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Clozaril and Rythmol

Determining the interaction of Clozaril and Rythmol and the possibility of their joint administration.

Check result:
Clozaril <> Rythmol
Relevance: 05.02.2023 Reviewer: Shkutko P.M., M.D., in

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Consumer:

Consumer information for this interaction is not currently available.MONITOR CLOSELY: Coadministration of clozapine with other agents that can cause neutropenia or agranulocytosis may increase the risk and/or severity of hematologic toxicity. Clozapine alone is associated with a significant risk of agranulocytosis, defined as an absolute neutrophil count (ANC) of less than 500/mm3. During premarketing trials in the U.S., at a time when the need for close monitoring of white blood cell counts was already recognized, the cumulative incidence of agranulocytosis at one year was estimated to be approximately 1.3%. The incidence has decreased postmarketing under a weekly WBC count monitoring system. Although the mechanism of clozapine-induced agranulocytosis is unknown, it is possible that causative factors may interact synergistically to increase the risk and/or severity of bone marrow suppression. A fatality rate of 3% has been reported for agranulocytosis associated with clozapine. MANAGEMENT: Caution and close monitoring are advised when clozapine is used with other agents that have a well-known potential to cause agranulocytosis or otherwise suppress bone marrow function, such as antineoplastic, antimalarial, and antirheumatic agents. MONITOR CLOSELY: Clozapine has the potential to prolong QT interval of the electrocardiogram. Theoretically, coadministration with other agents that can cause QT prolongation may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. Clozapine treatment alone has been associated with ventricular arrhythmia, torsade de pointes, cardiac arrest, and sudden death. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s). MANAGEMENT: Caution is recommended if clozapine is used in combination with other drugs that can prolong the QT interval. Serum electrolytes, including potassium, magnesium and calcium, should be measured at baseline and periodically during treatment, and any abnormalities corrected prior to initiating clozapine. Routine ECG assessment may detect QTc prolongation, but is not always effective in preventing arrhythmias. Clozapine treatment should be discontinued if the QTc interval exceeds 500 msec. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. References "Product Information. Clozaril (clozapine)." Novartis Pharmaceuticals, East Hanover, NJ. "Product Information. Tasigna (nilotinib)." Novartis Pharmaceuticals, East Hanover, NJ.

Professional:

MONITOR CLOSELY: Coadministration of clozapine with other agents that can cause neutropenia or agranulocytosis may increase the risk and/or severity of hematologic toxicity. Clozapine alone is associated with a significant risk of agranulocytosis, defined as an absolute neutrophil count (ANC) of less than 500/mm3. During premarketing trials in the U.S., at a time when the need for close monitoring of white blood cell counts was already recognized, the cumulative incidence of agranulocytosis at one year was estimated to be approximately 1.3%. The incidence has decreased postmarketing under a weekly WBC count monitoring system. Although the mechanism of clozapine-induced agranulocytosis is unknown, it is possible that causative factors may interact synergistically to increase the risk and/or severity of bone marrow suppression. A fatality rate of 3% has been reported for agranulocytosis associated with clozapine.

MANAGEMENT: Caution and close monitoring are advised when clozapine is used with other agents that have a well-known potential to cause agranulocytosis or otherwise suppress bone marrow function, such as antineoplastic, antimalarial, and antirheumatic agents.

MONITOR CLOSELY: Clozapine has the potential to prolong QT interval of the electrocardiogram. Theoretically, coadministration with other agents that can cause QT prolongation may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. Clozapine treatment alone has been associated with ventricular arrhythmia, torsade de pointes, cardiac arrest, and sudden death. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Caution is recommended if clozapine is used in combination with other drugs that can prolong the QT interval. Serum electrolytes, including potassium, magnesium and calcium, should be measured at baseline and periodically during treatment, and any abnormalities corrected prior to initiating clozapine. Routine ECG assessment may detect QTc prolongation, but is not always effective in preventing arrhythmias. Clozapine treatment should be discontinued if the QTc interval exceeds 500 msec. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References
  • "Product Information. Clozaril (clozapine)." Novartis Pharmaceuticals, East Hanover, NJ.
  • "Product Information. Tasigna (nilotinib)." Novartis Pharmaceuticals, East Hanover, NJ.
Clozaril

Generic Name: clozapine

Brand name: Clozaril, Fazaclo, Versacloz, Clopine, CloZAPine Synthon, Denzapine, Zaponex

Synonyms: n.a.

Rythmol

Generic Name: propafenone

Brand name: Rythmol, Rythmol SR

Synonyms: n.a.

In the course of checking the drug compatibility and interactions, data from the following reference sources was used: Drugs.com, Rxlist.com, Webmd.com, Medscape.com.

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