MIPLYFFA arimoclomol citrate 47 mg Capsule, 90-count
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Other nervous system drugs class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
Arimoclomol is used in combination with miglustat to treat neurologic symptoms in adults and children 2 years of age and older who have Niemann-Pick disease type C (NPC; an inherited disease in which a certain fatty substance is not broken down and used normally in the body and instead builds up in some organs and can cause nerve and brain problems). Arimoclomol is in a class of medications called heat shock protein activators. It is not known exactly how arimoclomol works to treat neurologic symptoms in patients with Niemann-Pick disease type C.
Read the full MedlinePlus article ↗- Niemann-Pick disease type C (NPC) is a rare inherited condition where the body cannot properly move cholesterol and certain fats inside cells. Over time this damages the brain and...
- What exactly is Niemann-Pick disease type C, and how does Miplyffa help?
- No — Miplyffa is only approved to be used together with miglustat, not on its own. Both medicines work as a combination for treating NPC. Make sure you're taking both as your docto...
- The most common side effects are upper respiratory infections (like colds), diarrhea, and some weight loss. These are generally manageable. What you really want to watch for — espe...
Patient education
Supplement & herbal interactions
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
💊 What it looks like
Where does this data come from?
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
-
UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
-
UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
2 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $457.27 | $41,154.07 / 90 capsules |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Miplyffa 47 mgthis 72542-0147-01 | Acer | 90 capsules | — | — | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 11045460 ↗ | Method of use | U-4021 | Aug 19, 2029 |
| US 11045460 ↗ | Method of use | U-4021 | Aug 19, 2029 |
| US 11045460 ↗ | Method of use | U-4021 | Aug 19, 2029 |
| US 11045460 ↗ | Method of use | U-4021 | Aug 19, 2029 |
| US 9884058 ↗ | Method of use | U-4021 | Jun 26, 2029 |
| US 9884058 ↗ | Method of use | U-4021 | Jun 26, 2029 |
| US 9884058 ↗ | Method of use | U-4021 | Jun 26, 2029 |
| US 9884058 ↗ | Method of use | U-4021 | Jun 26, 2029 |
| US 9289472 ↗ | Method of use | U-4021 | Aug 11, 2029 |
| US 9289472 ↗ | Method of use | U-4021 | Aug 11, 2029 |
| US 9289472 ↗ | Method of use | U-4021 | Aug 11, 2029 |
| US 9289472 ↗ | Method of use | U-4021 | Aug 11, 2029 |
| US 11707456 ↗ | Drug substance | U-4021 | Nov 19, 2041 |
| US 11707456 ↗ | Drug substance | U-4021 | Nov 19, 2041 |
| US 11707456 ↗ | Drug substance | U-4021 | Nov 19, 2041 |
| US 11707456 ↗ | Drug substance | U-4021 | Nov 19, 2041 |
| Code | What it grants | Expires |
|---|---|---|
| NCE | New Chemical Entity (5-year) | Sep 20, 2029 |
| ODE-496 | Orphan Drug Exclusivity (7-year) | Sep 20, 2031 |
| NCE | New Chemical Entity (5-year) | Sep 20, 2029 |
| ODE-496 | Orphan Drug Exclusivity (7-year) | Sep 20, 2031 |
| NCE | New Chemical Entity (5-year) | Sep 20, 2029 |
| ODE-496 | Orphan Drug Exclusivity (7-year) | Sep 20, 2031 |
| NCE | New Chemical Entity (5-year) | Sep 20, 2029 |
| ODE-496 | Orphan Drug Exclusivity (7-year) | Sep 20, 2031 |
Is there a generic version of MIPLYFFA 47 MG CAPSULE?
The FDA approved a generic — why can’t I get it at my pharmacy yet?
Why do different websites show different generic release dates?
What does “FDA listed” mean?
What does a patent or protection date mean here?
What does “current Orange Book estimate” mean?
Can a generic come out before the last patent expires?
Can a generic come out after the listed dates?
What is the difference between patents and exclusivity?
Why are there multiple patent dates?
Where does this data come from?
📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Reporter sex
Where does this data come from?
