Anafranil
Anafranil: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. For violations of liver function
- 11. Use in the elderly
- 12. Drug interactions
- 13. Analogs
- 14. Terms and conditions of storage
- 15. Terms of dispensing from pharmacies
- 16. Reviews
- 17. Price in pharmacies
Latin name: Anafranil
ATX code: N06AA04
Active ingredient: clomipramine (clomipramine)
Producer: Novartis Pharma (Switzerland)
Description and photo update: 2019-16-08
Prices in pharmacies: from 266 rubles.
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Anafranil is an antidepressant drug that has a pronounced sedative and moderate analgesic effect.
Release form and composition
- Film-coated tablets (10 pcs. In blisters, in a cardboard box 2 or 3 blisters);
- Solution for intramuscular and intravenous administration (in ampoules of 2 ml, in a cardboard box of 10 ampoules).
The active ingredient of Anafranil is clomipramine.
Auxiliary components in the composition of tablets: lactose, stearic acid, corn starch, magnesium stearate, anhydrous colloidal silicon dioxide, talc, titanium dioxide, glycerin 85%, vinylpyrrolidone / vinyl acetate copolymer, crystalline sucrose, hydroxypropyl methylcellulose, yellow, PVCP %, titanium dioxide 95%, polyethylene glycol 8000.
Excipients in the solution: water for injection, glycerol.
Pharmacological properties
Pharmacodynamics
Anafranil is indicated for the treatment of depressive syndrome in general, including its typical symptoms such as anxiety, depressed mood and psychomotor retardation. The first manifestations of the clinical effect are usually observed 2-3 weeks after the start of the course of treatment.
Also, clomipramine is characterized by a specific (different from its antidepressant effect) effect, manifested in obsessive-compulsive disorders.
The effect of Anafranil in chronic pain syndromes, both associated and not associated with somatic diseases, is probably due to an improvement in the transmission of nerve impulses, for which serotonin and noradrenaline are responsible.
Pharmacokinetics
Clomipramine is completely absorbed from the gastrointestinal tract. Its systemic bioavailability unchanged reaches approximately 50%. This decrease in bioavailability is due to the effect of the first pass through the liver, during which the active metabolite N-desmethylclomipramine is formed. Food intake does not significantly alter the bioavailability of clomipramine, however, sometimes there is a decrease in the rate of its absorption and, accordingly, an increase in the time to reach its maximum concentration in blood plasma.
With oral administration of Anafranil in a constant daily dose, the equilibrium concentrations of the active component in the blood plasma vary significantly in different patients. With a daily intake of the drug in a daily dose of 75 mg, the range of equilibrium plasma concentrations of clomipramine is 20‒175 ng / ml. The values of the equilibrium concentration of N-desmethylclomipramine, which is an active metabolite, are usually 40–85% higher than the corresponding figure for clomipramine.
Clomipramine binds to blood plasma proteins by approximately 97.6%. The apparent volume of distribution is approximately 12–17 l / kg of body weight. The concentration of the active substance in the cerebrospinal fluid is approximately 2% of its concentration in the blood plasma.
Clomipramine passes into breast milk, where its concentrations are almost similar to those in blood plasma.
Clomipramine is metabolized primarily by demethylation. As a result of this process, an active metabolite is formed - N-desmethylclomipramine. Several isoforms of cytochrome P 450 are involved in the reaction, mainly isoenzymes CYP1A2, CYP2C19 and CYP3A4. Clomipramine and N-desmethylclomipramine are converted to 8-hydroxyclomipramine or 8-hydroxy-N-desmethylclomipramine by hydroxylation. The in vivo activity of 8-hydroxymetabolites is not well understood.
Clomipramine also attaches a hydroxyl group at the 2-position, and N-desmethylclomipramine can be further demethylated to didesmethylclomipramine; 2- and 8-hydroxy metabolites are excreted mainly as glucuronides via the kidneys. The catalyst for the elimination of two active components of the drug - clomipramine and N-desmethylclomipramine - through the formation of 2- and 8-hydroxyclomipramine is the isoenzyme CYP2D6.
