Elavil

General information

Elavil is an antidepressant from the group of tricyclic antidepressants (TCAs) used to treat depressive disorders, anxiety and some types of chronic pain. The main active ingredient, amitriptyline, affects the central nervous system, improving mood and relieving emotional stress by changing the balance of neurotransmitters in the brain. The drug also has a sedative effect, which makes it useful in sleep disorders associated with depression.

Trade name

Elavil

International Nonproprietary Name (INN)

Amitriptyline

Form of release

The drug is available in the following forms:

• Coated tablets: 10 mg, 25 mg, 50 mg, 50 mg, 75 mg, 100 mg, 150 mg;
• Solution for injection (in some countries): 10 mg/mL in 1 ml ampoules.

Composition

Acting substance: amitriptyline hydrochloride.

Auxiliary components depend on the form of release:

• Tablets: lactose monohydrate, corn starch, microcrystalline cellulose, magnesium stearate, talc; the shell contains hypromellose, titanium dioxide, polyethylene glycol, dyes (for example, indigo carmine for a dosage of 25 mg);
• Injection solution: sodium chloride, water for injection, sometimes benzyl alcohol as a preservative.

The tablets are round in shape, the color varies depending on the dosage: from white (10 mg) to blue (25 mg) or yellow (50 mg).

The tablets have a round shape, the color varies depending on the dosage: from white (10 mg) to blue (25 mg) or yellow (50 mg).

Pharmacologic properties

Pharmacodynamics

Amitriptyline, the active ingredient in Elavil, acts by inhibiting the reuptake of serotonin and norepinephrine at synapses in the central nervous system. This process increases the concentration of these neurotransmitters in the intercellular space, which helps to improve mood and reduce depressive symptoms. The drug also has a pronounced anticholinergic effect by blocking muscarinic receptors, which explains its sedative properties and ability to reduce anxiety. In addition, amitriptyline blocks histamine H1 receptors and alpha-adrenoreceptors, which enhances the sedative effect and may cause orthostatic hypotension.

Antidepressant effect is manifested after 2-4 weeks of regular use, while the sedative effect is noticeable already in the first days. The drug also has analgesic properties, which is associated with the modulation of pain transmission pathways in the spinal cord and the effect on opioid systems. This makes Elavil effective in the treatment of neuropathic pain and migraine.

Pharmacokinetics

Absorption

After oral administration, amitriptyline is well absorbed from the gastrointestinal tract, with a bioavailability of 30-60% due to a first-pass effect through the liver. Maximum plasma concentration (Cmax) is reached in 2-6 hours. Food intake has no significant effect on the rate or extent of absorption.

Distribution

Amitriptyline is widely distributed in body tissues, including the brain, with a volume of distribution of 10-20 L/kg. Binding to plasma proteins (mainly albumin) reaches 95%, which ensures prolonged presence of the drug in the bloodstream. The active metabolite, nortriptyline, is also involved in the pharmacological action.

Metabolism

Metabolism occurs in the liver with the participation of isoenzymes CYP2D6, CYP2C19 and CYP3A4. The main pathway is demethylation to form nortriptyline, which then undergoes hydroxylation and conjugation with glucuronic acid. Metabolism of amitriptyline is characterized by significant interindividual variability, depending on genetic features of enzymatic activity.

Excretion

The half-life of amitriptyline is 10-28 hours, that of nortriptyline - 16-56 hours. It is excreted mainly by kidneys in the form of inactive metabolites (about 80%), a small part (2-5%) - in unchanged form. Complete excretion may take up to 7-10 days after discontinuation of administration. In liver or renal dysfunction, excretion is delayed.

Indications for use

Elavil is indicated for the treatment of the following conditions:

• Major depressive disorder (including endogenous depression);
• Anxiety-depressive states;
• Chronic neuropathic pain (such as in diabetic neuropathy);
• Migraine prevention;
• Depression-related insomnia;
• Enuresis in children (nocturnal urinary incontinence not associated with organic causes).

The drug is used both in monotherapy and in combination with other psychotropic agents.

