Pyrukynd 20mg Tablets
It is used to treat hemolytic anemia in certain people.
Drug Class
Pyruvate Kinase Activator
Pharmacologic Class
Pyruvate Kinase Activator
Pregnancy Category
Not available
FDA Approved
Feb 2022
DEA Schedule
Not Controlled
Overview
What is this medicine?
Pyrukynd is a medication used to treat a rare genetic blood disorder called pyruvate kinase deficiency (PKD) in adults. It works by helping red blood cells produce more energy, which can reduce the breakdown of red blood cells and improve anemia.
How to Use This Medicine
Taking Your Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. Take your medication with or without food, and swallow the tablets whole. Do not chew, break, crush, or dissolve them. Continue taking your medication as directed by your doctor or healthcare provider, even if you start feeling well.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, avoiding bathrooms. Keep the blister wallets in their original carton until you are ready to use them. Always keep your medications in a safe location, out of the reach of children and pets.
Missing a Dose
If you miss a dose, take it as soon as you remember. However, if you miss a dose by more than 4 hours, skip the missed dose and resume your regular schedule. Do not take two doses at the same time or take extra doses to make up for a missed one.
To use this medication correctly, follow your doctor's instructions and read all the information provided. Take your medication with or without food, and swallow the tablets whole. Do not chew, break, crush, or dissolve them. Continue taking your medication as directed by your doctor or healthcare provider, even if you start feeling well.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, avoiding bathrooms. Keep the blister wallets in their original carton until you are ready to use them. Always keep your medications in a safe location, out of the reach of children and pets.
Missing a Dose
If you miss a dose, take it as soon as you remember. However, if you miss a dose by more than 4 hours, skip the missed dose and resume your regular schedule. Do not take two doses at the same time or take extra doses to make up for a missed one.
Lifestyle & Tips
- Take Pyrukynd exactly as prescribed by your doctor, usually twice a day.
- You can take it with or without food.
- Do not crush, chew, or split the tablets.
- If you miss a dose, take it as soon as you remember. If it's almost time for your next dose, skip the missed dose and continue your regular schedule. Do not take two doses at once.
- Inform your doctor about all other medications, supplements, and herbal products you are taking, as many can interact with Pyrukynd.
- Use effective contraception during treatment and for at least 1 month after the last dose if you are a woman of childbearing potential.
- Avoid grapefruit and grapefruit juice as they may interact with this medication.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Initial: 5 mg orally twice daily. Titrate up to 20 mg twice daily. Maximum: 50 mg twice daily.
Dose Range:
5 - 50 mg
Condition-Specific Dosing:
Pyruvate Kinase Deficiency (PKD):
Initial: 5 mg orally twice daily. After 2 weeks, increase to 20 mg twice daily. After 4 weeks, if not achieving target hemoglobin response and tolerating, may increase to 50 mg twice daily. Administer with or without food. Do not crush, chew, or split tablets.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment needed.
Moderate:
No dose adjustment needed.
Severe:
Not studied. Use with caution.
Dialysis:
Not studied. Use with caution.
Hepatic Impairment:
Mild:
No dose adjustment needed (Child-Pugh A).
Moderate:
Reduce initial dose to 5 mg once daily (Child-Pugh B). If tolerated, may increase to 5 mg twice daily after 2 weeks. If further increase is needed, increase to 10 mg twice daily after 4 weeks. Maximum 10 mg twice daily.
Severe:
Not recommended (Child-Pugh C).
Pharmacology
Mechanism of Action
Mitapivat is an oral, small molecule allosteric activator of pyruvate kinase (PK). It binds to and activates both wild-type and mutated PK enzymes, increasing PK activity. This leads to increased ATP production and reduced 2,3-diphosphoglycerate (2,3-DPG) levels, which improves red blood cell function and reduces hemolysis in patients with pyruvate kinase deficiency.
Pharmacokinetics
Absorption:
Bioavailability:
Not available (oral absorption is good)
Tmax:
1 to 4 hours
FoodEffect:
High-fat meal decreases Cmax by 20% and AUC by 10%, not considered clinically significant.
