SAPHRIS

What it is

SAPHRIS is available as 5 mg and 10 mg wafers containing 5 mg asenapine (as maleate) and 10 mg asenapine (as maleate), respectively. The wafer is placed under the tongue and allowed to dissolve completely in saliva within seconds.

Approved indications

— Treatment of schizophrenia in adults. — Treatment of acute manic or mixed episodes associated with Bipolar 1 Disorder in adults as monotherapy or in combination with lithium or sodium valproate. — Prevention of relapse of manic or mixed episodes in Bipolar 1 Disorder in adults as monotherapy or in combination with lithium or sodium valproate.

Dosing overview

SAPHRIS wafers should be placed under the tongue and allowed to dissolve completely; they must not be chewed or swallowed, and food and drink should be avoided for 10 minutes after administration.

Key safety warnings

Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death compared to placebo, with a meta-analysis of 17 placebo-controlled trials showing a risk approximately 1.6 to 1.7 times that seen in placebo-treated patients. SAPHRIS is not approved for the treatment of patients with dementia-related psychosis. Neuroleptic Malignant Syndrome, characterised by hyperthermia, muscle rigidity, autonomic instability, altered consciousness and elevated serum creatine phosphokinase levels, may occur with SAPHRIS; if a patient develops signs and symptoms indicative of NMS, SAPHRIS must be discontinued. SAPHRIS may induce orthostatic hypotension and syncope, especially early in treatment, with elderly patients particularly at risk. SAPHRIS should be used with caution in elderly patients and those with known cardiovascular disease, cerebrovascular disease, or conditions predisposing to hypotension. In combined short-term and long-term trials, mean weight change was 0.8 kg for SAPHRIS; in short-term schizophrenia trials, 5.3% of asenapine-treated subjects experienced clinically significant weight gain (>7%) compared to 2.3% for placebo. In short-term bipolar mania trials, mean weight change was 1.3 kg for SAPHRIS, and 6.5% of asenapine-treated patients experienced clinically significant weight gain compared to 0.6% for placebo. SAPHRIS can elevate prolactin levels; hyperprolactinaemia may suppress hypothalamic GnRH, resulting in reduced pituitary gonadotropin secretion, which may inhibit reproductive function in both female and male patients. Hyperglycaemia has been reported in patients treated with atypical antipsychotics including SAPHRIS, although in clinical trials there were no significant differences in the incidence rates of hyperglycaemia-related adverse events compared to placebo. From short-term schizophrenia trials, there appears to be a dose-response relationship for akathisia in patients treated with asenapine, and for parkinsonism there was an increasing trend with higher doses.

Contraindications

SAPHRIS is contraindicated in patients who are hypersensitive to any component of the wafer or to asenapine; hypersensitivity reactions, including anaphylaxis and angioedema, have been observed in patients treated with asenapine.

PBS listing

SAPHRIS 5 mg sublingual wafer is listed on the PBS with a streamlined restriction and ex-manufacturer price of A$114.95. SAPHRIS 10 mg sublingual wafer is listed on the PBS with a streamlined restriction and ex-manufacturer price of A$191.62.

Regulatory history

SAPHRIS 5 mg and 10 mg sublingual wafer formulations were first listed on the ARTG on 11 March 2011. The TGA approved asenapine (Saphris) for the treatment of schizophrenia and acute manic or mixed episodes associated with Bipolar 1 Disorder in adults, as well as for the prevention of relapse in Bipolar 1 Disorder, with the decision made on 7 March 2011. In November 2014, the PBAC did not recommend SAPHRIS for the treatment of schizophrenia due to uncertain clinical benefit and high and uncertain cost-effectiveness.