Prescribing guide
Pombiliti + Opfolda (cipaglucosidase alfa-atga + miglustat)Weight-based dosing, treatment day timing, renal adjustment, infusion rate steps and prior authorization criteria for late-onset Pompe diseaseFor prescribers and their offices treating pompe disease: 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. Boxed warning: CPR equipment and medical support readily available at every infusion. Verify pregnancy status before initiating (contraindicated in pregnancy). Prior authorization for both products and a site of care before the first treatment day.
Example PA threshold
Cigna example: 18 or older; more than 40kg; used with Opfolda; no improvement in objective measures (FVC, 6MWT) after at least 1 year on Lumizyme or Nexviazyme; deficient GAA activity or biallelic pathogenic or likely pathogenic GAA variants; specialist prescriber.
Monitoring
Supervised infusion with anaphylaxis readiness at every dose; consider premedication, and pretreat if it was used with prior ERT; more frequent vitals in patients prone to fluid overload or with compromised cardiorespiratory function; CLcr for the Opfolda dose.
Support line
Amicus Assist 1-833-AMICUS-A (1-833-264-2872), Monday to Friday 8AM to 8PM ET; Patient Referral Form by fax 1-833-264-2873; co-pay assistance for eligible commercial patients; Amicus Patient Assistance Program.
Give your patient their plan
A one-page handout for starting Pombiliti + Opfolda, 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/pombilitiopfoldaBefore 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 |
|---|---|---|
| Send the Patient Referral Form | Complete the PRF and fax it to Amicus Assist at 1-833-264-2873. A Case Manager contacts the office and the patient, confirms whether prior authorization is required and explains financial assistance options. | Pombiliti + Opfolda support page (HCP) |
| Specialty pharmacy or direct purchase | Depending on treatment setting, Amicus Assist triages the PRF to the specialty pharmacy, which confirms the prescription and ancillary supplies with the office, or reviews the Direct Purchase process with the prescriber. | Pombiliti + Opfolda support page (HCP) |
| Network and distributors | Limited specialty pharmacy network: Accredo, CVS Specialty, Orsini. Specialty distributors: AmerisourceBergen Specialty Distribution, Cardinal Health SPD, CuraScript SD, McKesson Specialty Care Distribution, McKesson Plasma and Biologics (2023 ordering sheet). | Product ordering information |
| Pregnancy status | Verify pregnancy status in females of reproductive potential before initiating. Advise effective contraception during treatment and for at least 60 days after the last dose. | Pombiliti FDA label |
| Renal function | Opfolda dose depends on CLcr by Cockcroft-Gault as well as weight; reduce at CLcr 15 to 59mL/minute. | Opfolda FDA label |
| Pombiliti supply | 105mg single-dose vials in cartons of 1, 10 or 25 (NDC 71904-200-01, -02, -03). Store refrigerated at 2°C to 8°C in the original carton, protected from light; do not freeze. | Pombiliti FDA label |
| Calculate vials | Amicus: body weight (kg) x 20mg/kg, divided by 105mg per vial; if the result includes a fraction, round up to the next whole number. | Guide to Getting Started (HCP) |
| Opfolda supply | 65mg capsules in bottles of 4, 24 or 100 (NDC 71904-300-01, -02, -03). Store at 20°C to 25°C in the original container, protected from light. | Opfolda FDA label |
| Reconstitute | Let vials sit about 30 minutes at room temperature. Add 7.2mL Sterile Water for Injection down the inside wall; roll and tilt, do not invert, swirl or shake; yields 15mg/mL. Up to 24 hours at 2°C to 8°C if not used at once. | Pombiliti FDA label |
| Dilute | Withdraw 7mL per vial into 0.9% Sodium Chloride Injection to the Table 1 volume (250mL to 700mL by weight); final 0.5 to 4mg/mL. No pneumatic tube. Diluted solution up to 16 hours at 2°C to 8°C; infuse within 6 hours of removal. | Pombiliti FDA label |
| Billing codes | HCPCS J1203, injection, cipaglucosidase alfa-atga, 5mg, and G0138 for the infusion including supervised oral miglustat, as listed in the Cigna Pombiliti policy. | Cigna Pombiliti policy |
