Uptravi 600mcg Tablets
It is used to treat high blood pressure in the lungs.
Drug Class
Pulmonary Arterial Hypertension (PAH) Agent
Pharmacologic Class
Prostacyclin Receptor (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 of your lungs is too high. It works by relaxing and widening the blood vessels in your lungs, making it easier for your heart to pump blood and improving your 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 exactly. 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 your 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.
Missing 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 resume your regular schedule. Do not take two doses at the same time or take extra doses. If you miss three consecutive 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 exactly. 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 your 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.
Missing 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 resume your regular schedule. Do not take two doses at the same time or take extra doses. If you miss three consecutive days of medication, contact your doctor for guidance on what to do next.
Lifestyle & Tips
- Take Uptravi exactly as prescribed by your doctor, usually twice a day.
- Do not stop taking Uptravi suddenly, as this can worsen your condition. If you need to stop, your doctor will guide you on how to do so gradually.
- 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 double your dose.
- Report any new or worsening symptoms to your doctor immediately.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Initial: 200 mcg orally twice daily. Titrate by 200 mcg twice daily increments, usually weekly, to the highest tolerated dose up to 1600 mcg twice daily. Maintenance: Individualized highest tolerated dose.
Dose Range:
200 - 1600 mg
Condition-Specific Dosing:
Titration:
Increase by 200 mcg twice daily increments, usually weekly, to the highest tolerated dose.
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:
Consider starting with 200 mcg once daily, then titrate carefully. Avoid if possible.
Dialysis:
Consider starting with 200 mcg once daily, then titrate carefully. Avoid if possible.
Hepatic Impairment:
Mild:
No dose adjustment required (Child-Pugh A).
Moderate:
Start with 200 mcg once daily, then titrate carefully (Child-Pugh B).
Severe:
Avoid use (Child-Pugh C).
Pharmacology
Mechanism of Action
Selexipag is an oral prostacyclin receptor (IP receptor) agonist that is structurally distinct from prostacyclin. Selexipag is hydrolyzed by carboxylesterase 1 (CES1) to its active metabolite, ACT-333679, which is approximately 37-fold more potent than selexipag. Both selexipag and its active metabolite are selective for the IP receptor. Activation of the IP receptor leads to vasodilation, inhibition of platelet aggregation, and antiproliferative effects in the pulmonary vasculature, thereby reducing pulmonary vascular resistance.
Pharmacokinetics
Absorption:
Bioavailability:
Not available (high absorption)
Tmax:
Selexipag: 1-2 hours; Active metabolite (ACT-333679): 3-4 hours
FoodEffect:
High-fat meal decreases Cmax of selexipag by 25% and increases Tmax by 1 hour, but AUC is unchanged. Can be taken with or without food.
Distribution:
Vd:
Selexipag: 11.7 L; Active metabolite: 16.7 L
ProteinBinding:
Selexipag: >99%; Active metabolite: >99%
CnssPenetration:
Limited
Elimination:
HalfLife:
Selexipag: 1.3-2.5 hours; Active metabolite: 6.2-13.5 hours
Clearance:
Not available
ExcretionRoute:
Primarily fecal (93%), minor renal (7%)
Unchanged:
<1% (fecal and renal)
Pharmacodynamics
OnsetOfAction:
Not explicitly defined for chronic PAH therapy; effects are gradual with titration.
PeakEffect:
Corresponds to Tmax of active metabolite (3-4 hours).
DurationOfAction:
Sustained effect due to active metabolite and 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
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. 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 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.
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
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. 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 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 flushing
- Persistent or severe nausea, vomiting, or diarrhea
- Signs of bleeding (e.g., unusual bruising, nosebleeds, black/tarry stools)
- Worsening shortness of breath or chest pain
- Fainting or dizziness
- Swelling in your ankles or legs
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 modify the dose of any medication without first consulting your doctor to ensure your safety.
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 modify the dose of any medication without first consulting your doctor to ensure your safety.
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 this medication to both you and your baby.
Overdose Information
Overdose Symptoms:
- Severe 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 (1-800-222-1222). Management is supportive, focusing on symptomatic treatment.