After a single dose of the drug, approximately 2/3 of clomipramine is excreted in the form of water-soluble conjugates in the urine and approximately 1/3 in the faeces. Unchanged through the kidneys, approximately 2% of clomipramine and about 0.5% of desmethylclomipramine are excreted. For clomipramine, the plasma half-life is on average 21 hours (it can range from 12 to 36 hours), and the half-life of desmethylclomipramine is on average 36 hours.
Since in elderly patients the metabolic rate decreases, the concentration of clomipramine in the blood plasma is higher than in younger patients, and there is no dependence on the administered dose of Anafranil. Information on the effect of renal and liver dysfunction on the pharmacokinetic parameters of clomipramine is currently lacking.
Indications for use
- Depressive states of a neurotic, involutional, endogenous, reactive, organic nature;
- Depressive syndrome that developed against the background of schizophrenia;
- Personality disorder;
- Depressive states provoked by prolonged pain;
- Panic attacks of fear.
Anafranil is effective for chronic pain syndrome in cancer patients, patients with migraine, rheumatism, postherpetic neuralgia, peripheral neuropathy, narcolepsy and catalepsy.
Often, the drug is used to prevent migraines and relieve headaches.
Contraindications
- Heart attack;
- Alcohol and drug poisoning;
- Closed-angle glaucoma;
- Severe conduction disturbances;
- Age under 12;
- Pregnancy and lactation;
- Hypersensitivity to drug components.
According to the instructions, Anafranil is prescribed with caution in the following conditions:
- Chronic alcoholism;
- Bronchial asthma;
- Manic-depressive psychosis, schizophrenia, epilepsy;
- Suppression of the hematopoietic function of the bone marrow;
- Angina pectoris, chronic heart failure, hypertension, arrhythmia, heart block, stroke;
- Gastrointestinal motility disorders, renal and hepatic failure, thyrotoxicosis, urinary retention, prostatic hyperplasia;
- Elderly age.
Instructions for the use of Anafranil: method and dosage
Anafranil is taken orally, after a meal or during it, or injected intramuscularly or intravenously.
For the treatment of phobias, depression, obsessive states, Anafranil is taken orally 2-3 times a day, 25 mg.
During the first week, the daily dosage of the drug is gradually increased to 100-150 mg. After the condition improves, the patient is transferred to maintenance therapy - 50-100 mg per day.
The drug is administered intramuscularly at a dosage of 25-50 mg, after which the dose is increased by 25 mg every day, bringing it to 100-150 mg / day. After stabilization of the condition, the number of injections is reduced, the patient is transferred to taking the drug in tablets.
Intravenous 50-75 mg of Anafranil is administered for 1.5-3 hours. A single infusion is performed, before administration, the drug is dissolved in dextrose or sodium chloride solution. After the desired effect is achieved, the drug is continued for another 3-5 days.
As a maintenance treatment, the patient is prescribed the use of Anafranil in tablets.
For the treatment of narcolepsy, the drug is prescribed in a daily dosage of 25-75 mg, by mouth.
To relieve chronic pain, take tablets at a dosage of 10-150 mg / day.
For attacks of fear, Anafranil is taken at a dosage of 10 mg / day.
Elderly patients are prescribed the drug at a dosage of 10 mg / day, gradually increasing the dose to 30-50 mg.
For children, the drug is prescribed in a dose of 10 mg and it is increased for 10 days:
- For children 5-7 years old - up to 20 mg;
- For children 8-14 years old - up to 20-50 mg;
- For children over 14 years old - up to 50 mg and above.
Side effects
The use of Anafranil can cause side effects such as drowsiness, anxiety, anxiety, aggressiveness, impairment of memory and concentration, nightmares, psychosis, sleep disturbances, tinnitus, hallucinations, irritability, malaise, lability.
In addition, the drug in some cases is able to provoke tremors, blurred vision, tachycardia, dry mouth, constipation, increased sweating, arrhythmia, ataxia, collapse, hypotension, nausea and vomiting, hepatitis, heartburn.
With intravenous administration of Anafranil, thrombophlebitis may develop, burning sensation, lymphangitis, and a skin rash may appear.
In case of an overdose of the drug, drowsiness, ataxia, insomnia, anxiety, confusion, stupor, muscle stiffness, epileptic seizures, tachycardia, intracardiac conduction disorders occur: in rare cases, cardiac arrest.
Also, the use of Anafranil in high doses can cause shortness of breath, vomiting, mydriasis, respiratory depression, cyanosis, oliguria, increased sweating, anuria.
