Oral suspension (Ztalmy)
- Strengths
- 50 mg/mL
- Product note
- Shake vigorously for at least 1 minute, then wait 1 minute before measuring. Give with food.
Ganaxolone
Ztalmy
DailyMed-verified antiseizure indications
Indication / use
- Label / evidence summary
- Ztalmy: seizures associated with CDKL5 deficiency disorder from age 2 years.
- Role
- Maintenance
- Class
- Neuroactive steroid · Non-benzodiazepine GABAergic
Indications checked 26 September 2026. Product, route, age, and treatment-role limits apply. A DailyMed listing alone does not establish FDA approval.
- Ztalmy 50 mg/mL oral suspension U.S. label
CDKL5 deficiency disorder · 2 years and older · MaintenanceDose by weight, including the ≤28 kg boundary; give with food.
Formulations & strengths
U.S. products unless another country is named. Strengths are per unit or stated volume.
Brand & formulation labels
Each link names the product and formulation it covers. Archived labels do not establish current availability.
Dosing & administration
- Adult / product-specific schedule
- Weight >28 kg: start 50 mg three times daily; increase no faster than weekly through the table. Maximum 600 mg per dose, three times daily (1,800 mg/day).
- Pediatric
- Age ≥2 years, weight ≤28 kg: start 2 mg/kg per dose three times daily (6 mg/kg/day); weekly titration to at most 21 mg/kg per dose three times daily (63 mg/kg/day). Exactly 28 kg belongs in this group. Use the >28 kg schedule above that weight.
- Titration / repeat dosing
- Current schedule reaches the maximum on day 29 at the earliest; increase only as tolerated. Severe hepatic impairment requires the separate reduced schedule below. Withdraw gradually.
Ganaxolone: usual titration, age ≥2 years
| Treatment period | Weight ≤28 kg: mg/kg PER DOSE | Weight >28 kg: mg PER DOSE |
|---|---|---|
| Days 1–7 | 2 | 50 |
| Days 8–14 | 4 | 100 |
| Days 15–21 | 8 | 200 |
| Days 22–28 | 14 | 400 |
| Day 29 onward (maximum) | 21 | 600 |
All listed doses are given THREE TIMES DAILY with food. Increase no more often than every 7 days and only as tolerated. Maximum totals: 63 mg/kg/day at ≤28 kg; 1,800 mg/day at >28 kg. These are current U.S. label schedules.
Ganaxolone: severe hepatic impairment (Child-Pugh C)
| Treatment period | Weight ≤28 kg: mg/kg PER DOSE | Weight >28 kg: mg PER DOSE |
|---|---|---|
| Days 1–7 | 0.66 | 17 |
| Days 8–14 | 1.33 | 33 |
| Days 15–21 | 2.66 | 67 |
| Days 22–28 | 4.66 | 133 |
| Day 29 onward (maximum) | 7 | 200 |
All listed doses are given THREE TIMES DAILY with food; no faster than weekly titration. Maximum totals: 21 mg/kg/day at ≤28 kg; 600 mg/day at >28 kg. Use this reduced table only for severe hepatic impairment.
Practical administration
- Product instructions
- Give with food. Shake suspension for at least 1 minute, wait 1 minute, then measure with the prescribed oral syringe. Concentration: 50 mg/mL. Discard remaining suspension 30 days after opening.
Dose adjustment & concentrations
- Renal impairment
- Label pharmacokinetic study found no clinically important exposure change with renal impairment; dialysis dosing is not established here.
- Hepatic impairment
- No adjustment for Child-Pugh A/B. For Child-Pugh C use the separate reduced titration table; do not use the usual weight schedule.
- Serum reference information
- No established therapeutic concentration target in the prescribing information.
Safety
- Boxed warning
- No boxed warning in the retrieved label.
- Contraindications
- None listed in the retrieved U.S. label.
- Serious precautions & monitoring
- Monitor somnolence/sedation, mood and suicidal thoughts, and seizure control. Schedule V controlled substance; dependence and withdrawal require attention. Avoid abrupt discontinuation unless a serious adverse event warrants it.
Common / selected adverse effects
- Somnolence / sedation
- Fever
- Increased salivation
- Seasonal allergy
CDD trial: 50 ganaxolone versus 51 placebo recipients, up to 17 weeks. Somnolence/sedation combined: 44% versus 24%; trial titration was faster than the current schedule.