| Opfolda code | HCPCS J1202, miglustat, oral, 65mg, as listed in the Cigna Opfolda policy. Opfolda needs its own prior authorization under IP0598. | Cigna Opfolda policy |
| Co-pay assistance | Eligible commercially or privately insured patients may pay as little as $0 per month, subject to annual maximum limits. Not valid with Medicare, Medicaid, VA, TRICARE, DoD or similar programs. Infusion-related costs not covered for RI residents. | Pombiliti + Opfolda support page (HCP) |
| Patient Assistance Program | The Amicus Patient Assistance Program provides free product to eligible uninsured or underinsured patients. Amicus Assist can also identify independent charitable foundations. | Pombiliti + Opfolda support page (HCP) |
Prior authorization criteria and what to document
One public policy as the example: Cigna, August 15, 2026. Approval one year. This policy (Drug Coverage Policy IP0591) covers Pombiliti and added documentation requirements on August 15, 2026. Cigna reviews Opfolda under a matching policy, IP0598, effective July 15, 2026. IP0591 cites the July 2024 Pombiliti label, which is still the current text. 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 and weight | Patient is 18 years of age or older and weighs more than 40kg (policy wording; the label says 40kg or more) | Date of birth and current weight in the note | Cigna Pombiliti policy |
| Combination use | The medication will be used in combination with Opfolda (miglustat capsules) | Both orders on the request | Cigna Pombiliti policy |
| Not improving on ERT | No improvement in objective measures after at least one year on Lumizyme or Nexviazyme; examples are FVC and 6MWT | Serial FVC and 6MWT results with dates and ERT history | Cigna Pombiliti policy |
| Diagnosis, enzyme route | Late-onset Pompe disease with deficient acid alpha-glucosidase activity in blood, fibroblasts or muscle tissue [documentation required] | Enzyme assay report | Cigna Pombiliti policy |
| Diagnosis, genetic route | Biallelic pathogenic or likely pathogenic GAA variants [documentation required]; either route qualifies | Genetic test report | Cigna Pombiliti policy |
| Prescriber | Geneticist, neurologist, metabolic disorder sub-specialist or lysosomal storage disorder specialist, or in consultation with one | Prescriber specialty or consult note | Cigna Pombiliti policy |
| Dosing | Each dose must not exceed 20mg/kg IV no more frequently than once every 2 weeks. Other doses case by case | Order with current weight | Cigna Pombiliti policy |
| Opfolda request | Separate policy IP0598 with the same criteria A to F; Gaucher disease is listed as not covered for Opfolda | Second prior authorization request | Cigna Opfolda policy |
| Approval | 1 year; extended approvals if criteria and dosing still met | Updated criteria at each review | Cigna Pombiliti policy |
Pombiliti + Opfolda dosing and titration
| When | Label | Source |
|---|---|---|
| Pombiliti | 20mg/kg of actual body weight IV every other week over approximately 4 hours. Must be given with Opfolda. | Pombiliti FDA label |
| Opfolda | 50kg or more: 260mg orally every other week. 40kg to under 50kg: 195mg. 65mg capsules, swallowed whole with unsweetened beverages only. | Opfolda FDA label |
| Opfolda, renal | CLcr 30 to 59 or 15 to 29mL/minute: 195mg at 50kg or more; 130mg at 40kg to under 50kg. CLcr 60 to 89: no change. ESRD: effect on miglustat pharmacokinetics unknown. | Opfolda FDA label |
| Sequence | Fast at least 2 hours before Opfolda. Start Pombiliti approximately 1 hour after Opfolda. Continue fasting until 2 hours after Opfolda. | Opfolda FDA label |
| Switching | Start 2 weeks after the last ERT dose. | Pombiliti FDA label |
| Rate | 1mg/kg/hour, then up by 2mg/kg/hour every 30 minutes if no hypersensitivity or IARs, to a maximum of 7mg/kg/hour; maintain until complete. | Pombiliti FDA label |
| Volume by weight | 40 to 50kg: 250mL. 50.1 to 60kg: 300mL. 60.1 to 100kg: 500mL. 100.1 to 120kg: 600mL. 120.1 to 140kg: 700mL. | Pombiliti FDA label |
| Administration set | Inline low protein binding 0.2 micron filter; change if blocked. Do not infuse in the same line with other products. | Pombiliti FDA label |
| Before infusion | Consider antihistamines, antipyretics and/or corticosteroids. If premedication was used with previous ERT, pretreat before Pombiliti. | Pombiliti FDA label |
