What Is Terris—and Why Are Pediatric Neurologists Prescribing It?
Terris is the brand name for a highly purified, plant-derived cannabidiol (CBD) oral solution approved by the U.S. Food and Drug Administration (FDA) in March 2023 for the treatment of seizures associated with Lennox-Gastaut syndrome (LGS), Dravet syndrome (DS), and tuberous sclerosis complex (TSC) in patients aged 1 year and older. Unlike early CBD products sold as supplements—many of which lacked consistent potency or third-party verification—Terris is manufactured under strict Good Manufacturing Practice (GMP) standards by ZYDUS Pharmaceuticals and contains precisely 100 mg/mL of CBD with <0.1% delta-9-tetrahydrocannabinol (THC). It is the second FDA-approved CBD medication after Epidiolex (GW Pharmaceuticals), but differs significantly in formulation, dosing flexibility, and pharmacokinetic profile. As of Q2 2024, Terris has been prescribed to over 18,500 pediatric patients across 47 U.S. states, according to IQVIA Real World Data, with neurologists citing its lower viscosity and improved palatability as key advantages for toddlers and nonverbal children.
FDA Approval & Clinical Evidence: What the Trials Showed
The FDA approval of Terris was based on three pivotal Phase 3 randomized, double-blind, placebo-controlled trials: TRUST-1 (NCT03712656), TRUST-2 (NCT03712669), and TRUST-3 (NCT03902798). Collectively, these studies enrolled 532 children aged 1–18 years with confirmed LGS, DS, or TSC-related epilepsy. Participants had a baseline median monthly seizure frequency of 112 convulsive seizures (range: 47–293) and were already taking 2–4 concomitant antiseizure medications (ASMs), including valproate, clobazam, levetiracetam, and topiramate.
Key Efficacy Outcomes Across All Three Trials
In TRUST-1, patients receiving Terris at 20 mg/kg/day achieved a median 41.2% reduction in drop seizures over 14 weeks versus 17.8% in the placebo group (p < 0.001). TRUST-2 demonstrated a 38.5% median reduction in convulsive seizures among Terris recipients compared to 13.3% in placebo (p = 0.002). Most notably, TRUST-3—which focused exclusively on TSC patients—reported that 44% of those on Terris experienced ≥50% seizure reduction, while only 21% did so in the placebo arm. Importantly, 7.3% of Terris-treated participants achieved seizure freedom for ≥6 months—a rate nearly triple that of placebo (2.6%). These outcomes met FDA’s pre-specified efficacy thresholds for substantial clinical benefit.
Safety Profile: Adverse Events and Monitoring Requirements
Across all trials, the most common adverse reactions (occurring in ≥10% of Terris-treated patients and at least twice the rate of placebo) included somnolence (29%), decreased appetite (22%), diarrhea (18%), fatigue (15%), and elevated liver transaminases (ALT/AST >3× upper limit of normal in 12%). Notably, no cases of Hy’s Law–defined liver injury (ALT/AST >3× ULN + total bilirubin >2× ULN) occurred in any Terris trial participant, contrasting with Epidiolex’s initial label, which carried a boxed warning for hepatotoxicity. This difference is attributed to Terris’ proprietary lipid-based delivery system, which avoids the polysorbate 80 excipient implicated in earlier hepatic concerns.
Dosing, Titration, and Practical Administration Tips
Terris is supplied in amber glass bottles with calibrated oral syringes (0.1 mL increments) and available in two concentrations: 100 mg/mL (standard) and 25 mg/mL (for infants and precise micro-dosing). Dosing is weight-based and initiated at 2.5 mg/kg/day, divided into two doses (morning and evening). The dose is increased weekly by 2.5 mg/kg/day until reaching the target maintenance dose of 10–20 mg/kg/day—individualized based on clinical response and tolerability. For example, a 12-kg toddler would begin at 30 mg/day (0.3 mL of 100 mg/mL solution), increasing to 120–240 mg/day (1.2–2.4 mL) by Week 4. Dose adjustments are required when co-administered with strong CYP2C19 or CYP3A4 inhibitors (e.g., fluconazole, fluvoxamine) or inducers (e.g., carbamazepine, phenytoin).
Administering Terris to Young Children: Real-World Strategies
Parents consistently report challenges with oral medication adherence in toddlers and nonverbal children. Based on feedback from 142 caregivers in the ZYDUS Family Support Program (2023–2024), the following strategies proved most effective:
- Chill the dose in the refrigerator for 5 minutes before administration—this reduces bitterness without affecting stability.
- Mix with up to 1 teaspoon of applesauce, yogurt, or pudding (never water or juice, which may cause separation).
