Trazodone nda 018207?

Trazodone (NDA 018207)
First FDA‑approved in the late 1980s, NDA 018207 was filed by Pfizer and represents the original approval for trazodone hydrochloride, a serotonin antagonist‑reuptake inhibitor (SARI).

What is Trazodone?

• Class: SARI (Serotonin Antagonist and Reuptake Inhibitor)
• Mechanism of action:
  • Inhibits serotonin reuptake, raising extracellular serotonin.
  • Blocks 5‑HT₂A/2C receptors (reduces anxiety/insomnia).
  • Antagonizes α₁‑adrenergic receptors (can cause vasodilation).
• Primary uses:
  • Major Depressive Disorder (MDD) – as a monotherapy or adjunct.
  • Insomnia (often as a low‑dose “sleep aid” in older adults).
  • Off‑label: PTSD, anxiety, neuropathic pain, and certain sleep disorders.

Typical Dosing

• Administration: With food to reduce GI upset; take at bedtime unless using for depression (can be taken with meals if needed).

Pharmacokinetics (Adult)

• Absorption: Oral, ~50 % bioavailability.
• Metabolism: CYP3A4 (major); metabolized to active metabolite (N‑desmethyltrazodone).
• Half‑life: 6–12 hours (parent drug), 12–20 hours for metabolite.
• Excretion: Renal (~60 % unchanged) and fecal.
• Drug interactions:
  • CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir) → ↑ serum levels.
  • CYP3A4 inducers (e.g., carbamazepine, rifampin) → ↓ efficacy.
  • Serotonergic drugs (SSRIs, SNRIs, MAOIs, St. John’s wort) → risk of serotonin syndrome.
  • CNS depressants (benzodiazepines, alcohol) → additive sedation.

Common Adverse Effects

Serious Risks & Precautions

• Serotonin syndrome: Especially when combined with SSRIs, SNRIs, MAOIs, or triptans. Symptoms: agitation, hyperthermia, autonomic instability.
• QT prolongation & arrhythmias: Rare but can be serious; avoid concomitant QT‑prolonging agents (e.g., ondansetron, methadone, certain antipsychotics).
• Orthostatic hypotension: May increase fall risk in elderly.
• Pregnancy & Lactation: Category B; generally considered safe in pregnancy but avoid in the first trimester if possible; minimal breast‑milk excretion.
• Elderly: Start at lowest dose; monitor for dizziness/sedation.

How It Came About – NDA 018207

• Original approval: 1979–1981 (first in the US); NDA 018207 was the filing number.
• Clinical trials: Demonstrated efficacy for major depressive disorder with a favorable side‑effect profile compared to older tricyclics.
• Later approvals: Generic versions began in the 1990s; brand names include Trazodone, Austedo (for OCD), and various generics.

Bottom Line

Trazodone is a well‑established antidepressant with a unique dual action on serotonin and adrenergic receptors. It’s also widely used off‑label for insomnia because of its sedative properties. While generally safe when dosed appropriately, it carries risks of sedation, orthostatic hypotension, QT prolongation, and, rarely, serotonin syndrome.

If you’re considering trazodone or have questions about dosing, side effects, or drug interactions, please consult a licensed healthcare provider. They can tailor the therapy to your specific medical history and current medications.