| Infusion delay | Start must not exceed 3 hours from Opfolda. Otherwise reschedule both at least 24 hours after Opfolda was last taken. | Pombiliti FDA label |
| Missed Opfolda | Do not administer Pombiliti; reschedule at least 24 hours after Opfolda was last taken. If both are missed, restart as soon as possible. | Opfolda FDA label |
| Mild or moderate reaction | Consider holding or slowing and treat. If symptoms persist, stop 30 to 60 minutes and consider resuming at a reduced rate; if they still persist, discontinue and consider re-initiating within 7 to 14 days with premedication. | Pombiliti FDA label |
| After symptoms subside | Increase to the rate at which the reaction occurred, then consider stepwise increases every 30 minutes to the target rate. Monitor closely. | Pombiliti FDA label |
| Severe reaction | Discontinue immediately and treat. Weigh readministration; rechallenge at slower rates, and desensitization may be considered after severe hypersensitivity. | Pombiliti FDA label |
| Pediatric, hepatic | Not established in pediatric patients with LOPD. Effect of hepatic impairment on miglustat pharmacokinetics is unknown. | Opfolda FDA label |
Monitoring the Pombiliti + Opfolda label requires
| When | What | What the label says to do with it | Source |
|---|---|---|---|
| Before initiating | Pregnancy status in females of reproductive potential | Contraindicated in pregnancy; contraception during treatment and for at least 60 days after the last dose | Pombiliti FDA label |
| Before initiating | Creatinine clearance (Cockcroft-Gault) | Miglustat AUC rose 21%, 32% and 41% in mild, moderate and severe impairment; reduce Opfolda at CLcr 15 to 59mL/minute | Opfolda FDA label |
| Each infusion | Hypersensitivity, including anaphylaxis: dyspnea, rash, hypotension, bronchospasm, edema, pharyngeal edema, tongue swelling | 27% had hypersensitivity in trials, 3% severe, a further 3% anaphylaxis. If severe, discontinue and treat immediately | Pombiliti FDA label |
| During and hours after | IARs, more likely at higher infusion rates; 32% (48) across trials | 4 patients (3%) reported 11 severe IARs. Acute underlying illness raises risk; advanced disease raises risk of severe complications | Pombiliti FDA label |
| Each infusion, at-risk patients | Vital signs in patients prone to fluid overload, or with acute respiratory illness or compromised cardiac or respiratory function | More frequent vitals; some may need prolonged observation | Pombiliti FDA label |
| Ongoing | Anti-drug antibodies | ERT-experienced patients (N=65): ADA in 85% at baseline and 89% at week 52. No clear trend between IgE and IARs; effect on effectiveness unknown. Cross-reactive with alglucosidase alfa | Pombiliti FDA label |
Pombiliti + Opfolda drug interactions and contraindications
| Label category | Agents and what the label says | Source |
|---|---|---|
| Contraindications | Pregnancy, for Pombiliti in combination with Opfolda | Pombiliti FDA label |
| Drug interactions | Neither label has a drug interactions section. In vitro, miglustat is not a known substrate or inhibitor of the CYP enzymes tested; it is a substrate of P-gp, OCT1 and OCT2 and an inhibitor of MATE1 | Opfolda FDA label |
| Food | Co-administration of miglustat with food is predicted to delay absorption and decrease Cmax; hence the fasting window | Opfolda FDA label |
| Other Pompe therapy | Each product is indicated only in combination with the other. Amicus: neither should be taken with another Pompe treatment | Guide to Getting Started (HCP) |
| Lactation | Breastfeeding not recommended. No human milk data; cipaglucosidase alfa-atga and miglustat were present in rat milk | Pombiliti FDA label |
| Fertility | May impair female and male fertility, based on preimplantation loss in rats given the combination | Pombiliti FDA label |
| Geriatric | 17 patients (11%) were 65 to 74 and none were 75 or older in trials; too few to detect a difference in response | Pombiliti FDA label |
Why a first fill stalls, and the fix
- Prior authorization pending or deniedThe Cigna policy below asks for a lab report showing low GAA enzyme activity in blood, skin cells or muscle, or a genetic test showing changes in both GAA genes.
