Prescribing guide
Orladeyo (berotralstat)Dosing by age and weight, QTc limits, drug interactions and prior authorization criteria for hereditary angioedemaFor prescribers and their offices treating hereditary angioedema (HAE): what the pharmacy needs before it ships, what the prior authorization wants documented, the titration and the monitoring the label requires.
Dispensing gate
No REMS; Start Form to Empower Patient Services (CareMed Specialty Pharmacy only), prior authorization with C1-INH function and C4 results, and a required pharmacist counseling call before the first shipment.
Example PA threshold
Cigna example: age 2 or older, HAE type I or II with functional C1-INH under 50% of normal and low C4, documented; allergist, immunologist or HAE specialist; no combination prophylaxis.
Monitoring
No required labs; GI effects mostly early and self-limiting; no doses above the prescribed once-daily dose (QTc); review CYP2D6, CYP3A4 and P-gp interactions; weight-based pellet dose under 12.
Support line
Empower Patient Services 1-866-536-7693 (fax 1-844-336-7693), CareMed NCPDP 3306986, copay to as little as $0 for commercial plans, Quick Start while PA is pending.
Give your patient their plan
A one-page handout for starting Orladeyo, in plain language: what the first fill waits on, the first dates, who will call and the symptoms to report, with blank lines for the start date and your office's number. The link opens the patient's full first 90 days page, where their dates become calendar entries.
trialfriend.com/p/orladeyoBefore the first fill: REMS, labs and enrollment
The steps that the pharmacy, the REMS or the drugmaker's program will wait on, in the order they usually need to happen. A first fill of a specialty drug most often stalls on one of these rather than on the plan.
| Step | What it requires | Source |
|---|---|---|
| No REMS | The October 2026 label carries no boxed warning, no contraindications and no REMS, and none of the 5 FDA letters reviewed mentions one. | FDA label |
| Single dispensing channel | Orladeyo is dispensed exclusively through CareMed Specialty Pharmacy as part of Empower Patient Services. Empower runs benefits investigation, appeals and delivery. | Empower, prescriber site |
| Start Form | Digital Start Form, or fax to 1-844-336-7693, or email to Empower, with both sides of the insurance and prescription cards and supporting documentation. Check the Prior Authorization box for PA support. | Orladeyo Start Form |
| Prescription routes | Prescription section of the faxed Start Form, eRx to CareMed (NCPDP 3306986), or a verbal prescription by calling 1-866-536-7693. Emailed prescriptions need verbal confirmation. | Orladeyo Start Form |
| Quick Start | Complete section 4 of the Start Form. BioCryst describes the program as available to insured US patients 2 or older with a confirmed HAE diagnosis, subject to its terms. | Orladeyo Start Form |
| Counseling call | Required. The patient must complete an initial counseling conversation with an Empower pharmacist before Orladeyo can be shipped. | Orladeyo Start Form |
| Pediatric weight | For patients under 12, the Start Form asks for a weight recorded within 3 to 6 weeks of the prescription. | Orladeyo Start Form |
| Letter of medical necessity | Empower provides an LMN guide, and BioCryst suggests progress check-ins within the first 1 to 2 months. | Getting started, prescriber site |
Prior authorization criteria and what to document
One public policy as the example: Cigna, March 1, 2026. Approval approved a year at a time. Renewal needs a documented HAE type I or II diagnosis, a specialist and a favorable response the prescriber reports, such as fewer, milder or shorter attacks. This version took effect March 1, 2026, when Cigna added the pellets and lowered the age to 2. It cites the December 2025 label, before the October 2026 label added 150mg pellets from age 12. Other plans set their own criteria and approval lengths. It is here as an example of what a plan asks for, not as a rule.
