FDA

Vykat XR

Approved 26 Mar 2025OralTablet, extended release

The FDA lists this product in 3 strengths and forms.

Indications

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 )

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 )

Warnings and precautions

Hyperglycemia : Hyperglycemia, including diabetic ketoacidosis, has been reported. During treatment, monitor fasting glucose and HbA1c. Monitor fasting glucose more frequently during first few weeks of treatment in patients with risk factors for hyperglycemia. ( 2.3 , 5.1 ) Risk of Fluid Overload : Edema, including severe reactions associated with fluid overload, has been reported. Monitor for signs or symptoms of edema or fluid overload.

( 2.3 , 5.2 )

5.1Hyperglycemia

VYKAT XR increases blood glucose, due primarily to an inhibition of insulin release from the pancreas. Hyperglycemia, including severe adverse reactions associated with diabetic ketoacidosis, occurred in VYKAT XR-treated patients during clinical trials [see Adverse Reactions (6) ] . Precipitating conditions for diabetic ketoacidosis may include reduction in the dosages of concomitant antihyperglycemic medications, increase in the dosages of concomitant growth hormone, intercurrent illness, surgery, volume depletion or alcohol abuse.

Signs and symptoms of ketoacidosis include nausea, vomiting, abdominal pain, generalized malaise and shortness of breath. Before initiating VYKAT XR, test fasting plasma glucose (FPG) and HbA1c; optimize blood glucose in patients who have hyperglycemia. After initiating treatment with VYKAT XR, regularly monitor fasting glucose (FPG or fasting blood glucose) and HbA1c [see Dosage and Administration (2.3) ] . Monitor fasting glucose more frequently for the first few weeks of treatment with VYKAT XR in patients with risk factors for hyperglycemia, such as obesity, elevated FPG, HbA1c at the upper limit of normal or above, concomitant use of growth hormone, or concomitant use of systemic corticosteroids.

Contraindications

Warnings and precautions

( 2.3 , 5.2 )

5.1Hyperglycemia

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. 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 )

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Available data from case reports with diazoxide use during pregnancy are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or other adverse maternal outcomes. Adverse reactions, including hyperglycemia, alopecia, and hypertrichosis lanuginosa, have been reported in neonates exposed to diazoxide in utero prior to delivery (see Clinical Considerations ) . In animal reproduction studies, oral gavage administration of diazoxide choline to pregnant rats during organogenesis at dose exposures equal to the human exposure of 525 mg resulted in no malformations.

Maternal and fetal toxicities were observed at a dose approximately equal to the maximum recommended human dose (MRHD) of 525 mg based on AUC (see Data ) . The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations Fetal/Neonatal Adverse Reactions Diazoxide crosses the placenta and has been detected in cord blood. Based on adverse reactions reported in adults, in utero exposure of the infant prior to delivery may produce fetal or neonatal hyperbilirubinemia, thrombocytopenia, altered carbohydrate metabolism, and possibly other adverse reactions. Monitor infants who were exposed to diazoxide in utero for adverse reactions and treat accordingly.

Alopecia and hypertrichosis lanuginosa have occurred in a small number of infants whose mothers received oral diazoxide during the last 19 to 60 days of pregnancy. Abnormal hair growth was first noted at the age of one week and persisted when the infants were last seen at the ages of 5 months to one year. An infant born to a mother who was treated with oral diazoxide, 150 mg daily for 47 days prior to delivery, developed hyperglycemia which resolved after a 6-hour insulin infusion.

Because there was an inappropriately low plasma insulin concentration for the degree of hyperglycemia, it was considered compatible with transplacental transfer of diazoxide causing inhibition of release of insulin from the neonatal pancreas. Labor or Delivery Intravenous administration of diazoxide during labor may cause cessation of uterine contractions, which may require administration of oxytocic agents to reinstate labor.

