Pharmacological properties
Pharmacodynamics.
Doxepin belongs to the group of tricyclic antidepressants. The antidepressant effect is combined with anxiolytic and sedative. Doxepin inhibits the reuptake of biogenic amines (norepinephrine and serotonin) in synaptic structures. It also has antihistamine, anticholinergic and α1-adrenergic blocking effects. Does not cause euphoria or psychomotor agitation.
Pharmacokinetics. Doxepin is well absorbed from the gastrointestinal tract and quickly (2–4 hours after administration) reaches Cmax in the blood plasma. A stable therapeutic concentration in the blood is achieved 2 weeks after the start of treatment.
Doxepin is metabolized in the liver mainly by demethylation to form the main metabolite, desmethyldoxepin (nordoxepin). The binding of doxepin and its metabolites to plasma proteins is about 76%. The volume of distribution is about 20 l/kg body weight. T½ of doxepin is 8–24 hours, the main active metabolite is 33–80 hours. Doxepin passes through the placenta and BBB and passes into breast milk.
Application
Taken orally. the dose of the drug is selected individually depending on the severity of symptoms and therapeutic effect.
The dose of Doxepin is 30–300 mg/day. A dose of up to 100 mg can be used either once or divided. Doses exceeding 100 mg should be administered in 3 divided doses. The maximum single dose is 100 mg (use before bedtime). For moderate to severe symptoms, the usual starting dose is 75 mg/day. This dose is effective in most patients. In severe forms of the disease, the dose is increased to 300 mg (in 3 doses) per day.
In patients with insomnia, the total dose should be distributed so that the higher dose is administered in the evening. In cases where insomnia is reported as an adverse reaction, this dosage regimen may also be used or the dose should be reduced.
After achieving a satisfactory therapeutic effect, the dose of the drug should be adjusted to the minimum maintenance level.
Reduction in the severity of anxiety symptoms when taking Doxepin is achieved earlier than the antidepressant effect. The antidepressant effect appears after 2–3 weeks of treatment.
For elderly patients with moderate symptoms, half the usual recommended dose of doxepin hydrochloride (10–50 mg daily) is recommended. Satisfactory clinical effects were obtained after using Doxepin at a dose of 30–50 mg/day. The dose of the drug should be adjusted individually depending on the patient's clinical response.
Patients with impaired liver function should reduce doses.
Use of the drug Doxepin
Orally, usually at an initial dose of 30–75 mg/day in 3 divided doses. In patients with moderate or severe psychoneurotic symptoms, the dose can be gradually increased to 150 mg/day. To achieve a satisfactory result in severe depression, a maximum daily dose of 300 mg may be necessary. Once clinical effect is achieved, the dose can be reduced accordingly. Maintenance dose: 25–50 mg/day in 2–3 divided doses. Children over 12 years of age are prescribed at the rate of 0.5 mg/kg body weight per day in several doses. For sleep disorders, most of the daily dose is prescribed in the evening. An alternative method of treatment is to administer the entire daily dose (up to 150 mg) at bedtime (without reducing the effectiveness of treatment).
Side effects
Doxepin is generally well tolerated. Most side effects of moderate severity occur at the beginning of treatment and disappear after discontinuation of the drug or reduction in its dose. Some of the adverse reactions listed below are not specific to doxepin, but the possibility of these reactions should be considered due to the similarity of its pharmacological properties to other tricyclics.
Adverse reactions are distributed according to the frequency of manifestations: very often (1/10), often (1/100, 1/10), infrequently (1/1000, 1/100), rarely (1/10,000, 1/1000), very rare (1/10,000), unknown (frequency cannot be determined based on available information).
