SAFETY DATA

PYRUKYND® (mitapivat) demonstrated safety profile1

Among 155 who received PYRUKYND in clinical trials, 79% were exposed for longer than 24 weeks.

Adverse reactions (≥5%) in patients receiving PYRUKYND in ACTIVATE

PYRUKYND (n=40)PLACEBO (n=40)
Adverse ReactionsAll Grades (%) Grade ≥3 (%)All Grades (%) Grade ≥3 (%)
Back pain*15%08%0
Arthralgia†10%05%0
Hypertriglyceridemia‡8%5%3%0
Gastroenteritis8%3%00
Hot flush§8%000
Oropharyngeal pain8%05%0
Hypertension5%5%00
Arrhythmia||5%000
Breast discomfort5%000
Constipation5%000
Dry mouth5%000
Paresthesia5%000
PYRUKYND (n=40)
Adverse ReactionsAll Grades
(%) Grade ≥3
(%)
Back pain*15%0
Arthralgia†10%0
Hypertriglyceridemia‡8%5%
Gastroenteritis8%3%
Hot flush§8%0
Oropharyngeal pain8%0
Hypertension5%5%
Arrhythmia||5%0
Breast discomfort5%0
Constipation5%0
Dry mouth5%0
Paresthesia5%0
PLACEBO (n=40)
Adverse ReactionsAll Grades
(%) Grade ≥3
(%)
Back pain*8%0
Arthralgia†5%0
Hypertriglyceridemia‡3%0
Gastroenteritis00
Hot flush§00
Oropharyngeal pain5%0
Hypertension00
Arrhythmia||00
Breast discomfort00
Constipation00
Dry mouth00
Paresthesia00

*Includes back pain, sciatica, and flank pain.

†Includes arthralgia and joint swelling.

‡Includes hypertriglyceridemia and blood triglycerides increased.

§Includes hot flush and flushing.

||Includes arrhythmia, tachycardia, heart rate increased and atrial fibrillation.

Includes dry mouth and dry lip.

  • Laboratory abnormalities of PYRUKYND included increased urate (15%)
  • The adverse reactions reported in the population of patients who were regularly transfused (ACTIVATE-T) were consistent with that seen in ACTIVATE
  • Serious adverse reactions occurred in 10% of patients receiving PYRUKYND
  • Serious adverse reactions included atrial fibrillation, gastroenteritis, rib fracture, and musculoskeletal pain, which each occurred in 1 patient

VARIATIONS IN REPRODUCTIVE HORMONES

  • In ACTIVATE, increases in serum testosterone and decreases in serum estrone and estradiol were observed in men receiving PYRUKYND
  • 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

The most common laboratory abnormalities in patients receiving PYRUKYND1

ParameterPYRUKYND
(16 males) n (%)		PLACEBO
(15 males) n (%)
Reproductive hormone analyses#
Estrone decreased (males)9 (56.3)0
Estradiol decreased (males)2 (12.5)1 (6.7)
Blood testosterone increased (males)1 (6.3)1 (6.7)
PYRUKYND (16 males) n (%)
Parameter
Reproductive hormone analyses#
Estrone decreased (males)9 (56.3)
Estradiol decreased (males)2 (12.5)
Blood testosterone increased (males)1 (6.3)
PLACEBO (15 males) n (%)
Parameter
Reproductive hormone analyses#
Estrone decreased (males)0
Estradiol decreased (males)1 (6.7)
Blood testosterone increased (males)1 (6.7)
  • Laboratory abnormalities of PYRUKYND included increased urate (15%)
  • The adverse reactions reported in the population of patients who were regularly transfused (ACTIVATE-T) were consistent with that seen in ACTIVATE
  • Serious adverse reactions occurred in 10% of patients receiving PYRUKYND
  • Serious adverse reactions included atrial fibrillation, gastroenteritis, rib fracture, and musculoskeletal pain, which each occurred in 1 patient
  • In the clinical studies, there were no adverse events leading to discontinuation2,3

#Decreases in estrone and estradiol represent 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.

