ZTALMY is the first neuroactive steroid anticonvulsant

ZTALMY acts as a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors.1,2 It is the first and only treatment indicated specifically for seizures associated with CDD in patients 2 years of age and older.3

Learn about the dosing and administration of ZTALMY

DOSING

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PRESCRIBING RESOURCES

IMPORTANT SAFETY INFORMATION AND INDICATION

WARNINGS AND PRECAUTIONS

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    Somnolence and Sedation: ZTALMY can cause somnolence and sedation. In a clinical study somnolence and sedation appeared early during treatment and were generally dose related. Other CNS depressants, including opioids, antidepressants, and alcohol, could potentiate these effects. Monitor patients for these effects and advise them not to drive or operate machinery until they have gained sufficient experience on ZTALMY to gauge whether it adversely affects their ability to drive or operate machinery.

INDICATION AND USAGE

ZTALMY is indicated for the treatment of seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) in patients 2 years of age and older.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

  • •

    Somnolence and Sedation: ZTALMY can cause somnolence and sedation. In a clinical study somnolence and sedation appeared early during treatment and were generally dose related. Other CNS depressants, including opioids, antidepressants, and alcohol, could potentiate these effects. Monitor patients for these effects and advise them not to drive or operate machinery until they have gained sufficient experience on ZTALMY to gauge whether it adversely affects their ability to drive or operate machinery.

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    Suicidal Behavior and Ideation: Antiepileptic drugs (AEDs), including ZTALMY, increase the risk of suicidal thoughts or behavior. Monitor patients taking ZTALMY for the emergence or worsening of depression, suicidal thoughts or behavior, or any unusual changes in mood or behavior. Advise patients, caregivers, and their families to be alert for these behavioral changes and report behaviors of concern immediately to healthcare providers. When considering ZTALMY, or any other AED, balance the risk of suicidal thoughts or behaviors with the risk of untreated illness. If these symptoms emerge during treatment, consider whether it may be related to the AED or the underlying illness.

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    Withdrawal of Antiepileptic Drugs: As with most AEDs, withdraw ZTALMY gradually to minimize the risk of increased seizure frequency and status epilepticus. If withdrawal is needed because of a serious adverse event, rapid discontinuation can be considered.

ADVERSE REACTIONS

The most common adverse reactions (incidence of at least 5% and at least twice the rate of placebo) were somnolence (38%), pyrexia (18%), salivary hypersecretion (6%), and seasonal allergy (6%).

DRUG INTERACTIONS

Cytochrome P450 inducers will decrease ganaxolone exposure. Avoid concomitant use with strong or moderate CYP3A4 inducers; if unavoidable, consider a dosage increase of ZTALMY, but do not exceed the maximum recommended dosage.

USE IN SPECIFIC POPULATIONS

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    Pregnancy: Use caution when ZTALMY is administered to pregnant women as there are no adequate data on the developmental risk associated with use in pregnant women. In animal studies, developmental adverse effects were observed following exposure during organogenesis or throughout gestation and lactation.

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    Lactation: ZTALMY is excreted in human milk at concentrations resulting in a dose to the breastfed infant of less than 1% maternal dose. The effects of ZTALMY on milk production and the breastfed infant are unknown.

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    Hepatic Impairment: Administration of ZTALMY in patients with severe hepatic impairment (Child‑Pugh class C) results in elevated ganaxolone plasma concentrations. Therefore, dosage adjustment in these patients during titration and maintenance is required. No dosage adjustment is necessary in patients with mild (Child‑Pugh class A) or moderate (Child‑Pugh class B) hepatic impairment.

DRUG ABUSE AND DEPENDENCE

ZTALMY contains ganaxolone, a Schedule V controlled substance (CV). Advise patients of the potential for abuse and dependence. It is recommended that ZTALMY be tapered according to the dosage recommendations unless symptoms warrant immediate discontinuation.

Please see full Prescribing Information.

IMPORTANT SAFETY INFORMATION AND INDICATION

INDICATION AND USAGE

ZTALMY is indicated for the treatment of seizures associated with cyclin-dependent kinase-like 5 (CDKL5) deficiency disorder (CDD) in patients 2 years of age and older.