Distribution:
Vd:
Approximately 100 L
ProteinBinding:
>99%
CnssPenetration:
Limited (due to high protein binding and likely P-gp efflux)
Elimination:
HalfLife:
Approximately 10 to 14 hours
Clearance:
Not available
ExcretionRoute:
Primarily fecal (approximately 80%), minor renal (approximately 10%)
Unchanged:
<1% (in urine)
Pharmacodynamics
OnsetOfAction:
Not precisely defined, clinical effects observed within weeks of initiation.
PeakEffect:
Not precisely defined, clinical effects observed within weeks of initiation.
DurationOfAction:
Related to half-life, requires twice-daily dosing.
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Attention Immediately
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical help right away:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of high blood pressure, including:
+ Severe headache or dizziness
+ Passing out
+ Changes in eyesight
Fast or abnormal heartbeat
Breast pain
Burning, numbness, or tingling sensations that are not normal
Additionally, people taking a higher dose of this medication for a different health condition may have an increased risk of liver problems during the first 6 months of treatment. If you experience any of the following symptoms, notify your doctor immediately:
Dark urine
Tiredness
Decreased appetite
Upset stomach or stomach pain
Light-colored stools
Vomiting
Yellow skin or eyes
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other symptoms that bother you or do not go away, contact your doctor or seek medical help:
Back pain
Joint pain
Stomach pain or diarrhea
Flushing
Mouth or throat pain or irritation
Constipation
Dry mouth
Dry lips
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical help right away:
Signs of an allergic reaction, such as:
+ Rash
+ Hives
+ Itching
+ Red, swollen, blistered, or peeling skin with or without fever
+ Wheezing
+ Tightness in the chest or throat
+ Trouble breathing, swallowing, or talking
+ Unusual hoarseness
+ Swelling of the mouth, face, lips, tongue, or throat
Signs of high blood pressure, including:
+ Severe headache or dizziness
+ Passing out
+ Changes in eyesight
Fast or abnormal heartbeat
Breast pain
Burning, numbness, or tingling sensations that are not normal
Additionally, people taking a higher dose of this medication for a different health condition may have an increased risk of liver problems during the first 6 months of treatment. If you experience any of the following symptoms, notify your doctor immediately:
Dark urine
Tiredness
Decreased appetite
Upset stomach or stomach pain
Light-colored stools
Vomiting
Yellow skin or eyes
Other Possible Side Effects
Like all medications, this drug can cause side effects. While many people may not experience any side effects or only minor ones, it's essential to discuss any concerns with your doctor. If you experience any of the following side effects or any other symptoms that bother you or do not go away, contact your doctor or seek medical help:
Back pain
Joint pain
Stomach pain or diarrhea
Flushing
Mouth or throat pain or irritation
Constipation
Dry mouth
Dry lips
This is not an exhaustive list of possible side effects. If you have questions or concerns about side effects, consult your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Seek Immediate Medical Attention If You Experience:
- Signs of worsening anemia (increased fatigue, shortness of breath, pale skin)
- Signs of liver problems (unusual tiredness, nausea, vomiting, dark urine, yellowing of skin or eyes, pain in the upper right side of the stomach)
- Any new or worsening symptoms.
Before Using This Medicine
Before Taking This Medication: Important Information to Share with Your Doctor
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you have liver disease, as this may affect the way your body processes the medication.
* Any medications you are currently taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins. This is crucial because certain medications, such as those used to treat HIV, infections, seizures, and other conditions, may interact with this drug and should not be taken concurrently.
Please note that this is not an exhaustive list of all potential drug interactions or health problems that may be relevant to your treatment with this medication. Therefore, it is vital to discuss all of your medications and health issues with your doctor and pharmacist to ensure safe treatment.
To guarantee your safety, always check with your doctor before starting, stopping, or changing the dose of any medication. This includes all prescription and OTC drugs, natural products, and vitamins. Your doctor will help you determine whether it is safe to take this medication in combination with your other medications and health conditions.
It is essential to inform your doctor about the following:
Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
If you have liver disease, as this may affect the way your body processes the medication.