When taking the drug orally for the treatment of an overdose, the stomach is washed, and activated charcoal is taken. In severe cases, with arrhythmias, low blood pressure, coma, cholinesterase inhibitors are administered, artificial lung ventilation, and anticonvulsant therapy are performed. Diuresis and hemodialysis are considered ineffective.
Overdose
Anafranil overdose is accompanied by the appearance of symptoms similar to those described with an overdose of other tricyclic antidepressants. The most significant complications include disorders of the cardiovascular system and neurological disorders.
In children, accidental use of the drug in any dose should be regarded as a very serious and fatal accident.
Overdose symptoms usually appear within 4 hours after taking Anafranil and reach peak severity after 24 hours. Since clomipramine has an anticholinergic effect, causing slow absorption, and also participates in hepatoenteric recirculation and has a long half-life, the period of time during which the patient is at risk reaches 4-6 days.
The main symptoms of Anafranil overdose are:
- on the part of the cardiovascular system: heart failure, a marked decrease in blood pressure, shock, tachycardia, intracardiac conduction disturbances, arrhythmias (including "torsade de points"), lengthening of the QT interval; occasionally - cardiac arrest;
- from the side of the central nervous system: drowsiness, increased reflexes, stupor, muscle stiffness, ataxia, coma, agitation, anxiety, choreoathetoid movements, seizures, manifestations of serotonin syndrome (fever, delirium, myoclonus, coma);
- others: anuria or oliguria, depression of the respiratory center, sweating, cyanosis, mydriasis, fever, vomiting.
There is no specific antidote, so symptomatic and supportive therapy is mainly prescribed. If an overdose of the drug is suspected, especially in children, the patient must be hospitalized and left under medical supervision for at least 72 hours.
If the patient remains conscious, vomiting or gastric lavage should be provoked as soon as possible. If the patient is fainting, it is recommended to intubate the trachea with a cuffed tube before starting gastric lavage (this is done to prevent aspiration). Induce vomiting in this case is prohibited. It is advisable to carry out these measures even if 12 hours or more have passed since the moment of taking Anafranil in high doses, since the anticholinergic effect of clomipramine sometimes provokes delayed gastric emptying. To reduce the absorption of the drug, the intake of activated carbon is effective.
In the treatment of overdose, modern methods of intensive care are used, accompanied by constant monitoring of electrolytes and blood gas composition, as well as control of cardiac function. If necessary, emergency measures such as mechanical ventilation, anticonvulsant therapy and resuscitation methods are allowed. Since there is evidence that physostigmine can cause seizures, asystole and severe bradycardia, it is not recommended to use this drug for the treatment of Anafranil overdose.
The effectiveness of peritoneal dialysis and hemodialysis is considered minimal, since the concentration of clomipramine in the blood plasma is rather low.
special instructions
Before starting treatment with Anafranil, hypokalemia must be eliminated.
In the presence of liver diseases during drug therapy, the activity of liver enzymes should be monitored.
A good effect is given by the combination of Anafranil with benzodiazepines. In this case, during the course of treatment, the dosage of the drug is gradually increased (depending on tolerance), and benzodiazepine is canceled. It is desirable that the treatment lasts at least six months.
When treating with Anafranil, you should avoid driving vehicles and controlling potentially dangerous mechanisms that require a high concentration of attention.
The drug should be withdrawn gradually (to avoid adverse reactions).
Application during pregnancy and lactation
The experience of using Anafranil in pregnant women is limited. Due to the presence of individual reports of a possible relationship between treatment with tricyclic antidepressants and the occurrence of fetal malformations, prescribing the drug during pregnancy is contraindicated. An exception is when treatment is vital for the mother, outweighing the potential risks to the fetus.
If the mother took tricyclic antidepressants such as clomipramine throughout pregnancy, until the onset of labor, the newborns during the first few hours or days of life developed a withdrawal syndrome, expressed in a strong increase or decrease in blood pressure, shortness of breath, increased nervous excitability, drowsiness, intestinal colic, tremors, cramping, or seizures. To prevent the development of this syndrome, Anafranil is recommended to be phased out, if possible, at least 7 weeks before the expected onset of labor.
Since clomipramine passes into breast milk, you should either discontinue the drug, gradually reducing the dose, or stop breastfeeding.
