Uptravi 1600mcg Tablets
It is used to treat high blood pressure in the lungs.
Drug Class
Agent for pulmonary hypertension
Pharmacologic Class
Selective prostacyclin IP receptor agonist
Pregnancy Category
Not available
FDA Approved
Dec 2015
DEA Schedule
Not Controlled
Overview
What is this medicine?
Uptravi (selexipag) is a medication used to treat pulmonary arterial hypertension (PAH), a condition where blood pressure in the arteries leading to your lungs is too high. It works by relaxing and widening the blood vessels in your lungs, which helps your heart pump blood more easily and can improve your breathing and ability to exercise.
How to Use This Medicine
Taking Your Medication
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided with your prescription and follow the instructions closely. You can take this medication with or without food. Taking it with food may help reduce some side effects. Swallow the medication whole - do not chew, break, or crush it. Continue taking the medication as directed by your doctor or healthcare provider, even if you start to feel better.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, away from the bathroom. Keep all medications in a safe location, out of the reach of children and pets. Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so. If you have questions about disposing of your medication, consult your pharmacist. You may also want to check if there are any drug take-back programs in your area.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it is almost time for your next dose (less than 6 hours), skip the missed dose and take the next one at the regular time. Do not take two doses at the same time or take extra doses. If you miss three days of medication, contact your doctor for guidance on what to do next.
To get the most benefit from your medication, follow your doctor's instructions carefully. Read all the information provided with your prescription and follow the instructions closely. You can take this medication with or without food. Taking it with food may help reduce some side effects. Swallow the medication whole - do not chew, break, or crush it. Continue taking the medication as directed by your doctor or healthcare provider, even if you start to feel better.
Storing and Disposing of Your Medication
Store your medication at room temperature in a dry place, away from the bathroom. Keep all medications in a safe location, out of the reach of children and pets. Dispose of unused or expired medications properly. Do not flush them down the toilet or pour them down the drain unless instructed to do so. If you have questions about disposing of your medication, consult your pharmacist. You may also want to check if there are any drug take-back programs in your area.
What to Do If You Miss a Dose
If you miss a dose, take it as soon as you remember. However, if it is almost time for your next dose (less than 6 hours), skip the missed dose and take the next one at the regular time. Do not take two doses at the same time or take extra doses. If you miss three days of medication, contact your doctor for guidance on what to do next.
Lifestyle & Tips
- Take Uptravi exactly as prescribed by your doctor. Do not stop taking it suddenly, as this can worsen your condition.
- Swallow tablets whole. Do not crush, chew, or split the tablets.
- If you miss a dose, take it as soon as you remember, unless it's almost time for your next dose. Do not take two doses at once.
- Report any new or worsening side effects to your doctor.
- Avoid grapefruit juice as it may interact with the medication (though not a major interaction, it's a general precaution for CYP3A4 substrates).
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Initial dose of 200 mcg twice daily, titrated in increments of 200 mcg twice daily, usually weekly, to the highest tolerated dose up to 1600 mcg twice daily. The 1600 mcg tablet is the maximum individual dose.
Dose Range:
200 - 1600 mg
Condition-Specific Dosing:
Pulmonary Arterial Hypertension (PAH):
Initial 200 mcg twice daily, titrated weekly by 200 mcg twice daily increments to the highest tolerated dose up to 1600 mcg 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 (CrCl 50-80 mL/min)
Moderate:
No dose adjustment required (CrCl 30-49 mL/min)
Severe:
Consider starting at 200 mcg once daily, then titrating to twice daily if tolerated (CrCl < 30 mL/min)
Dialysis:
Consider starting at 200 mcg once daily, then titrating to twice daily if tolerated (ESRD requiring dialysis)
Hepatic Impairment:
Mild:
No dose adjustment required (Child-Pugh A)
Moderate:
Start at 200 mcg once daily, then titrate to twice daily if tolerated (Child-Pugh B)
Severe:
Avoid use (Child-Pugh C)
Pharmacology
Mechanism of Action
Selexipag is an orally available, selective IP prostacyclin receptor agonist. It is hydrolyzed by carboxylesterase 1 (CES1) to its active metabolite, ACT-333679. Both selexipag and its active metabolite are selective agonists of the prostacyclin receptor (IP receptor). Activation of the IP receptor leads to vasodilation, inhibition of platelet aggregation, and antiproliferative effects. These actions are beneficial in pulmonary arterial hypertension (PAH) by reducing pulmonary vascular resistance.