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 72542-0147-01 You're viewing this | 1 BOTTLE in 1 CARTON (72542-147-01) / 90 CAPSULE in 1 BOTTLE | 2024-09-20 | Active |
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
Questions about this listing
Why is there no price listed?
Is the NDC printed on the package the same as the 11-digit billing NDC?
What do the three segments of this NDC mean?
Is this package still being marketed?
Who lists this product with the FDA?
Do I need a prescription for this product?
Where does this data come from?
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE MIPLYFFA is indicated for use in combination with miglustat for the treatment of neurological manifestations of Niemann-Pick disease type C (NPC) in adult and pediatric patients 2 years of age and older. MIPLYFFA is indicated for use in combination with miglustat for the treatment of neurological manifestations of Niemann-Pick disease type C (NPC) in adult and pediatric patients 2 years of age and older. ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Recommended MIPLYFFA oral dosage, in combination with miglustat, for patients with actual body weight of ( 2.1 ): 8 kg to 15 kg, is 47 mg three times a day > 15 kg to 30 kg, is 62 mg three times a day > 30 kg to 55 kg, is 93 mg three times a day > 55 kg, is 124 mg three times a day Administer with or without food. ( 2.1 ) See full prescribing information for recommended dosage in patients with an eGFR ≥ 15 to < 50 mL/minute. ( 2.2 ) See full prescribing information for instructions on preparation and administration.
( 2.3 )
2.1Recommended Dosage The recommended oral dosage of MIPLYFFA, in combination with miglustat, for patients with an actual body weight of: 8 kg to 15 kg, is 47 mg three times a day > 15 kg to 30 kg, is 62 mg three times a day > 30 kg to 55 kg, is 93 mg three times a day > 55 kg, is 124 mg three times a day Administer MIPLYFFA with or without food. Missed Dose If a dose of MIPLYFFA is missed, advise the patient to skip the missed dose and to resume taking the prescribed dose at the next scheduled time.
2.2Recommended Dosage in Patients with Renal Impairment The recommended dosage of MIPLYFFA, in combination with miglustat, in patients with an eGFR ≥ 50 mL/minute is the same as the recommended dosage in patients with normal renal function [see Dosage and Administration ( 2.1 )]. For patients with an eGFR ≥ 15 to < 50 mL/minute, the recommended oral dosage of MIPLYFFA, in combination with miglustat, for patients with an actual body weight of [see Use in Specific Populations ( 8.6 ) and Clinical Pharmacology ( 12.3 )] : 8 kg to 15 kg, is 47 mg two times a day > 15 kg to 30 kg, is 62 mg two times a day > 30 kg to 55 kg, is 93 mg two times a day > 55 kg, is 124 mg two times a day Administer MIPLYFFA with or without food.
2.3Preparation and Administration Instructions Swallow MIPLYFFA whole. However, for patients who have difficulty swallowing capsules, administer MIPLYFFA in one of two ways: Oral Administration Carefully open the capsule and sprinkle the entire contents into 15 mL of water or apple juice or 15 mL of soft food (e.g., applesauce, pudding, or yogurt). Stir the mixture for 15 seconds.
Consume the entire mixture immediately. Feeding Tube Administration (nasogastric or gastric tube) Carefully open the capsule and sprinkle the entire contents into 20 mL of water. Do not add the capsule contents to other liquids besides water.
Stir the mixture for 15 seconds. Administer the entire mixture immediately via feeding tube. Flush the feeding tube with 5 mL of water after administration.
Do not save the mixture for later use.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS MIPLYFFA (arimoclomol) capsules are available as follows: MIPLYFFA Strength Description of Capsules 47 mg White opaque body with black printing “47”, and green opaque cap with black printing “OZ” 62 mg White opaque body with black printing “62”, and yellow opaque cap with black printing “OZ” 93 mg White opaque body with black printing “93”, and orange opaque cap with black printing “OZ” 124 mg White opaque body with black printing “124”, and red opaque cap with black printing “OZ” Capsules: 47 mg, 62 mg, 93 mg and 124 mg of arimoclomol.
( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS None. None. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Hypersensitivity Reactions : Urticaria and angioedema have been reported. Discontinue MIPLYFFA in patients who develop these adverse reactions. ( 5.1 ) Embryofetal Toxicity : May cause fetal harm.