From the nervous system and mental disorders: very often - drowsiness; Uncommon: headache, dizziness, insomnia, nightmares, confusion, disorientation, anxiety, numbness or paresthesia, tremor (usually moderate). When using the drug in high doses (especially in elderly patients), extrapyramidal symptoms may occur, including tardive dyskinesia; rarely - hallucinations, ataxia (in general, if several drugs acting on the central nervous system are used), convulsions (in patients prone to seizures, which may be caused by brain damage or alcohol and substance abuse); unknown - suicidal thoughts and behavior. Cases of suicidal thoughts and behavior have been reported during treatment with doxepin or immediately after its discontinuation.
Psychiatric manifestations, including mania and paranoid hallucinations, may be exacerbated by treatment with tricyclic antidepressants. Tinnitus has been reported occasionally.
From the side of the organ of vision: very rarely - visual impairment (blurredness).
From the vascular system: rarely - orthostatic hypotension, flushing.
From the heart: very rarely - tachycardia, ECG abnormalities (widening of the QRS complex, prolongation of the P-R interval).
From the immune system: uncommon - allergic reactions, including rash, facial swelling, increased photosensitivity, itching, urticaria. During treatment with tricyclic antidepressants, exacerbation of asthma is possible.
From the skin and subcutaneous tissue: rarely - increased sweating, the above allergic skin reactions; very rarely - alopecia.
From the blood and lymphatic system: rarely - eosinophilia and bone marrow dysfunction with symptoms such as agranulocytosis, leukopenia, thrombocytopenia, purpura and hemolytic anemia.
From the digestive system: very often - dryness of the mucous membrane of the mouth and nose, constipation; rarely - nausea, vomiting, dyspepsia, impaired taste, diarrhea, anorexia, stomatitis.
From the endocrine system: rarely - impaired secretion of antidiuretic hormone, gynecomastia, enlarged mammary glands, galactorrhea in women; isolated cases - changes in libido, swelling of the testicles, increase or decrease in blood glucose levels.
From the kidneys and urinary system: rarely - urinary retention (complaints may intensify in men with prostatic hypertrophy).
From the hepatobiliary system: rarely - jaundice.
General disorders: very often - fatigue, weakness, weight gain, chills, hyperpyrexia (in patients taking chlorpromazine at the same time).
Withdrawal of doxepin. If tricyclic antidepressants are stopped suddenly, withdrawal symptoms may occur, including insomnia, irritability, and excessive sweating. Withdrawal symptoms in infants whose mothers took tricyclic antidepressants during the third trimester include respiratory depression, convulsions, and hyperreflexia.
Adverse reactions
Withdrawal symptoms in infants whose mothers took tricyclic antidepressants during the third trimester include respiratory depression, convulsions, and hyperreflexia.
Doxepin is generally well tolerated. Most side effects of moderate severity occur at the beginning of treatment and disappear after discontinuation of the drug or reduction in its dose. Some of the adverse reactions listed below are not specific to Doxepin, but the possibility of these reactions should be taken into account due to the similarity of its pharmacological properties with other tricyclics. Adverse reactions are distributed according to the frequency of manifestations: very often (> 1/10); common (> 1/100, <1/10), uncommon (> 1/1000, <1/100), rare (> 1/10,000, <1/1000), very rare (> 1/10,000) unknown ( frequency cannot be determined from available information).
From the nervous system and mental disorders.
Very often drowsiness.
Uncommon: headache, dizziness, insomnia, nightmares, confusion, disorientation, anxiety, numbness or paresthesia, tremor (usually moderate). When using high doses (especially in elderly patients), extrapyramidal symptoms, including tardive dyskinesia, may occur.
Rarely, hallucinations, ataxia (only if several drugs acting on the central nervous system are used), seizures (in patients prone to seizures, which may be caused by brain damage or alcohol and substance abuse).
Unknown: Suicidal thoughts and behavior.
Cases of suicidal thoughts and behavior have been reported during treatment with Doxepin or immediately after its discontinuation.
Psychiatric manifestations, including mania and paranoid hallucinations, may be exacerbated by treatment with tricyclic antidepressants. Tinnitus has been reported occasionally.