- No record that the current treatment is not workingCigna asks that measured results, such as forced vital capacity or the 6-minute walk test, have not improved after at least 1 year on Lumizyme or Nexviazyme.
- Only one of the 2 medicines is approvedCigna reviews Pombiliti and Opfolda under separate policies with matching criteria. Each policy requires that the medicine be used with the other one.
- Age or weight outside the policyCigna approves adults 18 or older who weigh more than 40kg (about 88 lb), while the label's own wording is 40kg or more.
- The doctor is not a specialistCigna asks that each medicine be prescribed by, or with advice from, a geneticist, neurologist, metabolic specialist or lysosomal storage disorder specialist.
- A dose outside the plan's limitCigna approves up to 20mg/kg of Pombiliti, no more often than once every 2 weeks, and other doses are reviewed case by case.
- A pharmacy that cannot fill itAmicus lists a limited specialty pharmacy network of Accredo, CVS Specialty and Orsini. It also lists specialty distributors for sites that order directly.
- A copay you cannot payCommercial or private insurance: Amicus says eligible patients may pay as little as $0 per month, up to an annual maximum. The offer excludes Medicare, Medicaid, Veterans Administration, TRICARE and similar federal or state programs.
- Infusion costs in Rhode IslandAmicus says its co-pay help does not cover infusion-related costs for people who live in Rhode Island, in line with state law.
- No insurance, or not enough coverageThe Amicus Patient Assistance Program provides free product to eligible uninsured or underinsured people, and Amicus Assist gives details at 1-833-264-2872.
Amicus Assist
- A Case Manager who confirms whether a prior authorization is needed and explains eligibility and possible financial help
- A Patient Education Liaison who can help you prepare for each treatment day Pombiliti + Opfolda patient support page
- Co-pay assistance for eligible people with commercial or private insurance, who may pay as little as $0 per month, up to an annual maximum
- Co-pay help is not valid with Medicare, Medicaid, Veterans Administration, TRICARE, Department of Defense or similar federal or state programs
- The Amicus Patient Assistance Program, free product for eligible uninsured or underinsured people
- Help finding independent charitable foundations, which set their own rules and decide their own support
- Spanish-speaking Case Managers at the same number Product ordering information
- The MyDay Pompe app for treatment day, from the App Store or Google Play Pombiliti + Opfolda patient support page
Questions prescribers' offices ask about Pombiliti + Opfolda
What is the Pombiliti + Opfolda dose for late-onset Pompe disease?
The July 2024 labels (Pombiliti DailyMed version 8, August 2026; Opfolda version 5, November 2024) set Pombiliti 20mg/kg of actual body weight IV every other week, with Opfolda 260mg orally at 50kg or more or 195mg at 40kg to under 50kg. Indicated for adults weighing 40kg or more who are not improving on their current ERT. Start 2 weeks after the last ERT dose.
When is Opfolda taken relative to the Pombiliti infusion?
About 1 hour before the infusion starts, per the July 2024 labels, with no food or other beverages for at least 2 hours before and 2 hours after the capsules. Capsules are swallowed whole with unsweetened beverages only. If the infusion cannot start within 3 hours of Opfolda, reschedule both at least 24 hours after Opfolda was last taken.
