Uptravi 1000mcg Tablets
It is used to treat high blood pressure in the lungs.
Drug Class
Prostacyclin Receptor Agonist
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 these blood vessels, making it easier for your heart to pump blood through them. This can help improve your ability to exercise and slow down the worsening of your condition.
How to Use This Medicine
Taking Your Medication
To use this medication correctly, follow your doctor's instructions and read all the information provided. You can take this medication with or without food, but taking it with food may help reduce some side effects. It's essential to swallow the medication whole and not chew, break, or crush it.
Continue taking this medication as directed by your doctor or healthcare provider, even if you start feeling well. Adhering to your prescribed regimen is crucial to ensure the medication works effectively.
Storing and Disposing of Your Medication
Store this medication at room temperature in a dry place, avoiding the bathroom. Keep all medications in a safe location, out of the reach of children and pets. When disposing of unused or expired medications, do not flush them down the toilet or pour them down the drain unless instructed to do so. Instead, consult your pharmacist for guidance on the best disposal method. You may also want to explore local drug take-back programs for safe and responsible disposal.
Missing a Dose
If you miss a dose, take it as soon as you remember. However, if it's less than 6 hours until your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Avoid taking two doses at the same time or taking extra doses. If you miss three consecutive days of medication, contact your doctor for guidance on how to proceed.
To use this medication correctly, follow your doctor's instructions and read all the information provided. You can take this medication with or without food, but taking it with food may help reduce some side effects. It's essential to swallow the medication whole and not chew, break, or crush it.
Continue taking this medication as directed by your doctor or healthcare provider, even if you start feeling well. Adhering to your prescribed regimen is crucial to ensure the medication works effectively.
Storing and Disposing of Your Medication
Store this medication at room temperature in a dry place, avoiding the bathroom. Keep all medications in a safe location, out of the reach of children and pets. When disposing of unused or expired medications, do not flush them down the toilet or pour them down the drain unless instructed to do so. Instead, consult your pharmacist for guidance on the best disposal method. You may also want to explore local drug take-back programs for safe and responsible disposal.
Missing a Dose
If you miss a dose, take it as soon as you remember. However, if it's less than 6 hours until your next scheduled dose, skip the missed dose and resume your regular dosing schedule. Avoid taking two doses at the same time or taking extra doses. If you miss three consecutive days of medication, contact your doctor for guidance on how to proceed.
Lifestyle & Tips
- Take Uptravi exactly as prescribed by your doctor, usually twice a day.
- Take Uptravi with food to help reduce stomach upset.
- Do not crush, chew, or split the tablets. Swallow them whole.
- 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.
- If you stop taking Uptravi for 3 or more days, contact your doctor. You may need to restart at a lower dose and gradually increase it again.
- Report any new or worsening symptoms to your doctor immediately.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Initial dose of 200 mcg orally twice daily. Titrate in increments of 200 mcg twice daily, usually at weekly intervals, to the highest tolerated dose up to 1600 mcg twice daily.
Dose Range:
200 - 1600 mg
Condition-Specific Dosing:
Titration:
Titrate in increments of 200 mcg twice daily, usually at weekly intervals, 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, re-initiate 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 specific dose adjustment recommended for CrCl < 30 mL/min, but clinical experience is limited. Use with caution.
Dialysis:
No specific dose adjustment recommended, but clinical experience is limited. Use with caution.
Hepatic Impairment:
Mild:
No dose adjustment required (Child-Pugh A).
Moderate:
Reduce initial dose to 200 mcg once daily. If tolerated, increase to 200 mcg twice daily, then titrate carefully in increments of 200 mcg twice daily at weekly intervals to a maximum of 800 mcg twice daily (Child-Pugh B).
Severe:
Avoid use (Child-Pugh C).
Pharmacology
Mechanism of Action
Selexipag is a prodrug that is hydrolyzed by carboxylesterase 1 (CES1) to its active metabolite, ACT-333679. ACT-333679 is a selective prostacyclin IP receptor agonist. Activation of the IP receptor leads to vasodilation, inhibition of platelet aggregation, and anti-proliferative effects. These actions are beneficial in pulmonary arterial hypertension (PAH) by reducing pulmonary vascular resistance and improving hemodynamics.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 49% (selexipag), approximately 12% (active metabolite)
Tmax:
Selexipag: 1-2 hours; Active metabolite: 3-4 hours
FoodEffect:
A high-fat meal delays Tmax for both selexipag and its active metabolite but does not significantly affect AUC.
Distribution:
Vd:
Selexipag: ~11.5 L; Active metabolite: ~16.5 L
ProteinBinding:
>99% for both selexipag and its active metabolite
CnssPenetration:
Limited
Elimination:
HalfLife:
Selexipag: ~1.3 hours; Active metabolite: ~6.2-13.5 hours
Clearance:
Not readily available for parent drug; Active metabolite clearance is influenced by CYP2C8 and UGT1A3.
ExcretionRoute:
Primarily fecal (93%), minor urinary (7%)
Unchanged:
Negligible
Pharmacodynamics
OnsetOfAction:
Not precisely defined for clinical effect; hemodynamic effects observed within hours.
PeakEffect:
Peak plasma concentrations of active metabolite occur at 3-4 hours.