Drug interactions: toxicity & clinical action
| Partner / combination | Clinical effect | Clinical action |
|---|---|---|
| Strong/moderate CYP3A4 inducers | Reduced ganaxolone exposure and effectiveness. | Avoid if possible; if unavoidable, adjust within the labeled maximum and reassess when the inducer stops. |
| UGT inhibitors such as valproate | May increase ganaxolone exposure. | Consider reducing an established ganaxolone dose when an inhibitor is started; monitor sedation. |
| Opioids / benzodiazepines / other CNS depressants | Additive sedation. | Assess alertness, breathing and cumulative sedative burden. |
Pregnancy & contraception
- Fetal / neonatal risk
- No human ganaxolone pregnancy data are available in the Ztalmy label. Animal studies found fetal malformations and developmental impairment at exposures below the maximum adult therapeutic exposure.
Clinical evidence
Research summaries describe studied populations and outcomes; they do not add indications or constitute treatment recommendations.
Direct pivotal trial
Trial summary
- Primary endpoint
- Percent change from the 6-week baseline in 28-day major motor seizure frequency during the 17-week double-blind phase in participants with genetically confirmed CDKL5 deficiency disorder.
- Results
- Median major motor seizure-frequency reduction was approximately 31% with ganaxolone versus 7% with placebo, a 24-percentage-point difference between the reported median reductions (p=0.0036).
- Confidence intervals
- MARIGOLD publication: Hodges–Lehmann median treatment difference −27.1 percentage points (95% CI −47.9 to −9.6), distinct from subtracting the two group medians.
- Discontinuations
- MARIGOLD: 2/50 (4%) ganaxolone and 4/51 (8%) placebo participants discontinued the double-blind trial; these are all-cause discontinuations.
- Exposure duration
- 6-week baseline followed by 17 weeks of double-blind treatment, including titration and maintenance.
- Seizure-frequency results
- Study 1: 101 participants aged 2–19 with genetically confirmed CDD. Over 17 weeks, median reduction in major motor seizure frequency was 31% with ganaxolone versus 7% with placebo (rounded label values; p=0.0036).
- Responder rate
- The label presents responder distribution graphically; a single pooled percentage is not presented.
- Seizure freedom
- No seizure-freedom claim summarized.
Trial publications
Comparative evidence
- Findings
- Placebo-controlled registration study, predominantly with concomitant ASMs.
Mechanism of action
- Positive allosteric modulation of GABA-A receptors is the proposed antiseizure action; the precise therapeutic mechanism in CDD remains incompletely established.
- A neuroactive steroid derived from allopregnanolone. Its chemical class is distinct from benzodiazepines and barbiturates; a shared GABA-A action does not imply interchangeable dosing or clinical indications.
Pharmacology
Adult values unless specified. Vd/F denotes apparent oral distribution volume.
Pharmacokinetics
- Bioavailability
- Approximately 13% absolute bioavailability of the oral suspension in EMA product information. High-fat food increases exposure; administer with food as directed.
- Elimination half-life
- U.S. label: terminal half-life approximately 34 hours. EMA information separately reports 7.8–10.1 hours at steady state; the study context and measure differ.
- Volume of distribution
- Approximately 580 L (EMA product information).
- Active metabolite(s)
- No clinically established active-metabolite contribution. More than 50 metabolites, including long-lived sulfate conjugates, are described in EMA information.
- Active-metabolite half-life
- An active-metabolite half-life is not established. EMA reports half-lives up to 230 hours for some metabolites, without establishing them as clinically active.
- Protein binding
- Approximately 99%
- Metabolism / elimination
- CYP3A4/5 and other CYP enzymes, plus UGT pathways.
Do not substitute a metabolite or steady-state estimate for the U.S. terminal value or use half-life alone to change the three-times-daily regimen.
Molecular structure
NIH PubChem structure and record ↗
Product history
- Initial U.S. approval
- 2022
- Market / formulation history
- U.S. initial approval 2022; current titration revised October 2025.
- Brands
- Ztalmy
- Manufacturer / marketer
- Immedica Pharma US Inc (retrieved U.S. label)
- Generic availability
- Ztalmy is the referenced U.S. product; generic availability is jurisdiction- and date-dependent.
- Related drugs
- Methyl-substituted analog of the endogenous neurosteroid allopregnanolone.
Sources & review status
Indications and DailyMed PDFs checked: 2026-09-26. Other profile sources reviewed: 2026-09-15 · label revision noted at that review: 11/2025 (titration changed 10/2025). This is a draft reference; final review is pending.