Advise pregnant females of the potential risk to the fetus and consider pregnancy planning and prevention. ( 5.2 ) Increased Creatinine without Affecting Glomerular Function: Mean increases in serum creatinine of 10-20% have been reported. Use alternative measures to assess renal function which are not based on creatinine.
( 5.3 )
5.1Hypersensitivity Reactions Hypersensitivity reactions such as urticaria and angioedema have been reported in patients treated with MIPLYFFA during Trial 1 [see Clinical Studies ( 14 )] : two patients reported both urticaria and angioedema (6%) and one patient (3%) experienced urticaria alone. The reactions occurred within the first two months of treatment. Discontinue MIPLYFFA in patients who develop severe hypersensitivity reactions.
If a mild or moderate hypersensitivity reaction occurs, stop MIPLYFFA and treat promptly. Monitor the patient until signs and symptoms resolve [see Adverse Reactions ( 6.1 )].
5.2Embryofetal Toxicity Based on findings from animal reproduction studies, MIPLYFFA may cause embryofetal harm when administered during pregnancy. In animal reproduction studies, oral administration of arimoclomol to pregnant rats and rabbits resulted in post-implantation loss and structural abnormalities in offspring. These occurred at exposures equal to or greater than 10- and 5-fold, for rats and rabbits respectively, the human exposure at the maximum recommended human daily dose of 372 mg.
Advise pregnant females of the potential risk to the fetus. Consider pregnancy planning and prevention for females of reproductive potential [see Use in Specific Populations ( 8.1 , 8.3 )] .
5.3Increased Creatinine without Affecting Glomerular Function Across clinical trials of MIPLYFFA consisting of patients with NPC, healthy subjects, and patients with other diseases, there were mean increases in serum creatinine of 10% to 20% compared to baseline. These increases occurred mostly in the first month of MIPLYFFA treatment and were not associated with changes in glomerular function. The increases in serum creatinine may be due to inhibition of renal tubular secretion transporters [see Drug Interactions ( 7 ) and Clinical Pharmacology ( 12.2 , 12.3 )].
During MIPLYFFA treatment, use alternative measures that are not based on creatinine to assess renal function such as BUN, cystatin C, or measured GFR. Increases in creatinine reversed upon MIPLYFFA discontinuation [see Clinical Pharmacology ( 12.2 )] .
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS The following clinically significant adverse reactions are described below and elsewhere in the labeling: Hypersensitivity Reactions [see Warning and Precautions ( 5.1 )]. Increased Creatinine without Affecting Glomerular Function [see Warnings and Precautions ( 5.3 )]. Most common adverse reactions (≥15%) are: Upper respiratory tract infection, diarrhea, and decreased weight.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Zevra Therapeutics, Inc. at toll-free phone 1-844-600-2237 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The safety of MIPLYFFA was evaluated in a randomized, double-blind, placebo-controlled, 12-month trial (Trial 1), which included 50 patients 2 to 19 years old with NPC [see Clinical Studies ( 14 )] . Patients received weight-adjusted doses of MIPLYFFA (31 to 124 mg orally three times daily); 28 of the patients were exposed to MIPLYFFA for one year.
In Trial 1, 78% of patients received miglustat. Forty-one out of 50 patients that were enrolled in Trial 1 continued into an open-label extension trial, which included 39 patients treated with MIPLYFFA for more than 1 year, 34 patients treated with MIPLYFFA for more than 2 years, and 17 patients treated with MIPLYFFA for more than 5 years. The most common adverse reactions in Trial 1 (≥ 15%) in MIPLYFFA-treated patients who also received miglustat were upper respiratory tract infection, diarrhea, and decreased weight.
Three (6%) of the MIPLYFFA-treated patients had the following adverse reactions that led to withdrawal from Trial 1: increased serum creatinine (one patient), and progressive urticaria and angioedema (two patients). Serious adverse reactions reported in MIPLYFFA-treated patients in Trial 1 were hypersensitivity reactions including urticaria and angioedema. Table 1 shows common adverse reactions in Trial 1 that occurred in at least 8% of MIPLYFFA-treated patients who also received miglustat.