Learn about the dosing and administration of PYRUKYND

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References: 1. PYRUKYND. Prescribing information. Agios Pharmaceuticals, Inc.; 2022. 2. Data on file. Agios Pharmaceuticals, Inc. 3. Glenthøj A, van Beers EJ, Al-Samkari H, et al; Mitapivat in adult patients with pyruvate kinase deficiency receiving regular transfusions (ACTIVATE-T): a multicentre, open-label, single-arm, phase 3 trial. Lancet Haematol. Published online August 18, 2020. doi:10.1016/S2352-3026(22)00214-9.

Indication

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

Important Safety Information

Acute Hemolysis: Acute hemolysis with subsequent anemia has been observed following abrupt interruption or discontinuation of PYRUKYND in a dose-ranging study. Avoid abruptly discontinuing PYRUKYND. Gradually taper the dose of PYRUKYND to discontinue treatment if possible. When discontinuing treatment, monitor patients for signs of acute hemolysis and anemia including jaundice, scleral icterus, dark urine, dizziness, confusion, fatigue, or shortness of breath.

Adverse Reactions: Serious adverse reactions occurred in 10% of patients receiving PYRUKYND in the ACTIVATE trial, including atrial fibrillation, gastroenteritis, rib fracture, and musculoskeletal pain, each of which 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.

Drug Interactions:

  • Strong CYP3A Inhibitors and Inducers: Avoid concomitant use.
  • Moderate CYP3A Inhibitors: Do not titrate PYRUKYND beyond 20 mg twice daily.
  • Moderate CYP3A Inducers: Consider alternatives that are not moderate inducers. If there are no alternatives, adjust PYRUKYND dosage.
  • Sensitive CYP3A, CYP2B6, CYP2C Substrates Including Hormonal Contraceptives: Avoid concomitant use with substrates that have narrow therapeutic index.
  • UGT1A1 Substrates: Avoid concomitant use with substrates that have narrow therapeutic index.
  • P-gp Substrates: Avoid concomitant use with substrates that have narrow therapeutic index.

Hepatic Impairment: Avoid use of PYRUKYND in patients with moderate and severe hepatic impairment.

Please see full Prescribing Information for PYRUKYND.

Indication

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

Important Safety Information

Acute Hemolysis: Acute hemolysis with subsequent anemia has been observed
following abrupt interruption or discontinuation of PYRUKYND in a dose-ranging study. Avoid abruptly discontinuing PYRUKYND. Gradually taper the dose of PYRUKYND to discontinue treatment if possible. When discontinuing treatment, monitor patients for signs of acute hemolysis and anemia including jaundice, scleral icterus, dark urine, dizziness, confusion, fatigue, or shortness of breath.

Indication

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

Important Safety Information

Acute Hemolysis: Acute hemolysis with subsequent anemia has been observed following abrupt interruption or discontinuation of PYRUKYND in a dose-ranging study. Avoid abruptly discontinuing PYRUKYND. Gradually taper the dose of PYRUKYND to discontinue treatment if possible. When discontinuing treatment, monitor patients for signs of acute hemolysis and anemia including jaundice, scleral icterus, dark urine, dizziness, confusion, fatigue, or shortness of breath.

Adverse Reactions: Serious adverse reactions occurred in 10% of patients receiving PYRUKYND in the ACTIVATE trial, including atrial fibrillation, gastroenteritis, rib fracture, and musculoskeletal pain, each of which 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.

Drug Interactions:

  • Strong CYP3A Inhibitors and Inducers: Avoid concomitant use.
  • Moderate CYP3A Inhibitors: Do not titrate PYRUKYND beyond 20 mg twice daily.
  • Moderate CYP3A Inducers: Consider alternatives that are not moderate inducers. If there are no alternatives, adjust PYRUKYND dosage.
  • Sensitive CYP3A, CYP2B6, CYP2C Substrates Including Hormonal Contraceptives: Avoid concomitant use with substrates that have narrow therapeutic index.
  • UGT1A1 Substrates: Avoid concomitant use with substrates that have narrow therapeutic index.
  • P-gp Substrates: Avoid concomitant use with substrates that have narrow therapeutic index.

Hepatic Impairment: Avoid use of PYRUKYND in patients with moderate and severe hepatic impairment.

Please see full Prescribing Information for PYRUKYND.

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