LATUDA TABLET 40MG

SUMITOMO PHARMA ASIA PACIFIC PTE. LTD.

SUMITOMO PHARMA ASIA PACIFIC PTE. LTD.

Therapeutic

Prescription Only

TABLET, COATED

**14 DOSAGE AND ADMINISTRATION** **14.1 Schizophrenia** _**Adults**_ The efficacy of LATUDA has been established at doses of 40, 80, 120 and 160 mg/day. The recommended starting dose of LATUDA is 40 mg once daily. Initial dose titration is not required. Patients should be treated with the lowest effective dose that provides optimal clinical response and tolerability, which is expected to be 40 mg or 80 mg once daily for most patients. Dose increase should be based on physician judgement and observed clinical response. In the six week controlled trials, there was no suggestion of added benefit with the 120 mg/day dose compared to 40 and 80 mg/day. In the pooled analyses, added benefit occurred at 160 mg/day compared to lower doses. Doses above 80 mg may be considered for certain patients based on individual clinical judgement. The maximum recommended dose is 160 mg/day. LATUDA should be taken with food (at least 350 calories). Patients who have been receiving LATUDA for the treatment of schizophrenia, may continue maintenance therapy at the same dose. _**Adolescents**_ The recommended starting dose of LATUDA is 40 mg/day. In a placebo-controlled clinical trial, LATUDA has been shown to be effective at doses of 40mg/day and 80mg/day. The maximum recommended dose is 80mg/day. Patients should be treated with the lowest effective dose that provides optimal clinical response and tolerability. In the placebo-controlled clinical trial, no additional benefit was demonstrated for 80mg over 40mg. LATUDA should be taken with food. _Switching Antipsychotics_ There are no systematically collected data to specifically address switching patients from other antipsychotics to LATUDA or concerning concomitant administration with other antipsychotics. While immediate discontinuation of the previous antipsychotic treatment may be acceptable for some patients, more gradual discontinuation may be most appropriate for others. In all cases, the period of overlapping antipsychotic administration should be minimized. **14.2 Depressive Episodes Associated with Bipolar I Disorder** _**Adults**_ The recommended starting dose of LATUDA is 20 mg given once daily as monotherapy or as adjunctive therapy with lithium or valproate. Initial dose titration is not required. LATUDA has been shown to be effective in a dose range of 20 mg per day to 120 mg per day as monotherapy or as adjunctive therapy with lithium or valproate \[see Clinical Studies (5.2) – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_\]. The maximum recommended dose, as monotherapy or as adjunctive therapy with lithium or valproate, is 120 mg per day. In the monotherapy study, the higher dose range (80 mg to 120 mg per day) did not provide additional efficacy, on average, compared to the lower dose range (20 to 60 mg per day) \[see Clinical Studies (5.2) – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_\]. As the incidence of certain adverse events increase with dose \[see Adverse Reactions (11) – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_\] patients should be treated with the lowest effective dose of LATUDA. _**Pediatric Patients (13 – 17 years)**_ The recommended starting dose of LATUDA is 20 mg given once daily as monotherapy. Initial dose titration is not required. The dose may be increased after one week based on clinical response. LATUDA has been shown to be effective in a dose range of 20 mg per day to 80 mg per day as monotherapy. At the end of the clinical study, most of the patients (67%) received 20 mg or 40 mg once daily \[see Clinical Studies (5.2) – _please refer to the Product Insert/Patient Information Leaflet published on HSA for the full drug information_\]. The maximum recommended dose is 80 mg per day. The efficacy of LATUDA in the treatment of mania associated with bipolar disorder has not been established. **14.3 Administration Instructions** Administration with food substantially increases the absorption of LATUDA. Administration with food increases the AUC approximately 2-fold and increases the Cmax approximately 3-fold. In the clinical studies, LATUDA was administered with food. **14.4 Dose Modifications in Special Populations** _Renal Impairment_ After administration of a single dose of 40 mg to patients with mild, moderate and severe renal impairment, mean Cmax increased by 40%, 92%, and 54%, respectively and mean AUC(0–∞) increased by 53%, 91% and 2-times, respectively compared to healthy matched subjects. Caution should be exercised when starting LATUDA in patients with renal impairment. As the 20 mg tablet is not available in Singapore, it is not recommended that LATUDA be used in patients with moderate (creatinine clearance: 30 to <50 mL/min) or severe renal impairment (creatinine clearance <30 mL/min). _Hepatic Impairment_ In a single-dose study of 20 mg, LATUDA mean AUC (0–last) was 1.5-times higher in subjects with mild hepatic impairment (Child-Pugh Class A), 1.7-times higher in subjects with moderate hepatic impairment (Child-Pugh class B) and 3-times higher in subjects with severe hepatic impairment (Child-Pugh Class C) compared to the values for healthy matched subjects. Mean Cmax was 1.3, 1.2, and 1.3-times higher for mild, moderate and severe hepatic impaired patients, respectively, compared to the values for healthy matched subjects. Caution should be exercised when starting LATUDA in patients with hepatic impairment. As the 20 mg tablet is not available in Singapore, it is not recommended that LATUDA be used in patients with moderate (Child-Pugh Score = 7 to 9) or severe hepatic impairment (Child-Pugh Score = 10 to 15). **14.5 Dose Modifications Due to Drug Interactions** _Concomitant Use with CYP3A4 Inhibitors_ LATUDA should not be used in combination with a strong CYP3A4 inhibitor (e.g. ketoconazole) _\[see Contraindications\]_. If LATUDA is being prescribed and a moderate CYP3A4 inhibitor (e.g., diltiazem, atazanavir, erythromycin, fluconazole, verapamil etc.) is added to the therapy, the LATUDA dose should be reduced to half of the original dose level. Similarly, if a moderate CYP3A4 inhibitor is being prescribed and LATUDA is added to therapy, the recommended starting dose of LATUDA is 20 mg per day, the maximum recommended dose of LATUDA is 80 mg/day. Grapefruit and grapefruit juice should be avoided in patients taking LATUDA, since these may inhibit CYP3A4 and alter LATUDA concentrations. _Concomitant Use with CYP3A4 Inducers_ LATUDA should not be used concomitantly with a strong CYP3A4 inducer (e.g., rifampin, avasimibe, St. John’s wort, phenytoin, carbamazepine, etc.) _\[see Contraindications\]_. If LATUDA is used concomitantly with a moderate CYP3A4 inducer, it may be necessary to increase the LATUDA dose after chronic treatment (7 days or more) with the CYP3A4 inducer.