From the organs of vision.
Very rare: visual disturbances (blurredness).
From the vascular system.
Rarely, orthostatic hypotension, facial flushing.
From the cardiovascular system.
Very rarely, tachycardia, ECG abnormalities (widening of the QRS complex, prolongation of the PR interval).
From the immune system.
Uncommon: allergic reactions, including skin rashes, facial swelling, photosensitivity, itching, urticaria.
During treatment with tricyclic antidepressants, exacerbation of bronchial asthma is possible.
From the skin and subcutaneous tissue.
Rarely: increased sweating, allergic skin reactions listed above.
Very rarely alopecia.
From the blood and lymphatic systems.
Rarely: eosinophilia and bone marrow dysfunction with symptoms such as agranulocytosis, leukopenia, thrombocytopenia, purpura and hemolytic anemia.
From the gastrointestinal tract.
Very often, dry mucous membranes of the mouth and nose, constipation.
Rarely: nausea, vomiting, dyspepsia, impaired taste, diarrhea, anorexia, stomatitis.
From the endocrine system.
Rarely: impaired secretion of ADH, gynecomastia, enlarged mammary glands, galactorrhea in women.
Isolated cases of changes in libido, swelling of the testicles, increased or decreased blood glucose levels.
From the kidneys and urinary system.
Rarely, urinary retention (complaints may intensify in men with prostate hypertrophy).
From the digestive system.
Rarely jaundice.
General violations.
Very common: fatigue, weakness, weight gain, chills, hyperpyrexia (in patients taking chlorpromazine at the same time).
ABOUT.
If tricyclic antidepressants are stopped suddenly, withdrawal symptoms may occur, including insomnia, irritability, and excessive sweating.
special instructions
Patients with concomitant diseases or those taking other medications should use a single dosage regimen. this also applies to patients using drugs with anticholinergic effects.
Elderly people should also use this dosage regimen and adjust it with caution. These patients are prone to developing adverse reactions such as anxiety, confusion and orthostatic hypotension. Therefore, the initial dose should be prescribed with caution and under close monitoring of the patient's condition and response to the drug. Half the dose of doxepin may be sufficient for adequate clinical effect.
Patients should be warned that drowsiness may occur during treatment and that drinking alcohol may enhance the effect of the drug.
If the symptoms of psychosis or manic episodes worsen during treatment with doxepin, it may be necessary to reduce the dose of the drug or add a group of tranquilizers (neuroleptics) to the treatment regimen.
Although doxepin has less vascular effects than other tricyclic antidepressants, it should be used with caution in patients with severe cardiovascular disease (heart block, cardiac arrhythmia, and recent myocardial infarction).
Caution is required when using doxepin in patients with renal or hepatic impairment and in those with a history of epileptic seizures.
Suicide/suicidal ideation or clinical deterioration. Patients with severe depression are at risk of developing suicidal thoughts and actions, which may persist until remission is achieved. If improvement does not occur within the first few weeks of treatment or even more, patients require careful monitoring until improvement occurs. It is known from general clinical practice that the risk of suicidal thoughts or actions may increase in the early stages of treatment.
Other psychiatric conditions for which doxepin is prescribed also have an increased risk of suicide. Therefore, special precautions must be taken for such patients.
Careful monitoring is required throughout treatment for patients with a history of suicidal ideation or suicide attempts.
Careful monitoring of patients, especially high-risk groups, should be combined with the use of appropriate medications, especially in the early stages, followed by dosage adjustments if necessary. Patients (and those caring for them) should be informed of the need to monitor for any clinical worsening, suicidal behavior, ideation, or unusual change in behavior and to seek prompt medical attention if these symptoms occur.
A meta-analysis of placebo-controlled studies of antidepressants in adult patients with mental disorders showed an increased risk of suicidal behavior in patients under 25 years of age compared with placebo.
