Anafranil®
Contraindicated drug interactions
MAO inhibitors (linezolid, furazolidone, etc.)
Clomipramine should not be used for at least 2 weeks after discontinuation of MAO inhibitors due to the risk of developing conditions such as hypertensive crisis, fever, and symptoms of serotonin syndrome: myoclonus, agitation, seizures, delirium and coma. The same rule should be followed if a MAO inhibitor is used after previous treatment with clomipramine. In any of these cases, the initial doses of clomipramine or MAO inhibitors should be low and increased gradually, with constant monitoring of the drug's effects.
Current experience shows that clomipramine can be prescribed no earlier than 24 hours after discontinuation of reversible MAO A inhibitors such as moclobemide. But if a reversible MAO A inhibitor is used after discontinuation of the drug Anafranil®, the duration of the break should be at least 2 weeks.
Linezolid
(which is a non-selective MAO inhibitor of reversible action) should not be used simultaneously with clomipramine.
Medicines not recommended for simultaneous use
Antiarrhythmic drugs (eg, quinidine and propafenone)
should not be used simultaneously with tricyclic antidepressants, as they are potent inhibitors of the CYP2D6 isoenzyme.
Diuretic drugs.
Diuretics may cause hypokalemia, which in turn increases the risk of QTc prolongation and varicose veins. Correction of hypokalemia should be carried out before starting drug therapy. It may be necessary to correct other fluid and electrolyte imbalances, such as hypomagnesemia, before starting drug therapy.
Selective serotonin reuptake inhibitors (such as fluoxetine, paroxetine, or sertraline)
inhibit the CYP2D6 isoenzyme, other drugs of this group (for example, fluvoxamine) also inhibit the CYP1A2, CYP2C19 isoenzymes, which can lead to an increase in the concentration of clomipramine in the blood plasma and the development of corresponding undesirable effects. A 4-fold increase in the equilibrium concentration of clomipramine was observed when taken simultaneously with fluvoxamine (the concentration of N-desmethylclomipramine decreased by 2 times).
When clomipramine is used concomitantly with selective serotonin reuptake inhibitors or serotonin and norepinephrine reuptake inhibitors
,
tricyclic antidepressants and lithium preparations
, the development of serotonin syndrome is possible.
If necessary, use fluoxetine
, it is recommended to take a two to three week break between the use of clomipramine and fluoxetine - stop using fluoxetine 2-3 weeks before starting clomipramine therapy or start fluoxetine therapy 2-3 weeks after finishing clomipramine treatment.
Concomitant use of Anafranil® with selective serotonin reuptake inhibitors may lead to increased effects on the serotonin system.
Possible drug interactions
Drug interactions that enhance the therapeutic effects of Anafranil®
Concomitant use with inhibitors of the CYP2D6 isoenzyme
may result in up to a three-fold increase in concentrations of both active components in individuals with the rapid debrisoquine/sparteine metabolizer phenotype. At the same time, in these patients, metabolism decreases to a level characteristic of individuals with a poor metabolizer phenotype.
It is assumed that simultaneous use with inhibitors of the isoenzymes CYP1A2, CYP2C19 and CYP3A4
may lead to an increase in the concentration of clomipramine and a decrease in the concentration of N-desmethylclomipramine, which generally does not affect the pharmacological parameters.
When using the drug Anafranil® simultaneously with the antifungal drug terbinafine
(a potent inhibitor of the CYP2D6 isoenzyme) in oral form may increase the exposure and accumulation of clomipramine, as well as its N-demethylated metabolite. When clomipramine is used together with terbinafine, a dose adjustment of clomipramine is required.
Concomitant use with the H1-histamine receptor blocker cimetidine
(which is an inhibitor of some cytochrome P450 isoenzymes, including CYP2D6 and CYP3A4 isoenzymes) may lead to an increase in plasma concentrations of tricyclic antidepressants, which requires a reduction in the dose of the latter.
