Uptravi 200mcg 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 is a medicine used to treat a serious lung condition called pulmonary arterial hypertension (PAH). PAH causes high blood pressure in the arteries leading to your lungs, making your heart work harder. Uptravi works by relaxing these blood vessels, which helps to lower the blood pressure in your lungs and makes it easier for your heart to pump blood. This can 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, without chewing, breaking, or crushing it.
Continue taking this medication as directed by your doctor or healthcare provider, even if you're feeling well. This will help ensure you receive the full benefits of the treatment.
Storing and Disposing of Your Medication
To store your medication properly, keep it at room temperature in a dry place, avoiding the bathroom. Make sure to store all medications in a safe location, out of the reach of children and pets.
When disposing of unused or expired medication, do not flush it down the toilet or pour it down the drain unless instructed to do so. Instead, check with your pharmacist for guidance on the best disposal method. You may also want to explore local 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's less than 6 hours until your next scheduled dose, skip the missed dose and resume your regular dosing 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 advice 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, without chewing, breaking, or crushing it.
Continue taking this medication as directed by your doctor or healthcare provider, even if you're feeling well. This will help ensure you receive the full benefits of the treatment.
Storing and Disposing of Your Medication
To store your medication properly, keep it at room temperature in a dry place, avoiding the bathroom. Make sure to store all medications in a safe location, out of the reach of children and pets.
When disposing of unused or expired medication, do not flush it down the toilet or pour it down the drain unless instructed to do so. Instead, check with your pharmacist for guidance on the best disposal method. You may also want to explore local 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's less than 6 hours until your next scheduled dose, skip the missed dose and resume your regular dosing 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 advice 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 talking to your doctor, as this can worsen your condition.
- It is important to follow the titration schedule carefully. Your doctor will slowly increase your dose over several weeks to find the dose that works best for you and that you can tolerate.
- If you miss a dose, take it as soon as you remember. If it is almost time for your next dose, skip the missed dose and continue with your regular schedule. 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 slowly increase it again.
- Report any new or worsening symptoms, or any severe side effects, to your doctor immediately.
- Avoid grapefruit and grapefruit juice as they may interact with this medication.
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:
Pulmonary Arterial Hypertension (PAH):
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. If dose is not tolerated, reduce to the previous tolerated dose. If treatment is interrupted for 3 or more days, re-titrate from 200 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.
Moderate:
No dose adjustment required.
Severe:
Avoid use in patients with severe renal impairment (CrCl < 30 mL/min) or end-stage renal disease requiring dialysis due to limited clinical experience. If use is considered essential, a lower starting dose (e.g., 200 mcg once daily) and slower titration may be considered.
Dialysis:
Avoid use in patients requiring dialysis. If use is considered essential, a lower starting dose (e.g., 200 mcg once daily) and slower titration may be considered.
Hepatic Impairment:
Mild:
No dose adjustment required (Child-Pugh A).
Moderate:
Start with 200 mcg orally once daily. Titrate cautiously, if tolerated, to a maximum of 800 mcg once daily (Child-Pugh B).
Severe:
Avoid use (Child-Pugh C).
Pharmacology
Mechanism of Action
Selexipag is an oral prostacyclin receptor (IP receptor) agonist. It is selectively active at the IP receptor, which is expressed in vascular smooth muscle cells. Activation of the IP receptor leads to vasodilation, inhibition of platelet aggregation, and anti-proliferative effects. In patients with pulmonary arterial hypertension (PAH), these actions contribute to a reduction in pulmonary vascular resistance and improved hemodynamics.
Pharmacokinetics
Absorption:
Bioavailability:
Approximately 49%
Tmax:
Selexipag: 1-3 hours; Active metabolite (ACT-333679): 3-4 hours
FoodEffect:
Food does not have a clinically significant effect on the bioavailability of selexipag or its active metabolite.
