gepirone

Absorption: 14–17% absorbed following oral administration. Absorption ↑ with food.

Distribution: Widely distributed to extravascular tissues.

Metabolism/Excretion: Primarily metabolized in the liver via the CYP3A4 isoenzyme. Primarily excreted in the urine (81%), with 13% excreted in the feces.

Half-Life: 5 hr.

Time/Action Profile ⬆ ⬇

(antidepressant effect)

ROUTE	ONSET	PEAK	DURATION
PO	2 wk	8 wk	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
QTc interval >450 msec at baseline;
Congenital long QT syndrome;
Concurrent use of strong CYP3A4 inhibitors;
Severe hepatic impairment;
Concurrent use (or within 14 days) of MAO inhibitors or MAO-inhibitor-like drugs (linezolid or methylene blue).

Use Cautiously in:

History of suicide attempt;
Uncontrolled or significant cardiac disease, recent MI, HF, unstable angina, bradyarrhythmias, uncontrolled hypertension, 2nd- or 3rd-degree heart block, severe aortic stenosis, or uncontrolled hypothyroidism (↑ risk of torsades de pointes);
Electrolyte abnormalities (correct before initiating therapy);
Bipolar disorder;
Family history of bipolar disorder, depression, or suicide;
Moderate or severe renal impairment;
Moderate hepatic impairment;
OB: Use during 3rd trimester may result in neonatal serotonin syndrome requiring prolonged hospitalization, respiratory and nutritional support. Use during pregnancy only if potential maternal benefit justifies potential fetal risk;
Lactation: Safety not established in breastfeeding;
Pedi: Safety and effectiveness not established in children. May risk of suicide attempt/ideation, especially during early treatment or dose adjustment; risk may be greater in children or adolescents;
Geri: Maximum dose of 36.3 mg/day in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

CV: palpitations, peripheral edema, QT interval prolongation, tachycardia

Derm: ↑sweating

EENT: nasal congestion, nasopharyngitis

GI: diarrhea, nausea, abdominal pain, constipation, dry mouth, dyspepsia, vomiting

GU: breast tenderness

Metab: ↑appetite, weight gain

Neuro: dizziness, headache, insomnia, sedation, agitation, confusion, fatigue, jitteriness, paresthesia

Resp: dyspnea, upper respiratory tract infection

Misc: hypersensitivity reactions

Interactions ⬆ ⬇

Drug-drug:

MAO inhibitors or MAO-inhibitor-like drugs, such as linezolid or methylene blue, may cause serious, potentially fatal reactions, including hypertensive crisis or serotonin syndrome; concurrent use contraindicated. Allow ≥14 days between gepirone and use of MAO inhibitors or MAO-inhibitor-like drugs.
Strong CYP3A4 inhibitors, including ketoconazole, may significantly ↑ levels and risk of QT interval prolongation and torsades de pointes; concurrent use contraindicated.
Diuretics or glucocorticoids may ↑ risk of QT interval prolongation and torsades de pointes.
QT interval prolonging medications may ↑ risk of QT interval prolongation and torsades de pointes.
Moderate CYP3A4 inhibitors, including verapamil, may ↑ levels and risk of QT interval prolongation and torsades de pointes; ↓ gepirone dose.
Drugs that affect serotonergic neurotransmitter systems, including tricyclic antidepressants, SNRIs, fentanyl, lithium, buspirone, tramadol, meperidine, methadone, amphetamines, and triptans, may ↑ risk of serotonin syndrome.
Strong CYP3A4 inducers, including rifampin, may ↓ levels and effectiveness; avoid concurrent use.

Route/Dosage ⬆ ⬇

PO (Adults ): 18.2 mg once daily; may ↑ to 36.3 mg once daily on Day 4 based on clinical response and tolerability. May then further ↑ to 54.5 mg once daily after Day 7, and then to 72.6 mg once daily after Day 14. Concurrent use of moderate CYP3A4 inhibitor:↓ gepirone dose by 50%.
PO Geriatric Patients ): 18.2 mg once daily; may ↑ to 36.3 mg once daily after Day 7 based on clinical response and tolerability (max dose = 36.3 mg/day). Concurrent use of moderate CYP3A4 inhibitor:↓ gepirone dose by 50%.