There is no evidence of interaction between clomipramine (at a dose of 25 mg per day) and oral contraceptives
(15 or 30 mcg ethinyl estradiol per day) with constant use of the latter. There is no evidence that estrogens are inhibitors of the CYP2D6 isoenzyme, the main isoenzyme involved in the elimination of clomipramine, so there is no reason to expect their interaction. Although, with the simultaneous use of the tricyclic antidepressant imipramine and estrogens in high doses (50 mcg per day), in some cases, worsening side effects and an increase in the therapeutic effect of the antidepressant have been reported. It is unknown whether these data are significant with respect to the concomitant use of clomipramine and low-dose estrogens. With the simultaneous use of tricyclic antidepressants and estrogens in high doses (50 mcg per day), it is recommended to monitor the therapeutic effect of antidepressants and, if necessary, adjust the dosage regimen.
Concomitant use of antipsychotics
(for example, phenothiazine derivatives) may lead to increased plasma concentrations of tricyclic antidepressants, a decrease in the seizure threshold and the occurrence of seizures.
Combination with thioridazine
may lead to the development of severe heart rhythm disturbances.
Methylphenidate
may increase plasma concentrations of tricyclic antidepressants, possibly by inhibiting their metabolism. In this case, it may be necessary to reduce the dose of the latter.
With simultaneous use of valproic acid
and clomipramine may inhibit the CYP2C isoenzyme and/or uridyl diphosphate glucuronyl transferase, which may lead to increased plasma concentrations of clomipramine and desmethylclomipramine.
Drug interactions that reduce the therapeutic effects of Anafranil®
Concomitant use of clomipramine with inducers of CYP3A and CYP2C isoenzymes
, such as
rifampicin
or anticonvulsants (for example,
barbiturates (phenobarbital), carbamazepine and phenytoin
, which are inducers of cytochrome P450 isoenzymes, namely CYP3A4 CYP2C19), can lead to an acceleration of metabolism, a decrease in the concentration of clomipramine in the blood plasma and a decrease in the effectiveness of the drug Anafranil®.
Inducers of the CYP1A2 isoenzyme
(for example, nicotine/other components of cigarette smoke) reduce the concentrations of drugs with a tricyclic structure in the blood plasma. The steady-state concentration of clomipramine in patients who smoke cigarettes is 2 times lower than that in non-smokers (the concentration of N-desmethylclomipramine did not change).
With simultaneous use of ion exchange resins
(for example,
cholestyramine
or
colestipol
), a decrease in the concentration of clomipramine in the blood serum may occur. It is recommended to use clomipramine at least 2 hours before or 4-6 hours after applying resins.
St. John's wort
may lead to decreased plasma concentrations of clomipramine when used concomitantly.
Drug interactions that do not affect Anafranil®
Tricyclic antidepressants can potentiate the effect of drugs that have an anticholinergic effect (for example, phenothiazine derivatives, antiparkinsonian drugs, atropine, biperiden, H1-histamine receptor blockers
) on the organ of vision, central nervous system, intestines and bladder. In addition, with the simultaneous use of the above drugs, there is a risk of developing hyperthermia.
Clomipramine may reduce or completely eliminate the antihypertensive effects of guanethidine, betanidine, reserpine, clonidine and methyldopa
. Therefore, in cases where treatment of arterial hypertension is required simultaneously with clomipramine, drugs of other classes (for example, vasodilators or beta-blockers) should be used.
Tricyclic antidepressants may enhance the effects of ethanol
and other drugs that have a depressant effect on the central nervous system (for example,
barbiturates, benzodiazepines or anesthetics
).
Clomipramine may increase the effects of epinephrine
on the cardiovascular system,
norepinephrine, isoprenaline, ephedrine and phenylephrine
(including when these substances are part of local anesthetics).
Some tricyclic antidepressants may enhance the anticoagulant effect of coumarin derivatives
(for example,
warfarin
), possibly by inhibiting their metabolism (CYP2C9 isoenzyme). There is no data proving the ability of clomipromine to inhibit the metabolism of anticoagulants (warfarin). However, when using this class of drugs, monitoring the concentration of prothrombin in the blood plasma is recommended.
In addition, clomipramine is in vitro
and
in vivo
inhibitor of the activity of the CYP2D6 isoenzyme (sparteine oxidation). Thus, clomipramine may increase the concentrations of concomitantly used drugs that are metabolized primarily through the CYP2D6 isoenzyme.
Incompatibility
: solution of Anafranil® with
diclofenac
.