In patients with moderate prostatic hypertrophy, urinary retention may increase.
Doxepin contains lactose monohydrate, so patients with rare hereditary forms of galactose intolerance, glucose-galactose malabsorption syndrome, and Lapp lactase deficiency are not recommended to prescribe it.
Patients with hypersensitivity or intolerance to gluten should not use this drug, since its excipients include starch.
Use during pregnancy or breastfeeding. Animal reproductive studies did not reveal any adverse effects on the fetus; There have been no adequate and well-controlled studies in pregnant women. Thus, during pregnancy the drug is used only in cases where the expected benefit to the mother outweighs the potential risk to the fetus.
Doxepin passes into breast milk, so breastfeeding should be discontinued during treatment.
Children. The safety and effectiveness of doxepin in children have not been established.
The ability to influence reaction speed when driving vehicles or working with other mechanisms. During treatment with doxepin, it is forbidden to drive vehicles or operate complex mechanisms that require concentration, since the drug can lead to drowsiness and other negative reactions from the central nervous system.
Doxepin capsules 25 mg, 30 pcs.
For patients with concomitant diseases or patients taking other medications, a single dosage regimen is recommended. This also applies to patients taking drugs with anticholinergic effects.
Elderly patients should also use this dosage regimen and adjust it with caution. These patients are prone to developing the following adverse reactions: anxiety, confusion and orthostatic hypotension. Therefore, the initial dose should be prescribed with caution and under close monitoring of the patient's condition and response to the drug. For an appropriate clinical effect, half the dose of Doxepin may be sufficient.
Patients should be advised that drowsiness may occur during treatment. Drinking alcohol may enhance the effect of the drug.
If symptoms of psychosis or manic episodes worsen during treatment with doxepin, it may be necessary to reduce the dose of doxepin or add drugs from the antipsychotic group to the treatment regimen.
Although doxepin has less vascular effects than other tricyclic antidepressants, it should be used with caution in patients with severe cardiovascular disease (heart block, cardiac arrhythmia, and recent myocardial infarction).
Doxepin should be used with caution in patients with renal or hepatic impairment and in patients with a history of epileptic seizures.
Suicide/suicidal ideation or clinical worsening
Patients with severe depression are at risk of developing suicidal thoughts and actions, which may persist until remission is achieved. Since it is possible that improvement does not occur during the first few weeks of treatment or even longer, careful monitoring of patients' condition is necessary for improvement. It is known from general clinical practice that the risk of suicidal thoughts or actions may increase in the early stages of treatment.
Other psychiatric conditions for which doxepin is prescribed also have an increased risk of suicide. Therefore, such patients must take special safety precautions.
Patients with a history of suicidal thoughts or suicide attempts should be closely monitored throughout treatment. Careful monitoring of patients, especially high-risk groups, should be combined with the administration of appropriate medications, especially in the early stages, followed by dose adjustments if necessary. Patients (and those caring for them) should be informed of the need to monitor for any clinical worsening, suicidal behavior, thoughts or unusual changes in behavior and to seek immediate medical attention if these symptoms occur.
A meta-analysis of placebo-controlled studies of antidepressants in adult patients with mental disorders showed an increased risk of suicidal behavior in patients under 25 years of age compared with placebo.
In patients with moderate prostatic hypertrophy, urinary retention may increase.
Doxepin contains lactose, therefore patients with rare hereditary forms of galactose intolerance, glucose-galactose malabsorption syndrome, Lapp lactase deficiency are not recommended to prescribe this drug.
Patients with gluten sensitivity or intolerance should not use doxepin as its excipients include corn starch.