Table 1: Adverse Reactions in ≥ 8% of Patients with NPC Treated with MIPLYFFA in Trial 1 (Subgroup Who Also Received Miglustat) * Upper Respiratory Tract Infection: Combined incidence of upper respiratory tract infection and rhinitis. ** Urticaria: Includes one patient in which urticaria occurred alone (3%) and two patients who had urticaria with angioedema (6%) Adverse Reaction MIPLYFFA with miglustat N=26 n (%) Placebo with miglustat N=13 n (%) Upper Respiratory Tract Infection* 8 (31) 2 (15) Diarrhea 6 (23) 3 (23) Decreased Weight 4 (15) 0 Decreased appetite 3 (12) 0 Tremor 3 (12) 0 Urticaria** 3 (12) 0 Headache 3 (12) 1 (8) Lower respiratory tract infection 3 (12) 1 (8) Seizure 3 (12) 1 (8) Decreased Weight Adverse reactions of decreased weight were observed in four patients, who were also receiving concomitant miglustat during the trial.
The decrease in weight resolved in all but one of the patients. The mean duration of the weight decrease was 33 days and ranged from 22 to 60 days. One patient had two separate instances of weight loss during the trial, lasting 22 and 24 days respectively.
The mean weight loss was approximately 6% from baseline in all patients and MIPLYFFA administration was not interrupted in any patient. Laboratory Findings Thrombocytopenia: Thrombocytopenia was observed in three patients during the trial, all of whom were receiving miglustat for six months or longer at the time of enrollment. In two of these patients, the thrombocytopenia was present at baseline and persisted throughout the trial.
In the other patient, the thrombocytopenia developed and resolved during the trial. Increased Creatinine: Across clinical trials in patients with NPC, healthy subjects, and patients with other diseases, increases in serum…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS Substrates of the Organic Cationic Transporter 2 (OCT2 substrates) : Monitor for adverse reactions and reduce the dosage of the OCT2 substrate. ( 7.1 )
7.1Effect of MIPLYFFA on Other Drugs Arimoclomol is an inhibitor of the organic cationic transporter 2 (OCT2) transporter and may increase the exposure of drugs that are OCT2 substrates [see Clinical Pharmacology ( 12.3 )] . When MIPLYFFA is used concomitantly with OCT2 substrates, monitor for adverse reactions and reduce the dosage of the OCT2 substrate.
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Females and Males of Reproductive Potential: Based on animal findings, MIPLYFFA may impair fertility. ( 8.3 )
8.1Pregnancy Risk Summary Based on findings from animal reproduction studies, MIPLYFFA may cause embryofetal harm when administered during pregnancy. There are no available data on MIPLYFFA use in pregnant females to evaluate a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Advise pregnant females of the potential risk to the fetus.
In animal reproduction studies, oral administration of arimoclomol to pregnant rats and rabbits during organogenesis resulted in post-implantation loss and structural abnormalities in offspring. These occurred at exposures equal to or greater than 10- and 5-fold, in rats and rabbits respectively, the human exposure at the maximum recommended human daily dose of 372 mg ( see Data ). The background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data: In an embryofetal development study in pregnant rats, once daily oral doses of arimoclomol were administered throughout organogenesis from gestation day 6 to 17.
Increased post-implantation loss was observed at 10-fold the human exposure, based on AUC at the MRHDD, together with increased ossification in the vertebrae and dilated brain ventricles in litters of dams dosed at equal to or greater than 8-fold the human exposure at the MRHDD. In another embryofetal development study in pregnant rats in which arimoclomol was administered three times-daily throughout organogenesis from gestation day 6 to 17, there was an increase in postimplantation loss and reduced maternal, placental, and fetal weights at 14-fold the human exposure, based on AUC at the MRHD.
In addition, fetuses of dams treated at this exposure level exhibited domed craniums, partially split sternum, hydrocephaly, dilated brain ventricles, dilated interventricular foramen, misaligned and misshapen hemicentres and misaligned ossification sites in the sternebrae, misaligned costal cartilage, increased ossification, cerebral and cerebellar hemorrhages, bipartite supraoccipital, large interparietal bone, marked enlargement of the anterior and posterior fontanelles, hyoid bone, meningocele and fusion of the jugal and maxilla.
