Vykat Xr (diazoxide choline)

Dosage of diazoxide choline is expressed in terms of diazoxide choline.

Administer diazoxide choline orally once daily with or without food.

The tablets should be swallowed whole and should not be split, crushed, or chewed.

If a dose of diazoxide choline is missed, take the missed dose as soon as it is remembered. Do not take 2 doses at the same time to make up for a missed dose. If a dosage interruption of <7 days occurs, resume diazoxide choline at the previous dosage. If a dosage interruption of >=7 days occurs, re-titrate as appropriate per Table 1.

Store tablets at 20-25degreesC (excursions permitted to 15-30degreesC). Store in tightly closed container. Protect from humidity; do not remove desiccant.

No dosing information is available for this tab.

No dosing information is available for this tab.

Diazoxide is primarily metabolized by cytochrome P-450 (CYP) isoenzyme 1A2 and to a lesser extent by CYP3A4.

In vitro studies indicate that diazoxide choline is an inhibitor of CYP1A2. Diazoxide choline does not inhibit CYP2B6, 2C19, 2C8, 2C9, 2D6, or 3A4. In vitro studies indicate that diazoxide choline does not induce CYP1A2, CYP2B6, or CYP3A4 at the therapeutic dose range.

In vitro studies indicate that diazoxide choline is a substrate for organic anion transporter (OAT) 1, OAT3, and breast cancer resistance protein (BCRP).

In vitro studies indicate that diazoxide choline is an inhibitor of OAT1 and OAT3. It does not inhibit P-glycoprotein (P-gp), BCRP, multidrug and toxin extrusion (MATE) 1/2-K, organic anion transporting polypeptide (OATP) 1B1/3, or organic cation transporter (OCT) 1/2 at the therapeutic dose range.

Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

Diazoxide/Dual Strong Cyp3a4 & Moderate Cyp1a2 Inducers

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Diazoxide is a substrate of both CYP3A4 and CYP1A2. Inducers of CYP3A4 and CYP1A2 may induce the metabolism of diazoxide.(1)

CLINICAL EFFECTS: Concomitant administration may result in decreased concentration and effectiveness of diazoxide.(1)

PREDISPOSING FACTORS: Induction effects may be more likely with regular use of the inducer for longer than 1-2 weeks.

PATIENT MANAGEMENT: Concomitant use of diazoxide with dual strong CYP3A4 and moderate CYP1A2 inducers is not recommended.

DISCUSSION: A PBPK analysis suggests that concomitant use of diazoxide with rifampin (a strong CYP3A4 inducer and moderate CYP1A2 inducer) may decrease the maximum concentration (Cmax) and area-under-curve (AUC) of diazoxide by 14% to 30% and 40% to 70%, respectively, compared to diazoxide alone.(1) Dual strong CYP3A4 and moderate 1A2 inducers linked to this monograph include: fosphenytoin, phenytoin, and rifampin.

There are no severe interactions for this drug.

Moderate Interaction: Assess the risk to the patient and take action as needed.

Diazoxide/Strong Cyp1a2 Inhibitors

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Inhibitors of CYP1A2 may inhibit the metabolism of diazoxide.(1)

CLINICAL EFFECTS: Concurrent use of inhibitors of CYP1A2 may result in elevated levels of and toxicity from diazoxide including hyperglycemia and fluid retention.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer recommends a dose reduction of diazoxide when use concomitantly with strong CYP1A2 inhibitors.(1) -For patients weighing 20 kg to < 30 kg: Give 25 mg for four weeks, then increase by 25 mg every two weeks for a target maintenance dose of 75 mg -For patients weighing 30 kg to <40 kg: Give 50 mg for two weeks, then increase to a target maintenance dose of 100 mg -For patients weighing 40 kg to <65 kg: Give 50 mg for two weeks, then increase by 50 mg every two weeks for a target maintenance dose of 150 mg -For patients weighing 65 kg to <100 kg: Give 100 mg for two weeks, then increase by 50 mg every two weeks for a target maintenance dose of 250 mg -For patients weighing 100 kg to <135 kg: Give 100 mg for weeks 1 and 2, increase to 200 mg for weeks 3 and 4, increase to 300 mg for weeks 5 and 6, then increase to a target maintenance dose of 325 mg

