Uptravi 1200mcg 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 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 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 closely. You can take this medication with or without food. Taking it with food may help reduce some side effects. Swallow the tablet 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.
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 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 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 tablet 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.
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 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 guidance on what to do next.
Lifestyle & Tips
- Take Uptravi exactly as prescribed by your doctor, usually twice a day, with or without food.
- 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 safely.
- 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 (within 6 hours). Do not double your dose.
- Report any new or worsening side effects to your doctor.
- Regularly monitor your blood pressure and heart rate as advised by your doctor.
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Initial dose 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.
Dose Range:
200 - 1600 mg
Condition-Specific Dosing:
missed_dose:
If a dose is missed, the patient should take the next dose as soon as possible, unless the next scheduled dose is within 6 hours. If more than 3 consecutive doses are missed, consider re-titrating from a lower dose.
discontinuation:
Avoid abrupt discontinuation; if treatment is interrupted for 3 or more days, re-titrate from a lower dose.
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:
No dose adjustment required (CrCl <30 mL/min).
Dialysis:
No dose adjustment required for patients on dialysis. Selexipag and its active metabolite are not significantly removed by dialysis.
Hepatic Impairment:
Mild:
No dose adjustment required (Child-Pugh A).
Moderate:
Initial dose 200 mcg once daily, then titrate carefully. Maximum recommended dose is 800 mcg once daily (Child-Pugh B).
Severe:
Avoid use (Child-Pugh C).
Confidence:
High
Pharmacology
Mechanism of Action
Selexipag is an oral, selective prostacyclin IP receptor agonist. It is hydrolyzed by carboxylesterase 1 (CES1) to its active metabolite, ACT-333679. Both selexipag and its active metabolite are selective agonists for the prostacyclin receptor (IP receptor). Activation of the IP receptor leads to vasodilation, inhibition of platelet aggregation, and antiproliferative effects. In pulmonary arterial hypertension (PAH), this mechanism helps to reduce pulmonary vascular resistance and improve symptoms.
Pharmacokinetics
Absorption:
Bioavailability:
Not directly reported for selexipag, but rapid and extensive absorption. Absolute bioavailability of active metabolite is approximately 49%.
Tmax:
1-3 hours (selexipag); 3-4 hours (active metabolite)
FoodEffect:
Food does not significantly affect the bioavailability of selexipag or its active metabolite, but may delay 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 (selexipag); 3.2 L/h (active metabolite)
ExcretionRoute:
Mainly fecal (93%), minor renal (7%)
Unchanged:
<1% (selexipag); <1% (active metabolite)
Pharmacodynamics
OnsetOfAction:
Not precisely defined for clinical effect, but pharmacodynamic effects (e.g., vasodilation) occur within hours of dosing.
PeakEffect:
Correlates with Tmax of active metabolite (3-4 hours).
DurationOfAction:
Due to the longer half-life of the active metabolite, effects are sustained with 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 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, 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, 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 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, 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
- Severe jaw pain
- Dizziness or lightheadedness (signs of low blood pressure)
- Unusual bleeding or bruising
- Significant swelling in your hands, ankles, or feet
- Signs of liver problems (e.g., yellowing of skin/eyes, dark urine, severe nausea/vomiting, unusual tiredness)
- 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, any of its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
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 medications and health conditions.
Remember, do not start, stop, or change 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, any of its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced, including any symptoms that occurred.
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 medications and health conditions.
Remember, do not start, stop, or change the dose of any medication without first consulting your doctor to ensure your safety.
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, be sure to discuss this with your doctor. Your doctor will need to weigh the benefits and risks of this medication for both you and your baby to determine the best course of action.
Overdose Information
Overdose Symptoms:
- Severe headache
- Nausea
- Vomiting
- Flushing
- Hypotension (low blood pressure)
- Dizziness
- Tachycardia (fast heart rate)
What to Do:
In case of suspected overdose, seek immediate medical attention. Call 911 or your local emergency number. For poison control, call 1-800-222-1222. Management is supportive, focusing on vital signs and symptom management.
Drug Interactions
Major Interactions
- Strong CYP2C8 inhibitors (e.g., Gemfibrozil): Concomitant use significantly increases exposure to the active metabolite of selexipag. Avoid co-administration. If unavoidable, consider reducing selexipag dose to once daily and monitor for adverse effects.
