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Latuda (Lurasidone Hydrochloride) - Drug Interactions, Contraindications, Overdosage, etc

 
 



DRUG INTERACTIONS

Given the primary CNS effects of LATUDA, caution should be used when it is taken in combination with other centrally acting drugs and alcohol.

Potential for Other Drugs to Affect LATUDA

LATUDA is not a substrate of CYP1A1, CYP1A2, CYP2A6, CYP4A11, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP2E1 enzymes. This suggests that an interaction of LATUDA with drugs that are inhibitors or inducers of these enzymes is unlikely.

LATUDA is predominantly metabolized by CYP3A4; interaction of LATUDA with strong and moderate inhibitors or inducers of this enzyme has been observed (Table 9). LATUDA should not be used in combination with strong inhibitors or inducers of this enzyme [see Contraindications ( 4 )].

Table 9: Summary of Effect of Coadministered Drugs on Exposure to LATUDA in Healthy Subjects or Patients with Schizophrenia
  Coadministered drug   Dose schedule   Effect on LATUDA pharmacokinetics   Recommendation
    Coadministered drug   LATUDA   C max   AUC  
  Ketoconazole
(strong CYP3A4 inhibitor)
 400 mg/day
for 5 days
 10 mg
single dose
 6.9-times
LATUDA alone
 9-times
LATUDA alone
 Should not be coadministered with LATUDA
  Diltiazem
(moderate CYP3A4 inhibitor)
 240 mg/ day
for 5 days
 20 mg
single dose
 2.1- times
LATUDA alone
 2.2- times
LATUDA alone
 LATUDA dose should not exceed 40 mg/day if coadministered
  Rifampin
(strong CYP3A4 inducer)
 600 mg/day
for 8 days
 40 mg
single dose
 1/7th of LATUDA alone  1/5th of LATUDA alone  Should not be coadministered with LATUDA
  Lithium
 600 mg BID
for 8 days
 120 mg/day
for 8 days
 0.9-times LATUDA alone  1.1- times LATUDA alone  No LATUDA dose adjustment required.

Potential for LATUDA to Affect Other Drugs

Digoxin (P-gp substrate): Coadministration of LATUDA (120 mg/day) at steady state with a single dose of digoxin (0.25 mg) increased Cmax and AUC(0-24) for digoxin by approximately 9% and 13%, respectively relative to digoxin alone. Digoxin dose adjustment is not required when coadministered with LATUDA.

Midazolam (CYP3A4 substrate): Coadministration of LATUDA (120 mg/day) at steady state with a single dose of 5 mg midazolam increased midazolam Cmax and AUC(0-24) by approximately 21% and 44%, respectively relative to midazolam alone. Midazolam dose adjustment is not required when coadministered with LATUDA.

Oral Contraceptive (estrogen/progesterone): Coadministration of LATUDA (40 mg/day) at steady state with an oral contraceptive (OC) containing ethinyl estradiol and norelgestimate resulted in equivalent AUC(0-24) and Cmax of ethinyl estradiol and norelgestromin relative to OC administration alone. Also, sex hormone binding globulin levels were not meaningfully affected by coadministration of LATUDA and OC. Dose adjustment of OC dose is not required when coadministered with LATUDA.

OVERDOSAGE

Human Experience

In premarketing clinical studies involving more than 2096 patients and/or healthy subjects, 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.

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.

CONTRAINDICATIONS

LATUDA is contraindicated in any patient with a known hypersensitivity to lurasidone HCl or any components in the formulation. Angioedema has been observed with lurasidone [ see Adverse Reactions ( 6.6 ) ].

LATUDA is contraindicated with strong CYP3A4 inhibitors (e.g., ketoconazole) and strong CYP3A4 inducers (e.g., rifampin) [ see Drug Interactions (7.1) ].

DRUG ABUSE AND DEPENDENCE

Controlled substance

LATUDA is not a controlled substance.

Abuse

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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