Pharmacokinetics
Absorption:
Bioavailability:
Not explicitly stated, but well absorbed
Tmax:
Selexipag: 1-3 hours; Active metabolite (ACT-333679): 3-4 hours
FoodEffect:
High-fat meal does not significantly affect AUC or Cmax of selexipag or its active metabolite. Can be taken with or without food.
Distribution:
Vd:
Selexipag: 11.5 L; Active metabolite: 13.7 L
ProteinBinding:
Selexipag: >99%; Active metabolite: >99%
CnssPenetration:
Limited
Elimination:
HalfLife:
Selexipag: 0.8-2.5 hours; Active metabolite: 6.2-13.5 hours
Clearance:
Primarily hepatic
ExcretionRoute:
Primarily fecal (93%), minor renal (5%)
Unchanged:
<1%
Pharmacodynamics
OnsetOfAction:
Not precisely defined for clinical effect, but vasodilation occurs rapidly.
PeakEffect:
Not precisely defined for clinical effect, but related to active metabolite peak concentration.
DurationOfAction:
Sustained effect due to active metabolite's longer half-life, allowing twice-daily dosing.
Confidence:
Medium
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Attention Immediately
Although rare, this medication can cause severe and potentially life-threatening side effects. If you experience 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, or swelling of the mouth, face, lips, tongue, or throat
- New or worsening trouble breathing
- Wheezing or coughing
- Feeling extremely tired or weak
Other Possible Side Effects
Like all medications, this drug can cause side effects, although not everyone will experience them. Some people may have no side effects or only mild ones. If you are bothered by any of the following side effects or if they do not go away, contact your doctor or seek medical help:
- Headache
- Diarrhea, upset stomach, or vomiting
- Jaw pain
- Muscle or joint pain
- Pain in the arms or legs
- Flushing
- Decreased appetite
Reporting Side Effects
This list does not include all possible side effects. If you have questions or concerns about side effects, contact your doctor for medical advice. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.
Although rare, this medication can cause severe and potentially life-threatening side effects. If you experience 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, or swelling of the mouth, face, lips, tongue, or throat
- New or worsening trouble breathing
- Wheezing or coughing
- Feeling extremely tired or weak
Other Possible Side Effects
Like all medications, this drug can cause side effects, although not everyone will experience them. Some people may have no side effects or only mild ones. If you are bothered by any of the following side effects or if they do not go away, contact your doctor or seek medical help:
- Headache
- Diarrhea, upset stomach, or vomiting
- Jaw pain
- Muscle or joint pain
- Pain in the arms or legs
- Flushing
- Decreased appetite
Reporting Side Effects
This list does not include all possible side effects. If you have questions or concerns about side effects, contact your doctor for medical advice. 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:
- Severe or persistent headache
- Persistent or severe flushing
- Severe or persistent nausea, vomiting, or diarrhea (especially if leading to dehydration)
- Signs of bleeding (e.g., unusual bruising, nosebleeds, blood in urine or stool)
- Symptoms of low blood pressure (e.g., dizziness, lightheadedness, fainting)
- New or worsening shortness of breath or chest pain
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 as a result of the allergy.
If you have liver disease, as this may affect how your body processes the medication.
* If you are currently taking gemfibrozil, as this can interact with the medication.
Please note that this is not an exhaustive list of potential interactions. To ensure your safety, it is crucial to discuss all of your medications, including prescription and over-the-counter drugs, natural products, and vitamins, with your doctor and pharmacist. Additionally, inform them about any health problems you are experiencing.
Remember, before starting, stopping, or changing the dose of any medication, including this one, you must consult with your doctor to confirm that it is safe to do so in conjunction 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 as a result of the allergy.
If you have liver disease, as this may affect how your body processes the medication.
* If you are currently taking gemfibrozil, as this can interact with the medication.
Please note that this is not an exhaustive list of potential interactions. To ensure your safety, it is crucial to discuss all of your medications, including prescription and over-the-counter drugs, natural products, and vitamins, with your doctor and pharmacist. Additionally, inform them about any health problems you are experiencing.
Remember, before starting, stopping, or changing the dose of any medication, including this one, you must consult with your doctor to confirm that it is safe to do so in conjunction with your other medications and health conditions.
Precautions & Cautions
It is essential to inform all of your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. If you are pregnant, planning to become pregnant, or are currently breast-feeding, be sure to discuss this with your doctor. You and your doctor will need to carefully weigh the benefits and risks of using this medication to ensure the best possible outcome for both you and your baby.
