Overview
11 DESCRIPTION VYKAT XR contains diazoxide choline. Diazoxide choline is very slightly soluble to soluble in solvents dichloromethane, tetrahydrofuran, acetonitrile, and methanol and practically insoluble in solvents methyl tert -butyl ether. The pKa is 8.44 ± 0.01 Diazoxide choline is 7-Chloro-3-methyl-1λ6, 2,4-benzothiadiazin-2-ide 1,1-dioxide 2- hydroxyethyl(trimethyl)azanium.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action The exact mechanism of action of diazoxide choline in the treatment of hyperphagia in patients 4 years of age and older with Prader-Willi syndrome (PWS) is unknown. 12.2 Pharmacodynamics VYKAT XR resulted in a reduction in fasting plasma insulin from baseline through 1 year of treatment. Diazoxide increases blood glucose, due primarily to an inhibition of insulin release from the pancreas. Other pharmacodynamic effects of VYKAT XR include increased uric acid, renin secretion and IgG concentrations, and decreased cortisol secretion. 12.3 Pharmacokinetics Absorption Following oral administration, diazoxide choline is hydrolyzed to diazoxide prior to absorption. Peak diazoxide concentrations occur after 16 hours.
Indications
- 1 INDICATIONS AND USAGE VYKAT XR is indicated for the treatment of hyperphagia in adults and pediatric patients 4 years of age and older with Prader-Willi syndrome (PWS). VYKAT XR is indicated for the treatment of hyperphagia in adults and pediatric patients 4 years of age and older with Prader-Willi syndrome (PWS). ( 1 )
Common Doses
- 25 mg
- 50 mg
- 75 mg
- 100 mg
Dosage
2 DOSAGE AND ADMINISTRATION 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
Contraindications
- 4 CONTRAINDICATIONS 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 )
Side Effects
- 6 ADVERSE REACTIONS 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.
Interactions
- 7 DRUG INTERACTIONS 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.