| Element | What the policy asks | In the chart | Source |
|---|---|---|---|
| Age | 2 or older | Date of birth on the request | Cigna policy |
| HAE type | Type I or II; HAE with normal C1-INH (type III) does not qualify | Diagnosis in the chart note; ICD-10 D84.1 on the Start Form | Cigna policy |
| C1-INH function | Below 50% of normal at baseline, by the lab's reference values | Lab report, marked documentation required | Cigna policy |
| C4 | Lower than normal at baseline, by the lab's reference values | Lab report, marked documentation required | Cigna policy |
| Prescriber | Allergist or immunologist, or a physician who specializes in HAE or related disorders | Specialty on the request, or the consult note | Cigna policy |
| Combination | Not covered with other HAE prophylaxis such as Cinryze, Haegarda or Takhzyro; on-demand and short-term procedural use of other agents is allowed | Medication list and transition directions | Cigna policy |
| Renewal | Documented HAE type I or II, specialist, and a favorable response per the prescriber (fewer, less severe or shorter attacks); approval for 1 year | Attack log and chart note against the pretreatment baseline | Cigna policy |
| BioCryst checklist | Attack frequency, severity and sites, emergency visits, current and prior HAE therapies with dates and response, family history, LMN and patient impact letter | BioCryst notes most insurers want an updated chart note every 3 to 6 months | Orladeyo Start Form |
Orladeyo dosing and titration
| When | Label | Source |
|---|---|---|
| 12 and older | 150mg orally once daily with food, as a capsule or one 150mg pellet packet. | FDA label |
| 2 to under 12, by weight | Pellets once daily with food: 72mg (12kg to under 24kg), 96mg (24kg to under 32kg), 108mg (32kg to under 40kg), 132mg (40kg or more). | FDA label |
| Pellet administration | Pour the packet into the mouth and swallow with a non-acidic liquid, or sprinkle on about 15mL of soft, non-acidic food at or below room temperature. A meal just before or after. Do not chew or crush; discard if not eaten within 10 minutes. No yogurt or applesauce. | FDA label |
| Hepatic impairment | Child-Pugh A, no change. Child-Pugh B or C: 110mg capsules once daily with food at 12 and older; avoid in ages 2 to under 12. | FDA label |
| Persistent GI reactions | At 12 and older, consider 110mg capsules once daily with food. At 2 to under 12, consider the risks and benefits of continuing. | FDA label |
| Renal impairment | No change for mild to moderate; no change for severe at 12 and older; avoid severe impairment at 2 to under 12. Not recommended in ESRD (CLcr or eGFR under 15, or hemodialysis). | FDA label |
| Missed dose | BioCryst's prescriber FAQ says a forgotten dose may be taken later the same day, with no more than one dose per calendar day. The label itself sets no missed-dose rule. | Orladeyo HCP FAQs |
| Supply | Every capsule strength and pellet packet comes in a 28-day carton: 4 shellpacks of 7 capsules, or 4 wallets of 7 packets. Refills fall about every 28 days. | FDA label |
| Pharmacokinetics | Steady state in about 6 to 12 days, about 5-fold accumulation, median half-life about 93 hours. Pellets and capsules gave no clinically significant exposure difference at the adult dose. | FDA label |
| Label alignment | The capsule NDA was aligned with the new pellet labeling on December 23, 2025 (S-005), 12 days after the pellet NDA was approved. | FDA letter |
Monitoring the Orladeyo label requires
| When | What | What the label says to do with it | Source |
|---|---|---|---|
| Any time | Doses above the prescribed once-daily dose | Not recommended; QTc increase observed above 150mg daily in adults, concentration dependent | FDA label |
| Early weeks | Abdominal pain, vomiting, diarrhea | At 150mg: abdominal pain 23% vs 10%, vomiting 15% vs 3%, diarrhea 15% vs 0; mostly early, less frequent over time, typically self-resolved; no GI discontinuations at 150mg | FDA label |
| As indicated | Transaminases | One patient on 150mg discontinued for asymptomatic ALT above 8 times ULN with normal bilirubin; no patient on 110mg or placebo exceeded 3 times ULN | FDA label |
| First 1 to 2 months | Follow-up visit | BioCryst suggests progress check-ins within the first 1 to 2 months; the label sets no visit schedule | Getting started, prescriber site |