Moderate Interactions
- Moderate CYP2C8 inhibitors (e.g., Clopidogrel, Deferasirox): May increase exposure to the active metabolite. Monitor for adverse effects.
- Strong CYP2C8 inducers (e.g., Rifampin): May decrease exposure to the active metabolite, potentially reducing efficacy. Avoid co-administration.
Confidence Interactions
Monitoring
Baseline Monitoring
Liver function tests (ALT, AST, bilirubin)
Rationale: To establish baseline and identify pre-existing hepatic impairment, which requires dose adjustment or contraindication.
Timing: Prior to initiation of therapy.
Renal function (eGFR, CrCl)
Rationale: To establish baseline, though no dose adjustment is needed for renal impairment.
Timing: Prior to initiation of therapy.
Blood pressure and heart rate
Rationale: To establish baseline and monitor for potential hypotension or tachycardia, common side effects.
Timing: Prior to initiation of therapy.
Routine Monitoring
Blood pressure and heart rate
Frequency: Regularly during dose titration and periodically thereafter.
Target: Maintain within patient's normal range, avoiding symptomatic hypotension.
Action Threshold: Symptomatic hypotension or persistent significant decrease from baseline; persistent tachycardia.
Symptoms of PAH (e.g., dyspnea, fatigue, exercise capacity)
Frequency: Regularly, especially during titration and at follow-up visits.
Target: Improvement or stabilization of symptoms.
Action Threshold: Worsening symptoms, indicating inadequate response or disease progression.
Adverse effects (e.g., headache, jaw pain, flushing, nausea, diarrhea, myalgia, arthralgia, edema)
Frequency: Regularly, especially during dose titration.
Target: Tolerance of side effects.
Action Threshold: Intolerable side effects requiring dose reduction or discontinuation.
Symptom Monitoring
- Headache (very common, especially during titration)
- Jaw pain (common, related to vasodilation)
- Flushing (common, related to vasodilation)
- Nausea
- Diarrhea
- Vomiting
- Myalgia (muscle pain)
- Arthralgia (joint pain)
- Pain in extremities
- Hypotension (dizziness, lightheadedness)
- Edema (peripheral swelling)
- Anemia (monitor for signs like fatigue, pallor)
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. A pregnancy registry is available.
Trimester-Specific Risks:
First Trimester:
Potential for developmental toxicity observed in animal studies (e.g., skeletal malformations, reduced fetal weight).
Second Trimester:
Potential for developmental toxicity observed in animal studies.
Third Trimester:
Potential for developmental 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. Due to the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with Uptravi.
Infant Risk:
Risk of serious adverse reactions in breastfed infants; advise against breastfeeding.
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. Clinical studies did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. However, older patients may be more sensitive to the drug's effects, particularly hypotension. Monitor closely for adverse effects.
Clinical Information
Clinical Pearls
- Uptravi requires careful dose titration to optimize efficacy and manage side effects. Patients should be educated on the importance of adherence to the titration schedule.
- Common side effects like headache, jaw pain, and flushing are often transient and may lessen with continued therapy. Patients should be counseled on these expected effects.
- Abrupt discontinuation of Uptravi should be avoided as it can lead to clinical worsening of PAH. If treatment is interrupted for more than 3 days, re-titration from a lower dose is recommended.
- Patients should be advised to swallow tablets whole and not to crush, chew, or split them.
- Strong CYP2C8 inhibitors (like gemfibrozil) are a major interaction; co-administration should be avoided or dose adjusted with careful monitoring.
Alternative Therapies
- Epoprostenol (Flolan, Veletri)
- Treprostinil (Remodulin, Tyvaso, Orenitram)
- Iloprost (Ventavis)
- Riociguat (Adempas)
- PDE5 inhibitors (e.g., Sildenafil, Tadalafil)
- Endothelin Receptor Antagonists (e.g., Bosentan, Ambrisentan, Macitentan)
Cost & Coverage
Average Cost:
Approximately $10,000 - $15,000+ per 60 tablets (for 1 month supply, depending on strength)
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 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, including the amount taken and the time it happened.