Overdose Information
Overdose Symptoms:
- Headache
- Flushing
- Nausea
- Vomiting
- Diarrhea
- Hypotension (low blood pressure)
What to Do:
In case of suspected overdose, seek immediate medical attention or call a poison control center (e.g., 1-800-222-1222). Management is supportive and symptomatic.
Drug Interactions
Major Interactions
- Strong CYP2C8 inhibitors (e.g., Gemfibrozil): Co-administration significantly increases exposure to the active metabolite, requiring a dose reduction of selexipag.
- Strong CYP2C8 inducers (e.g., Rifampin): Co-administration significantly decreases exposure to the active metabolite, potentially reducing efficacy.
Moderate Interactions
- Moderate CYP2C8 inhibitors/inducers: May require monitoring or dose adjustment.
Confidence Interactions
Monitoring
Baseline Monitoring
Liver Function Tests (LFTs)
Rationale: To establish baseline hepatic function, especially given hepatic metabolism and potential for hepatic impairment dose adjustments.
Timing: Prior to initiation of therapy.
Pregnancy Test
Rationale: For females of reproductive potential, due to potential fetal harm.
Timing: Prior to initiation of therapy.
Routine Monitoring
Blood Pressure
Frequency: Periodically, especially during dose titration
Target: Individualized, monitor for symptomatic hypotension
Action Threshold: Symptomatic hypotension or significant drop from baseline; consider dose reduction or discontinuation.
Heart Rate
Frequency: Periodically
Target: Individualized
Action Threshold: Significant tachycardia or bradycardia, especially if symptomatic.
Symptoms of PAH (e.g., dyspnea, fatigue, exercise capacity)
Frequency: Regularly during follow-up visits
Target: Improvement or stabilization of symptoms
Action Threshold: Worsening symptoms may indicate inadequate response or disease progression.
Adverse Effects (e.g., headache, flushing, jaw pain, nausea, vomiting, diarrhea, myalgia, arthralgia)
Frequency: Regularly, especially during dose titration
Target: Tolerable levels
Action Threshold: Intolerable or severe adverse effects may require dose reduction or discontinuation.
Symptom Monitoring
- Headache (often dose-dependent)
- Flushing
- Jaw pain
- Nausea
- Vomiting
- Diarrhea
- Myalgia (muscle pain)
- Arthralgia (joint pain)
- Hypotension (dizziness, lightheadedness)
- Bleeding (unusual bruising, nosebleeds, gum bleeding)
Special Patient Groups
Pregnancy
Based on animal data, selexipag 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. Females of reproductive potential should use effective contraception during treatment.
Trimester-Specific Risks:
First Trimester:
Potential for fetal harm based on animal studies (e.g., teratogenicity, embryolethality at high doses).
Second Trimester:
Potential for fetal harm based on animal studies.
Third Trimester:
Potential for fetal harm based on animal studies.
Lactation
It is not known whether selexipag or its active metabolite are excreted in human milk. Due to the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with selexipag.
Infant Risk:
Moderate risk (L3) or Not available (due to lack of human data and potential for serious adverse effects).
Pediatric Use
Safety and effectiveness in pediatric patients have not been established. Use is not recommended.
Geriatric Use
No overall differences in safety or effectiveness were observed between elderly (âĨ65 years) and younger patients. However, greater sensitivity of some older individuals cannot be ruled out. Dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range.
Clinical Information
Clinical Pearls
- Selexipag requires careful dose titration to optimize efficacy and manage dose-dependent side effects. Patients should be educated on the importance of adherence to the titration schedule.
- Common side effects (headache, flushing, jaw pain, GI upset) are related to its vasodilatory mechanism and often improve with continued therapy or dose adjustment.
- Do not abruptly discontinue selexipag, as this can lead to clinical worsening of PAH.
- Tablets must be swallowed whole; crushing, chewing, or splitting can alter drug release and absorption.
- Consider dose adjustment or avoidance with strong CYP2C8 inhibitors/inducers due to significant impact on active metabolite exposure.
Alternative Therapies
- Endothelin Receptor Antagonists (ERAs): Ambrisentan (Letairis), Bosentan (Tracleer), Macitentan (Opsumit)
- Phosphodiesterase-5 Inhibitors (PDE5i): Sildenafil (Revatio), Tadalafil (Adcirca)
- Soluble Guanylate Cyclase (sGC) Stimulators: Riociguat (Adempas)
Cost & Coverage
Average Cost:
High (e.g., $10,000 - $20,000+) per 30 tablets
Insurance Coverage:
Specialty Tier (requires prior authorization, often subject to high co-pays or co-insurance)
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 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 details about the medication taken, the amount, and the time it happened.