However, this has not been reported with diazoxide when administered orally. Use caution in administering VYKAT XR during labor. Data Animal Data Diazoxide choline was administered orally to pregnant rats during the period of organogenesis at doses of 40, 100, and 160 mg/kg/day (0.3, 0.6, and 1.2 times the MRHD of 525 mg based on AUC). No malformations were observed; however, decreased fetal body weights, delayed skeletal ossification, and increased fetal resorptions were observed at 160 mg/kg/day (a dose approximately equal to the MRHD based on AUC) which was a maternally toxic dose.

In a study in which rabbits were administered diazoxide intravenously, evidence of skeletal and cardiac teratogenic effects was noted at unknown multiples of the MRHD for diazoxide choline.

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.

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 which 77 patients who had completed Study 1 and Study 2-OLE were randomized in a 1:1 ratio to VYKAT XR or placebo [see Clinical Studies (14) ] .

Study 3: A long-term, open-label, maintenance study in 77 patients who had completed Study 1 and Study 2-OLE. Adverse reactions leading to discontinuation in VYKAT XR-treated patients included aggression, diabetes mellitus, fluid retention, hirsutism, hyperglycemia, lower respiratory tract infection, peripheral edema, pulmonary edema, and papular rash. The primary safety analyses are based on Study 1. The most common adverse reactions (10% or more and at least 2% greater than in placebo) in Study 1 were hypertrichosis, edema, hyperglycemia, and rash.

Table 3 presents adverse reactions that occurred in at least 5% of patients in Study 1 receiving VYKAT XR and 2% more frequently in VYKAT XR-treated patients than placebo. Table 3: Adverse Reactions Occurring in ≥5% of Patients with PWS Receiving VYKAT XR and at Least 2% Greater than Placebo in Study 1 Adverse Reaction VYKAT XR (N=84) Placebo (N=42) Hypertrichosis 36% 14% Edema Edema includes peripheral edema, periorbital edema, swelling face, pulmonary edema, and peripheral swelling. 27% 12% Hyperglycemia Hyperglycemia includes type 2 diabetes mellitus. 17% 5% Rash Rash includes contact dermatitis, erythema multiforme, maculo-papular rash, papular rash, and urticaria. 12% 2% Pyrexia 6% 0% Arthralgia 5% 2% Influenza 5% 2% Nasopharyngitis 5% 2% In Study 2-RWP, the adverse reactions that occurred most frequently (at least 5%) and to a greater extent than placebo included: Immune System Disorders: Seasonal allergy Investigations: Increased weight Nervous System Disorders: Hyperphagia, anxiety, affect lability, anger, compulsive hoarding, suicidal ideation Respiratory Disorders: Streptococcal pharyngitis, upper respiratory infection Skin and Subcutaneous Tissue Disorders: Hirsutism Erythema multiforme was reported in one subject in Study 1.

One subject in Study 3 experienced a serious adverse reaction of diabetic ketoacidosis. Adverse Reactions from Clinical Trials or Postmarketing Experience of Diazoxide in An Unapproved Population The following adverse reactions associated with use of diazoxide for an unapproved population have been identified in clinical studies or post-marketing reports. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

Immune System Disorders: Hypersensitivity Investigations: Increased serum uric acid, transient neutropenia, thrombocytopenia, decreased hemoglobin/hematocrit, eosinophilia Respiratory Disorders: Pulmonary hypertension Special Senses: Cataracts Musculoskeletal and Connective Tissue Disorders: Abnormal facial features Most common adverse reactions (incidence ≥10% and at least 2% greater than in placebo) are hypertrichosis, edema, hyperglycemia, and rash.

( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Soleno Therapeutics, Inc. at 1-833-765-3661 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Vykat XR

Indications

Contraindications

Warnings and precautions

5.1Hyperglycemia

Two medicines in one question?

Vykat XR

Indications

Contraindications

Warnings and precautions

5.1Hyperglycemia

Two medicines in one question?

5.2Risk of Fluid Overload

Interactions

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

Composition

Strengths and forms

Official product information

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