Drug Interactions
Contraindicated Interactions
- Strong CYP2C8 inhibitors (e.g., Gemfibrozil)
- Strong CYP2C8 inducers (e.g., Rifampin)
Moderate Interactions
- Moderate CYP2C8 inhibitors (e.g., Clopidogrel, Deferasirox) - monitor for adverse effects.
- Moderate CYP2C8 inducers (e.g., Carbamazepine, Phenytoin) - monitor for efficacy.
Monitoring
Baseline Monitoring
Diagnosis of Pulmonary Arterial Hypertension (PAH)
Rationale: Confirm appropriate indication for therapy.
Timing: Prior to initiation
Liver Function Tests (ALT, AST, Bilirubin)
Rationale: Assess baseline hepatic function, as drug is metabolized by liver and severe hepatic impairment is a contraindication.
Timing: Prior to initiation
Renal Function Tests (e.g., eGFR, CrCl)
Rationale: Assess baseline renal function, as dose adjustment may be needed in severe impairment.
Timing: Prior to initiation
Routine Monitoring
Clinical assessment of PAH symptoms (e.g., dyspnea, fatigue, exercise capacity)
Frequency: Regularly (e.g., every 3-6 months or as clinically indicated)
Target: Improvement or stabilization of symptoms
Action Threshold: Worsening symptoms may indicate need for dose adjustment or alternative therapy.
Blood Pressure
Frequency: Regularly, especially during dose titration
Target: Individualized, avoid symptomatic hypotension
Action Threshold: Symptomatic hypotension or significant drop in BP may require dose reduction.
Liver Function Tests (ALT, AST, Bilirubin)
Frequency: Periodically, especially if hepatic impairment is suspected or during dose adjustments.
Target: Within normal limits or stable
Action Threshold: Significant elevations may require dose reduction or discontinuation.
Symptom Monitoring
- Headache
- Jaw pain
- Nausea
- Vomiting
- Diarrhea
- Flushing
- Myalgia
- Arthralgia
- Hypotension
- Anemia
- Worsening dyspnea
- Chest pain
- Syncope
- Peripheral edema
Special Patient Groups
Pregnancy
There are no adequate and well-controlled studies of Uptravi in pregnant women. Animal studies showed teratogenicity at exposures greater than clinical exposure. Use during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Trimester-Specific Risks:
First Trimester:
Potential for teratogenicity observed in animal studies.
Second Trimester:
Potential for adverse developmental effects.
Third Trimester:
Potential for adverse developmental effects.
Lactation
It is unknown if selexipag or its active metabolite are present in human milk. Selexipag and its active metabolite were present in the milk of lactating rats. Due to the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with Uptravi.
Infant Risk:
Potential for serious adverse reactions in breastfed infants; advise against breastfeeding.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
Geriatric Use
No specific dose adjustment is required based on age alone. However, consider age-related decreases in renal and hepatic function when determining dose and monitoring.
Clinical Information
Clinical Pearls
- Selexipag requires careful, gradual dose titration to optimize tolerability and achieve the highest tolerated dose, which is crucial for efficacy in PAH.
- Abrupt discontinuation of selexipag can lead to clinical worsening of PAH and should be avoided. If discontinuation is necessary, it should be done gradually under medical supervision.
- Common side effects (e.g., headache, jaw pain, nausea, flushing) are often dose-dependent and tend to decrease in frequency and severity over time with continued therapy.
- Patients should be strongly cautioned against co-administration with strong CYP2C8 inhibitors (like gemfibrozil) or inducers (like rifampin) due to significant changes in drug exposure.
- Uptravi is a long-term therapy for PAH; patient adherence and consistent dosing are vital for optimal outcomes.
Alternative Therapies
- Other prostacyclin pathway agents (e.g., epoprostenol, treprostinil, iloprost)
- Endothelin receptor antagonists (e.g., ambrisentan, bosentan, macitentan)
- Phosphodiesterase-5 (PDE5) inhibitors (e.g., sildenafil, tadalafil)
- Soluble guanylate cyclase (sGC) stimulators (e.g., riociguat)
Cost & Coverage
Average Cost:
Very expensive (e.g., $10,000 - $20,000+) per 30 tablets
Insurance Coverage:
Specialty Tier (requires prior authorization)
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 is a good idea to consult with your pharmacist. If you have any questions or concerns about this medication, do not 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 detailed information, including the name of the medication taken, the amount, and the time it occurred.