In an embryofetal development study in pregnant rabbits, arimoclomol was administered once daily by oral gavage throughout organogenesis from gestation day 7 to 19. Increased incidences of minor skeletal variations (bent hyoid and unossified phalanx) were observed at 5-fold the human AUC at the MRHDD, coinciding with an adverse reduction of maternal body weight. In a pre- and postnatal development study in pregnant rats, oral arimoclomol was administered from gestation day 6 to lactation day 21.
Increased embryofetal lethality and reduced pup weight, with a slight reduction in maternal body weight gain, were observed at 10-fold the human AUC at the MRHDD.
8.2Lactation Risk Summary There are no data on the presence of arimoclomol in human or animal milk, the effects on the breastfed infant, or the effects on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for MIPLYFFA and any potential adverse effects on the breastfed infant from MIPLYFFA or from the underlying maternal condition.
8.3Females and Males of Reproductive Potential MIPLYFFA may cause embryofetal harm when administered to a pregnant female [see Use in Specific Populations ( 8.1 )] . Contraception Females: Consider pregnancy planning and prevention for females of reproductive potential. Infertility Based on findings from animal…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary Based on findings from animal reproduction studies, MIPLYFFA may cause embryofetal harm when administered during pregnancy. There are no available data on MIPLYFFA use in pregnant females to evaluate a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Advise pregnant females of the potential risk to the fetus.
In animal reproduction studies, oral administration of arimoclomol to pregnant rats and rabbits during organogenesis resulted in post-implantation loss and structural abnormalities in offspring. These occurred at exposures equal to or greater than 10- and 5-fold, in rats and rabbits respectively, the human exposure at the maximum recommended human daily dose of 372 mg ( see Data ). The background risk of major birth defects and miscarriage for the indicated population is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data: In an embryofetal development study in pregnant rats, once daily oral doses of arimoclomol were administered throughout organogenesis from gestation day 6 to 17.
Increased post-implantation loss was observed at 10-fold the human exposure, based on AUC at the MRHDD, together with increased ossification in the vertebrae and dilated brain ventricles in litters of dams dosed at equal to or greater than 8-fold the human exposure at the MRHDD. In another embryofetal development study in pregnant rats in which arimoclomol was administered three times-daily throughout organogenesis from gestation day 6 to 17, there was an increase in postimplantation loss and reduced maternal, placental, and fetal weights at 14-fold the human exposure, based on AUC at the MRHD.
In addition, fetuses of dams treated at this exposure level exhibited domed craniums, partially split sternum, hydrocephaly, dilated brain ventricles, dilated interventricular foramen, misaligned and misshapen hemicentres and misaligned ossification sites in the sternebrae, misaligned costal cartilage, increased ossification, cerebral and cerebellar hemorrhages, bipartite supraoccipital, large interparietal bone, marked enlargement of the anterior and posterior fontanelles, hyoid bone, meningocele and fusion of the jugal and maxilla.
In an embryofetal development study in pregnant rabbits, arimoclomol was administered once daily by oral gavage throughout organogenesis from gestation day 7 to 19. Increased incidences of minor skeletal variations (bent hyoid and unossified phalanx) were observed at 5-fold the human AUC at the MRHDD, coinciding with an adverse reduction of maternal body weight. In a pre- and postnatal development study in pregnant rats, oral arimoclomol was administered from gestation day 6 to lactation day 21.
Increased embryofetal lethality and reduced pup weight, with a slight reduction in maternal body weight gain, were observed at 10-fold the human AUC at the MRHDD.
🧒 Pediatric Use ▾
8.4Pediatric Use The safety and effectiveness of MIPLYFFA in combination with miglustat for the treatment of neurological manifestations of NPC have been established in pediatric patients 2 years of age and older. Use of MIPLYFFA in combination with miglustat for this indication is supported by evidence from a randomized, double-blind, placebo-controlled 12-month trial (Trial 1) [see Clinical Studies ( 14 )]. The safety and effectiveness of MIPLYFFA have not been established in pediatric patients younger than 2 years of age.