Contraindications

The use of Elavil is prohibited in the following conditions:

• Hypersensitivity to amitriptyline or other tricyclic antidepressants;
• Recently suffered myocardial infarction (within 1-2 months);
• Severe arrhythmias, heart block (e.g., AV blockade of II-III degree);
• Closed-angle glaucoma;
• Urinary retention (e.g., prostate adenoma);
• Simultaneous administration of MAO inhibitors (14-day interval required);
• Severe hepatic insufficiency;
• Pregnancy (especially first trimester) and breastfeeding;
• Age less than 6 years of age (for any indication).

Method of administration and dosage

How to take

Elavila tablets are taken orally with water (about 100-200 ml), preferably in the evening or before bedtime due to sedative effect. Food intake does not affect efficacy, but to reduce gastric irritation, it is recommended to take the drug during or after meals. The dosage is increased gradually, under the supervision of a physician.

Dosages

Adults

• Depression: initial dose - 25-50 mg/day (at bedtime), maintenance dose - 75-150 mg/day, maximum 300 mg/day;
• Chronic pain, migraine: 10-25 mg/day, if necessary up to 100 mg/day;
• Anxiety: 50-100 mg/day, divided into 2-3 doses or once in the evening.

Children

• Enuresis (6-12 years): 10-25 mg before bedtime, maximum 1 mg/kg/day;
• Depression (over 12 years of age): 10 mg 3 times daily, up to 100 mg/day if needed.

Dose adjustment

• Hiver failure: dose reduction by 50% in mild/moderate form, contraindicated in severe form;
• Renal insufficiency: correction is not required when creatinine clearance is above 10 ml/min;
• Elderly patients: initial dose - 10-25 mg/day, maximum 100 mg/day;
• Drug withdrawal: gradual dose reduction by 25-50 mg every 3-5 days to prevent withdrawal syndrome.

Side effects

The following adverse reactions may occur when taking Elavil:

• Nervous system: drowsiness, dizziness, confusion, tremor;
• Anticholinergic effects: dry mouth, constipation, urinary retention, blurred vision;
• Cardiovascular system: orthostatic hypotension, tachycardia, prolongation of QT interval;
• Gastrointestinal tract: nausea, increased appetite, weight gain;
• Skin: sweating, rash, photosensitivity;
• Endocrine system: decreased libido, impotence.

Most side effects diminish after 1-2 weeks of treatment.

Overdose

Symptoms

Overdose is manifested by dry mouth, confusion意识, hallucinations, seizures, arrhythmias, coma. The critical dose is above 500 mg in adults, above 10 mg/kg in children.

A critical dose is above 500 mg in adults, above 10 mg/kg in children.

First aid measures

• Gastric lavage (within 1-2 hours after ingestion);
• Take activated charcoal (1 g/kg body weight);
• EKG and respiration monitoring, symptomatic therapy;
• Injection of sodium bicarbonate in arrhythmias.

Hemodialysis is ineffective.

Interaction with other drugs

Influence on the effect of other drugs

• Increases the effect of sedatives, opioids, alcohol;
• Decreases the effectiveness of antihypertensive drugs (clonidine, guanethidine);
• Enhances the toxicity of MAO inhibitors (risk of serotonin syndrome);
• increases the concentration of warfarin in the blood.

Compatibility with alcohol and food

Alcohol increases sedation and toxicity, its use is prohibited. Food does not affect absorption, but acidic foods may increase gastric irritation.

Special Instructions

Use in pregnancy and breastfeeding

Elavil is contraindicated in the I trimester of pregnancy due to the risk of fetal malformations. In the II-III trimesters it is used only for vital indications. It penetrates into breast milk, therefore breastfeeding is prohibited.

Effect on driving and mechanisms

The drug causes drowsiness and slowed reactions, driving and working with mechanisms are contraindicated during the first weeks of treatment.

Particularities of use in elderly people and children

Elderly patients are prescribed minimal doses due to the risk of falls and arrhythmias. In children under 6 years of age, the drug is contraindicated, over 6 years of age it is used only for enuresis or depression under strict supervision.

Storage conditions

Store at a temperature of 15-25 ° C in a dry, protected from light, out of reach of children. Shelf life of tablets - 3 years, solution - 2 years.