vykat xr

Prior to initiation, test fasting plasma glucose and HbA1c; optimize blood glucose in patients who have hyperglycemia. ( 2.1 ) Do not substitute with diazoxide oral suspension. ( 2.1 ) Administer orally once daily. ( 2.2 ) Recommended starting dosage and titration schedule is based on patient’s body weight. ( 2.2 ) Weight Starting Dosage Titration Dosage Titration Dosage Target Maintenance Dose Weeks 1 and 2 Weeks 3 and 4 Weeks 5 and 6 20 to <30 kg 25 mg 50 mg 75 mg 100 mg 30 to <40 kg 75 mg 150 mg 150 mg 150 mg 40 to <65 kg 75 mg 150 mg 225 mg 225 mg 65 to <100 kg 150 mg 225 mg 300 mg 375 mg 100 to <135 kg 150 mg 300 mg 375 mg 450 mg ≥135 kg 150 mg 300 mg 450 mg 525 mg The maximum recommended dosage is 5.8 mg/kg/day or 525 mg per day. ( 2.2 ) Interrupt VYKAT XR or reduce dosage for clinically significant elevations in fasting glucose or HbA1c; consider dosage reduction or interruption for clinically significant fluid overload. ( 2.3 ) See full prescribing information for VYKAT XR dosage modifications due to drug interactions ( 2.4 ) Following dosage interruption or a missed dose of 7 days or more, re-titrate according to Table 1 or Table 2 . ( 2.5 ) 2.1 Important Recommendations Prior to VYKAT XR Initiation Laboratory Testing Prior to VYKAT XR Initiation Prior to initiating treatment with VYKAT XR, test fasting plasma glucose (FPG) and HbA1c and optimize blood glucose in…

The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Hyperglycemia [see Warnings and Precautions (5.1) ] Risk of Fluid Overload [see Warnings and Precautions (5.2) ] Adverse Reactions from Clinical Studies of VYKAT XR in Patients with PWS Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In the clinical study development program for treatment of hyperphagia in patients aged 4 years and older with PWS, a total of 125 patients received at least 1 dose of VYKAT XR. Patients received dosages of VYKAT XR up to 5.8 mg/kg/day (up to a maximum dosage of 525 mg/day) for up to 4.86 years (median: 3.0 years) in the following studies: Study 1: 13-week, randomized, double-blind, placebo-controlled, parallel-arm study in which 126 patients were randomized in a 2:1 ratio to VYKAT XR or placebo and received at least one dose of VYKAT XR. Study 2-OLE: A long-term, open-label, maintenance treatment period in 115 patients (mean duration 2.6 years; maximum duration 4.3 years) who had previously been enrolled in Study 1. Study 2-RWP: A 16-week, double-blind, placebo-controlled, randomized withdrawal treatment period, in…

VYKAT XR is contraindicated in patients with known hypersensitivity to diazoxide, other components of VYKAT XR, or to thiazides. Erythema multiforme has been reported with VYKAT XR [see Adverse Reactions (6) ] . Known hypersensitivity to diazoxide, other components of VYKAT XR, or to thiazides. ( 4 )

An overdosage of VYKAT XR may cause marked hyperglycemia, which may be associated with ketoacidosis [see Warnings and Precautions (5.1) ] . No specific antidotes for VYKAT XR are known. Monitor ketones in patients with severe hyperglycemia following overdose and consider insulin treatment if necessary. Treat severe hyperglycemia associated with ketoacidosis with prompt insulin administration and restoration of fluid and electrolyte balance. Because of VYKAT XR’s long half-life (approximately 106 hours) in patients with PWS, the symptoms of overdosage (hyperglycemia, with or without ketoacidosis) require prolonged surveillance for periods up to three weeks or until blood sugar levels stabilize within the patient’s normal range. Consider contacting a Poison Help line (1-800-222-1222) or a medical toxicologist for overdosage management recommendations for VYKAT XR.

U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.

