Table 2
Lurasidone receptor binding profile and receptor-related effects
| Ki (nM)* | Effects associated with activity on the receptor | |
|---|---|---|
| D2 | 0.994 | Antipsychotic effects. Akathisia (15%), parkinsonism (11%), dystonia (5%), hyperprolactinemia (8.3% for women, 1.9% for men) |
| 5-HT2A | 0.47 | Antipsychotic effects. Improves extrapyramidal symptoms |
| 5-HT7 | 0.495 | Antipsychotic effects. Improves cognition, mood |
| 5-HT1A | 6.38 | Improves cognition, mood. Nausea (12%), vomiting (8%) |
| α-1 | 48 | Orthostatic hypotension (5%), sedation (22%) |
| α-2C | 10.8 | Improves cognition |
| H1 | >1000 | No significant adverse effects mediated through H1 receptor because of low binding affinity |
| M1 | >1000 | No significant adverse effects mediated through M1 receptor because of low binding affinity |
| *Ki dissociation constant; the lower the number, the higher affinity of the compound for the receptor Source: Adapted from reference 1, expert opinion, and lurasidone data on file, 2008 | ||
Contraindications
Lurasidone is contraindicated in patients with known sensitivity to lurasidone hydrochloride. Because of the risk for pharmacokinetic drug-drug interactions, lurasidone is contraindicated for patients who are taking strong CYP3A4 inhibitors (eg, ketoconazole) or inducers (eg, rifampin).
Similar to other medications in its class, lurasidone carries a “black-box” warning of increased mortality in elderly patients with dementia-related psychosis and it is not FDA-approved for treating this condition. Animal teratogenicity studies using lurasidone, 25 mg/kg/d and 50 mg/kg/d, did not show adverse effects during organogenesis, and lurasidone is classified as pregnancy category B (animal studies failed to demonstrate risk to the fetus and there are no adequate and well-controlled studies in pregnant women, or animal studies have shown an adverse effect, but adequate and well-controlled studies in pregnant women have failed to demonstrate a risk to the fetus in any trimester). The use of lurasidone in geriatric and pediatric populations was not studied.1
Dosing
Lurasidone is manufactured as 40 mg and 80 mg tablets. The recommended starting dose is 40 mg/d and the maximum recommended dose is 80 mg/d.1 In clinical trials, lurasidone, 120 mg/d, was associated with increased incidence of adverse effects without added benefit.
Lurasidone doesn’t require initial dose titration and should be given with food that provides ≥350 calories to improve medication absorption. Dose adjustment is recommended for use in patients with moderate or severe renal or hepatic impairment and when coadministered with CYP3A4 moderate inhibitors; the dose in these patients should not exceed 40 mg/d.
Related Resource
- Citrome L. Lurasidone for schizophrenia: a review of the efficacy and safety profile for this newly approved second-generation antipsychotic. Int J Clin Pract. 2010 Epub ahead of print.
Drug Brand Names
- Ketoconazole • Nizoral
- Lurasidone • Latuda
- Olanzapine • Zyprexa
- Rifampin • Rifadin
Disclosure
The authors report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.