Pyrukynd 50mg 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 (PK) deficiency. It works by helping an enzyme in your red blood cells work better, 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 as directed, with or without food, and swallow the tablets whole. Do not chew, break, crush, or dissolve them. Continue taking your medication as prescribed 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 the missed one.
To use this medication correctly, follow your doctor's instructions and read all the information provided. Take your medication as directed, with or without food, and swallow the tablets whole. Do not chew, break, crush, or dissolve them. Continue taking your medication as prescribed 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 the missed one.
Lifestyle & Tips
- Take Pyrukynd exactly as prescribed by your doctor, usually twice a day.
- You can take Pyrukynd with or without food.
- Do not stop taking Pyrukynd without talking to your doctor.
- Inform your doctor about all other medications, supplements, and herbal products you are taking, as many can interact with Pyrukynd.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Initial 50 mg orally twice daily. May increase to 100 mg twice daily after 4 weeks, then to 150 mg twice daily after another 4 weeks, up to a maximum of 300 mg twice daily.
Dose Range:
50 - 300 mg
Condition-Specific Dosing:
Pyruvate Kinase Deficiency:
Initial 50 mg orally twice daily. Titrate based on clinical response and tolerability. May increase to 100 mg twice daily after 4 weeks, then to 150 mg twice daily after another 4 weeks. Maximum dose is 300 mg twice daily.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment required.
Moderate:
No dose adjustment required.
Severe:
No dose adjustment required.
Dialysis:
Not studied in patients with end-stage renal disease (ESRD) requiring dialysis. Use with caution.
Hepatic Impairment:
Mild:
No dose adjustment required.
Moderate:
Initial 20 mg orally twice daily. Maximum dose 100 mg twice daily.
Severe:
Initial 10 mg orally twice daily. Maximum dose 50 mg twice daily.
Pharmacology
Mechanism of Action
Mitapivat is an oral, small molecule allosteric activator of pyruvate kinase (PK). It binds to and activates the PK enzyme, increasing its enzymatic activity. In patients with pyruvate kinase deficiency, this leads to increased ATP production and reduced 2,3-bisphosphoglycerate (2,3-BPG) levels, which improves red blood cell health and reduces hemolysis.
Pharmacokinetics
Absorption:
Bioavailability:
Not available (oral drug)
Tmax:
2-4 hours
FoodEffect:
High-fat meal decreases Cmax by 20% and AUC by 10%. Can be taken with or without food.
Distribution:
Vd:
Approximately 200 L
ProteinBinding:
>99%
CnssPenetration:
Limited (high protein binding, P-gp substrate)
Elimination:
HalfLife:
Approximately 10-12 hours
Clearance:
Not available
ExcretionRoute:
Fecal (approximately 80%), Renal (approximately 15%)
Unchanged:
<1% (in urine)
Pharmacodynamics
OnsetOfAction:
Not precisely defined for clinical effect, but PK activation occurs rapidly.
PeakEffect:
Not precisely defined for clinical effect.
DurationOfAction:
Related to half-life, requiring twice-daily dosing.
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
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 immediate medical attention:
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
Abnormal sensations, such as burning, numbness, or tingling
Signs of liver problems, which may include:
+ Dark urine
+ Tiredness
+ Decreased appetite
+ Upset stomach or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes (jaundice)
Note: People taking higher doses of this medication for other health conditions have an increased risk of liver problems, especially during the first 6 months of treatment.
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:
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 immediate medical attention:
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
Abnormal sensations, such as burning, numbness, or tingling
Signs of liver problems, which may include:
+ Dark urine
+ Tiredness
+ Decreased appetite
+ Upset stomach or stomach pain
+ Light-colored stools
+ Vomiting
+ Yellow skin or eyes (jaundice)
Note: People taking higher doses of this medication for other health conditions have an increased risk of liver problems, especially during the first 6 months of treatment.
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:
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:
- Increased fatigue or weakness
- Yellowing of the skin or eyes (jaundice)
- Dark urine
- Unexplained nausea, vomiting, or abdominal pain
- Unusual bleeding or bruising
- Signs of infection (fever, chills)
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 use of this 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, should not be taken with this drug. There are many potential drug interactions, so it is vital to disclose all medications you are taking.
To ensure your safety, it is crucial to provide your doctor and pharmacist with a comprehensive list of all your medications, including prescription and OTC drugs, natural products, and vitamins, as well as any health problems you have. This will enable them to verify that it is safe for you to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without first consulting 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 use of this 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, should not be taken with this drug. There are many potential drug interactions, so it is vital to disclose all medications you are taking.
To ensure your safety, it is crucial to provide your doctor and pharmacist with a comprehensive list of all your medications, including prescription and OTC drugs, natural products, and vitamins, as well as any health problems you have. This will enable them to verify that it is safe for you to take this medication with your other medications and health conditions. Never start, stop, or change the dose of any medication without first consulting your doctor.
Precautions & Cautions
It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Regular blood tests and other laboratory evaluations should be performed as directed by your doctor to monitor your condition.
To minimize the risk of hemolytic anemia (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 symptoms of hemolysis to your doctor, such as jaundice (yellow skin or eyes), dark urine, dizziness, confusion, fatigue, or shortness of breath.
Avoid consuming grapefruit and grapefruit juice while taking this medication, as it may interact with the drug. Additionally, be aware that this medication can cause elevated triglyceride levels. If you have a history of hypertriglyceridemia, 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.