| Under 12 | Body weight | Dose band changes at 24kg, 32kg and 40kg; BioCryst asks for a weight within 3 to 6 weeks of each prescription | Orladeyo Start Form |
| Efficacy reference | Attack rate | Trial 1: 1.31 attacks per 28 days on 150mg vs 2.35 on placebo, a 44.2% reduction (95% CI 23.0 to 59.5), seen from the first month | FDA label |
Orladeyo drug interactions and contraindications
| Label category | Agents and what the label says | Source |
|---|---|---|
| P-gp inducers | Avoid; they may lower berotralstat levels and reduce efficacy. Berotralstat is a P-gp and BCRP substrate. | FDA label |
| P-gp and BCRP inhibitors | The earlier advice to reduce to 110mg with P-gp or BCRP inhibitors was removed in November 2023 (S-002). | FDA letter |
| Cyclosporine | A P-gp and BCRP inhibitor; berotralstat Cmax fell 7% and AUC rose 24% to 27%. The current label sets no dose change. | FDA label |
| CYP2D6 and CYP3A4 substrates | Berotralstat 150mg is a moderate inhibitor of both. For narrow-margin substrates, closely monitor or modify the substrate dose. | FDA label |
| Desogestrel | Etonogestrel AUC rose 2.6-fold with berotralstat 150mg; consider benefits and risks of the combination. | FDA label |
| P-gp substrates | At twice the maximum dose berotralstat inhibits P-gp; monitor or modify narrow-margin P-gp substrates. It is not a BCRP inhibitor (rosuvastatin exposure fell about 20%). | FDA label |
| CYP2C9 and CYP2C19 | Weak inhibitor at 150mg once daily. | FDA label |
| Pregnancy and lactation | Insufficient human pregnancy data; no data on human milk, with pup plasma about 2% of maternal in rats. | FDA label |
Why a first fill stalls, and the fix
- Prior authorization pending or deniedCigna asks for HAE type I or type II with functional C1 inhibitor below 50% of normal and a low C4 level, both documented. It also wants an allergist, immunologist or HAE specialist. The policy marks both lab results as required documents, so the office sends the reports.
- HAE with normal C1 inhibitorCigna's policy says HAE with normal C1 inhibitor, sometimes called type III, does not meet its criteria. BioCryst's Start Form notes most insurers want extra records for this diagnosis, such as how other causes were ruled out. The allergist's office decides what records to send with the request.
- Orladeyo with another prevention medicineCigna lists Orladeyo taken alongside another HAE prevention therapy, such as Takhzyro, Haegarda or Cinryze, as not medically necessary. The same policy allows other medicines for on-demand treatment and short-term procedure prophylaxis.
- The first box has not shippedBioCryst's Start Form says Orladeyo cannot ship until the patient finishes a counseling call with an Empower pharmacist. Calling Empower back at 1-866-536-7693 is usually the fix.
- A copay you cannot payWith commercial insurance, BioCryst's copay program can bring the cost to as little as $0. It is not valid for prescriptions paid in whole or in part by federal or state programs, such as Medicare or Medicaid. Our help paying page lists charity funds that may cover costs.
Empower Patient Services (BioCryst, with CareMed Specialty Pharmacy)
- A specialty pharmacy and support team in one, with a dedicated patient support manager reachable by phone, text or email
- Copay Assistance Program, as little as $0 for treatment, not valid for prescriptions paid in whole or in part by federal or state programs
- Help with the insurance process, plus refill reminders and shipments coordinated by time and place
- On average, a first shipment in less than a week after Empower Patient Services receives the prescription
- An online portal for monthly refills, medication reminders and progress tracking
- Quick Start program, for insured US patients 2 or older with a confirmed HAE diagnosis, subject to its terms, while the approval is pending Orladeyo Start Form
- Appeal specialists for insurance appeals, and pharmacists available 24/7 for clinical questions Empower, prescriber site
Questions prescribers' offices ask about Orladeyo
What is the Orladeyo dose by age and weight?
150mg orally once daily with food for patients 12 and older, as a capsule or a 150mg pellet packet, per the October 2026 label. Ages 2 to under 12 take oral pellets by weight: 72mg for 12kg to under 24kg, 96mg for 24kg to under 32kg, 108mg for 32kg to under 40kg and 132mg for 40kg or more.
Why are extra Orladeyo doses not allowed?
