Doxepin hydrochloride, SILENOR®, SINEQUAN®

Brand name

  • SILENOR®
  • SINEQUAN®

Drug Class

  • Tricyclic Anti-depressants

Preparations

  • SILENOR: Tablets 3 and 6 mg

  • SINEQUAN: Capsules 10 mg and 25 mg

Indications

  1. Major Depression Disorder 
  2. Insomnia: (Hypnotic effect)

Pharmacology

  • Mechanism of Action: Antagonism of H1 receptor.

  • Pharmacodynamics: No effect on QT intervals in ECG in daily doses of 6 mg or 50 mg.

Metabolism

Pharmacokinetics:

  • Absorption: Orally >>> Peak concentration: 3.5 hours >>> half life: 15.3 hours
  • Distribution: 80% bound to plasma proteins, highly lipophilic and widely distributed throughout the body tissues.
  • Metabolism: Primarily metabolized by hepatic cytochrome P450 (Isozymes CYP2C19 & CYP2D6)
  • Excretion: Urine mainly

Dosing

Insomnia (Hypnotic effect):

  1. Adults: 6 mg/day >>> 3 mg/day for some patients
  2. Elderly: (≥ 65 years old): 3 mg/day >>> 6 mg/day if clinically indicated
  3. Hepatic Impairment: initiate with 3 mg/day

MDD: (Daily dose is usually administered tid)

  1. Mild MDD:
    1. Initial dose: 30 mg/day, Optimum dose: good clinical response is obtained in 30-50 mg/day almost. Max dose: 150 mg/day
  2. Moderate/Severe MDD:
    1. Initial dose: 75 mg daily in divided doses (Usually tid). Optimum dose: up to 150 mg/day. Max dose: 300 mg a day in divided doses.

Hepatic impairment & Elderlies: Dosage reduction may be required

Drug Interactions

  • CNS Depressants

  • Sedating Antihistamines

  • Alcohol

  • Cimetidine (A maximum dose of 3 mg is recommended in adults and elderly whencimetidine is co-administered)

  • Selective Serotonin Reuptake Inhibitors

  • Medications inhibit Cytochrome P-450 (CYP2C19 and CYP2D6 Isoenzymes) >>> Enzyme inhibitor effect

  • Medications induce Cytochrome P-450 >>> Hepatic Enzyme Inducers: eg: Barbiturates, phenytoin, carbamazepine

  • Monoamine oxidase inhibitors (MAOIs)

  • Sympathomimetic Agents

  • Guanethidine and related agents

  • Tolazamide

Adverse Effects

Most Frequent:

  • Somnolence
  • Sedation
  • Nausea
  • Dizziness
  • Dry mouth
  • Upper respiratory tract infection

Less Common: (< 1%)

  • Cardiac disorders: tachycardia.
  • Ear and labyrinth disorders: hypoacusis, motion sickness, tinnitus.
  • Eye disorders: blepharospasm, diplopia, eye pain, vision blurred, visual disturbance.
  • Gastrointestinal disorders: abdominal pain upper, diarrhoea, gastrooesophageal reflux disease, gingival recession, toothache, tooth fracture.
  • General disorders: fatigue, feeling abnormal, hangover, oedema peripheral, pitting oedema, sluggishness.
  • Infections and infestations: bronchitis, eye infection, fungal infection, gastroenteritis viral, herpes zoster, infective tenosynovitis, influenza, laryngitis, lower respiratory tract infection, onychomycosis, sinusitis, tooth abscess, urinary tract infection, viral infection.
  • Injury, poisoning and procedural complications: back injury, excoriation, foot fracture, hand fracture, skin laceration, upper limb fracture.
  • Investigations: blood pressure decreased, electrocardiogram abnormal.
    Metabolism and nutrition disorders: decreased appetite, hypokalaemia, increased appetite.
  • Musculoskeletal and connective tissue disorders: joint range of motion decreased, muscle cramp, myalgia, neck pain, pain in extremity.
  • Neoplasm benign, malignant and unspecified (incl cysts and polyps): lung adenocarcinoma stage I, malignant melanoma.
  • SILENOR Product Monograph Page 11 of 30
  • Nervous system disorders: ageusia, ataxia, disturbance in attention, lethargy, migraine, sleep paralysis, tremor.
  • Psychiatric disorders: depression, elevated mood, libido decreased, nightmare.
  • Renal and urinary disorders:
  • Reproductive system and breast disorders: breast cyst.
  • Respiratory, thoracic and mediastinal disorders: cough, nasal congestion, nasopharyngeal disorder, pharyngolaryngeal pain, sinus congestion.
  • Skin and subcutaneous tissue disorders: dermatitis contact, erythema, pruritus generalized, rash, rosacea, skin lesion.
  • Vascular disorders: blood pressure inadequately controlled, haematoma.