DISCUSSION: In a clinical study with fluvoxamine (a strong CYP1A2 inhibitor), fluvoxamine increased single dose diazoxide maximum concentration (Cmax) by 17.5% and area-under-curve (AUC) by 60% compared to the same parameter measured on single dose in the absence of fluvoxamine co-administration.(1) Strong CYP1A2 inhibitors linked to this monograph include: angelica root, enasidenib, enoxacin, fluvoxamine, and rofecoxib.(2,3)

*Known hypersensitivity to diazoxide, other components of diazoxide choline, or thiazides. Erythema multiforme has been reported with diazoxide choline.

There are no contraindication contraindications for this drug.

• Chronic heart failure
• Chronic obstructive pulmonary disease
• Interstitial lung disease
• Ketoacidosis
• Morbid obesity
• Pneumonia
• Respiratory depression
• Sleep apnea

• Diabetes mellitus
• Edema
• Gout
• Hyperkalemia
• Hyperuricemia
• Hypokalemia
• Kidney disease with reduction in glomerular filtration rate (GFr)

The most common adverse reactions (incidence >=10% and >=2% greater than in placebo) reported with diazoxide choline in clinical studies were hypertrichosis, edema, hyperglycemia, and rash.

There are no severe adverse reactions for this drug.

More Frequent

• Edema
• Hirsutism
• Hyperglycemia
• Skin rash

Rare or Very Rare

• Anemia
• Arthralgia
• Cataracts
• Eosinophilia
• Fever
• Hypersensitivity drug reaction
• Hyperuricemia
• Influenza
• Neutropenic disorder
• Pharyngitis
• Pulmonary hypertension
• Suicidal ideation
• Symptoms of anxiety
• Thrombocytopenic disorder
• Upper respiratory infection
• Weight gain

No enhanced messaging available.

Safety and efficacy of diazoxide choline have been established in pediatric patients >=4 years of age with hyperphagia and PWS. Use of diazoxide choline in this age group is supported by data from a 16-week, randomized, double-blind, placebo-controlled, withdrawal study period that included 77 adults and pediatric patients (ages 7-29 years of age) with hyperphagia and PWS. Safety and effectiveness were comparable between pediatric and adult patients in this study. Additional safety data supporting use in this population is provided by 3 additional studies (one randomized, double-blind, placebo-controlled study and two long-term, open-label maintenance studies) in adults and pediatric patients with hyperphagia and PWS. Safety and efficacy in pediatric patients <4 years of age with hyperphagia and PWS have not been established.

There are insufficient data regarding diazoxide choline use in pregnant women. Diazoxide crosses the placenta and has been detected in cord blood. Based on data from case reports, in utero exposure of the infant to diazoxide may produce fetal or neonatal hyperbilirubinemia, thrombocytopenia, altered carbohydrate metabolism, and other adverse reactions. Alopecia, hypertrichosis lanuginosa, and hyperglycemia have also been reported in a small number of infants whose mothers received diazoxide during the last 19 to 60 days of pregnancy. The IV administration of diazoxide (parenteral preparation no longer commercially available in the US) during labor may cause cessation of uterine contractions, requiring administration of oxytocic agents to reinstate labor; this has not been reported with oral diazoxide.

In animal studies, diazoxide choline was administered to pregnant rats during organogenesis, and decreased fetal body weights, delayed skeletal ossification, and increased fetal resorptions were observed at 160 mg/kg per day (a dose approximately equal to the maximum recommended human dose).

Diazoxide is present in human milk. However, effects of diazoxide on breastfed infants or milk production are not known. If breastfeeding while receiving diazoxide choline, because of the risk for hyperglycemia, consider monitoring the infant's blood glucose, especially during the neonatal period.

The manufacturer makes no specific dosage recommendations for geriatric patients.

No geriatric patients (>=65 years of age) were included in any studies involving diazoxide choline; the oldest patient was 29 years of age. This is reflective of the average lifespan of patients with PWS, with recent data demonstrating a mean age at death of 29.5 years.