QTc prolongation was observed in adults at doses above 150mg once daily and was concentration dependent, per the October 2026 label (section 5.1). At 3 times the maximum dose, mean QTcF rose 15.9 msec. Orladeyo is not for acute attacks; patients keep their usual rescue medication.
When does the label call for the 110mg capsule?
Two situations, per the October 2026 label (sections 2.3 and 2.4): moderate or severe hepatic impairment (Child-Pugh B or C) in patients 12 and older, and persistent GI adverse reactions, where 110mg once daily may be considered. In patients 2 to under 12, avoid use with Child-Pugh B or C; for persistent GI effects, weigh continuing.
Does Orladeyo have a REMS or required labs?
No. The October 2026 label has no REMS, no boxed warning, no contraindications and no required monitoring labs. The gates before the first shipment are prior authorization and a pharmacist counseling call from Empower Patient Services, which dispenses through CareMed Specialty Pharmacy only.
What do insurers ask for to approve Orladeyo?
The Cigna policy shown here, effective March 1, 2026, asks for age 2 or older, HAE type I or II with functional C1-INH below 50% of normal and low C4 (both documented), and an allergist, immunologist or HAE specialist. It approves 1 year at a time, excludes HAE with normal C1-INH and combination prophylaxis, and cites the December 2025 label.
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Sources
- ORLADEYO- berotralstat hydrochloride capsule; ORLADEYO- berotralstat hydrochloride pellet: prescribing information, revised 10/2026, and Patient Information, issued 10/2026, BioCryst Pharmaceuticals Inc., via DailyMed, 2026-10-23.
- Empower Patient Services | ORLADEYO (berotralstat) Patient Support, BioCryst Pharmaceuticals, Inc., 2026-11-10.
- Hereditary Angioedema (HAE) FAQs | ORLADEYO (berotralstat), BioCryst Pharmaceuticals, Inc., 2026-11-10.
- Empower Patient Services | ORLADEYO (berotralstat), BioCryst Pharmaceuticals, Inc., 2026-11-10.
- Prescribing ORLADEYO (berotralstat) | HAE Prophylactic Therapy, BioCryst Pharmaceuticals, Inc., 2026-11-10.
- Getting started with ORLADEYO, Start Form and Documentation Checklist (US.ORL.03422 07/26), BioCryst Pharmaceuticals, Inc., 2026-07.
- ORLADEYO (berotralstat) FAQs | HAE Oral Treatment, BioCryst Pharmaceuticals, Inc., 2026-11-10.
- BioCryst Announces U.S. FDA Approval of ORLADEYO 150 mg Oral Pellets for Adults and Adolescents with HAE, BioCryst Pharmaceuticals, Inc., via GlobeNewswire, 2026-10-21.
- Drug Coverage Policy IP0096, Hereditary Angioedema, Orladeyo, Cigna, 2026-03-01.
- Hereditary angioedema: MedlinePlus Genetics, U.S. National Library of Medicine, 2024-03-11.
- NDA 214094/S-006 supplement approval letter, alignment with the oral pellet labeling approved under NDA 219776/S-003, FDA, 2026-10-16.
- NDA 219776 approval letter, Orladeyo (berotralstat) oral pellets for pediatric patients 2 to less than 12 years, FDA, 2025-12-11.
- NDA 214094/S-005 supplement approval letter, alignment with the NDA 219776 oral pellet labeling, FDA, 2025-12-23.
- NDA 214094/S-003 supplement approval letter, nausea added as a postmarketing adverse reaction, FDA, 2024-10-21.
- NDA 214094/S-002 supplement approval letter, P-gp and BCRP inhibitor dose advice removed and desogestrel interaction added, FDA, 2023-11-21.
- Drugs@FDA records for NDA 214094 (Orladeyo capsules) and NDA 219776 (Orladeyo oral pellets), via openFDA, FDA, 2026-11-10.
A reference drawn from the October 23, 2026 label, the drugmaker's published program and one public insurer policy shown as an example, checked on November 10, 2026. Labels and policies change; the label on DailyMed and the plan's current policy govern. Trial Friend is not a medical provider. It reports what these documents say and does not judge whether a drug is safe or right for any patient; that is the prescriber's decision. Not a substitute for the prescribing information.