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

ADVERSE REACTIONS

The most common adverse reactions (incidence of at least 5% and at least twice the rate of placebo) were somnolence (38%), pyrexia (18%), salivary hypersecretion (6%), and seasonal allergy (6%).

DRUG INTERACTIONS

Cytochrome P450 inducers will decrease ganaxolone exposure. Avoid concomitant use with strong or moderate CYP3A4 inducers; if unavoidable, consider a dosage increase of ZTALMY, but do not exceed the maximum recommended dosage.

USE IN SPECIFIC POPULATIONS

DRUG ABUSE AND DEPENDENCE

ZTALMY contains ganaxolone, a Schedule V controlled substance (CV). Advise patients of the potential for abuse and dependence. It is recommended that ZTALMY be tapered according to the dosage recommendations unless symptoms warrant immediate discontinuation.

Please see full Prescribing Information.

References:

  1. ZTALMY [package insert]. Radnor, PA: Marinus Pharmaceuticals, Inc.; 2023.
  2. Marinus Pharmaceuticals, Inc. Accessed June 1, 2022. https://ir.marinuspharma.com/news/news-details/2022/Marinus-Pharmaceuticals-Announces-FDA-Approval-of-ZTALMY-ganaxolone-for-CDKL5-Deficiency-Disorder/default.aspx
  3. Martinez Botella G, Salituro FG, Harrison BL, et al. J Med Chem. 2015;58(8):3500-3511.
  4. During MJ, Ryder KM, Spencer DD. Nature. 1995;376(6536):174-177.
  5. Treiman DM. Epilepsia. 2001;42(Suppl 3):8-12.
  6. Fritschy JM. Front Mol Neurosci. 2008;1:5.
  7. Goodkin HP, Sun C, Yeh JL, Kapur J. Epilepsia. 2007;48(Suppl 5):109-113. Erratum in: Epilepsia. 2007;48(12):2380.
  8. Brooks-Kayal AR, Shumate MD, Jin H, Rikhter TY, Coulter DA. Nat Med. 1998;4(10):1166-1172. Erratum in: Nat Med. 1999;5(5):590.
  9. González MI, Cruz Del Angel Y, Brooks-Kayal A. Epilepsia. 2013;54(4):616-624.
  10. Fehr S, Wilson M, Downs J, et al. Eur J Hum Genet. 2013;21:266-273.
  11. Epilepsy Foundation website. Accessed June 1, 2022. https://www.epilepsy.com/causes
  12. Olsen RW. Gaba. In: Davis KL, Charney D, Coyle JT, Nemeroff C, eds. Neuropsychopharmacology: The Fifth Generation of Progress. Lippincott, Williams, & Wilkins; 2002:159-168.
  13. Synaptic transmissions. In: Purves D, Augustine GJ, Fitzpatrick D, Hall WC, LaMantia A-S, McNamara JO, Williams SM, eds. Neuroscience. 3rd ed. Sinauer Associates, Inc. 2004:93-127.
  14. Reddy DS, Rogawski MA. Neurosteroids — endogenous regulators of seizure susceptibility and role in the treatment of epilepsy. In: Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV, eds. Jasper's Basic Mechanisms of the Epilepsies. 4th ed. National Center for Biotechnology Information; 2012. Accessed June 1, 2022. https://www.ncbi.nlm.nih.gov/books/NBK98218/
  15. Stell BM, Brickley SG, Tang CY, Farrant M, Mody I. Proc Natl Acad Sci U S A. 2003;100(24):14439-14444.
  16. Knight EMP, Amin S, Bahi-Buisson N, et al. Lancet Neurol. 2022;21(5):417-427.
  17. Herd MB, Belelli D, Lambert JJ. Pharmacol Ther. 2007;116(1):20-34.
  18. Lan NC, Gee KW. Horm Behav. 1994;28(4):537-544.
  19. Chuang SH, Reddy DS. J Pharmacol Exp Ther. 2018;365(3):583-601.
  20. Hosie AM, Wilkins ME, da Silva HM, Smart TG. Nature. 2006;444(7118):486-489.
  21. Hosie AM, Wilkins ME, Smart TG. Pharmacol Ther. 2007;116(1):7-19.