General

Pronunciation:
gan-ax-oh-lone

Trade Name(s)

• Ztalmy

Ther. Class.

anticonvulsants

Pharm. Class.

gamma aminobutyric acid gaba enhancers

Controlled Substance Schedule: V

Indications

Seizures associated with cyclin-dependent kinase-like 5 deficiency disorder.

Action

Although not fully understood, thought to be related to positive allosteric modulation of GABA-A receptors.

Therapeutic Effect(s):

Reduction in frequency of major motor seizures.

Pharmacokinetics

Absorption: Extent of absorption following oral administration unknown. Extent of absorption ↑ by high-fat meal.

Distribution: Unknown.

Protein Binding: 99%.

Metabolism and Excretion: Metabolized by the CYP3A4/5, CYP2B6, CYP2C19, and CYP2D6 isoenzymes. Primarily excreted in the feces (55%; 2% as unchanged drug), with 18% excreted in the urine.

Half-life: 34 hr.

TIME/ACTION PROFILE (plasma concentrations)

Contraindication/Precautions

Contraindicated in:

• None.

Use Cautiously in:

• All patients (may ↑ risk of suicidal thoughts/behaviors);
• Severe hepatic impairment (↓ dose);
• OB:   Safety not established in pregnancy;
• Lactation:  Safety not established in breastfeeding;
• Pedi:   Children <2 yr (safety and effectiveness not established).

Adverse Reactions/Side Effects

EENT: nasal congestion

GI: ↑ salivation

Neuro: sedation, SUICIDAL THOUGHTS/BEHAVIOR

Resp: gait disturbance, upper respiratory tract infection

Misc: fever

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

• Use with  benzodiazepines  or other  CNS depressants, including  opioids,  nonbenzodiazepine sedative/hypnotics,  anxiolytics,  muscle relaxants, and  alcohol, could potentiate sedation.
•  Strong CYP3A inducers, including  rifampin, and  moderate CYP3A inducers  may ↓ levels and effectiveness; consider ↑ ganaxolone dose.

Route/Dosage

PO (Adults and Children  ≥2 yr and >28 kg): 150 mg 3 times daily for 7 days (Days 1–7); then 300 mg 3 times daily for 7 days (Days 8–14); then 450 mg 3 times daily for 7 days (Days 15–21); then 600 mg 3 times daily (Day 22 and thereafter).

PO (Adults and Children  ≥2 yr and ≤28 kg): 6 mg/kg 3 times daily for 7 days (Days 1–7); then 11 mg/kg 3 times daily for 7 days (Days 8–14); then 16 mg/kg 3 times daily for 7 days (Days 15–21); then 21 mg/kg 3 times daily (Day 22 and thereafter).

Hepatic Impairment 
PO (Adults and Children  ≥2 yr and >28 kg): Severe hepatic impairment:  50 mg 3 times daily for 7 days (Days 1–7); then 100 mg 3 times daily for 7 days (Days 8–14); then 150 mg 3 times daily for 7 days (Days 15–21); then 200 mg 3 times daily (Day 22 and thereafter).

Hepatic Impairment 
PO (Adults and Children  ≥2 yr and ≤28 kg): Severe hepatic impairment:  2 mg/kg 3 times daily for 7 days (Days 1–7); then 3.66 mg/kg 3 times daily for 7 days (Days 8–14); then 5.33 mg/kg 3 times daily for 7 days (Days 15–21); then 7 mg/kg 3 times daily (Day 22 and thereafter).

Availability

Oral suspension (cherry flavor): 50 mg/mL

Assessment

• Assess for depression, nervousness, restlessness, panic attacks, and suicidal thoughts or behaviors.
• Monitor for somnolence and sedation (drowsiness, hypersomnia, lethargy).
• Assess for withdrawal signs and symptoms. Ganaxolone should be withdrawn gradually due to risk of ↑ seizure frequency and status epilepticus.

Implementation

• PO Administer three times daily with food.
• Shake bottle for 1 min; then let stand for 1 min before measuring. Use provided PO syringe to measure and administer dose. Store at room temperature. Discard suspension after 30 days of first opening.

Patient/Family Teaching

• Explain purpose and side effects of medication to patient. Advise patient to read  Patient Information  before starting therapy. Take missed dose as soon as remembered. If it is close to the time of next dose, omit and take at normal time. Do not take two doses at same time or extra doses.
• Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking other medications.
• Advise patient about effects on impaired judgment, thinking, and motor skills, and to be cautious while driving until known response of medication.
• Instruct patient and caregiver to notify health care professional immediately if changes in mood or suicidal thoughts or behaviors occur.
• Advise patient not to discontinue medication without consulting health care professional.
• Advise patient about the potential for medication abuse and physical dependence.
• Rep:  Advise women of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding. Health care providers are encouraged to enroll patients exposed to ganaxolone during pregnancy in the North American Antiepileptic Drug (NAAED) Pregnancy Registry (1-888-233-2334 or http://www.aedpregnancyregistry.org/).

Evaluation/Desired Outcomes

Reduction in frequency of major motor seizures.