Pyrukynd 5mg Tab Taper Pack
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 medicine used to treat a rare genetic blood disorder called pyruvate kinase (PK) deficiency in adults. It works by helping your 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 as directed, with or without food. Swallow the tablet whole - do not chew, break, crush, or dissolve it. 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 the bathroom. 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 as directed, with or without food. Swallow the tablet whole - do not chew, break, crush, or dissolve it. 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 the bathroom. 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, with or without food.
- Do not stop taking Pyrukynd without talking to your doctor, as your symptoms may worsen.
- Inform your doctor about all other medications, supplements, and herbal products you are taking, as Pyrukynd can interact with many drugs.
- Report any new or worsening symptoms, especially signs of liver problems (yellow skin/eyes, dark urine, severe stomach pain) or unusual bleeding/bruising.
- Maintain good hydration as advised by your doctor.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Initial: 5 mg orally twice daily (BID) for 2 weeks. Increase to 20 mg BID for 2 weeks. Then increase to 50 mg BID. Maximum: 50 mg BID.
Dose Range:
5 - 50 mg
Condition-Specific Dosing:
Pyruvate Kinase Deficiency:
Initial: 5 mg orally BID for 2 weeks. Increase to 20 mg BID for 2 weeks. Then increase to 50 mg BID. Maximum: 50 mg BID. Dose adjustments based on hemoglobin response and tolerability.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment required (eGFR 60-89 mL/min/1.73 m^2)
Moderate:
No dose adjustment required (eGFR 30-59 mL/min/1.73 m^2)
Severe:
Avoid use (eGFR <30 mL/min/1.73 m^2) due to lack of data
Dialysis:
Avoid use due to lack of data
Hepatic Impairment:
Mild:
No dose adjustment required (Child-Pugh A)
Moderate:
Reduce initial dose to 5 mg BID. Maximum dose 20 mg BID (Child-Pugh B)
Severe:
Avoid use (Child-Pugh C) due to lack of data
Pharmacology
Mechanism of Action
Mitapivat is an oral, allosteric activator of pyruvate kinase (PK). It binds to and activates wild-type and mutated pyruvate kinase (PK) enzymes, including the most common PKLR mutations, leading to increased PK activity. This results in increased adenosine triphosphate (ATP) production and reduced 2,3-bisphosphoglycerate (2,3-BPG) levels in red blood cells, which improves red blood cell function and reduces hemolysis in patients with pyruvate kinase deficiency.
Pharmacokinetics
Absorption:
Bioavailability:
Not explicitly quantified, but well absorbed
Tmax:
2-4 hours
FoodEffect:
High-fat meal decreases Cmax by 20% and AUC by 10%, not clinically significant. Can be taken with or without food.
Distribution:
Vd:
Approximately 230 L
ProteinBinding:
Approximately 99%
CnssPenetration:
Limited
Elimination:
HalfLife:
Approximately 10-12 hours
Clearance:
Not explicitly stated, but primarily hepatic
ExcretionRoute:
Fecal (approximately 78%), Urine (approximately 12%)
Unchanged:
<1% (in urine)
Pharmacodynamics
OnsetOfAction:
Within weeks (based on clinical response)
PeakEffect:
Not precisely defined, but steady state achieved within 3-5 days
DurationOfAction:
Related to half-life, effects persist as long as drug is present
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
Abnormal sensations, such as burning, numbness, or tingling
Liver problems, which may be indicated by:
+ 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 unusual symptoms, 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
Abnormal sensations, such as burning, numbness, or tingling
Liver problems, which may be indicated by:
+ 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 unusual symptoms, 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:
- Yellowing of the skin or eyes (jaundice)
- Dark urine
- Severe stomach pain
- Unusual tiredness or weakness
- Nausea or vomiting
- Easy bruising or bleeding
- Signs of infection (fever, chills, sore throat)
- Any new or worsening symptoms of anemia (e.g., increased fatigue, shortness of breath, dizziness)
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 symptoms you experienced.
