Ztalmy (ganaxolone)

Ganaxolone is available as a 50 mg/mL oral suspension.

Ganaxolone is administered orally 3 times daily as an oral suspension; the drug must be taken with food. Shake the bottle thoroughly for at least 1 minute, then wait 1 minute before measuring and administering the dose. An oral syringe must be used for measuring and administering the drug.

Store ganaxolone upright in the original bottle at 20 to 25degreesC; excursions permitted from 15 to 30degreesC. Close the cap tightly after each use. Use within 30 days of first opening the bottle; discard any remaining drug.

No dosing information is available for this tab.

Ganaxolone is metabolized by cytochrome P-450 (CYP) isoenzymes 3A4/5, 2B6, 2C19, 2D6, and UGT1A3, UGT1A6, UGT1A9, UGT2B7, and UGT2B15.

In vitro, ganaxolone is not an inhibitor of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4/5 or an inducer of CYP1A2, CYP2B6, or CYP3A4 at clinically relevant concentrations.

Ganaxolone does not inhibit UGT1A1, UGT1A3, UGT1A4, UGT1A6, UGT1A9, or UGT2B7.

Ganaxolone does not inhibit breast cancer resistance protein (BCRP), P-glycoprotein (P-gp), multidrug and toxin extrusion protein (MATE) 1, MATE2-K, organic anion transporter (OAT) 1, OAT3, organic cation transporter (OCT) 1, OCT2, organic anion transporter protein (OATP) 1B1, OATP1B3, or bile salt export pump (BSEP) at clinically relevant concentrations. Ganaxolone is not a substrate of BCRP, P-gp, OCT1, OCT2, OATP1B1, or OATP1B3 at clinically relevant concentrations.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Ganaxolone/Strong Or Moderate Cyp3a4 Inducers

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Ganaxolone is a substrate of CYP3A4. Strong or moderate inducers of CYP3A4 may induce the metabolism of ganaxolone.(1)

CLINICAL EFFECTS: The concurrent administration of strong or moderate CYP3A4 inducers may result in decreased levels and effectiveness of ganaxolone.(1)

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

PATIENT MANAGEMENT: The manufacturer of ganaxolone states that concurrent use with strong or moderate CYP3A4 inducers should be avoided. If concurrent use is unavoidable, consider increasing the dose of ganaxolone. Do not exceed the recommended maximum daily dose.(1) In patients who are stable on ganaxolone and are initiated on anticonvulsants that are CYP3A4 inducers, consider increasing the dose of ganaxolone. Do not exceed the recommended maximum daily dose.(1)

DISCUSSION: Co-administration of rifampin, a strong CYP3A4 inducer, decreased the ganaxolone concentration maximum (Cmax) by 57% and area-under-curve (AUC) by 68%.(1) Strong inducers of CYP3A4 include: apalutamide, barbiturates, carbamazepine, encorafenib, enzalutamide, fosphenytoin, ivosidenib, lumacaftor, mitotane, phenobarbital, phenytoin, primidone, rifampin, rifapentine, and St. John's wort. Moderate inducers of CYP3A4 include: belzutifan, bosentan, cenobamate, dabrafenib, dipyrone, efavirenz, elagolix, etravirine, fexinidazole, lesinurad, lorlatinib, mavacamten, mitapivat, modafinil, nafcillin, pacritinib, pexidartinib, repotrectinib, rifabutin, sotorasib, telotristat ethyl, thioridazine, and tovorafenib.(2-3)

There are no moderate interactions for this drug.

*None.

There are no contraindication contraindications for this drug.

• Child-pugh class C hepatic impairment
• Disease of liver
• Suicidal
• Suicidal ideation

There are no moderate contraindications for this drug.

Common adverse reactions occurring at an incidence >=5% for ganaxolone and at least twice the rate of placebo are somnolence, pyrexia, salivary hypersecretion, and seasonal allergy.

More Frequent

• Seasonal allergic rhinitis

Rare or Very Rare

• Suicidal ideation

More Frequent

• Drowsy
• Fever
• Sedation
• Sialorrhea

Less Frequent

• Bronchitis
• Gait abnormality
• Influenza
• Nasal congestion
• Upper respiratory infection

Rare or Very Rare

• Accidental fall

No enhanced messaging available.

Safety and efficacy for the treatment of seizures associated with CDD in pediatric patients 2 years of age and older were established in the principle efficacy study (Study 1).

Safety and efficacy in pediatric patients <2 years of age have not been established. Oral administration of ganaxolone to juvenile rats from postnatal day 7 through postnatal day 91 resulted in deaths associated with sedation as well as developmental toxicity at clinically relevant doses. Neurobehavioral (locomotor activity, auditory startle response, learning and memory) and reproductive function were not affected. Widespread neurodegeneration in multiple brain regions was observed in rats exposed to ganaxolone on postnatal day 7; effects on neurobehavioral function were not assessed.

There are no adequate data in humans to determine if there is any risk associated with the use of ganaxolone during pregnancy. In animal studies, adverse effects on development (i.e., fetal malformations, neurobehavioral and growth impairment) were observed in mice or rats during organogenesis (mice) or throughout gestation and lactation (rats) at maternal exposures lower than those occurring at the maximum recommended human dose. Widespread neurodegeneration in the cortex, thalamus, and hippocampus was observed in rats exposed to ganaxolone on postnatal day 7. A no-effect dose was not identified. Brain development in rats on postnatal day 7 corresponds to a period of brain development in humans that begins during the third trimester of pregnancy and continues for the first several months to years after birth.

Women who are pregnant while receiving ganaxolone should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry at 888-233-2334 or https://www.aedpregnancyregistry.org.

Ganaxolone is excreted in human milk. Following a single oral dose of ganaxolone 300 mg, exposures in human milk were approximately 4 times higher than those in maternal plasma. The calculated maximum relative infant dose of ganaxolone is approximately 0.157 mg/kg per day based on an average milk intake of 150 mL/kg per day, which is <1% of the maternal dose, and approximately 0.24% of the labeled pediatric dose of 63 mg/kg per day. It is not known whether ganaxolone affects milk production or the breast-fed infant.

Consider the benefits of breast-feeding along with the importance of ganaxolone to the woman and any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

The manufacturer makes no specific dosage recommendations for geriatric patients.

Safety and efficacy of ganaxolone have not been established in patients 65 years of age and older. CDD is largely a disease of pediatric and young adult patients.