ZTALMY is the first neuroactive steroid anticonvulsant

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

Learn about the dosing and administration of ZTALMY

DOSING

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PRESCRIBING RESOURCES

IMPORTANT SAFETY INFORMATION AND INDICATION

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.

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, pyrexia, salivary hypersecretion, and seasonal allergy.

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.; 2022.
  2. Marinus Pharmaceuticals announces FDA approval of ZTALMY (ganaxolone) for CDKL5 deficiency disorder. Marinus Pharmaceuticals, Inc. https://ir.marinuspharma.com/news/news-details/2022/Marinus-Pharmaceuticals-Announces-FDA-Approval-of-ZTALMY-ganaxolone-for-CDKL5-Deficiency‑Disorder/default.aspx. Accessed June 1, 2022.
  3. Knight EMP, Amin S, Bahi-Buisson N, et al. Safety and efficacy of ganaxolone in patients with CDKL5 deficiency disorder: results from the double-blind phase of a randomised, placebo-controlled, phase 3 trial. Lancet Neurol. 2022;21(5):417-427.
  4. Martinez Botella G, Salituro FG, Harrison BL, et al. Neuroactive Steroids. 1. Positive allosteric modulators of the (γ-aminobutyric acid)A receptor: structure-activity relationships of heterocyclic substitution at C-21. J Med Chem. 2015;58(8):3500-3511.
  5. During MJ, Ryder KM, Spencer DD. Hippocampal GABA transporter function in temporal-lobe epilepsy. Nature. 1995;376(6536):174-177.
  6. Treiman DM. GABAergic mechanisms in epilepsy. Epilepsia. 2001;42 (Suppl 3):8-12.
  7. Fritschy JM. Epilepsy, E/I balance and GABA(A) receptor plasticity. Front Mol Neurosci. 2008;1:5.
  8. Goodkin HP, Sun C, Yeh JL, Kapur J. GABAA. Receptor internalization during seizures. Epilepsia. 2007;48(Suppl 5):109-113. Erratum in: Epilepsia. 2007;48(12):2380.
  9. Brooks-Kayal AR, Shumate MD, Jin H, Rikhter TY, Coulter DA. Selective changes in single cell GABAA receptor subunit expression and function in temporal lobe epilepsy. Nat Med. 1998;4(10):1166-1172. Erratum in: Nat Med. 1999;5(5):590.
  10. González MI, Cruz Del Angel Y, Brooks-Kayal A. Down-regulation of gephyrin and GABAA receptor subunits during epileptogenesis in the CA1 region of hippocampus. Epilepsia. 2013;54(4):616-624.
  11. Fehr S, Wilson M, Downs J, et al. The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy. Eur J Hum Genet. 2013;21:266-273.
  12. Epilepsy Foundation website. Causes of epilepsy. https://www.epilepsy.com/causes. Accessed June 1, 2022.
  13. 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.
  14. 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.
  15. 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, editors. Jasper's Basic Mechanisms of the Epilepsies. 4th ed. National Center for Biotechnology Information; 2012. https://www.ncbi.nlm.nih.gov/books/NBK98218/. Accessed June 1, 2022.
  16. Stell BM, Brickley SG, Tang CY, Farrant M, Mody I. Neuroactive steroids reduce neuronal excitability by selectively enhancing tonic inhibition mediated by δ subunit-containing GABAA receptors. Proc Natl Acad Sci U S A. 2003;100(24):14439-14444.
  17. Herd MB, Belelli D, Lambert JJ. Neurosteroid modulation of synaptic and extrasynaptic GABA(A) receptors. Pharmacol Ther. 2007;116(1):20-34.
  18. Chuang SH, Reddy DS. 3β-Methyl-neurosteroid analogs are preferential positive allosteric modulators and direct activators of extrasynaptic δ-subunit γ-aminobutyric acid type a receptors in the hippocampus dentate gyrus subfield. J Pharmacol Exp Ther. 2018;365(3):583-601.
  19. Hosie AM, Wilkins ME, da Silva HM, Smart TG. Endogenous neurosteroids regulate GABAA receptors through two discrete transmembrane sites. Nature. 2006;444(7118):486-489.
  20. Hosie AM, Wilkins ME, Smart TG. Neurosteroid binding sites on GABAA receptors. Pharmacol Ther. 2007;116(1):7-19.