Distribution:
Vd:
Selexipag: ~11.7 L; Active metabolite: ~16.5 L
ProteinBinding:
>99% for both selexipag and its active metabolite
CnssPenetration:
Limited
Elimination:
HalfLife:
Selexipag: ~1.3-2.5 hours; Active metabolite: ~6.2-13.5 hours
Clearance:
Not available
ExcretionRoute:
Primarily fecal (93%), with minor renal excretion (7%)
Unchanged:
Less than 1% of selexipag is excreted unchanged in urine.
Pharmacodynamics
OnsetOfAction:
Not precisely defined, but effects on pulmonary vascular resistance are observed within hours of administration.
PeakEffect:
Peak plasma concentrations of the active metabolite are reached within 3-4 hours, correlating with peak pharmacodynamic effects.
DurationOfAction:
Due to the longer half-life of the active metabolite, effects persist for approximately 12 hours, supporting twice-daily dosing.
Confidence:
High
Safety & Warnings
Side Effects
Urgent Side Effects: Seek Medical Help Right Away
While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. Immediately contact your doctor or seek medical attention if you experience any of the following symptoms, which may indicate a serious allergic reaction or other severe side effect:
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. Contact your doctor or seek medical help if you experience any of the following side effects or if they persist or bother you:
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. Immediately contact your doctor or seek medical attention if you experience any of the following symptoms, which may indicate a serious allergic reaction or other severe side effect:
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. Contact your doctor or seek medical help if you experience any of the following side effects or if they persist or bother you:
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 headache
- Severe jaw pain
- Persistent or severe nausea, vomiting, or diarrhea
- Dizziness or lightheadedness (signs of low blood pressure)
- Unusual bleeding or bruising
- Signs of liver problems (e.g., yellowing of skin or eyes, dark urine, severe stomach pain)
- Worsening shortness of breath, chest pain, or fainting spells
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 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 disclose all of your:
Prescription and over-the-counter (OTC) medications
Natural products
Vitamins
* Health problems
Your doctor and pharmacist need this information to assess potential interactions and determine whether it is safe for you to take this medication. Never start, stop, or adjust the dosage of any medication without first consulting 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 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 disclose all of your:
Prescription and over-the-counter (OTC) medications
Natural products
Vitamins
* Health problems
Your doctor and pharmacist need this information to assess potential interactions and determine whether it is safe for you to take this medication. Never start, stop, or adjust the dosage of any medication without first consulting your doctor.
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 during pregnancy or breast-feeding to make an informed decision about its use.
Overdose Information
Overdose Symptoms:
- Severe headache
- Nausea
- Vomiting
- Diarrhea
- Hypotension (low blood pressure)
- Flushing
- Dizziness
- Tachycardia (fast heart rate)
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, focusing on vital signs and symptomatic treatment.
Drug Interactions
Contraindicated Interactions
- Strong CYP2C8 inhibitors (e.g., Gemfibrozil): Concomitant use is contraindicated due to significant increase in exposure to the active metabolite, leading to increased risk of adverse reactions.
Major Interactions
- Strong CYP2C8 inducers (e.g., Rifampin): Concomitant use should be avoided as it may significantly decrease exposure to the active metabolite, potentially reducing efficacy.
Moderate Interactions
- Moderate CYP2C8 inhibitors (e.g., Clopidogrel, Deferasirox): May increase exposure to the active metabolite. Monitor for adverse reactions and consider dose reduction if necessary.
- Moderate CYP2C8 inducers (e.g., Carbamazepine, Phenytoin): May decrease exposure to the active metabolite. Monitor for reduced efficacy and consider dose adjustment if necessary.
Minor Interactions
- Other antiplatelet agents: Increased risk of bleeding, monitor for signs of bleeding.
Monitoring
Baseline Monitoring
Diagnosis of PAH (WHO Group 1)
Rationale: Confirm appropriate indication for therapy.
Timing: Prior to initiation
Liver function tests (ALT, AST, bilirubin)
Rationale: To establish baseline and assess for hepatic impairment, especially given metabolism and hepatic dose adjustments.
Timing: Prior to initiation
Renal function (CrCl)
Rationale: To assess for severe renal impairment and guide dosing considerations.