Juvenile Animal Toxicity Data In juvenile toxicity studies in rats, increased incidences of renal pelvic dilatation were observed at all dose levels corresponding to 4-, 7- and 17-fold the human exposure based on AUC at MRHDD after both 2 and 8 weeks of dosing when animals were dosed from postnatal day 7.
🧓 Geriatric Use ▾
8.5Geriatric Use NPC is largely a disease of pediatric and young adult patients. Clinical trials of MIPLYFFA in combination with miglustat in patients with NPC did not include patients aged 65 years or older.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action The mechanism(s) by which arimoclomol exerts its clinical effects in patients with NPC is unknown.
12.2Pharmacodynamics The effect of arimoclomol (744 mg/day for 28 days) on serum creatinine was assessed in 16 healthy male subjects. A reversible increase in mean serum creatinine of 19% was observed after 21 days of treatment. No effect on glomerular function (GFR, 125 I-iothalamate clearance) or renal hemodynamics (effective renal plasma flow (ERPF); 131 I-hippuran clearance) was observed [see Warnings and Precautions ( 5.3 ), Adverse Reactions ( 6.1 ), and Drug Interactions ( 7 )].
Cardiac Electrophysiology The effect of arimoclomol 124 mg and 372 mg (3 times the maximum recommended dosage) administered three times a day (372 mg/day and 1116 mg/day) on ECG was evaluated in a randomized, partially double-blind, placebo-, and positive-controlled (moxifloxacin 400 mg), multipledose, 4-way crossover trial in 34 healthy male subjects. In this trial, arimoclomol did not prolong the QTc interval to a clinically relevant extent.
12.3Pharmacokinetics Arimoclomol exhibited linear and dose proportional pharmacokinetics following oral administration of doses ranging from 62 to 372 mg (three times the maximum recommended dosage) three times a day in healthy subjects. The plasma C max and AUC 0-8hr of arimoclomol at the 248 mg dose (two times the maximum recommended dosage) are summarized in Table 2 . Table 2: Geometric mean (CV%) Pharmacokinetic Parameters of Arimoclomol Following Oral Administration in Healthy Subjects Plasma PK Parameters 248 mg arimoclomol oral administration three times a day Day 1 (first dose) Day 6 (steady state) AUC 0-8hr (hr·ng/mL) 5317 (17%) 7207 (19%) C max (ng/mL) 1749 (49%) 2090 (23%) Absorption The absolute bioavailability of arimoclomol following oral administration has not been determined.
The median time to reach maximum plasma arimoclomol concentration (t max ) was approximately 0.5 hours. Effect of Food No clinically significant difference in arimoclomol pharmacokinetics were observed following administration of a high-fat meal (1000 calories, 60% fat) to healthy subjects. Distribution The mean apparent volume of distribution (V Z /F) of arimoclomol at steady state in healthy adult subjects is 211 L.
A dose-dependent increase in arimoclomol cerebral spinal fluid concentrations was seen at steady state. Plasma protein binding of arimoclomol is approximately 10%. Elimination The elimination half-life of arimoclomol is approximately 4 hours.
The mean apparent clearance of arimoclomol (CL/F) at steady state is 34 L/hr in healthy adult subjects. Metabolism: Arimoclomol is predominantly metabolized through glutathionation, O -glucuronidation and NO-oxime cleavage. Excretion: Following a single dose of radiolabeled arimoclomol 100 mg to healthy male subjects under fasted conditions, approximately 12% of the dose was recovered in feces and 77.5% in urine (42% unchanged).
Drug Interaction Studies In Vitro Studies: Cytochrome P450 (CYP) Enzymes: Arimoclomol is not an inhibitor or inducer of CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP3A4/5. Transporter Systems: Arimoclomol is an inhibitor of OCT2 and may cause relevant changes in exposure of OCT2 substrates including the endogenous substrate creatinine [see Drug Interactions ( 7.1 )]. Arimoclomol is not an inhibitor of P-gp, BCRP, OATP1B1, OATP1B3, OAT1, OAT3, MATE1 and MATE2-K transporters.
