Uptravi 400mcg Tablets
It is used to treat high blood pressure in the lungs.
Drug Class
Pulmonary Arterial Hypertension Agent
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 the blood vessels in your lungs, making it easier for your heart to pump blood, which can improve your ability to exercise and slow down the worsening of your condition.
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 minimize some side effects. It's essential to swallow the medication whole - do not chew, break, or crush it.
Continue taking your medication as directed by your doctor or healthcare provider, even if you start feeling well. This will help ensure that you receive the full benefits of the treatment.
Storing and Disposing of Your Medication
To keep your medication effective and safe, store it at room temperature in a dry place, away from the bathroom. Keep all medications in a secure location, out of the reach of children and pets. When your medication is no longer needed or has expired, dispose of it properly. Do not flush it down the toilet or pour it down the drain unless instructed to do so by your pharmacist. If you have questions about disposing of your medication, consult with your pharmacist, who can also inform you about any drug take-back programs in your area.
Missing a Dose
If you miss a dose, take it as soon as you remember. However, if it's almost time for your next dose (less than 6 hours), skip the missed dose and return to your regular schedule. Do not take two doses at the same time or take extra doses. If you miss three consecutive days of your medication, contact your doctor for guidance on how to proceed.
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 minimize some side effects. It's essential to swallow the medication whole - do not chew, break, or crush it.
Continue taking your medication as directed by your doctor or healthcare provider, even if you start feeling well. This will help ensure that you receive the full benefits of the treatment.
Storing and Disposing of Your Medication
To keep your medication effective and safe, store it at room temperature in a dry place, away from the bathroom. Keep all medications in a secure location, out of the reach of children and pets. When your medication is no longer needed or has expired, dispose of it properly. Do not flush it down the toilet or pour it down the drain unless instructed to do so by your pharmacist. If you have questions about disposing of your medication, consult with your pharmacist, who can also inform you about any drug take-back programs in your area.
Missing a Dose
If you miss a dose, take it as soon as you remember. However, if it's almost time for your next dose (less than 6 hours), skip the missed dose and return to your regular schedule. Do not take two doses at the same time or take extra doses. If you miss three consecutive days of your medication, contact your doctor for guidance on how to proceed.
Lifestyle & Tips
- Take Uptravi exactly as prescribed by your doctor, usually twice a day. Do not stop taking it suddenly without consulting your doctor, as this can worsen your condition.
- Do not crush, chew, or split the tablets. Swallow them whole.
- 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.
- If you interrupt treatment for 3 or more days, contact your doctor as you may need to restart at a lower dose and re-titrate.
- Be aware of common side effects like headache, jaw pain, nausea, diarrhea, and flushing, especially during dose titration. These often lessen over time.
- Report any signs of bleeding or unusual bruising to your doctor.
- Avoid grapefruit juice as it may interact with this medication.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Initial dose 200 mcg orally twice daily, titrated in increments of 200 mcg twice daily, usually weekly, to the highest tolerated dose up to 1600 mcg twice daily.
Dose Range:
200 - 1600 mg
Condition-Specific Dosing:
Titration:
Increase by 200 mcg twice daily, usually weekly, to the highest tolerated dose. If dose is not tolerated, reduce to the previous tolerated dose. If treatment is interrupted for 3 or more days, restart at 200 mcg twice daily and re-titrate.
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 (CrCl < 30 mL/min). Clinical experience is limited.
Dialysis:
No dose adjustment required. Clinical experience is limited.
Hepatic Impairment:
Mild:
No dose adjustment required (Child-Pugh A).
Moderate:
Initial dose 200 mcg once daily. Titrate cautiously in increments of 200 mcg once daily, usually weekly, to the highest tolerated dose. Maximum recommended dose is 800 mcg once daily (Child-Pugh B).
Severe:
Avoid use (Child-Pugh C).
Pharmacology
Mechanism of Action
Selexipag is an oral, selective prostacyclin IP receptor agonist. It is hydrolyzed by carboxylesterase 1 to its active metabolite, ACT-333679, which is approximately 37 times more potent than selexipag. 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 available (absolute bioavailability not determined due to high first-pass metabolism)
Tmax:
1-2 hours (selexipag), 3-4 hours (active metabolite)
FoodEffect:
Food does not significantly affect the bioavailability of selexipag or its active metabolite, but delays Tmax.
