Diazoxide choline

Diazoxide choline is a prescription medication indicated for the treatment of hyperphagia in adults and
pediatric patients 4 years of age and older with Prader-Willi syndrome (PWS). 

• Diazoxide choline is available under the following different brand names: Vykat XR.

Common side effects of Diazoxide choline include:

• hypertrichosis
• edema
• hyperglycemia
• rash

Serious side effects of Diazoxide choline include:

• hyperglycemia symptoms include increased thirst, increased hunger, urinating more than usual, weight loss, and higher urine volume
• diabetic ketoacidosis symptoms include nausea, vomiting, abdominal pain, tiredness, and trouble breathing
• fluid overload symptoms include difficulty in breathing, edema in the legs, ankles, or feet, and unusual swelling anywhere else in the body

Rare side effects of Diazoxide choline include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Tablet, extended release

• 25 mg
• 75 mg
• 150 mg

Prader-Willi syndrome

Adult dosage

• Titrate once daily oral dose according to weight
  • Maximum dose: 5.8 mg/kg/day or 525 mg/day
  • Weight between 40 kg and 64 kg
    • Weeks 1-2: 75 mg
    • Weeks 3-4: 150 mg
    • Weeks 5-6: 225 mg
    • Target maintenance dose: 225 mg
  • Weight between 65 and 99 kg
    • Weeks 1-2: 150 mg
    • Weeks 3-4: 225 mg
    • Weeks 5-6: 300 mg
    • Target maintenance dose: 375 mg
  • Weight between 100 and 134 kg
    • Weeks 1-2: 150 mg
    • Weeks 3-4: 300 mg
    • Weeks 5-6: 375 mg
    • Target maintenance dose: 450 mg
  • Weighing 135 and more
    • Weeks 1-2: 150 mg
    • Weeks 3-4: 300 mg
    • Weeks 5-6: 450 mg
    • Target maintenance dose: 525 mg

Pediatric dosage

• Titrate once daily oral dose according to body weight
  • Maximum dose: 5.8 mg/kg/day or 525 mg/day
  • See adult dosing if weight is 65 kg and more
  • Weighing between 20 and 29 kg
    • Weeks 1-2: 25 mg
    • Weeks 3-4: 50 mg
    • Weeks 5-6: 75 mg
    • Target maintenance dose: 100 mg
  • Weighing between 30 and 39 kg
    • Weeks 1-2: 75 mg
    • Weeks 3-6: 150 mg
    • Target maintenance dose: 150 mg
  • Weighing between 40 and 64 kg
    • Weeks 1-2: 75 mg
    • Weeks 3-4: 150 mg
    • Weeks 5-6: 225 mg
    • Target maintenance dose: 225 mg

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

his information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Hypersensitivity to diazoxide, other product ingredients, or thiazides

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Diazoxide choline?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Diazoxide choline?”

Cautions

Hyperglycemia

• Diazoxide choline increases blood glucose, primarily by inhibition of pancreatic insulin release
• Hyperglycemia, including severe adverse reactions associated with diabetic ketoacidosis, reported
• Precipitating conditions for diabetic ketoacidosis may include a reduced dose of concomitant antihyperglycemic medications, increased dose 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
• Obtain fasting plasma glucose and HbA1c and optimize blood glucose in patients with hyperglycemia; monitor fasting glucose levels frequently for the first few weeks in patients with risk factors (e.g., obesity, elevated glucose, HbA1c is greater than or equal to ULN, concomitant growth hormone or systemic corticosteroids)
• Advise patients of signs and symptoms of hyperglycemia (e.g., excessive thirst, increased urination, increased appetite with weight loss)
• If hyperglycemia occurs after initiating treatment, monitor fasting glucose as clinically indicated and at least twice weekly until fasting glucose decreases to normal levels; consider monitoring ketones with worsening hyperglycemia
• If hyperglycemia is treated with antihyperglycemic medication, continue monitoring fasting glucose at least once weekly for 8 weeks, and then every 2 weeks and as clinically indicated
• Consider consultation with a clinician with expertise in the treatment of hyperglycemia and counsel patients on lifestyle changes
• Based on hyperglycemia severity, dosage interruption, reduction, or discontinuation may be required to avoid progression to ketoacidosis

Fluid overload

• Edema, including general, localized, and peripheral edema, reported
• Severe adverse reactions associated with fluid overload, including pulmonary edema, were reported during clinical trials
• Antidiuretic property of diazoxide may lead to significant fluid retention, which may precipitate congestive heart failure in patients with compromised cardiac reserve
• Diazoxide choline has not been studied in patients with compromised cardiac reserve and should be used with caution
• Monitor for signs or symptoms of edema or fluid overload and consider appropriate clinical management, which may include dosage reduction or treatment interruption if clinically significant

Drug interaction overview

• Substrate of CYP1A2 and CYP34
• Inhibitor of CYP1A2 (in vitro)
• Strong CYP1A2 inhibitors
  • Modify dose
  • Reduce diazoxide choline dose coadministered with strong CYP1A2 inhibitors, owing to increased frequency and/or severity of adverse effects
• CYP1A2 substrates
  • Monitor
  • Coadministration may increase CYP1A2 substrates systemic exposure
  • Determine action based on substrate prescribing recommendations
• Strong CYP3A4 inhibitors
  • Monitor/modify therapy
  • Monitor frequency and severity of adverse reactions from diazoxide choline
  • Coadministration with strong CYP3A4 inhibitors may necessitate a dosage reduction of Diazoxide choline
• Dual strong CYP3A4 / moderate CYP1A2 inducers
  • Avoid
  • Coadministration with dual strong CYP3A4 / moderate CYP1A2 inducers (e.g., rifampin) may decrease diazoxide choline systemic exposure
• Highly protein-bound drugs
  • Monitor/modify therapy
  • Monitor drugs that are highly protein bound with narrow therapeutic indexes (e.g., warfarin, phenytoin) for potential increased systemic exposure
  • Monitor international normalized ratio (INR) in patients using warfarin and phenytoin serum levels; dosage adjustment may be necessary
• Thiazide or other diuretics
  • Monitor/modify therapy
  • Monitor for signs and symptoms of hyperglycemia and hyperuricemia if diazoxide choline is coadministered with diuretics
  • Both diazoxide and thiazides or other diuretics may produce hyperglycemia and hyperuricemia
  • Dosage adjustment of diazoxide choline or diuretics may be needed if coadministered

Pregnancy and Lactation

• 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

Clinical considerations

• Adverse reactions, including hyperglycemia, alopecia, and hypertrichosis lanuginosa, were reported in neonates exposed to diazoxide in utero
• Crosses the placenta has been detected in cord blood
• Based on adverse reactions reported in adults, in utero exposure of the infant 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 them accordingly

Labor or delivery

• IV 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 during labor

Lactation

• Diazoxide is present in human milk
• There is no data on the effects of breastfed infants or milk production

Clinical considerations

• Owing to potential adverse reactions, including hyperglycemia, monitoring blood glucose in infants may be advisable, especially during the neonatal period