Interactions
With the simultaneous use of ethanol, antidepressants, barbiturates, benzodiazepines and general anesthetics, a significant increase in the inhibitory effect on the central nervous system, respiratory depression and hypotensive effect is possible. doxepin increases the anticholinergic effect of amantadine. phenothiazines, antiparkinsonian drugs, atropine, biperiden, antihistamines increase the risk of side effects from the central nervous system, vision, intestines, and bladder. when used simultaneously with antihistamines, clonidine, the inhibitory effect on the central nervous system increases; with atropine, the risk of paralytic intestinal obstruction increases; with drugs that cause extrapyramidal reactions, body weight and the frequency of extrapyramidal effects increase. with simultaneous use of doxepin with indirect anticoagulants (coumarin or indadione derivatives), an increase in the anticoagulant activity of the latter is possible. Doxepin may increase depression caused by corticosteroids. when used in combination with anticonvulsants, it is possible to enhance the inhibitory effect on the central nervous system, reduce the threshold of convulsive readiness (when used in high doses) and reduce the effectiveness of the latter. drugs for the treatment of thyrotoxicosis increase the risk of developing agranulocytosis. doxepin reduces the effectiveness of phenytoin and α-blockers. inhibitors of microsomal oxidation (cimetidine) prolong t½, increase the risk of developing toxic effects of doxepin (a dose reduction of doxepin may be required by 20–30%), inducers of microsomal liver enzymes (barbiturates, carbamazepine, phenytoin, nicotine and oral contraceptives) reduce plasma concentrations and effectiveness of doxepin. fluoxetine and fluvoxamine increase the concentration of doxepin in the blood plasma (a 50% reduction in the dose of doxepin may be required). when used simultaneously with anticholinergic blockers, phenothiazines and benzodiazepines, there is a mutual enhancement of the sedative and central anticholinergic effects and an increased risk of epileptic seizures (lowering the threshold for convulsive readiness); Phenothiazines may also increase the risk of neuroleptic malignant syndrome. with simultaneous use of doxepin with clonidine, guanethidine, betanidine, reserpine and methyldopa - a decrease in the hypotensive effect of the latter; with cocaine - the risk of developing cardiac arrhythmia. Estrogen-containing oral contraceptives and estrogens may increase the bioavailability of doxepin; antiarrhythmic drugs (quinidine) increase the risk of developing rhythm disturbances (possibly slowing down the metabolism of doxepin). simultaneous use with disulfiram and acetaldehydrogenase inhibitors provokes delirium. incompatible with MAO inhibitors (possible increased frequency of periods of hyperpyrexia, severe convulsions, hypertensive crisis and patient death). Pimozide and probucol can increase cardiac arrhythmia, which is manifested by prolongation of the q-t interval on the ecg. the effect on the cardiovascular system of epinephrine, norepinephrine, isoprenaline, ephedrine and phenylephrine is enhanced (including when these agents are part of local anesthetics) and the risk of developing heart rhythm disturbances, tachycardia, and severe hypertension increases. simultaneous use of α-adrenergic receptor blockers for intranasal administration or for use in ophthalmology (with significant systemic absorption) may enhance the vasoconstrictor effect of the latter. when used in combination with thyroid hormones, there is a mutual enhancement of the therapeutic effect and toxic effect (including cardiac arrhythmia and stimulating effect on the central nervous system). M-anticholinergics and antipsychotics increase the risk of developing hyperpyrexia (especially in hot weather).
Interaction with other drugs and other types of interactions.
With the simultaneous use of ethanol, antidepressants, barbiturates, benzodiazepines and general anesthetics, a significant increase in the inhibitory effect on the central nervous system, respiratory depression and hypotensive effect is possible.