How is Opfolda dosed in renal impairment?
The July 2024 Opfolda label reduces the dose to 195mg at 50kg or more and 130mg at 40kg to under 50kg for CLcr 15 to 59mL/minute by Cockcroft-Gault. No adjustment at CLcr 60 to 89mL/minute. The label says the effect of end stage renal disease on miglustat pharmacokinetics is unknown.
What are the Pombiliti infusion rate steps?
The July 2024 Pombiliti label starts at 1mg/kg/hour and increases by 2mg/kg/hour every 30 minutes, to 3, 5 and then a maximum of 7mg/kg/hour, if there are no signs of hypersensitivity or IARs. Total duration is approximately 4 hours. Table 1 gives mL/hour by weight band for 250mL to 700mL bags.
What are the Pombiliti + Opfolda prior authorization criteria?
Cigna policy IP0591, effective August 15, 2026, approves 1 year for adults 18 or older weighing more than 40kg, used with Opfolda. It requires no improvement in objective measures after at least 1 year on Lumizyme or Nexviazyme, documented GAA deficiency or biallelic GAA variants, and a specialist prescriber. Opfolda is reviewed under the matching policy IP0598.
Free email alert
Get an email when the Pombiliti + Opfolda label changes
One email the day the FDA revises the Pombiliti + Opfolda prescribing information, with a summary of what changed. No trial alerts or newsletter, and you can stop anytime.
Label changes for Pombiliti + Opfolda only, usually a few a year and some years none. Stop anytime. We never share your email. Privacy policy
Sources
- POMBILITI (cipaglucosidase alfa-atga) for injection, for intravenous use, prescribing information, Revised: 7/2024 (SPL version 8, effective August 12, 2026), Amicus Therapeutics US, LLC, via DailyMed and openFDA, 2026-08-12.
- OPFOLDA (miglustat) capsules, for oral use, prescribing information and Patient Information, Revised: 7/2024 (SPL version 5, effective November 27, 2024), Amicus Therapeutics US, LLC, via DailyMed and openFDA, 2024-11-27.
- POMBILITI (cipaglucosidase alfa-atga) for injection, for intravenous use, prescribing information, Initial U.S. Approval: 2023, FDA, Drugs@FDA, 2023-09-28.
- How To Take - Pombilitiopfolda Patient, Amicus Therapeutics, 2026-07.
- Support + Resources / Support And Tools - Pombilitiopfolda Patient, Amicus Therapeutics, 2026-07.
- Support + Resources - Pombilitiopfolda HCP, Amicus Therapeutics, 2026-02.
- Guide to Getting Started: Treatment Day Checklist and Frequently Asked Questions for Healthcare Providers (PP-AT-US-0004-0125), Amicus Therapeutics, 2025-02.
- POMBILITI + OPFOLDA Product Ordering Information (PP-AT-US-0017-0523), Amicus Therapeutics, 2023.
- Pompe Disease – Enzyme Replacement Therapy – Pombiliti, Drug Coverage Policy IP0591, Cigna, 2026-08-15.
- Pompe Disease – Enzyme Stabilization Therapy – Opfolda, Drug Coverage Policy IP0598, Cigna, 2026-07-15.
- BioMarin Completes Acquisition of Amicus Therapeutics, BioMarin Pharmaceutical Inc., via BioSpace press releases, 2026-04-27.
- BLA 761204/S-004 supplement approval letter, Pombiliti (cipaglucosidase alfa-atga), FDA, 2024-07-25.
- NDA 215211/S-002 supplement approval letter, Opfolda (miglustat) capsules, FDA, 2024-07-25.
- BLA 761204 approval letter, Pombiliti (cipaglucosidase alfa-atga), FDA, 2023-09-28.
- NDA 215211 approval letter, Opfolda (miglustat) capsules, FDA, 2023-09-28.
A reference drawn from the August 12, 2026 label, the drugmaker's published program and one public insurer policy shown as an example, checked on November 11, 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.
The author has done professional work for companies whose products are discussed in this article. No company reviewed, paid for or had any input into it.