Slipaid

Approved Indications:

• Major Depressive Disorder (MDD): For the treatment of moderate to severe depression.
• Anxiety Disorders: Particularly associated with depressive illness.
• Insomnia: Low-dose doxepin (≤6 mg) is indicated for sleep maintenance insomnia in adults.
• Pruritus: Topical and oral formulations indicated for chronic urticaria and other dermatologic conditions with significant itching.
• Neurodermatitis and eczema (topical form): For symptomatic relief of itching and inflammation.

Clinically Accepted Off-label Uses:

• Chronic pain syndromes: As an adjunct for neuropathic pain and fibromyalgia.
• Irritable bowel syndrome (IBS): For abdominal pain and discomfort relief.
• Migraine prophylaxis: Occasionally used in refractory cases.
• Post-traumatic stress disorder (PTSD) and other anxiety spectrum conditions.

Route: Oral (capsules, tablets, oral concentrate); Topical (cream).

Adults:

• Depression/Anxiety:
• Initial: 75 mg/day in divided doses or at bedtime.
• Maintenance: 75–150 mg/day; up to 300 mg/day in hospitalized patients.
• Max: 300 mg/day (oral); doses >150 mg typically divided.
• Insomnia (low-dose formulation):
• 3 mg or 6 mg orally once daily within 30 minutes of bedtime.
• Avoid within 3 hours of a meal.
• Topical for pruritus:
• Apply a thin film (5% cream) up to 4 times daily.

Pediatrics:

• Not recommended for use in children for depression or insomnia.
• Use only under specialist guidance for select dermatologic conditions.

Elderly:

• Start at lower doses (e.g., 10–25 mg/day) due to increased sensitivity and fall risk.
• Avoid high doses for insomnia.

Renal/Hepatic Impairment:

• Use with caution; initiate at lowest possible dose.
• Monitor hepatic function and CNS adverse effects.

Doxepin is a tricyclic antidepressant (TCA) that exerts its effects by inhibiting the reuptake of norepinephrine and serotonin at presynaptic nerve terminals, increasing their synaptic availability. It also has potent antagonistic activity at histamine H1 receptors, accounting for its sedative and antipruritic properties. Additionally, it exhibits antagonism at muscarinic cholinergic and alpha-adrenergic receptors, contributing to both therapeutic and side effect profiles.

• Absorption: Well absorbed orally; bioavailability ~50–70%.
• Onset of action: Sedative effects begin within hours; antidepressant effects take 2–4 weeks.
• Distribution: Widely distributed; crosses blood-brain barrier and placenta; protein binding ~76–80%.
• Metabolism: Hepatic via CYP450 enzymes (primarily CYP2D6); active metabolite is desmethyldoxepin.
• Half-life: Doxepin: 8–24 hours; Desmethyldoxepin: ~28–31 hours.
• Elimination: Excreted in urine and feces, primarily as metabolites.

• Pregnancy: FDA Category C
• Animal studies show adverse effects; human data are limited.
• Use only if potential benefits justify the risk.
• Lactation:
• Excreted in small amounts in breast milk.
• Possible sedation or adverse effects in nursing infants.
• Caution advised; monitor infant or consider alternative therapy.

• Primary Class: Tricyclic Antidepressant (TCA)
• Subclass: Dibenzoxepin TCA; also acts as a potent H1 receptor antagonist (especially at low doses)

• Known hypersensitivity to doxepin or other TCAs.
• Use of monoamine oxidase inhibitors (MAOIs) within the past 14 days.
• Narrow-angle glaucoma.
• Urinary retention.
• Severe liver disease (relative contraindication for high doses).
• Suicidal tendencies or acute intoxication with alcohol, sedatives, or psychotropics.

• Suicidality risk: Antidepressants increase suicide risk in children, adolescents, and young adults.
• Sedation: Significant CNS depressant; avoid operating machinery or driving.
• Anticholinergic effects: Dry mouth, blurred vision, constipation, and urinary retention.
• Cardiac risks: May cause arrhythmias, QT prolongation; caution in cardiac disease.
• Withdrawal symptoms: Avoid abrupt discontinuation; taper gradually.
• CNS depression potentiation: Increased sedation with alcohol or CNS depressants.
• Glaucoma and urinary retention: Worsening possible due to anticholinergic action.

Common (dose-dependent):

• CNS: Drowsiness, dizziness, fatigue, confusion (especially elderly).
• Anticholinergic: Dry mouth, constipation, urinary retention, blurred vision.
• GI: Nausea, vomiting, increased appetite, weight gain.

Less common:

• Orthostatic hypotension
• Headache
• Sweating
• Sexual dysfunction

Serious/Rare:

• Arrhythmias, ECG changes
• Seizures
• Agranulocytosis, leukopenia
• Jaundice/hepatotoxicity
• Extrapyramidal symptoms
• Worsening depression or suicidality

• MAOIs: Contraindicated; risk of hypertensive crisis or serotonin syndrome.
• CNS depressants: Additive sedation (e.g., alcohol, benzodiazepines).
• CYP2D6 inhibitors (e.g., fluoxetine, paroxetine): May increase plasma levels of doxepin.
• Anticholinergic agents: Increased risk of cognitive impairment and constipation.
• QT-prolonging drugs: Increased risk of cardiac arrhythmias.
• Antihypertensives: May blunt or potentiate effects depending on agent.

• Doxepin is included in updated insomnia treatment guidelines for sleep maintenance (low-dose use).
• Recent data support safe use of low-dose doxepin (<6 mg) in elderly for insomnia with minimal anticholinergic burden.
• TCAs, including doxepin, are being more cautiously used in older adults due to anticholinergic and cardiovascular risks.
• Ongoing pharmacovigilance for off-label use in chronic pain and functional GI disorders.

• Store at 20°C to 25°C (68°F to 77°F)
• Protect from light and moisture.
• Oral concentrate: Must be diluted before use and stored as per instructions.
• Topical formulations: Keep tightly closed; do not freeze.
• Keep out of reach of children.