If you have liver disease, as this may affect the safety and efficacy of 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 and effective treatment.
To guarantee your safety, always check with your doctor before starting, stopping, or changing the dose of any medication, including this one. This will help prevent potential interactions and ensure that you can take this medication safely 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 symptoms you experienced.
If you have liver disease, as this may affect the safety and efficacy of 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 and effective treatment.
To guarantee your safety, always check with your doctor before starting, stopping, or changing the dose of any medication, including this one. This will help prevent potential interactions and ensure that you can take this medication safely 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. Regular blood tests and other laboratory assessments should be conducted as directed by your doctor 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, such as jaundice (yellowing of the skin or eyes), dark urine, dizziness, confusion, fatigue, or shortness of breath.
Grapefruit and grapefruit juice should be avoided while taking this medication, as they may interact with the drug. Additionally, be aware that this medication can 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.
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, such as jaundice (yellowing of the skin or eyes), dark urine, dizziness, confusion, fatigue, or shortness of breath.
Grapefruit and grapefruit juice should be avoided while taking this medication, as they may interact with the drug. Additionally, be aware that this medication can 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.
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 such as headache, nausea, insomnia, or elevated liver enzymes.
What to Do:
In case of suspected overdose, contact a poison control center immediately (e.g., 1-800-222-1222 in the US) or seek emergency medical attention. Management should be supportive and directed at treating symptoms.
Drug Interactions
Contraindicated Interactions
- Strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, enzalutamide, mitotane, St. John's Wort): May significantly decrease mitapivat exposure, leading to loss of efficacy.
Major Interactions
- Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, ritonavir, itraconazole): May significantly increase mitapivat exposure. Mitapivat dose reduction may be required (e.g., max 5 mg BID).
- Sensitive CYP3A4 substrates (e.g., midazolam, simvastatin, oral contraceptives): Mitapivat is a moderate CYP3A4 inducer; may decrease exposure of these drugs, leading to reduced efficacy.
- Sensitive CYP2B6 substrates (e.g., bupropion, efavirenz): Mitapivat is a CYP2B6 inducer; may decrease exposure of these drugs.
- UGT substrates (e.g., raltegravir, dolutegravir, lamotrigine): Mitapivat is a UGT inducer; may decrease exposure of these drugs.
- OATP1B1/1B3 substrates (e.g., statins like rosuvastatin, atorvastatin, valsartan): Mitapivat is an OATP1B1/1B3 inhibitor; may increase exposure of these drugs.
- P-gp substrates (e.g., digoxin, dabigatran): Mitapivat is a P-gp inhibitor; may increase exposure of these drugs.
Moderate Interactions
- Moderate CYP3A4 inducers (e.g., bosentan, efavirenz, etravirine, modafinil, nafcillin): May decrease mitapivat exposure. Monitor for reduced efficacy.
- Moderate CYP3A4 inhibitors (e.g., diltiazem, erythromycin, fluconazole, verapamil): May increase mitapivat exposure. Monitor for adverse effects.
Minor Interactions
- Weak CYP3A4 inducers/inhibitors: Clinically insignificant interactions expected.
Monitoring
Baseline Monitoring
Hemoglobin (Hb)
Rationale: To establish baseline and assess response to treatment.
Timing: Prior to initiation of therapy
Reticulocyte count
Rationale: Indicator of red blood cell production and hemolysis.
Timing: Prior to initiation of therapy
Indirect bilirubin, LDH, Haptoglobin
Rationale: Markers of hemolysis.
Timing: Prior to initiation of therapy
Liver function tests (ALT, AST, total bilirubin)
Rationale: To assess hepatic function and monitor for drug-induced liver injury.
Timing: Prior to initiation of therapy
Renal function (eGFR)
Rationale: To assess baseline renal function and guide dosing in impairment.