Women taking this medication should be aware that birth control pills and other hormone-based contraceptives may be less effective. To prevent pregnancy, use an additional form of birth control, such as a condom, while taking this drug.
If you are pregnant, plan to become pregnant, or are breastfeeding, consult your doctor to discuss the potential benefits and risks of this medication to you and your baby.
To minimize the risk of hemolytic anemia (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 symptoms of hemolysis to your doctor, such as jaundice (yellow skin or eyes), dark urine, dizziness, confusion, fatigue, or shortness of breath.
Avoid consuming grapefruit and grapefruit juice while taking this medication, as it may interact with the drug. Additionally, be aware that this medication can cause elevated triglyceride levels. If you have a history of hypertriglyceridemia, 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.
Women taking this medication should be aware that birth control pills and other hormone-based contraceptives may be less effective. To prevent pregnancy, use an additional form of birth control, such as a condom, while taking this drug.
If you are pregnant, plan to become pregnant, or are 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:
In case of suspected overdose, contact a poison control center immediately (1-800-222-1222) or seek emergency medical attention.
Drug Interactions
Contraindicated Interactions
- Strong CYP3A inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's Wort): May significantly decrease mitapivat exposure, leading to loss of efficacy.
Major Interactions
- Moderate CYP3A inducers (e.g., efavirenz, bosentan): May decrease mitapivat exposure, leading to loss of efficacy. Avoid coadministration.
- Strong CYP3A inhibitors (e.g., ketoconazole, clarithromycin, ritonavir): May increase mitapivat exposure. Reduce mitapivat dose.
- Moderate CYP3A inhibitors (e.g., fluconazole, diltiazem): May increase mitapivat exposure. Reduce mitapivat dose.
Moderate Interactions
- P-glycoprotein (P-gp) substrates (e.g., digoxin, dabigatran): Mitapivat is a P-gp inhibitor; may increase concentrations of P-gp substrates. Monitor and adjust dose of P-gp substrate as needed.
- Breast Cancer Resistance Protein (BCRP) substrates (e.g., rosuvastatin): Mitapivat is a BCRP inhibitor; may increase concentrations of BCRP substrates. Monitor and adjust dose of BCRP substrate as needed.
Monitoring
Baseline Monitoring
Complete Blood Count (CBC) with Reticulocytes
Rationale: To establish baseline hematologic parameters and assess severity of anemia/hemolysis.
Timing: Prior to initiation of therapy.
Liver Function Tests (LFTs)
Rationale: To establish baseline liver function, as dose adjustments are needed for hepatic impairment.
Timing: Prior to initiation of therapy.
Routine Monitoring
Complete Blood Count (CBC) with Reticulocytes
Frequency: Periodically (e.g., every 4-8 weeks during titration, then every 3-6 months or as clinically indicated)
Target: Improvement in hemoglobin, reduction in reticulocyte count, reduction in indirect bilirubin.
Action Threshold: Lack of response or worsening parameters may indicate need for dose adjustment or re-evaluation.
Liver Function Tests (LFTs)
Frequency: Periodically (e.g., every 3-6 months or as clinically indicated)
Target: Within normal limits or stable from baseline.
Action Threshold: Significant elevations may require dose adjustment or discontinuation.
Symptom Monitoring
- Signs and symptoms of worsening anemia (e.g., increased fatigue, pallor, shortness of breath, dizziness)
- Signs and symptoms of hemolysis (e.g., jaundice, dark urine, scleral icterus)
- Signs and symptoms of liver dysfunction (e.g., unexplained nausea, vomiting, abdominal pain, dark urine, yellowing of skin or eyes)
Special Patient Groups
Pregnancy
Based on animal studies, Pyrukynd may cause fetal harm. There are no adequate and well-controlled studies in pregnant women. Discuss potential risks and benefits with your healthcare provider if you are pregnant or plan to become pregnant.
Trimester-Specific Risks:
First Trimester:
Potential for fetal harm based on animal data.
Second Trimester:
Potential for fetal harm based on animal data.
Third Trimester:
Potential for fetal harm based on animal data.
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 14 days after the last dose.
Infant Risk:
Unknown, but potential for serious adverse reactions.
Pediatric Use
Safety and effectiveness have not been established in pediatric patients.
Geriatric Use
No overall differences in safety or effectiveness were observed between elderly patients and younger adult patients. No specific dose adjustment is required based on age alone.
Clinical Information
Clinical Pearls
- Pyrukynd is the first and only FDA-approved oral therapy for pyruvate kinase deficiency.
- Dose titration is crucial for optimizing response and managing tolerability.
- Patients should be educated on the importance of consistent dosing and potential drug interactions, especially with CYP3A inducers/inhibitors.
- Regular monitoring of hematologic parameters and liver function is essential.
Alternative Therapies
- Blood transfusions (supportive care for anemia)
- Splenectomy (surgical intervention for severe hemolysis)
- Iron chelation therapy (for transfusion-dependent patients)
Cost & Coverage
Average Cost:
Highly variable, typically >$20,000 per 60 tablets (50mg)
Insurance Coverage:
Specialty Tier (requires prior authorization, often subject to step therapy)
General Drug Facts
If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe and effective treatment, 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 for more information. If you have any questions or concerns about your 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 reporting the incident, be prepared to provide details about the medication taken, the amount, and the time it occurred.