PYRUKYND

PYRUKYND is an FDA-registered drug product whose active ingredient is MITAPIVAT. It is labelled by Agios Pharmaceuticals, Inc. taken by oral and marketed as a human prescription drug product. Identifiers on file: NDC 71334-205, application NDA216196, label effective 20260630. It is one of 2 FDA drug label records sharing the active ingredient MITAPIVAT. This page reproduces the FDA-approved label text so you can check what a product is, who makes it and how it is supplied before discussing it with a pharmacist or prescriber.

Across FDA labelling, products containing MITAPIVAT are most often described in connection with: pyruvate kinase, treatment hemolytic, anemia adults, usage pyrukynd, activator indicated. Wording differs between labels, and the full indications section on this page takes precedence when it is present.

1 INDICATIONS AND USAGE PYRUKYND is indicated for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency. PYRUKYND is a pyruvate kinase activator indicated for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency. ( 1 )

2 DOSAGE AND ADMINISTRATION Starting dosage: 5 mg orally twice daily with or without food. ( 2.1 ) See Full Prescribing Information for dose titration and taper schedule. ( 2.1 , 2.3 ) The tablet should be swallowed whole. ( 2.1 ) 2.1 Recommended Dose PYRUKYND is taken with or without food and swallowed whole. Do not split, crush, chew, or dissolve the tablets. The starting dosage for PYRUKYND is 5 mg orally twice daily. To gradually increase hemoglobin (Hb), titrate PYRUKYND from 5 mg twice daily to 20 mg twice daily, and then to the maximum recommended dose of 50 mg twice daily, with these dose increases occurring every 4 weeks (see Table 1). Assess Hb and transfusion requirement before increasing to the next dose level, as some patients may reach and maintain normal Hb at 5 mg twice daily or 20 mg twice daily. Discontinue PYRUKYND if no benefit has been observed by 24 weeks, based on the hemoglobin and hemolysis laboratory results and transfusion requirements. Table 1: Dose Titration Schedule Duration Dosage Week 1 through Week 4 5 mg twice daily Week 5 through Week 8 If Hb is below normal range or patient has required a transfusion within the last 8 weeks: Increase to 20 mg twice daily and maintain for 4 weeks. If Hb is within normal range and patient has not required a transfusion within the last 8 weeks: Maintain 5 mg twice daily. Week 9 through Week 12 If Hb is below normal range or patient has required a transfusion within the last 8 weeks: Increase to 50 mg twice daily and maintain thereafter. If Hb is within normal range and patient has not required a transfusion within the last 8 weeks: Maintain current dose (5 mg twice daily or 20 mg twice daily). Maintenance If Hb decreases, consider up-titration to the maximum of 50 mg twice daily as per the above schedule. 2.2 Missed Dose If a dose of PYRUKYND is missed by 4 hours or less, administer the dose as soon as possible. If a dose of PYRUKYND is missed by more than 4 hours, do not administer a replacement dose, and wait until the next scheduled dose. Subsequently, return to the normal dosing schedule. 2.3 Interruption or Discontinuation To reduce the risk of acute hemolysis, avoid abrupt interruption or abrupt discontinuation of PYRUKYND when possible [see Warnings and Precautions (5.1) ] . Taper the dose to gradually discontinue the medication (see Table 2). Monitor patients for signs of acute hemolysis and worsening of anemia. Table 2 Dose Taper Schedule Current Dose Dose Taper Schedule Day 1-7 Day 8-14 Day 15 5 mg twice daily 5 mg once daily Discontinue N/A 20 mg twice daily 20 mg once daily 5 mg once daily Discontinue 50 mg twice daily 50 mg once daily 20 mg once daily Discontinue Abbreviations: N/A = not applicable. 2.4 Recommended Dosage for Drug Interactions Strong CYP3A Inhibitors Avoid co-administration of strong CYP3A inhibitors with PYRUKYND [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ] . Moderate CYP3A Inhibitors Monitor Hb and for increased risks of adverse reactions from PYRUKYND. When used with a moderate CYP3A inhibitor, do not titrate PYRUKYND beyond 20 mg twice daily [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ] . Strong CYP3A Inducers Avoid co-administration of strong CYP3A inducers with PYRUKYND [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ] . Moderate CYP3A Inducers Consider alternative therapies that are not moderate CYP3A inducers during treatment with PYRUKYND. If there are no alternative therapies, monitor Hb and titrate beyond the 50 mg twice daily dose, if necessary, but do not exceed a maximum recommended dose of 100 mg twice daily [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ] . 2.5 Dose Modifications for Adverse Reactions and Hemoglobin Levels Above Normal If a dose reduction is required because of an adverse reaction or tolerability, or for Hb above normal, the dose may be reduced to the next lower dose level, 20 mg twice daily or 5 mg twice daily. If a patient needs to discontinue PYRUKYND, the dose taper schedule (Table 2) should be followed. In situations where the risk to the patient due to the adverse reaction or Hb above normal is greater than the risk of acute hemolysis due to sudden withdrawal of the drug, treatment may be stopped without taper and patients should be monitored for signs of acute hemolysis.

