SINEQUAN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SINEQUAN (SINEQUAN).
Inhibits reuptake of serotonin and norepinephrine in the CNS; also has anticholinergic, antihistaminergic, and sedative effects.
| Metabolism | Hepatic via CYP2D6 and other CYP450 enzymes; active metabolite desmethyldoxepin. |
| Excretion | Renal (approximately 30-40% as unchanged drug, with extensive hepatic metabolism to metabolites; minor biliary/fecal excretion). |
| Half-life | Terminal elimination half-life: 8–24 hours (parent drug); steady state achieved in 2–4 weeks; clinical context: may require dose adjustment in hepatic impairment. |
| Protein binding | 80–85% bound to plasma proteins (albumin). |
| Volume of Distribution | Vd: 13–17 L/kg; high, indicating extensive tissue distribution including CNS. |
| Bioavailability | Oral: variable, 30–70% due to first-pass metabolism; intramuscular: 100%. |
| Onset of Action | Oral: 1–3 weeks for antidepressant effect; 1–2 hours for sedation. Intramuscular: 1–3 hours for antidepressant effect; 30–60 minutes for sedation. |
| Duration of Action | Oral: 24–36 hours after single dose; chronic dosing maintains steady state. Intramuscular: 12–24 hours. Clinical notes: sustained antidepressant effect requires daily dosing; sedation may persist with continued use. |
| Molecular Weight | 279.38 |
Initial: 50-150 mg/day PO divided 1-3 times daily; max 300 mg/day. Maintenance: lowest effective dose.
| Dosage form | CONCENTRATE |
| Renal impairment | No specific guidelines; caution in severe impairment (CrCl <30 mL/min) with dose reduction of 25-50%. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: avoid use. |
| Pediatric use | Not recommended for children <12 years. Adolescents: initial 25-50 mg/day PO in divided doses; max 100 mg/day based on weight (1-3 mg/kg/day). |
| Geriatric use | Start with lowest dose (10-25 mg/day PO); increase slowly; max 150 mg/day due to anticholinergic effects and QT prolongation risk. |
| 1st trimester | Associated with congenital malformations; avoid use. Risk of cardiovascular defects if used after 4-10 weeks. |
| 2nd trimester | May cause fetal tachycardia, irritability; use only if maternal benefit outweighs risk. |
| 3rd trimester | Late third trimester use may cause neonatal withdrawal (tachycardia, irritability, poor feeding) and anticholinergic effects. |
Clinical note
Comprehensive clinical and safety monograph for SINEQUAN (SINEQUAN).
| Placental transfer | Doxepin crosses the placenta. Umbilical cord plasma concentrations reach 40-60% of maternal plasma levels. |
| Breastfeeding | Doxepin and its active metabolite are excreted into breast milk. Cases of infant sedation and respiratory depression have been reported. Use with caution; consider risk of accumulation in neonates. |
■ FDA Black Box Warning
Increased risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders.
| Serious Effects |
History of hypersensitivity to doxepin or any tricyclic antidepressantConcomitant use with MAOIs (within 14 days of MAOI therapy)Recent myocardial infarctionAngle-closure glaucomaUrinary retention (due to anticholinergic effects)
| Precautions | Suicidality risk, Serotonin syndrome, Cardiotoxicity (QT prolongation), Anticholinergic effects (e.g., urinary retention, angle-closure glaucoma), Sedation impairs ability to drive |
| Food/Dietary | Avoid grapefruit and grapefruit juice as it may increase doxepin levels. Avoid alcohol. High-fat meals may delay absorption but not significantly reduce efficacy. |
Loading safety data…
| Lactation Rating |
| L4 |
| Teratogenic Risk | First trimester: Limited data; no consistent evidence of major malformations in humans, but animal studies show fetal abnormalities at high doses. Second and third trimesters: Risk of neonatal withdrawal (irritability, respiratory distress, feeding difficulties) and anticholinergic effects (ileus, urinary retention). Avoid near term due to potential neonatal sedation. |
| Fetal Monitoring | Monitor for maternal anticholinergic effects (constipation, blurred vision). Fetal ultrasound for growth and amniotic fluid if used long-term. Neonatal monitoring for withdrawal symptoms and respiratory status for 48 hours postpartum. |
| Fertility Effects | Animal studies suggest doxepin may impair fertility via hormonal disruption. Human data limited; case reports of altered libido and menstrual irregularities. May affect sperm parameters in males. |
| Clinical Pearls | Sinequan (doxepin) is a tricyclic antidepressant with potent antihistamine effects; it is also used for insomnia at low doses. Start at low doses in elderly to avoid anticholinergic side effects. Monitor for QTc prolongation, especially in patients with cardiac disease or electrolyte imbalances. Do not discontinue abruptly; taper to avoid withdrawal symptoms. |
| Patient Advice | May cause drowsiness; avoid driving or operating machinery until you know how it affects you. · Do not stop taking this medication suddenly; follow your doctor's instructions for tapering. · Avoid alcohol; it can increase drowsiness and other side effects. · Notify your doctor if you experience rapid heartbeat, fainting, or difficulty urinating. · Take exactly as prescribed; do not increase dose without consulting your doctor. · It may take 2-4 weeks to feel the full antidepressant effect. |