Anafranil film-coated tablets 25 mg 30 pcs. in Kazan
When using Anafranil in doses exceeding the average therapeutic one, or if the plasma concentration of clomipramine exceeds the average therapeutic one, there is a risk of prolongation of the QTc interval and the occurrence of bidirectional spindle-shaped ventricular tachycardia (“torsade de points”). This occurs when taken together with selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors. In this regard, it is necessary to avoid co-administration of clomipramine and drugs that cause its accumulation. It is also necessary to avoid co-administration with drugs that cause prolongation of the QTc interval. It has been established that hypokalemia is a risk factor for prolongation of the QTc interval and the occurrence of bidirectional spindle-shaped ventricular tachycardia (“torsade de points”). Therefore, hypokalemia must be eliminated before starting Anafranil therapy. Due to the risk of serotonin toxicity and QTc prolongation, adhere to recommended dosages and increase dosage with caution when coadministered with drugs that prolong the QT interval and serotonergic drugs. With simultaneous use of Anafranil with serotonergic drugs, such as selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, tricyclic antidepressants or lithium preparations, the development of serotonin syndrome with symptoms such as fever, myoclonus, agitation, convulsions, delirium is possible. and coma. If it is necessary to prescribe fluoxetine, it is recommended to take a two to three week break between the use of Anafranil and fluoxetine (see section “Interaction with other drugs”, serotonergic drugs). Many patients with panic disorders experience increased anxiety at the beginning of treatment with Anafranil. This paradoxical increase in anxiety is most pronounced in the first days of therapy and usually subsides within two weeks.
In patients with schizophrenia receiving tricyclic antidepressants, activation of psychosis is sometimes observed.
In patients with liver disease, periodic monitoring of liver enzyme activity is recommended.
Anafranil, like other tricyclic antidepressants, is prescribed in combination with electroconvulsive therapy only under close medical supervision. Severe depression is characterized by a risk of suicidal actions, which can persist until reliable remission is achieved. Patients with depression, both adults and children, may experience increased depression and/or suicidal behavior or other psychiatric symptoms, whether or not they are receiving antidepressant therapy. Antidepressants increased the risk of suicidal ideation and behavior in short-term studies in children and adolescents with depression and other psychiatric illnesses.
All patients taking Anafranil for any indication should be monitored for clinical deterioration, suicidal behavior and other psychiatric symptoms, especially during the initial phase of therapy or when the dose of the drug is changed. In such patients, changes in the treatment regimen, including possible drug discontinuation, should be considered, especially if such changes are pronounced, appeared suddenly, or were not observed in the patient initially.
Families and caregivers of patients (both children and adults) taking antidepressants for psychiatric or non-psychiatric indications should be advised to monitor patients for the risk of other psychiatric symptoms, including suicidal behavior, and to report them immediately. symptoms to your treating physicians.
When writing a prescription for Anafranil, the minimum number of tablets should be specified to reduce the risk of overdose. In this case, it is necessary to follow an adequate treatment regimen. There is evidence that while taking Anafranil, there is a lower number of deaths due to overdose than when taking other tricyclic antidepressants.
Before performing general or local anesthesia, the anesthesiologist should be warned that the patient is taking Anafranil.
An increased incidence of dental caries has been reported with long-term treatment with tricyclic antidepressants. Therefore, in case of long-term therapy with Anafranil, regular examination of the patient by a dentist is recommended.
The use of diuretics can lead to the development of hypokalemia, which increases the risk of prolongation of the QTc interval and the occurrence of bidirectional spindle-shaped ventricular tachycardia (“torsade de points”). Before starting Anafranil therapy, hypokalemia must be corrected.
Abrupt withdrawal of Anafranil should be avoided, as this may lead to adverse reactions. If a decision is made to discontinue treatment, the drug should be withdrawn gradually, as quickly as the clinical situation allows. It should be borne in mind that abrupt withdrawal of the drug may be accompanied by the development of certain symptoms.
Anafranil, film-coated tablets, contains lactose and sucrose. Patients with rare hereditary diseases such as galactose and fructose intolerance, severe lactase intolerance, sucrose-isomaltase deficiency or glucose-galactose malabsorption should not take Anafranil film-coated tablets.
Impact on the ability to drive a car and operate machinery
Patients who experience drowsiness and other central nervous system disorders (including blurred vision) while taking Anafranil should not drive a car, operate machinery, or engage in other activities that require increased attention and quick reaction.