Distribution:
Vd:
11.5 L (selexipag), 16.7 L (active metabolite)
ProteinBinding:
>99% (selexipag and active metabolite)
CnssPenetration:
Limited
Elimination:
HalfLife:
0.8-2.5 hours (selexipag), 6.2-13.5 hours (active metabolite)
Clearance:
Not available
ExcretionRoute:
Fecal (93%), Renal (7%)
Unchanged:
Not available
Pharmacodynamics
OnsetOfAction:
Not precisely quantified, but effects on pulmonary vascular resistance are observed within hours of dosing.
PeakEffect:
Correlates with peak plasma concentrations of the active metabolite (3-4 hours).
DurationOfAction:
Sustained effect due to the longer half-life of the active metabolite, supporting twice-daily dosing.
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Attention Immediately
While rare, some people may experience severe and potentially life-threatening side effects when 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
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 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:
Headache
Diarrhea
Upset stomach or vomiting
Jaw pain
Muscle or joint pain
Pain in arms or legs
Flushing
Decreased appetite
Reporting Side Effects
This list is not exhaustive, and you may experience other 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.
While rare, some people may experience severe and potentially life-threatening side effects when 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
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 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:
Headache
Diarrhea
Upset stomach or vomiting
Jaw pain
Muscle or joint pain
Pain in arms or legs
Flushing
Decreased appetite
Reporting Side Effects
This list is not exhaustive, and you may experience other 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:
- Severe or persistent headache
- Severe or persistent jaw pain
- Dizziness or lightheadedness (signs of low blood pressure)
- Unusual bleeding or bruising
- Severe nausea, vomiting, or diarrhea that does not improve
- Signs of worsening PAH (e.g., increased shortness of breath, chest pain, swelling in legs/ankles)
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 medication's safety and efficacy.
* If you are currently taking gemfibrozil, as this can interact with the medication.
This list is not exhaustive, and it is crucial to discuss all your medications, including prescription and over-the-counter drugs, natural products, and vitamins, with your doctor and pharmacist. They will help you determine if it is safe to take this medication with your existing treatments and health conditions.
Remember, do not start, stop, or adjust the dose of any medication without first consulting your doctor to ensure your safety and the effectiveness of your treatment.
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 medication's safety and efficacy.
* If you are currently taking gemfibrozil, as this can interact with the medication.
This list is not exhaustive, and it is crucial to discuss all your medications, including prescription and over-the-counter drugs, natural products, and vitamins, with your doctor and pharmacist. They will help you determine if it is safe to take this medication with your existing treatments and health conditions.
Remember, do not start, stop, or adjust the dose of any medication without first consulting your doctor to ensure your safety and the effectiveness of your treatment.
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 breast-feeding, you must discuss this with your doctor. This conversation will help you understand the potential benefits and risks of this medication to both you and your baby, allowing you to make an informed decision.
Overdose Information
Overdose Symptoms:
- Severe headache
- Nausea
- Vomiting
- Diarrhea
- Flushing
- Hypotension (dizziness, lightheadedness)
- Tachycardia (fast heart rate)
What to Do:
In case of overdose, seek immediate medical attention or call a Poison Control Center (1-800-222-1222). Supportive care should be provided as clinically indicated.
Drug Interactions
Major Interactions
- Strong CYP2C8 inhibitors (e.g., Gemfibrozil): Concomitant use is contraindicated. Gemfibrozil significantly increases exposure to selexipag and its active metabolite.
Moderate Interactions
- Strong CYP2C8 inducers (e.g., Rifampin): May decrease exposure to selexipag and its active metabolite, potentially reducing efficacy. Avoid concomitant use.
- Moderate CYP2C8 inhibitors (e.g., Clopidogrel, Deferasirox): May increase exposure to selexipag and its active metabolite. Consider dose reduction of selexipag.
- Strong CYP3A4 inhibitors (e.g., Ketoconazole, Itraconazole, Ritonavir, Clarithromycin): May increase exposure to selexipag and its active metabolite. Monitor for adverse effects.
- Strong CYP3A4 inducers (e.g., Carbamazepine, Phenytoin, St. John's Wort): May decrease exposure to selexipag and its active metabolite. Monitor for reduced efficacy.
