Drug Interactions between clozapine and lapatinib
This report displays the potential drug interactions for the following 2 drugs:
- clozapine
- lapatinib
Interactions between your drugs
cloZAPine lapatinib
Applies to: clozapine and lapatinib
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
- (2001) "Product Information. Clozaril (clozapine)." Novartis Pharmaceuticals
- (2007) "Product Information. Tasigna (nilotinib)." Novartis Pharmaceuticals
Drug and food interactions
cloZAPine food
Applies to: clozapine
GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.
MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.
References
- Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
- Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
- (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
- (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
lapatinib food
Applies to: lapatinib
GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of lapatinib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits.
ADJUST DOSING INTERVAL: Food can significantly increase the oral bioavailability of lapatinib. According to the manufacturer, lapatinib peak plasma concentration (Cmax) was approximately 2.5- and 3-fold higher and systemic exposure (AUC) 3- and 4-fold higher when administered with a low fat meal (5% fat; 500 calories) or with a high-fat meal (50% fat; 1000 calories), respectively, compared to fasting. Dividing the daily dose also resulted in an approximately 2-fold higher systemic exposure at steady state compared to the same total dose administered once daily.
MANAGEMENT: Patients treated with lapatinib should preferably avoid the consumption of grapefruit or grapefruit juice. The manufacturer recommends that lapatinib be administered at least one hour before or one hour after a meal. The lapatinib dose is administered once daily and should not be divided.
References
- (2007) "Product Information. Tykerb (lapatinib)." Novartis Pharmaceuticals
cloZAPine food
Applies to: clozapine
Caffeine may increase clozapine serum concentrations and exacerbate psychotic symptoms. The mechanism is unknown but may be related to competition for the same metabolic pathway. No specific intervention is necessary; however, if an interaction is suspected it is recommended that caffeine intake be avoided.
References
- Carrillo JA, Jerling M, Bertilsson L (1995) "Interaction between caffeine and clozapine - comment." J Clin Psychopharmacol, 15, p. 376-7
- Odom-White A, de Leon J (1996) "Clozapine levels and caffeine." J Clin Psychiatry, 57, p. 175-6
- Vainer JL, Chouinard G (1994) "Interaction between caffeine and clozapine." J Clin Psychopharmacol, 14, p. 284
- Hagg S, Spiset O, Mjorndal T, Dalqvist R (2000) "Effect of caffeine on clozapine pharmacokinetics in healthy volunteers." Br J Clin Pharmacol, 49, p. 59-63
Therapeutic duplication warnings
No warnings were found for your selected drugs.
Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.
See also
Drug Interaction Classification
Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
No interaction information available. |
Further information
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