Doxepin enhances the anticholinergic effect of amantadine. Phenothiazines, antiparkinsonian drugs, atropine, biperiden, antihistamines increase the risk of side effects from the central nervous system, vision, intestines, and bladder. When used simultaneously with antihistamines and clonidine, the inhibitory effect on the central nervous system increases; with atropine - the risk of paralytic intestinal obstruction increases; with drugs that cause extrapyramidal reactions - body weight and the frequency of extrapyramidal effects increase. With the simultaneous use of Doxepin with indirect anticoagulants (coumarin or indadione derivatives), the anticoagulant activity of the latter may increase. Doxepin may enhance depression caused by corticosteroids. When used together with anticonvulsants, it is possible to enhance the inhibitory effect on the central nervous system, reduce the threshold of convulsive activity (when used in high doses) and reduce the effectiveness of the latter. Drugs used to treat thyrotoxicosis increase the risk of developing agranulocytosis. Reduces the effectiveness of phenytoin and a-blockers. Inhibitors of microsomal oxidation (cimetidine) prolong the half-life, increase the risk of developing toxic effects of Doxepin (a dose reduction of Doxepin may be required by 20-30%), inducers of microsomal liver enzymes (barbiturates, carbamazepine, phenytoin, nicotine and oral contraceptives) reduce plasma concentrations and reduce the effectiveness of doxepin. Fluoxetine and fluvoxamine increase plasma concentrations of Doxepin (a 50% reduction in Doxepin dose may be required). When used simultaneously with anticholinergic blockers, phenothiazines and benzodiazepines, there is a mutual enhancement of the sedative and central anticholinergic effects and an increased risk of epileptic seizures (lowering the threshold of convulsive activity); Phenothiazines may also increase the risk of neuroleptic malignant syndrome. With simultaneous use of Doxepin with clonidine, guanethidine, betanidine, reserpine and methyldopa - a decrease in the hypotensive effect of the latter; with cocaine - the risk of developing cardiac arrhythmias. Estrogen-containing oral contraceptives and estrogens may increase the bioavailability of Doxepin; antiarrhythmic drugs (quinidine) increase the risk of developing rhythm disturbances (possibly slowing down the metabolism of Doxepin). Concomitant use with disulfiram and acetaldehydrogenase inhibitors provokes delirium.
Incompatible with MAO inhibitors (possible increased frequency of periods of hyperpyrexia, severe convulsions, hypertensive crises and patient death). Pimozide and probucol may increase cardiac arrhythmias, which is manifested by prolongation of the QT interval on the ECG. The effect on the cardiovascular system of epinephrine, norepinephrine, isoprenaline, ephedrine and phenylephrine is enhanced (including when these agents are part of local anesthetics) and the risk of developing heart rhythm disturbances, tachycardia, and severe arterial hypertension increases. The simultaneous use of a-adrenergic receptors for intranasal administration or for use in ophthalmology (with significant systemic absorption) may enhance the vasoconstrictor effect of the latter. When used together with thyroid hormones, there is a mutual enhancement of the therapeutic effect and toxic effects (including cardiac arrhythmias and stimulating effects on the central nervous system). M-anticholinergics and antipsychotics increase the risk of developing hyperpyrexia (especially in hot weather).
Overdose
Symptoms: drowsiness, anxiety, dry mouth, stupor, blurred vision, arrhythmia. If such symptoms occur, the drug should be discontinued and the patient examined.
In case of severe overdose, a decrease/increase in blood pressure, dilated pupils, tachycardia, urinary retention (bladder atony), ileus, hyperthermia/hypothermia, respiratory depression, increased sweating, convulsions, coma are possible.
Treatment: discontinuation of the drug, gastric lavage, artificial ventilation, monitoring the cardiovascular system, use of sleeping pills. If necessary, administer physostigmine salicylate 1–3 mg. Therapy is symptomatic. Hemodialysis and forced diuresis are ineffective.
Note!
Description of the drug Doxepin caps. 10mg No. 30 on this page is a simplified author’s version of the apteka911 website, created on the basis of the instructions for use.
Before purchasing or using the drug, you should consult your doctor and read the manufacturer's original instructions (attached to each package of the drug). Information about the drug is provided for informational purposes only and should not be used as a guide to self-medication. Only a doctor can decide to prescribe the drug, as well as determine the dose and methods of its use.