DurationOfAction:
Sustained effects with twice-daily dosing, consistent with active metabolite half-life.
Safety & Warnings
Side Effects
Important Side Effects to Report to Your Doctor Immediately
Although rare, some people may experience severe and potentially life-threatening side effects while taking this medication. If you experience any of the following symptoms, seek medical attention 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. However, many people do not experience any side effects or only have mild ones. If you experience any of the following side effects or any other symptoms that concern 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
Note: This is not an exhaustive list of all 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 experience any of the following symptoms, seek medical attention 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. However, many people do not experience any side effects or only have mild ones. If you experience any of the following side effects or any other symptoms that concern 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
Note: This is not an exhaustive list of all 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:
- Severe or persistent headache
- Severe jaw pain
- Severe or persistent nausea, vomiting, or diarrhea
- Dizziness or lightheadedness (signs of low blood pressure)
- Unusual bleeding or bruising
- Swelling in your ankles or feet
- Shortness of breath or chest pain that worsens
- Signs of liver problems (e.g., yellowing of skin/eyes, dark urine, severe stomach 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.
If you have liver disease, as this may affect the safety and efficacy of the medication.
* 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 modify the dosage of any medication without first consulting your doctor to ensure your safety and the effectiveness of your treatment plan.
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.
* 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 modify the dosage of any medication without first consulting your doctor to ensure your safety and the effectiveness of your treatment plan.
Precautions & Cautions
It is essential to inform all 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, 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:
- Severe hypotension (very low blood pressure)
- Severe flushing
- Severe headache
- Nausea
- Vomiting
- Diarrhea
What to Do:
In case of suspected 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
Contraindicated Interactions
- Strong CYP2C8 inhibitors (e.g., Gemfibrozil)
Major Interactions
- Strong CYP2C8 inducers (e.g., Rifampin) - avoid concomitant use
Moderate Interactions
- UGT1A3 inhibitors (potential for increased exposure of active metabolite, monitor for adverse effects)
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 (CrCl)
Rationale: To assess baseline renal function, though no specific dose adjustment for renal impairment is typically needed.
Timing: Prior to initiation of therapy.
Blood pressure and heart rate
Rationale: Selexipag can cause hypotension and tachycardia.
Timing: Prior to initiation of therapy.
Routine Monitoring
Blood pressure and heart rate
Frequency: Regularly during dose titration and periodically thereafter.
Target: Maintain within clinically acceptable limits; avoid symptomatic hypotension.
Action Threshold: Significant or symptomatic hypotension, persistent tachycardia.
Signs and symptoms of PAH progression or improvement
Frequency: Regular clinical assessment (e.g., every 3-6 months or as clinically indicated).
Target: Improvement in exercise capacity, functional class, and hemodynamics.
Action Threshold: Worsening symptoms, functional class decline.
Adverse effects (e.g., headache, jaw pain, nausea, diarrhea, flushing, myalgia)
Frequency: Regularly, especially during dose titration.
Target: Minimize severity; manage with dose reduction if necessary.
Action Threshold: Intolerable or severe adverse effects requiring dose reduction or discontinuation.
Symptom Monitoring
- Headache
- Jaw pain
- Nausea
- Diarrhea
- Flushing
- Myalgia
- Arthralgia
- Hypotension
- Vomiting
- Pain in extremities
Special Patient Groups
Pregnancy
There are no adequate and well-controlled studies of selexipag in pregnant women. Animal studies have shown adverse effects on embryo-fetal development. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Trimester-Specific Risks:
First Trimester:
Risk cannot be ruled out based on animal data.
Second Trimester:
Risk cannot be ruled out based on animal data.
Third Trimester:
Risk cannot be ruled out based on animal data.
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:
Potential for serious adverse reactions; unknown risk.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
Geriatric Use
No specific dose adjustment is required based on age. However, caution should be exercised during dose titration in elderly patients due to the potential for increased sensitivity to adverse effects.
Clinical Information
Clinical Pearls
- Uptravi is a prodrug; its active metabolite (ACT-333679) is responsible for the pharmacologic activity.
- The dose titration is crucial for patient tolerability and should be done gradually, typically weekly, based on individual tolerability.
- Patients should be educated on common side effects like headache, jaw pain, and flushing, which are related to its mechanism of action and often diminish over time.
- Concomitant use with strong CYP2C8 inhibitors (e.g., gemfibrozil) is contraindicated due to significantly increased exposure to the active metabolite.
- Patients should be advised not to stop treatment abruptly without consulting their physician, as this could lead to worsening of PAH.
Alternative Therapies
- Other prostacyclin pathway agents (e.g., epoprostenol, treprostinil, iloprost)
- Endothelin receptor antagonists (ERAs) (e.g., ambrisentan, bosentan, macitentan)
- Phosphodiesterase-5 inhibitors (PDE5i) (e.g., sildenafil, tadalafil)
- Soluble guanylate cyclase (sGC) stimulators (e.g., riociguat)
Cost & Coverage
Average Cost:
Highly variable, typically >$10,000 per 30 tablets
Insurance Coverage:
Specialty Tier (requires prior authorization)
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 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, including the amount taken and the time it happened, to ensure you receive the best possible care.