Table 4 displays clinically significant drug interactions with VYKAT XR. Table 4: Clinically Significant Drug Interactions with VYKAT XR Strong CYP1A2 Inhibitors See www.fda.gov/CYPandTransporterInteractingDrugs for examples of strong CYP1A2 and CYP3A4 inhibitors, sensitive CYP1A2 substrates, and dual strong CYP3A4 / moderate 1A2 inducers. Prevention or Management Reduce the dosage of VYKAT XR when concomitantly used with strong inhibitors of CYP1A2 [see Dosage and Administration (2.4) ] . Mechanism and Clinical Effect(s) VYKAT XR is a CYP1A2 substrate. Concomitant use of VYKAT XR with strong CYP1A2 inhibitors increases exposure of diazoxide, which may increase the frequency and/or severity of adverse reactions from VYKAT XR [see Clinical Pharmacology (12.3) ] . CYP1A2 Substrates Prevention or Management Concomitant use of VYKAT XR with CYP1A2 substrates is not recommended. Mechanism and Clinical Effect(s) VYKAT XR is an inhibitor of CYP1A2. Concomitant use of VYKAT XR with CYP1A2 substrates increases exposure of these substrates. This may increase the frequency and/or severity of adverse reactions from such substrates. Strong CYP3A4 Inhibitors Prevention or Management Monitor the frequency and severity of adverse reactions from VYKAT XR. A dosage reduction of VYKAT XR may be needed when used concomitantly with strong CYP3A4 inhibitors. Mechanism and Clinical Effect(s) Concomitant use of VYKAT XR with strong CYP3A4 inhibitors increases exposure of diazoxide, which may increase the frequency and/or severity of adverse reactions from VYKAT XR [see Clinical Pharmacology (12.3) ] . Dual Strong CYP3A4 / Moderate 1A2 Inducers Prevention or Management Concomitant use of VYKAT XR with dual strong CYP3A4/moderate CYP1A2 inducers is not recommended. Mechanism and Clinical Effect(s) VYKAT XR is a substrate of CYP3A4 and CYP1A2. Concomitant use of VYKAT XR with strong CYP3A4/moderate 1A2 inducers may decrease exposure of VYKAT XR. This may decrease the efficacy of VYKAT XR [see Clinical Pharmacology (12.3) ] . Drugs Highly Bound to Protein Prevention or Management Monitor international normalized ratio (INR) in patients who use coumarin or its derivatives concomitantly with VYKAT XR. Dosage modification of coumarin or its derivatives may be needed when used concomitantly with VYKAT XR. Monitor diphenylhydantoin serum levels when VYKAT XR is used concomitantly with diphenylhydantoin. Dosage modification of diphenylhydantoin may be needed when used concomitantly with VYKAT XR. Mechanism and Clinical Effect(s) Diazoxide is highly bound to serum proteins. Diazoxide may displace other drugs which are also highly bound to protein resulting in higher or lower blood levels of the concomitantly used drugs. The impact of protein binding displacement is expected to be clinically important for drugs with narrow therapeutic range such as coumarin or its derivatives and diphenylhydantoin. Protein binding displacement may result in an increased risk of adverse reactions due to higher blood levels of coumarin or its derivative or loss of efficacy due to lower exposures of diphenylhydantoin. Thiazide or Other Diuretics Prevention or Management Monitor for signs and symptoms of hyperglycemia [see Warnings and Precautions (5.1) ] and hyperuricemia when VYKAT XR is used concomitantly with thiazides or other diuretics. Dosage adjustment of VYKAT XR or diuretics may be needed when VYKAT XR is concomitantly used with diuretics. Mechanism and Clinical Effect(s) Both diazoxide and thiazides or other diuretics may produce hyperglycemia and hyperuricemia. The concomitant use of VYKAT XR with thiazides or other diuretics may potentiate the hyperglycemic and hyperuricemic effects of diazoxide [see Adverse Reactions (6) and Clinical Pharmacology (12.2) ] . Strong CYP1A2 Inhibitors: Reduce VYKAT XR dosage. ( 2.4 , 7 ) CYP1A2 Substrates: Concomitant use with VYKAT XR is not recommended. ( 7 ) See full prescribing information for additional clinically significant drug interactions. ( 7 )