Timing: Prior to initiation of therapy
Routine Monitoring
Hemoglobin (Hb)
Frequency: Every 4 weeks for the first 3 months, then periodically as clinically indicated
Target: Individualized, aiming for increase from baseline
Action Threshold: Consider dose adjustment or discontinuation if no meaningful increase in Hb or if Hb falls below baseline.
Reticulocyte count
Frequency: Every 4 weeks for the first 3 months, then periodically as clinically indicated
Target: Individualized, aiming for decrease from baseline
Action Threshold: Consider dose adjustment if persistently high or increasing.
Indirect bilirubin, LDH
Frequency: Every 4 weeks for the first 3 months, then periodically as clinically indicated
Target: Individualized, aiming for decrease from baseline
Action Threshold: Consider dose adjustment if persistently high or increasing.
Liver function tests (ALT, AST, total bilirubin)
Frequency: Every 4 weeks for the first 3 months, then periodically as clinically indicated
Target: Within normal limits or stable
Action Threshold: Elevations >3x ULN or signs of liver injury warrant dose interruption or discontinuation.
Symptom Monitoring
- Fatigue
- Dyspnea
- Jaundice (yellowing of skin or eyes)
- Dark urine
- Abdominal pain
- Unusual bleeding or bruising
- Signs of infection
- Any new or worsening symptoms
Special Patient Groups
Pregnancy
There are no adequate and well-controlled studies of Pyrukynd in pregnant women. Animal studies showed adverse developmental effects (embryo-fetal lethality, reduced fetal weight, skeletal variations) at exposures higher than clinical. Pyrukynd should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Trimester-Specific Risks:
First Trimester:
Potential for embryo-fetal toxicity based on animal data.
Second Trimester:
Potential for embryo-fetal toxicity based on animal data.
Third Trimester:
Potential for embryo-fetal toxicity based on animal data.
Lactation
It is not known whether mitapivat or its metabolites are excreted in human milk. Due to the potential for serious adverse reactions in the breastfed infant, advise patients not to breastfeed during treatment with Pyrukynd and for 3 days after the last dose.
Infant Risk:
High (L5 - Contraindicated)
Pediatric Use
The safety and effectiveness of Pyrukynd in pediatric patients have not been established. Not approved for use in pediatric patients.
Geriatric Use
No overall differences in safety or effectiveness were observed between elderly patients (âĨ65 years) and younger patients. No specific dose adjustment is required based on age alone, but consider age-related decreases in hepatic, renal, or cardiac function and concomitant disease or other drug therapy.
Clinical Information
Clinical Pearls
- Pyrukynd is the first and only approved disease-modifying therapy for Pyruvate Kinase Deficiency (PKD).
- The 5mg 'Taper Pack' is designed for the initial titration phase of treatment.
- Patients should be carefully monitored for hemoglobin response and signs of hemolysis (e.g., reticulocyte count, bilirubin, LDH) to assess efficacy.
- Due to significant drug-drug interactions, a thorough medication review is crucial before initiating and during treatment, especially with CYP3A4 inducers/inhibitors and substrates of CYP2B6, UGT, OATP1B1/1B3, and P-gp.
- Liver function tests should be monitored regularly due to potential for hepatotoxicity.
- Patients may experience initial increases in bilirubin as hemolysis improves, which is generally not a concern unless accompanied by other signs of liver injury.
Alternative Therapies
- Red blood cell transfusions (supportive care)
- Splenectomy (surgical intervention, often considered in severe cases)
- Iron chelation therapy (if iron overload from transfusions)
- Folic acid supplementation (to support erythropoiesis)
Cost & Coverage
Average Cost:
$20,000 - $30,000+ per 60 tablets (1 month supply of 50mg BID)
Insurance Coverage:
Specialty Tier (requires prior authorization, may have high co-pays)
General Drug Facts
If your symptoms or health issues persist or worsen, it's 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 be sure to check with your pharmacist for more information. If you have any questions or concerns about your medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek medical attention. When seeking help, be prepared to provide details about the medication taken, the amount, and the time it happened.