Minor Interactions
- Other vasodilators (e.g., PDE5 inhibitors, endothelin receptor antagonists): May increase risk of systemic hypotension. Monitor blood pressure.
- Antiplatelet agents (e.g., Aspirin, Clopidogrel): May increase risk of bleeding due to selexipag's antiplatelet effects. Monitor for signs of bleeding.
Monitoring
Baseline Monitoring
Liver function tests (ALT, AST, bilirubin)
Rationale: To assess baseline hepatic function, especially given dose adjustments for hepatic impairment.
Timing: Prior to initiation of therapy.
Renal function (eGFR, CrCl)
Rationale: To assess baseline renal function, though no dose adjustment is typically needed for renal impairment.
Timing: Prior to initiation of therapy.
Blood pressure and heart rate
Rationale: Selexipag can cause systemic hypotension and flushing.
Timing: Prior to initiation of therapy.
Routine Monitoring
Blood pressure and heart rate
Frequency: Regularly, especially during dose titration and if symptoms of hypotension occur.
Target: Maintain within clinically acceptable limits for the patient.
Action Threshold: Significant or symptomatic hypotension; consider dose reduction or discontinuation.
Symptoms of PAH (e.g., dyspnea, fatigue, exercise capacity)
Frequency: Regularly, at each follow-up visit.
Target: Improvement or stabilization of symptoms.
Action Threshold: Worsening symptoms; consider re-evaluation of treatment strategy.
Adverse effects (e.g., headache, jaw pain, nausea, diarrhea, flushing, myalgia)
Frequency: Regularly, especially during dose titration.
Target: Tolerable level of side effects.
Action Threshold: Intolerable side effects; consider dose reduction or discontinuation.
Symptom Monitoring
- Headache
- Jaw pain
- Nausea
- Diarrhea
- Flushing
- Myalgia
- Pain in extremities
- Hypotension (dizziness, lightheadedness)
- Vomiting
- Anemia (fatigue, pallor)
Special Patient Groups
Pregnancy
There are no adequate and well-controlled studies of selexipag in pregnant women. Animal studies have shown adverse developmental effects. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Trimester-Specific Risks:
First Trimester:
Potential for embryo-fetal toxicity observed in animal studies.
Second Trimester:
Potential for embryo-fetal toxicity observed in animal studies.
Third Trimester:
Potential for embryo-fetal toxicity observed in animal studies.
Lactation
It is not known if selexipag or its active metabolite are excreted in human milk. Selexipag and its active metabolite were excreted in the milk of lactating rats. Because of the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with selexipag.
Infant Risk:
Risk of serious adverse reactions in breastfed infants.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established. Use is not recommended.
Geriatric Use
No specific dose adjustment is required based on age. However, caution should be exercised in elderly patients due to the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant disease or other drug therapy.
Clinical Information
Clinical Pearls
- Selexipag is a prostacyclin pathway agent, but unlike inhaled or parenteral prostacyclins, it is an oral tablet, offering convenience.
- The dose titration is crucial for patient tolerability. Patients often experience dose-dependent side effects (headache, jaw pain, nausea, diarrhea, flushing) which tend to improve with continued therapy.
- Sudden discontinuation can lead to clinical worsening of PAH. If treatment is interrupted for 3 or more days, re-initiation should be at a lower dose with re-titration.
- Contraindicated with strong CYP2C8 inhibitors like gemfibrozil due to significantly increased exposure.
- Patients with moderate hepatic impairment (Child-Pugh B) require a reduced starting dose and maximum dose. Avoid use in severe hepatic impairment (Child-Pugh C).
Alternative Therapies
- Endothelin Receptor Antagonists (ERAs): Ambrisentan, Bosentan, Macitentan
- PDE5 Inhibitors: Sildenafil, Tadalafil
- Guanylate Cyclase Stimulators: Riociguat
- Prostacyclin Analogues (PGI2): Epoprostenol, Treprostinil (oral, inhaled, subcutaneous, intravenous), Iloprost (inhaled)
Cost & Coverage
Average Cost:
Varies widely, typically several thousand USD per 30 tablets
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'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 emergency medical attention. When seeking help, be prepared to provide details about the medication taken, the amount, and the time it happened.