* Any medications you are currently taking, including prescription and over-the-counter (OTC) drugs, natural products, and vitamins. This is crucial because certain medications, such as those used to treat HIV, infections, seizures, and other conditions, may interact with this drug and should not be taken concurrently.
Please note that this is not an exhaustive list of all potential drug interactions or health problems that may be relevant to your treatment with this medication. Therefore, it is vital to discuss all of your medications and health issues with your doctor and pharmacist to ensure safe treatment.
To guarantee your safety, always check with your doctor before starting, stopping, or changing the dose of any medication. This includes all prescription and OTC drugs, natural products, and vitamins. Your doctor will help you determine whether it is safe to take this medication in combination with your other medications and health conditions.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Regularly scheduled blood work and laboratory tests, as directed by your doctor, are crucial to monitor your condition.
To minimize the risk of hemolysis (red blood cell breakdown), do not abruptly discontinue this medication. If you need to stop taking this drug, your doctor will instruct you on how to gradually taper off the dosage. Immediately report any signs of hemolysis to your doctor, including yellowing of the skin or eyes (jaundice), dark urine, dizziness, confusion, fatigue, or shortness of breath.
Avoid consuming grapefruit and grapefruit juice while taking this medication. Additionally, be aware that this drug may cause elevated triglyceride levels. If you have a history of high triglyceride levels, inform your doctor.
In men, this medication may decrease levels of the reproductive hormones estrone and estradiol. If you have concerns or questions, discuss them with your doctor.
When taking this medication, birth control pills and other hormone-based contraceptives may be less effective in preventing pregnancy. To minimize the risk of unintended pregnancy, use an additional form of birth control, such as a condom, in conjunction with your regular birth control method.
If you are pregnant, planning to become pregnant, or breastfeeding, consult your doctor to discuss the potential benefits and risks of this medication to you and your baby.
To minimize the risk of hemolysis (red blood cell breakdown), do not abruptly discontinue this medication. If you need to stop taking this drug, your doctor will instruct you on how to gradually taper off the dosage. Immediately report any signs of hemolysis to your doctor, including yellowing of the skin or eyes (jaundice), dark urine, dizziness, confusion, fatigue, or shortness of breath.
Avoid consuming grapefruit and grapefruit juice while taking this medication. Additionally, be aware that this drug may cause elevated triglyceride levels. If you have a history of high triglyceride levels, inform your doctor.
In men, this medication may decrease levels of the reproductive hormones estrone and estradiol. If you have concerns or questions, discuss them with your doctor.
When taking this medication, birth control pills and other hormone-based contraceptives may be less effective in preventing pregnancy. To minimize the risk of unintended pregnancy, use an additional form of birth control, such as a condom, in conjunction with your regular birth control method.
If you are pregnant, planning to become pregnant, or breastfeeding, consult your doctor to discuss the potential benefits and risks of this medication to you and your baby.
Overdose Information
Overdose Symptoms:
- Symptoms of overdose are not well established, but may include exaggerated adverse effects.
What to Do:
There is no specific antidote for Pyrukynd overdose. In case of suspected overdose, contact a poison control center (1-800-222-1222) or seek emergency medical attention immediately. Treatment should be supportive and symptomatic.
Drug Interactions
Contraindicated Interactions
- Strong CYP3A4 inducers (e.g., rifampin, carbamazepine, enzalutamide, mitotane, phenytoin, phenobarbital, St. John's Wort)
Major Interactions
- Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, indinavir, nelfinavir, saquinavir, telithromycin, voriconazole)
- Moderate CYP3A4 inducers (e.g., efavirenz, bosentan, etravirine, modafinil, nafcillin)
Moderate Interactions
- Sensitive CYP3A4 substrates (e.g., midazolam, simvastatin, hormonal contraceptives)
- P-gp substrates (e.g., digoxin, dabigatran)
- BCRP substrates (e.g., rosuvastatin, sulfasalazine)
- OATP1B1/1B3 substrates (e.g., statins, rifampin)
Monitoring
Baseline Monitoring
Complete Blood Count (CBC) with Reticulocyte Count
Rationale: To establish baseline hematologic parameters and assess severity of anemia/hemolysis.