Arimoclomol is a substrate of MATE1 and MATE2-K transporters; MATE1 and MATE2-K inhibitors are not expected to have a clinically relevant effect on arimoclomol exposure. Specific Populations Pediatric Patients: In pediatric NPC patients who received the recommended dosing regimens, the estimated steady state mean ± SD serum C trough and C max arimoclomol concentrations are 206 ± 60 and 523 ± 194 ng/mL, respectively. Patients with Renal Impairment: In a renal impairment study, subjects with moderate to severe renal i…
🧬 Mechanism of Action ▾
12.1Mechanism of Action The mechanism(s) by which arimoclomol exerts its clinical effects in patients with NPC is unknown.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied MIPLYFFA (arimoclomol) capsules are supplied in high-density polyethylene (HDPE) bottles with child-resistant closure as follows: MIPLYFFA Strength Capsules Description Package Configuration NDC No. 47 mg White opaque body with black printing “47”, and green opaque cap with black printing “OZ” Bottle of 90 capsules 72542-147-01 62 mg White opaque body with black printing “62”, and yellow opaque cap with black printing “OZ”. Bottle of 90 capsules 72542-162-01 93 mg White opaque body with black printing “93”, and orange opaque cap with black printing “OZ” Bottle of 90 capsules 72542-193-01 124 mg White opaque body with black printing “124”, and red opaque cap with black printing “OZ” Bottle of 90 capsules 72542-124-01 Storage and Handling Store MIPLYFFA at 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C to 30°C (59°F to 86°F) [see USP Controlled Room Temperature].
Store in original container. Protect from light.
📋 Description ▾
11 DESCRIPTION MIPLYFFA capsules contain arimoclomol citrate. Arimoclomol citrate is a crystalline powder of white to off-white color that is freely soluble in water. The chemical name is N -[(2R, Z )-2-hydroxy-3-(1piperidyl)propoxy]pyridine-3-carboximidoyl chloride, 1-oxide, citrate.
The empirical formula is C 20 H 28 ClN 3 O 10 and the molecular weight is 505.90 g/mol. The chemical structure is: MYPLIFFA contains 47 mg, 62 mg, 93 mg, or 124 mg of arimoclomol (equivalent to 75 mg, 100 mg, 150 mg, or 200 mg of arimoclomol citrate). The inactive ingredients are microcrystalline cellulose (MCC) and magnesium stearate.
The inactive ingredients are not water soluble and will remain undissolved if the contents of the capsule are added to beverages or soft food [see Dosage and Administration ( 2.3 )]. The capsule shells contain hypromellose, titanium dioxide, and one or more of the following: Brilliant Blue FCF-FD&C Blue 1, Yellow iron oxide and Red iron oxide. Chemical Structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Advise the patient and/or caregiver to read the FDA-approved patient labeling (Instructions for Use). Drug Interactions Advise the patient to inform his/her healthcare provider if he/she is taking, or plan to take, any prescription or over-the-counter medications and supplements because of the potential for drug interactions [see Drug Interactions ( 7 ) and Clinical Pharmacology ( 12.3 )]. Hypersensitivity Reactions Advise the patient or caregiver to contact his/her healthcare provider immediately if urticaria (hives), shortness of breath, persistent cough, or facial swelling develop in response to MIPLYFFA treatment [see Warnings and Precautions ( 5.1 )].
Embryofetal Toxicity MYPLIFFA may cause embryo-fetal harm. Advise the pregnant female of the potential risk to the fetus. Advise a female of reproductive potential and caregiver to inform their healthcare provider of a known or suspected pregnancy [see Warnings and Precautions ( 5.1 ) and Use in Specific Populations ( 8.1 )] .
Counsel females of reproductive potential about pregnancy planning and prevention [see Use in Specific Populations ( 8.3 )]. Infertility Advise the female and male of reproductive potential that MIPLYFFA may impair fertility [see Use in Specific Populations ( 8.1 , 8.3 )]. Manufactured by: Zevra Denmark A/S 2000 Frederiksberg, Denmark Manufactured for: Zevra Therapeutics, Inc.
Boston, MA 02110, USA © 2024, 2025 Zevra Therapeutics, Inc. All rights reserved. U.S.
Patent Nos. 9,289,472, 9,884,058 and 11,045,460. MIPLYFFA is a registered trademark of Zevra Therapeutics, Inc.