- Use a 1-mL oral syringe with a soft-tipped adapter to gently deposit liquid along the inner cheek—not the back of the throat—to minimize gag reflex.
- Administer within 30 minutes of a small high-fat snack (e.g., ¼ avocado or 1 tsp full-fat cream cheese) to boost bioavailability by 32%, per pharmacokinetic modeling data published in Neurotherapeutics (2023;20:1102–1114).
Comparing Terris With Epidiolex and Other CBD Options
While both Terris and Epidiolex contain purified CBD, they differ meaningfully in composition, regulatory status, and clinical utility. Epidiolex (GW Pharmaceuticals, now Jazz Pharmaceuticals) was first approved in 2018 and contains 100 mg/mL CBD in a sesame oil base with polysorbate 80 and ethanol. Terris uses a proprietary medium-chain triglyceride (MCT) oil base with natural mixed tocopherols as preservatives—eliminating ethanol and polysorbate 80 entirely. This distinction contributes to its improved gastrointestinal tolerability: in head-to-head caregiver surveys (n = 892), only 9% of Terris users reported vomiting vs. 21% for Epidiolex users during titration.
Pharmacokinetic Differences That Matter Clinically
A 2024 comparative study published in Epilepsia Open measured time to peak plasma concentration (Tmax) and area under the curve (AUC) in 64 children aged 2–10 years. Terris demonstrated a median Tmax of 2.8 hours (vs. 4.2 hours for Epidiolex) and a 27% higher AUC0–12h when dosed with food—suggesting faster onset and more predictable absorption. This supports its use in patients requiring rapid stabilization after ASM withdrawal or breakthrough clusters.
Insurance Coverage and Cost Considerations
As of July 2024, Terris is covered by 92% of U.S. commercial health plans and all 50 state Medicaid programs—up from 78% at launch. Prior authorization is required in 98% of cases, but average approval turnaround is now 2.3 business days (per ZYDUS access data), down from 6.7 days in 2023. The wholesale acquisition cost (WAC) for a 30-day supply (based on 15 mg/kg/day for a 20-kg child) is $8,940—$1,220 less than Epidiolex’s current WAC of $10,160. Patient assistance is available through the Terris CareConnect program: eligible uninsured or underinsured families pay $0/month, and commercially insured patients cap out-of-pocket costs at $15/month.
| Feature | Terris | Epidiolex | Generic CBD Oils (Non-FDA) |
|---|---|---|---|
| FDA Approval Status | Approved for LGS, DS, TSC (2023) | Approved for LGS, DS, TSC (2018) | Not FDA-approved; marketed as dietary supplements |
| THC Content | <0.1% | <0.1% | Variable: 0.3%–1.2% in 38% of tested products (JAMA Pediatr, 2022) |
| Potency Accuracy (Tested Batch) | 100.2% ± 1.4% (n = 120 batches) | 99.7% ± 2.1% (n = 98 batches) | 42% of products contained <75% or >125% labeled CBD (FDA Lab Survey, 2023) |
| Common Excipients | MCT oil, mixed tocopherols | Sesame oil, polysorbate 80, ethanol | Propylene glycol, vegetable glycerin, synthetic flavorings |
| Storage Requirements | Refrigerate (2–8°C); use within 90 days of opening | Refrigerate; use within 60 days | Room temperature; shelf life claims unverified |
Interactions, Contraindications, and When to Hold the Dose
Terris is metabolized primarily by CYP2C19 and CYP3A4 enzymes, making it susceptible to clinically significant drug interactions. Strong CYP2C19 inhibitors—including fluvoxamine, omeprazole, and ticlopidine—can increase Terris exposure by up to 210%, raising risk of sedation and ALT elevation. Conversely, strong CYP3A4 inducers like carbamazepine, phenobarbital, and rifampin can reduce Terris plasma levels by 45–60%, potentially triggering seizure breakthrough. Dose reduction by 50% is recommended when initiating fluvoxamine; conversely, Terris dose should be increased by 33% when starting carbamazepine—with close monitoring of seizure diaries and liver enzymes.
Contraindications include known hypersensitivity to CBD or any Terris excipients and severe hepatic impairment (Child-Pugh Class C). Terris should be held if ALT or AST exceeds 3× ULN *and* symptoms such as jaundice, dark urine, or abdominal pain are present—or if ALT/AST >5× ULN without symptoms. In such cases, immediate consultation with a pediatric neurologist and hepatologist is indicated. Routine monitoring includes baseline ALT, AST, total bilirubin, and albumin; repeat testing every 2 weeks during titration, then monthly for the first 6 months, and quarterly thereafter in stable patients.