Timing: Prior to initiation
Blood pressure and heart rate
Rationale: To establish baseline and monitor for common adverse effects (hypotension, tachycardia).
Timing: Prior to initiation
Routine Monitoring
Signs and symptoms of PAH (e.g., dyspnea, fatigue, syncope)
Frequency: Regularly during titration and maintenance
Target: Improvement or stabilization
Action Threshold: Worsening symptoms may indicate need for dose adjustment or alternative therapy.
Blood pressure and heart rate
Frequency: During titration and periodically thereafter
Target: Maintain within acceptable limits; avoid symptomatic hypotension or severe tachycardia.
Action Threshold: Symptomatic hypotension or persistent tachycardia may require dose reduction or interruption.
Adverse effects (e.g., headache, jaw pain, nausea, diarrhea, flushing, myalgia, arthralgia)
Frequency: Regularly, especially during titration
Target: Tolerable level
Action Threshold: Intolerable side effects may require dose reduction or discontinuation.
Liver function tests (ALT, AST, bilirubin)
Frequency: Periodically, especially in patients with hepatic impairment or if symptoms of liver injury develop.
Target: Within normal limits or stable
Action Threshold: Significant elevations may warrant investigation and dose adjustment or discontinuation.
Symptom Monitoring
- Headache
- Jaw pain
- Nausea
- Diarrhea
- Flushing
- Myalgia
- Arthralgia
- Vomiting
- Pain in extremities
- Hypotension (dizziness, lightheadedness)
- Tachycardia
- Signs of bleeding (unusual bruising, petechiae, dark stools)
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.
Trimester-Specific Risks:
First Trimester:
Animal studies showed developmental toxicity (e.g., skeletal malformations, reduced fetal weight) at exposures higher than clinical. Risk in humans during first trimester is unknown.
Second Trimester:
Risk in humans during second trimester is unknown.
Third Trimester:
Risk in humans during third trimester is unknown.
Lactation
It is unknown if selexipag or its active metabolite are excreted in human milk. Due to the potential for serious adverse reactions in breastfed infants, breastfeeding is not recommended during treatment with selexipag.
Infant Risk:
Potential for serious adverse reactions (e.g., cardiovascular effects) in breastfed infants. Risk level L3 (Moderate Caution).
Pediatric Use
The safety and effectiveness of selexipag in pediatric patients have not been established. Use is not recommended.
Geriatric Use
No specific dose adjustment is required based on age. However, elderly patients may be more sensitive to the effects of the drug, and dose titration should be done cautiously, monitoring for adverse effects.
Clinical Information
Clinical Pearls
- Uptravi requires careful dose titration to optimize efficacy and minimize side effects. Patients should be educated on the importance of adherence to the titration schedule.
- Common side effects like headache, jaw pain, nausea, and diarrhea are often dose-dependent and tend to be more prominent during the initial titration phase. These often improve with continued therapy.
- Abrupt discontinuation of Uptravi can lead to worsening of PAH symptoms. Patients should be advised not to stop the medication without consulting their physician.
- Concomitant use with strong CYP2C8 inhibitors (e.g., gemfibrozil) is contraindicated due to increased exposure to the active metabolite and risk of adverse events.
- Patients with moderate hepatic impairment require a lower starting dose and slower titration due to reduced clearance of the active metabolite.
- Uptravi is a highly protein-bound drug, but drug interactions based on protein displacement are not anticipated to be clinically significant.
Alternative Therapies
- Other prostacyclin pathway agents (e.g., Epoprostenol, Treprostinil, Iloprost)
- Endothelin receptor antagonists (ERAs) (e.g., Ambrisentan, Macitentan, Bosentan)
- Phosphodiesterase-5 (PDE5) inhibitors (e.g., Sildenafil, Tadalafil)
- Soluble guanylate cyclase (sGC) stimulators (e.g., Riociguat)
Cost & Coverage
Average Cost:
Highly variable, 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 medical attention. When seeking help, be prepared to provide details about the medication taken, the amount, and the time it occurred.