Renal Impairment

PO (Adults ): CCr <50 mL/min: 18.2 mg once daily; may ↑ to 36.3 mg once daily after Day 7 based on clinical response and tolerability (max dose = 36.3 mg/day). Concurrent use of moderate CYP3A4 inhibitor:↓ gepirone dose by 50%.

Hepatic Impairment

PO (Adults ): Moderate hepatic impairment: 18.2 mg once daily; may ↑ to 36.3 mg once daily after Day 7 based on clinical response and tolerability (max dose = 36.3 mg/day). Concurrent use of moderate CYP3A4 inhibitor:↓ gepirone dose by 50%.

Availability ⬆ ⬇

Extended-release tablets: 18.2 mg; 36.3 mg; 54.5 mg; 72.6 mg

Assessment ⬆ ⬇

Assess for personal or family history of bipolar disorder, mania, or hypomania before starting therapy.
Monitor for signs and symptoms of serotonin syndrome (agitation, change in balance, confusion, hallucinations, fever, fast/abnormal heartbeat, flushing, muscle twitching/stiffness, seizures, shivering/shaking, sweating a lot, severe diarrhea, vomiting, severe headache).
Monitor for depression and suicidal thoughts and behaviors.
Obtain baseline ECG and during therapy, especially after ↑ in dose. Do not start or ↑ dose if QTc interval >450 msec. Monitor ECG frequently in patients with risk factors for QTc interval prolongation.

Lab Test Considerations:

Monitor electrolytes (potassium and magnesium) before, during, and with dose titration. Correct abnormalities.

Implementation ⬆ ⬇

PO: Administer with food at same time each day. DNC: Swallow tablets whole; do not split, crush, or chew.
Discontinuing therapy:If treatment ≥4 wk, gradually taper the dose over 2–4 wk to minimize withdrawal symptoms and detect reemerging symptoms. For brief treatment 2–3 wk, taper over 1–2 wk. If <2 wk treatment, no taper is needed. Reasons for a slower taper >4 wk include history of antidepressant withdrawal symptoms or receiving high doses of antidepressants. If intolerable withdrawal symptoms occur, resume the previously prescribed dose and/or ↓ dose at a more gradual rate. Select patients (history of discontinuation syndrome) on long-term treatment (>6 mo) may benefit from tapering over >3 mo.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication to patient. Advise patient to read Patient Information before starting therapy. Advise to take as directed. If a dose is missed, take as soon as remember. If it is time for next dose, skip the missed dose and take at regularly scheduled dose. Do not take two doses at the same time.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
Advise patient/caregivers of signs and symptoms of suicidal ideation and behavior, especially during early treatment and with dose adjustments, and to report symptoms to health care professional.
Inform patient to notify health care professional immediately of faintness, loss of consciousness, or heart palpitations and to seek immediate medical attention if needed.
Instruct patient about the risk of serotonin syndrome and to notify health care professional or seek immediate medical attention if needed.
Advise patient/caregiver to observe for signs of activation of mania or hypomania and notify health care professional if symptoms occur.
Advise patient not change dose or stop taking without notifying health care professional.
Rep: Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Advise patient that use late in pregnancy may lead to an risk for neonatal complications. The pregnancy exposure registry monitors pregnancy outcomes in women exposed to antidepressants. Health care providers are encouraged to register patients by calling the National Pregnancy Registry for Antidepressants at 1-866-961-2388 or https://womensmentalhealth.org/research/pregnancyregistry/antidepressants/. Monitor breastfed infants for adverse reactions (irritability, restlessness, excessive somnolence, decreased feeding, weight loss).

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