4 CONTRAINDICATIONS None None ( 4 )

6 ADVERSE REACTIONS The following clinically significant adverse reaction is described elsewhere in labeling: Acute Hemolysis with Abrupt Treatment Discontinuation [see Warn ings and Preca utions (5.1) ]. Hepatocellular Injury in Another Condition [see Warnings and Precautions (5.2) ] . The most common adverse reactions including laboratory abnormalities (≥ 10%) in patients with PK deficiency were estrone decreased (males), increased urate, back pain, estradiol decreased (males), and arthralgia. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Agios Pharmaceuticals at 1-833-228-8474 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial 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. A total of 155 patients received PYRUKYND, 79% of whom were exposed for longer than 24 weeks. PYRUKYND was administered up to 50 mg orally twice daily in 67 patients with PK deficiency in the ACTIVATE trial (N=40) and the ACTIVATE-T trial (N=27) [see Clinical Studies (14) ] . ACTIVATE Trial In the ACTIVATE trial patients with PK deficiency who were not regularly transfused received PYRUKYND in incremental doses up to 50 mg twice daily (N=40) or placebo (N=39). Serious adverse reactions occurred in 10% of patients receiving PYRUKYND in the ACTIVATE Trial, including atrial fibrillation, gastroenteritis, rib fracture, and musculoskeletal pain, which each occurred in 1 patient. In the ACTIVATE trial, the most common adverse reactions including laboratory abnormalities (≥10%) in patients with PK deficiency were estrone decreased (males), increased urate, back pain, estradiol decreased (males), and arthralgia. Table 3 summarizes the adverse reactions in the ACTIVATE trial. Table 3: Adverse Reactions (≥ 5%) in Patients Receiving PYRUKYND in ACTIVATE PYRUKYND (N=40) Placebo (N=39) Adverse Reaction All Grades (%) Grade ≥3 (%) All Grades (%) Grade ≥3 (%) Back pain a 15% 0 8% 0 Arthralgia b 10% 0 5% 0 Hypertriglyceridemia c 8% 5% 3% 0 Gastroenteritis 8% 3% 0 0 Hot flush d 8% 0 0 0 Oropharyngeal pain 8% 0 5% 0 Hypertension 5% 5% 0 0 Arrhythmia e 5% 0 0 0 Breast discomfort 5% 0 0 0 Constipation 5% 0 0 0 Dry mouth f 5% 0 0 0 Paresthesia 5% 0 0 0 Grades: Per the CTCAE definition. Grouped Term Definitions a Includes back pain, sciatica, and flank pain. b Includes arthralgia and joint swelling. c Includes hypertriglyceridemia and blood triglycerides increased. d Includes hot flush and flushing. e Includes arrhythmia, tachycardia, heart rate increased and atrial fibrillation. f Includes dry mouth and dry lip. Laboratory abnormalities of PYRUKYND included increased urate (15%). Variations in Reproductive Hormones In ACTIVATE, increases in serum testosterone and decreases in serum estrone and estradiol were observed in men receiving PYRUKYND (Table 4). These changes in hormones persisted throughout the study period. In patients who discontinued PYRUKYND and had follow-up hormone measurements, the hormone changes returned close to the baseline levels 28 days after discontinuing PYRUKYND. In female patients, sex hormone analysis was limited due to physiologic variations in hormones during the menstrual cycle and the use of hormonal contraceptives. Table 4: Laboratory Abnormalities in Reproductive Hormones in Men Receiving PYRUKYND ACTIVATE Parameter PYRUKYND (16 males) n (%) Placebo (15 males)n (%) Reproductive hormone analyses a Estrone decreased (males) Estradiol decreased (males) Blood testosterone increased (males) 9 (56.3) 2 (12.5) 1 (6.3) 0 1 (6.7) 1 (6.7) a Decreases in estrone and estradiol to below the lower limit of the reference range and increases in testosterone to above the upper limit of the reference range where baseline was within normal limits. ACTIVATE-T Trial The adverse reactions reported in the population of patients who were regularly transfused (ACTIVATE-T) were consistent with that seen in ACTIVATE.

FDA lists 2 drug label records with MITAPIVAT as the active ingredient. The most common dosage forms and the manufacturers with the most records are summarised below; strengths, pack sizes and inactive ingredients can still differ between apparently similar products.

What is PYRUKYND used for?
1 INDICATIONS AND USAGE PYRUKYND is indicated for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency. PYRUKYND is a pyruvate kinase activator indicated for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency. ( 1 )

Who makes PYRUKYND?
Agios Pharmaceuticals, Inc. is the labeler of record for PYRUKYND. 2 FDA label records share the active ingredient MITAPIVAT, so generic and branded versions may come from different companies; the manufacturer named on your pack is the one that matters for any enquiry.

What form does PYRUKYND come in?
administered by oral. Strengths and pack sizes vary by label, so compare the NDC on your pack with the identifier listed on this page.

Is PYRUKYND prescription or over-the-counter?
The FDA label for this product is recorded as human prescription drug. Marketing status can differ between strengths and countries, so check the dispensing rules where you live.

Are there other products containing MITAPIVAT?
Yes. 2 FDA drug label records list MITAPIVAT as the active ingredient. Products with the same active ingredient can usually be substituted only when a prescriber or pharmacist confirms it is appropriate.

Has PYRUKYND been recalled?
No FDA recall record in our database matches this product name or manufacturer. Recall data is updated periodically, so a very recent notice may not appear here yet.

Where does this information come from?
All content is reproduced from FDA Structured Product Labelling data via openFDA. It is provided for identification and reference only and is not medical advice.