Contraindications

  • Hypersensitivity to TCAs

  • Hepatic Impairment (Relative Contraindication- If no alternatives)

  • Renal Impairment (Relative Contraindication- If no alternatives)

  • SSRIs

  • CNS Depressants

  • Sedating Antihistamines

  • Alcohol

  • Cimetidine (A maximum dose of 3 mg is recommended in adults and elderly when cimetidine is co-administered)

  • Selective Serotonin Reuptake Inhibitors

  • Medications inhibit Cytochrome P-450 (CYP2C19 and CYP2D6 Isoenzymes) >>> Enzyme inhibitor effect

  • Medications induce Cytochrome P-450 >>> Hepatic Enzyme Inducers: eg: Barbiturates, phenytoin, carbamazepine

  • Monoamine oxidase inhibitors (MAOIs)

  • Sympathomimetic Agents

  • Guanethidine and related agents

  • Tolazamide

Pregnancy and Breastfeeding

  • Pregnancy: No available category, No studies have done yet.

  • Lactation: Not recommended in nursing mother.

Precautions

  • Geriatrics (≥ 65 years of age): may cause confusionand over-sedation in elderly >>> use with caution.

 

  • Pediatrics (< 18 years of age): Safety has not been evaluated.

 

  • Complex sleep-related behaviours:
    1. Potentially dangerous behaviours >>> after taking a sedative- hypnotic >>> eg: Sleep-driving behaviours, not fully awake, preparing and eating food, making phone calls, leaving the house, having sex.
    2. Sleep-driving” may occur at therapeutic doses >>> Synergistic effect withAlcohol & other CNS depressants, Anti-histamins.
    3. Mental alertness: Use with caution in tasks requiring mental alertness >>> Avoid driving!

 

  • Potential for Abuse: Caution!>>> Carefully evaluate patients for history of drug abuse.

 

  • Administer with caution in patients with depression>>> Depression could be intensified >>> Suicide risk & suicidality & worsening of depression >>> Carefully monitor the patient.

 

  • Patients with severe Sleep-apnea: Not recommended

 

  • Administration time: within 30 minutesof bedtime >>> should confine their activities to those necessary to prepare for bed >>> should not be taken within 3 hours of a meal.

 

  • Over dosage:
  1. Symptoms: Excessive drowsiness, alterations of consciousness, unresponsiveness.
  2. ECG: Q-T Prolongation >>> slow intravenous administration of physostigmine salicylatemay reverse most of the cardiovascular & CNS anticholinergic manifestations of tricyclic overdose.
  3. Treatment: Symptomatic and supportive >>> No specific antidote.

 


  • Caution in concomitant use with Monoamine oxidase inhibitors(MAOIs): >>> potentiate other drug effects >>> Serotonin syndrome! >>> At least 14 days should be elapsed before starting either medications.

 

  • Caution in concomitant use with Selective Serotonin Reuptake Inhibitors >>> sufficient time should be elapsed >>>at least 5 weeks.

  • Sympathomimetic Agents:Caution in co-administration nasal drops and local anaesthetics.

 

  • Anticholinergic Agents: Caution in co-administration >>> Deliriumglaucomaattackurinary retention or paralytic ileus.

  • Caution in co administration with Guanethidine and related agents >>> Antihypertensive effect may reduce.

  • Caution in co administration with Tolazamide: Severe hypoglycaemia.

  • Hepatic &Renal ImpairmentSINEQUAN should be used with caution.

Section

This document is prepared by the “Mental Health for All” team. This document is provided for information purposes only and does not necessarily represent endorsement by or an official position of the Essentials of Medicine. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient’s medical history.

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