For violations of liver function
Patients with liver disease need periodic monitoring of the activity of liver enzymes.
While taking Anafranil, care must be taken in patients with severe liver disease, as well as in patients with tumors of the adrenal medulla (for example, neuroblastoma, pheochromocytoma), since in this case clomipramine is able to provoke the development of a hypertensive crisis.
Use in the elderly
Anafranil should be used with extreme caution in patients with cardiovascular diseases, mainly arrhythmias, intracardiac conduction disorders (for example, AV-blockade of I – III degrees) or cardiovascular insufficiency. In such patients, as in elderly patients, regular ECG and monitoring of cardiac performance are recommended.
When taking Anafranil to patients suffering from chronic constipation, special care is required. It can cause paralytic ileus in both bed rest patients and elderly patients.
Drug interactions
Clomipramine can reduce or completely neutralize the antihypertensive effect of alphamethyldopa, guanethidine, clonidine, reserpine and betanidine. Therefore, in cases where taking Anafranil must be combined with the treatment of hypertension, it is advisable to use drugs of other classes (for example, beta-blockers or vasodilators).
Clomipramine can enhance the effect of anticholinergics, which include antihistamines, phenothiazines, biperiden, atropine, antiparkinsonian drugs, on the bladder, intestines, central nervous system and the organ of vision.
Anafranil is able to potentiate the effect of alcoholic beverages and other drugs that depress the central nervous system (for example, anesthetics, benzodiazepines or barbiturates).
It is not recommended to prescribe clomipramine for at least 2 weeks after stopping MAO inhibitors due to the risk of developing such severe conditions and symptoms as fever and hypertensive crisis, as well as the appearance of signs of serotonin syndrome: delirium, agitation, myoclonus, convulsive seizures and coma. The same should be done if an MAO inhibitor is prescribed after previous therapy with clomipramine. In any of these situations, the initial doses of MAO inhibitors or Anafranil should be low, after which they are gradually increased, while constantly monitoring the effect of drugs on the body.
The available clinical experience confirms that Anafranil can be prescribed no earlier than 1 day after the withdrawal of MAO-A inhibitors of the reverse action (these include moclobemide). However, after the cancellation of Anafranil, the use of a reverse MAO-A inhibitor is permissible only with a minimum interruption in treatment of at least 2 weeks.
The combined use of clomipramine with selective serotonin reuptake inhibitors can increase the effect on the serotonin system.
When Anafranil is combined with norepinephrine and serotonin reuptake inhibitors or selective serotonin reuptake inhibitors, lithium preparations and tricyclic antidepressants, serotonin syndrome is likely to develop, accompanied by symptoms such as delirium, agitation, fever, myoclonus, convulsive states and coma. If you need to take fluoxetine, you should take a break of 2-3 weeks between the use of Anafranil and fluoxetine: stop taking fluoxetine 2-3 weeks before starting treatment with Anafranil, or prescribe fluoxetine 2-3 weeks after stopping Anafranil.
Clomipramine can enhance the effects on the cardiovascular system of phenylephrine, epinephrine, ephedrine, isoprenaline and norepinephrine (including when these substances are part of local anesthetics).
Co-administration of Anafranil with inhibitors of the isoenzyme CYP2D6 can lead to an increase in the concentration of clomipramine and its main metabolite N-desmethylclomipramine by 3 times in patients with the phenotype of a rapid metabolizer of debrisoquine / sparteine. At the same time, in such patients, the metabolism slows down to a level characteristic of patients with the phenotype of a weak metabolizer. It is assumed that the combination of Anafranil with inhibitors of the isoenzymes CYP3A4, CYP2C19 and CYP1A2 may lead to an increase in clomipramine levels and a decrease in N-desmethylclomipramine levels.
Taking MAO inhibitors (for example, moclobemide) in conjunction with clomipramine is contraindicated, since they are potent inhibitors of CYP2D6 in vivo. Selective serotonin reuptake inhibitors (sertraline, paroxetine or fluoxetine) are inhibitors of CYP2D6, other drugs in this category (for example, fluvoxamine) are also inhibitors of CYP2C19 and CYP1A2, which can provoke an increase in the concentration of clomipramine in the blood plasma of side reactions and the occurrence of unwanted adverse reactions. When Anafranil was taken together with fluvoxamine, the equilibrium concentration of clomipramine increased by 4 times and the concentration of N-desmethylclomipramine decreased by 2 times.