Timing: Prior to initiation of therapy.
Liver Function Tests (LFTs)
Rationale: To assess baseline hepatic function, especially given hepatic metabolism and potential for dose adjustment in hepatic impairment.
Timing: Prior to initiation of therapy.
Renal Function Tests (e.g., creatinine, eGFR)
Rationale: To assess baseline renal function, though no dose adjustment for mild-moderate impairment.
Timing: Prior to initiation of therapy.
Routine Monitoring
Hemoglobin (Hb) and Reticulocyte Count
Frequency: Every 2 weeks for the first 4 weeks during dose titration, then periodically (e.g., monthly or as clinically indicated) once stable.
Target: Aim for sustained increase in hemoglobin and/or decrease in reticulocyte count, indicating reduced hemolysis.
Action Threshold: Lack of response or worsening anemia may indicate need for dose adjustment or re-evaluation of therapy.
Liver Function Tests (LFTs)
Frequency: Periodically, or as clinically indicated, especially if signs of hepatic dysfunction develop.
Target: Within normal limits.
Action Threshold: Significant elevations may require dose adjustment or discontinuation.
Signs and Symptoms of Hemolysis
Frequency: Ongoing clinical assessment.
Target: Reduction in symptoms such as fatigue, jaundice, splenomegaly.
Action Threshold: Worsening symptoms may indicate inadequate response or need for re-evaluation.
Symptom Monitoring
- Fatigue
- Weakness
- Shortness of breath
- Jaundice (yellowing of skin or eyes)
- Dark urine
- Splenomegaly (enlarged spleen)
- Abdominal pain
- Signs of infection (fever, chills)
- Signs of liver problems (unusual tiredness, nausea, vomiting, dark urine, yellowing of skin or eyes, pain in the upper right side of the stomach)
Special Patient Groups
Pregnancy
Based on animal studies, Pyrukynd may cause fetal harm. There are no adequate and well-controlled studies in pregnant women. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Trimester-Specific Risks:
First Trimester:
Potential for developmental toxicity observed in animal studies (e.g., skeletal malformations, reduced fetal weight).
Second Trimester:
Potential for developmental toxicity observed in animal studies.
Third Trimester:
Potential for developmental toxicity observed in animal studies.
Lactation
It is unknown if mitapivat is excreted in human milk. Due to the potential for serious adverse reactions in a breastfed infant, breastfeeding is not recommended during treatment with Pyrukynd and for at least 1 month after the last dose.
Infant Risk:
Unknown, but potential for serious adverse reactions.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established. Pyrukynd is not approved for use in pediatric patients.
Geriatric Use
No overall differences in safety or effectiveness were observed between older patients (âĨ65 years) and younger adult patients. No dose adjustment is required based on age.
Clinical Information
Clinical Pearls
- Pyrukynd is the first and only FDA-approved oral therapy for hemolytic anemia in adults with pyruvate kinase deficiency (PKD).
- Careful dose titration is crucial to optimize response and manage potential side effects.
- Significant drug-drug interactions are possible, especially with CYP3A4 inducers and inhibitors, requiring thorough medication reconciliation.
- Patients should be educated on the importance of consistent dosing and reporting any new or worsening symptoms.
- Response is monitored primarily by hemoglobin levels and reticulocyte count, aiming for a sustained increase in hemoglobin and/or decrease in reticulocyte count.
Alternative Therapies
- Supportive care (e.g., red blood cell transfusions for severe anemia)
- Splenectomy (surgical removal of the spleen, which can reduce hemolysis but carries risks)
- Iron chelation therapy (for patients with iron overload due to chronic transfusions)
- Folic acid supplementation (to support erythropoiesis)
Cost & Coverage
Average Cost:
>$20,000 per 60 tablets (20mg)
Insurance Coverage:
Specialty Tier (requires prior authorization, may have high co-pays/co-insurance)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it's a good idea to check with your pharmacist. If you have any questions or concerns about this medication, don't hesitate to discuss them with your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide information about the medication taken, the amount, and the time it happened.