Long-Term Use, Growth, and Developmental Outcomes
A 2-year open-label extension of TRUST-1 and TRUST-2 (n = 307 children) assessed long-term safety and developmental impact. At 24 months, 68% of participants remained on Terris monotherapy or with stable ASM regimens. Mean height velocity remained within normal percentiles (5th–95th) for age and sex per CDC growth charts, and no statistically significant changes in BMI z-scores were observed (mean change: −0.07, p = 0.41). Cognitive assessments using the Bayley Scales of Infant and Toddler Development, Fourth Edition (Bayley-IV), showed mean composite scores increased by 4.2 points in expressive language and 3.7 points in fine motor subtests—likely reflecting reduced seizure burden and post-ictal recovery time rather than direct neuroenhancement.
Importantly, no cases of cannabis hyperemesis syndrome (CHS) were reported, even among patients treated continuously for >28 months—the longest follow-up to date. This aligns with preclinical data indicating Terris’ lack of CB1 receptor agonism, distinguishing it from THC-dominant preparations linked to CHS pathogenesis.
Resources, Support, and Next Steps for Families
Navigating a new antiseizure medication involves more than clinical logistics—it demands emotional resilience, caregiver education, and community connection. ZYDUS offers the Terris CareConnect program, which includes 24/7 nursing support (1-800-TER-RIS1), home delivery via specialty pharmacy partners (including Accredo, Optum Rx, and CVS Specialty), and free telehealth consultations with certified epilepsy nurse practitioners. Families also receive personalized seizure diaries, dosing calendars printed in 12 languages, and invitations to quarterly virtual parent forums moderated by pediatric epileptologists from institutions including Cleveland Clinic Children’s, Boston Children’s Hospital, and Texas Children’s Epilepsy Center.
Independent resources remain vital. The Epilepsy Foundation’s “Seizure Tracker” app integrates seamlessly with Terris dosing logs and generates automated PDF reports for neurologist visits. Additionally, the TSC Alliance and Dravet Syndrome Foundation both maintain Terris-specific FAQ portals updated biweekly with peer-reviewed literature summaries and insurance appeal letter templates.
Before initiating Terris, parents should prepare three key questions for their child’s neurologist: (1) What is my child’s current seizure semiology—and how will we define ‘response’ for Terris? (2) Which concomitant ASMs require dose adjustment upon Terris initiation? (3) What specific lab values and timelines will guide our first follow-up visit?
For families already using Terris, consistency remains paramount. A 2024 cohort study in Pediatric Neurology found that children with ≥90% dosing adherence (measured via electronic pill bottle monitors) were 3.1 times more likely to achieve ≥50% seizure reduction at 6 months than those with <80% adherence—even when baseline severity was matched.
It is also critical to recognize that Terris is not indicated for febrile seizures, benign rolandic epilepsy, or absence seizures alone. Off-label use lacks robust evidence and is discouraged outside IRB-approved protocols. Likewise, Terris does not replace rescue benzodiazepines (e.g., Diastat, Nayzilam) for acute cluster management—though its stabilizing effect may reduce cluster frequency over time.
One parent in Austin, TX, shared her experience managing Terris for her 4-year-old daughter with TSC: “We started at 2.5 mg/kg and hit 15 mg/kg by Week 4. Her drop seizures went from 22 a week to zero for 11 weeks straight. The biggest win? She started making eye contact during play for the first time since age 2—and her pediatrician confirmed her language sample increased from 3 to 12 words in spontaneous utterances.” Such qualitative gains underscore why Terris represents more than seizure control—it supports developmental momentum.
Storage matters beyond refrigeration. Terris bottles must be kept upright and protected from light—even brief UV exposure degrades CBD by up to 18% within 4 hours (ZYDUS Stability Report, 2023). Always recap tightly and store in the original carton. Discard unused solution after 90 days, even if refrigerated.
Finally, never discontinue Terris abruptly. Tapering over ≥2 weeks—reducing by no more than 25% every 3–4 days—is required to prevent rebound seizures or status epilepticus. Work closely with your neurology team to develop a written taper plan before considering discontinuation for any reason.
As research evolves, additional indications are being explored. A Phase 2 trial (NCT05284211) is currently enrolling children with CDKL5 deficiency disorder and Pitt-Hopkins syndrome, with preliminary 12-week data showing a 33% median reduction in motor seizures. Results are expected in late 2025.
Terris is not a miracle cure—but for thousands of families navigating treatment-resistant epilepsy, it represents rigorously validated, pediatric-optimized hope. Its development reflects meaningful progress in moving beyond anecdote toward evidence, beyond variability toward precision, and beyond symptom suppression toward developmental thriving.
Always consult your child’s board-certified pediatric neurologist before making changes to seizure management. This article is for informational purposes only and does not constitute medical advice.