Antiarrhythmic drugs (such as propafenone and quinidine) should not be used with Anafranil because they are potent inhibitors of CYP2D6.
Co-administration of the drug with a blocker of histamine H 2 -receptors cimetidine, which is an inhibitor of certain isoenzymes of cytochrome P 450 (including CYP3A4 and CYP2D6), may lead to an increase in the concentration of clomipramine in plasma, which may require a dose adjustment downward.
The combination of Anafranil with antipsychotics (for example, phenothiazines) can lead to an increase in the plasma content of clomipramine, a decrease in the seizure threshold and provoke seizures. The combination with thioridazine increases the risk of severe arrhythmias.
There is no information confirming the interaction of clomipramine (in a daily dose of 25 mg) and oral contraceptives (0.015 or 0.03 mg of ethinylestradiol per day) with constant intake of the latter. It has not been proven that estrogens are inhibitors of CYP2D6, the most important enzyme involved in the elimination of clomipramine, so their interaction should not be assumed. In some cases, with the simultaneous administration of estrogens in high doses (daily dose of 0.05 mg) and the tricyclic antidepressant imipramine, an increase in adverse reactions and an intensification of the therapeutic effect of the antidepressant were reported. It is not known whether these data can be considered significant for clomipramine and estrogens at low doses. With the combination of Anafranil and estrogens in high doses (0,05 mg per day), it is advisable to monitor the therapeutic effect of the antidepressant and, if necessary, adjust the dosage regimen.
Methylphenidate (Ritalin) may increase the concentration of clomipramine, presumably due to the suppression of its metabolism. When used together with Anafranil, a dose reduction of the latter may be required.
Sometimes clomipramine can enhance the anticoagulant effect of coumarins (for example, warfarin), probably by slowing down their metabolism, which is carried out using the isoenzyme CYP2C9. There are no data supporting the ability of clomipramine to inhibit the metabolism of anticoagulants. However, when taking this antidepressant, it is desirable to monitor the concentration of prothrombin in plasma.
The combination of Anafranil with drugs - inducers of CYP2C and CYP3A, which include rifampicin or anticonvulsants (phenytoin, barbiturates, phenobarbital, carbamazepine, etc.), may cause a decrease in the level of clomipramine in plasma.
Known inducers of CYP1A2 (for example, nicotine and other components of cigarette smoke) reduce the content of clomipramine in blood plasma. The equilibrium concentration of the active ingredient Anafranil in patients who smoke cigarettes is 2 times lower than that in non-smoking patients (while the concentration of N-desmethylclomipramine remains unchanged).
Clomipramine both in vitro and in vivo (K i = 2.2 microM) inhibits the activity of CYP2D6, which is responsible for the oxidation of spartein. Therefore, this drug can increase the concentration of drugs metabolized mainly with the participation of CYP2D6, when taken simultaneously with Anafranil in patients with a strong metabolizer phenotype.
Analogs
Anafranil analogs are Anafranil SR, Clominal, Clofranil and Clomipramine.
Terms and conditions of storage
Store in a dark place, out of the reach of children, at a temperature not exceeding 30 ° C.
The shelf life is 5 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Anafranil
According to reviews, Anafranil is considered a good effective drug. It helps to get rid of obsessive and oppressive thoughts and ideas, successfully fights depression, restores patients' desire to live. However, since the drug has many side effects, only a doctor should prescribe it.
The price of Anafranil in pharmacies
The approximate price of Anafranil in the form of tablets is 299-332 rubles (the package includes 30 pcs.). You can buy a solution for intramuscular and intravenous administration for about 652--673 rubles (the package includes 10 ampoules).
Anafranil: prices in online pharmacies
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Drug name Price Pharmacy |
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Anafranil 25 mg film-coated tablets 30 pcs. 266 r Buy |
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Anafranil tablets p.o. 25mg 30 pcs. 308 RUB Buy |
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Anafranil SR 75 mg film-coated tablets of prolonged action 10 pcs. 355 RUB Buy |
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Anafranil SR tablets p.o. prolonged action 75mg 10 pcs. 379 r Buy |
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
