUTE ONSET PEAK DURATION

PO 1–3 wk unknown unknown

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Concurrent

use of MAO inhibitors or MAO-like drugs (linezolid or

methylene blue); Concurrent use of ritonavir; Seizure

disorders; Arteriovenous malformation, severe head injury,

CNS tumor, CNS infection, severe stroke, anorexia

nervosa, bulimia, or abrupt discontinuation of alcohol,

benzodiazepines, barbiturates, or antiepileptic drugs

(qrisk of seizures); Lactation: Potential for serious adverse

reactions in nursing infants.

Use Cautiously in: Renal/hepatic impairment (p

dose recommended) (Forfivo XL not recommended in

patients with renal or hepatic impairment); Recent history

of MI; History of suicide attempt; Unstable cardiovascular

status; Mayqrisk of suicide attempt/ideation

especially during early treatment or dose adjustment;

this risk appears to be greater in adolescents or children;

Psychiatric illness; Angle-closure glaucoma; OB:

Use only if benefit to patient outweighs potential risk to

fetus; Geri:qrisk of drug accumulation;qsensitivity to

effects.

Exercise Extreme Caution in: Severe hepatic

cirrhosis (pdose required); Pedi:qrisk of suicidal

thinking and behavior. Observe carefully, especially at

initiation of therapy and duringqorpin dose.

Adverse Reactions/Side Effects

CNS: HOMICIDAL THOUGHTS/BEHAVIOR, SEIZURES, SUICIDAL

THOUGHTS/BEHAVIOR, agitation, headache, aggression,

anxiety, delusions, depression, hallucinations,

hostility, insomnia, mania, panic, paranoia, psychoses.

CV: hypertension. GI: dry mouth, nausea, vomiting,

change in appetite, weight gain, weight loss. Derm:

photosensitivity. Endo: hyperglycemia, hypoglycemia,

syndrome of inappropriate ADH secretion. Neuro:

tremor.

Interactions

Drug-Drug: Concurrent use with MAO-inhibitors

mayqrisk of hypertensive reactions; concurrent use

contraindicated; at least 14 days should elapse between

discontinuation of MAO inhibitor and initiation of bupropion

(or visa versa). Concurrent use with MAO-inhibitor

like drugs, such as linezolid or methylene

blue mayqrisk of hypertensive reactions; concurrent

use contraindicated; do not start therapy in patients receiving

linezolid or methylene blue; if linezolid or

methylene blue need to be started in a patient receiving

bupropion, immediately discontinue bupropion and

monitor for 2 wk or until 24 hr after last dose of linezolid

or methylene blue, whichever comes first (may resume

bupropion therapy 24 hr after last dose of linezolid

or methylene blue).qrisk of adverse reactions

when used with amantadine or levodopa.qrisk of

seizures with phenothiazines, antidepressants,

theophylline, corticosteroids, OTC stimulants/anorectics,

or cessation of alcohol or benzodiazepines

(avoid or minimize alcohol use). Ritonavir, lopinavir/

ritonavir, and efavirenz mayplevels; may

need toqbupropion dose. Mayqcitalopram levels.

Carbamazepine maypblood levels and effectiveness.

Concurrent use with nicotine replacement may cause

hypertension.qrisk of bleeding with warfarin. Bupropion

and one of its metabolites inhibit the CYP2D6 enzyme

system and mayqlevels and risk of toxicity from

antidepressants (SSRIs and tricyclic), haloperidol,

risperidone, thioridazine, haloperidol, beta

blockers, flecainide, and propafenone. Mayplevels

and efficacy of tamoxifen. Maypthe efficacy of tamoxifen.

Maypdigoxin levels.

Route/Dosage

Depression

PO (Adults): Immediate-release—100 mg twice

daily initially; after 3 days mayqto 100 mg 3 times

daily; after at least 4 wk of therapy, mayqup to 450

mg/day in divided doses (not to exceed 150 mg/dose;

wait at least 6 hr between doses at the 300 mg/day dose

or at least 4 hr between doses at the 450-mg/day dose).

Sustained-release—150 mg once daily in the morning;

after 3 days, mayqto 150 mg twice daily with at

least 8 hr between doses; after at least 4 wk of therapy,

mayqto a maximum daily dose of 400 mg given as 200

mg twice daily. Extended-release (Wellbutrin XL)—

150 mg once daily in the morning, may beqafter 4

days to 300 mg once daily; some patients may require

up to 450 mg/day as a single daily dose. Extended-release

(Aplenzin)—174 mg once daily in the morning,

may beqafter 4 days to 348 mg once daily; some patients

may require up to 522 mg/day as a single daily

dose. Extended-release (Forfivo XL)—450 mg once

daily (should NOT be used as initial therapy; it should

only be used in patients who have been receiving 300 mg/day of another bupropion formulation for at least 2

wk and require titration up to 450 mg/day or in those

patients receiving 450 mg/day of another bupropion

formulation).

Hepatic Impairment

PO (Adults): Moderate-to-severe hepatic impairment

(Aplenzin)—Max dose: 174 mg every other

day.

Seasonal Affective Disorder

PO (Adults): Extended-release (Wellbutrin XL)—

150 mg/day in the morning; if dose is well tolerated,q

to 300 mg/day in one wk. Doses should be tapered to

150 mg/day for 2 wk before discontinuing; Extendedrelease

(Aplenzin)—174 mg once daily in the morning,

may beqafter 7 days to 348 mg once daily.

Hepatic Impairment

PO (Adults): Moderate-to-severe hepatic impairment

(Aplenzin)—Max dose: 174 mg every other

day.

Smoking cessation

PO (Adults): Zyban—150 mg once daily for 3 days,

then 150 mg twice daily for 7–12 wk (doses should be

at least 8 hr apart).

Availability (generic available)

Tablets: 75 mg, 100 mg. Cost: Generic—75 mg

$79.43/100, 100 mg $106.01/100. Sustained-release

tablets: 100 mg, 150 mg, 200 mg. Cost: Generic—

100 mg $51.12/180, 150 mg $59.60/180, 200

mg $52.33/180. Extended-release tablets (Wellbutrin

XL): 150 mg, 300 mg. Cost: Generic—150 mg

$74.84/90, 300 mg $63.94/90. Extended-release

tablets (Aplenzin): 174 mg, 348 mg, 522 mg. Cost:

174 mg $359.09/30, 348 mg $473.36/30, 522 mg

$1,077.23/30. Extended-release tablets (Forfivo

XL): 450 mg. Cost: $176.40/30.

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