Potential for Other Drugs to Affect LATUDA
LATUDA is predominantly metabolized by CYP3A4. LATUDA should not be used concomitantly with strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir, voriconazole, mibefradil, etc.) or strong CYP3A4 inducers (e.g., rifampin, avasimibe, St. John's wort, phenytoin, carbamazepine, etc.) [see Contraindications (4)]. The LATUDA dose should be reduced to half of the original level when used concomitantly with moderate inhibitors of CYP3A4 (e.g., diltiazem, atazanavir, erythromycin, fluconazole, verapamil, etc.). If LATUDA is used concomitantly with a moderate CYP3A4 inducer, it may be necessary to increase the LATUDA dose [see Dosage and Administration ].
Lithium: It is not necessary to adjust the LATUDA dose when used concomitantly with lithium (Figure 1).
Valproate: It is not necessary to adjust the LATUDA dose when used concomitantly with valproate. A dedicated drug-drug interaction study has not been conducted with valproate and LATUDA. Based on pharmacokinetic data from the bipolar depression studies valproate levels were not affected by lurasidone, and lurasidone concentrations were not affected by valproate.
Grapefruit: Grapefruit and grapefruit juice should be avoided in patients taking LATUDA, since these may inhibit CYP3A4 and alter LATUDA concentrations [see Dosage and Administration (2.5)].
Figure 1: Impact of Other Drugs on LATUDA Pharmacokinetics
Potential for LATUDA to Affect Other Drugs
No dose adjustment is needed for lithium, substrates of P-gp, CYP3A4 (Figure 2) or valproate when coadministered with LATUDA.).
Figure 2: Impact of LATUDA on Other Drugs
In premarketing clinical studies, accidental or intentional overdosage of LATUDA was identified in one patient who ingested an estimated 560 mg of LATUDA. This patient recovered without sequelae. This patient resumed LATUDA treatment for an additional two months.
Management of Overdosage
Consult a Certified Poison Control Center for up-to-date guidance and advice. There is no specific antidote to LATUDA, therefore, appropriate supportive measures should be instituted and close medical supervision and monitoring should continue until the patient recovers. Consider the possibility of multiple-drug overdose.
Cardiovascular monitoring should commence immediately, including continuous electrocardiographic monitoring for possible arrhythmias. If antiarrhythmic therapy is administered, disopyramide, procainamide, and quinidine carry a theoretical hazard of additive QT-prolonging effects when administered in patients with an acute overdose of LATUDA. Similarly, the alpha-blocking properties of bretylium might be additive to those of LATUDA, resulting in problematic hypotension.
Hypotension and circulatory collapse should be treated with appropriate measures. Epinephrine and dopamine should not be used, or other sympathomimetics with beta-agonist activity, since beta stimulation may worsen hypotension in the setting of LATUDA-induced alpha blockade. In case of severe extrapyramidal symptoms, anticholinergic medication should be administered.
Gastric lavage (after intubation if patient is unconscious) and administration of activated charcoal together with a laxative should be considered.
The possibility of obtundation, seizures, or dystonic reaction of the head and neck following overdose may create a risk of aspiration with induced emesis.
- Known hypersensitivity to lurasidone HCl or any components in the formulation. Angioedema has been observed with lurasidone [see Adverse Reactions ].
- Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir, voriconazole, mibefradil, etc.) [see Drug Interactions].
- Strong CYP3A4 inducers (e.g., rifampin, avasimibe, St. John's wort, phenytoin, carbamazepine, etc.) [see Drug Interactions].
DRUG ABUSE AND DEPENDENCE
LATUDA is not a controlled substance.
LATUDA has not been systematically studied in humans for its potential for abuse or physical dependence or its ability to induce tolerance. While clinical studies with LATUDA did not reveal any tendency for drug-seeking behavior, these observations were not systematic and it is not possible to predict the extent to which a CNS-active drug will be misused, diverted and/or abused once it is marketed. Patients should be evaluated carefully for a history of drug abuse, and such patients should be observed carefully for signs of LATUDA misuse or abuse (e.g., development of tolerance, drug-seeking behavior, increases in dose).
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