Uptravi 800mcg Tablets
It is used to treat high blood pressure in the lungs.
Drug Class
Antihypertensive, Pulmonary
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 rare lung condition called pulmonary arterial hypertension (PAH). It works by relaxing the blood vessels in your lungs, 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 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 medication whole - do not chew, break, or crush it. Continue taking the 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 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 return to your regular schedule. Do not take two doses at the same time or take extra doses. If you miss three 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 medication whole - do not chew, break, or crush it. Continue taking the 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 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 return to your regular schedule. Do not take two doses at the same time or take extra doses. If you miss three 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, about 12 hours apart.
- Do not stop taking Uptravi suddenly without talking to your doctor, as this can worsen your condition.
- If you miss a dose, take it as soon as you remember, but do not take two doses at the same time. If you miss doses for 3 or more days, contact your doctor as you may need to restart at a lower dose.
- Uptravi can be taken with or without food.
- Report any new or worsening side effects to your doctor.
- Avoid grapefruit juice as it may interact with this medication (though minor interaction, generally good advice for many drugs).
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Initial dose 200 mcg twice daily, titrated 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 200 mcg twice daily, titrated in increments of 200 mcg twice daily, usually at weekly intervals, to the highest tolerated dose up to 1600 mcg twice daily. Doses should be taken approximately 12 hours apart. If a dose is missed, the patient should take the next dose as soon as possible, but should not take two doses at the same time. If doses are missed for 3 or more days, re-titration may be necessary.
Pediatric Dosing
Neonatal:
Not established
Infant:
Not established
Child:
Not established
Adolescent:
Not established
Dose Adjustments
Renal Impairment:
Mild:
No dose adjustment needed (CrCl 50-80 mL/min)
Moderate:
No dose adjustment needed (CrCl 30-49 mL/min)
Severe:
Consider starting at 200 mcg once daily, then titrate cautiously. Max dose 800 mcg twice daily. (CrCl <30 mL/min)
Dialysis:
Not studied in patients on dialysis. Avoid use if possible, or consider starting at 200 mcg once daily and titrate cautiously. Max dose 800 mcg twice daily.
Hepatic Impairment:
Mild:
No dose adjustment needed (Child-Pugh A)
Moderate:
Start at 200 mcg once daily. Max dose 800 mcg once daily (Child-Pugh B)
Severe:
Avoid use (Child-Pugh C)
Pharmacology
Mechanism of Action
Selexipag is an orally available, selective prostacyclin IP receptor agonist. It is a prodrug that is hydrolyzed by carboxylesterase 1 (CES1) to its active metabolite, ACT-333679. Activation of the IP receptor leads to vasodilation, inhibition of platelet aggregation, and antiproliferative effects, which are beneficial in pulmonary arterial hypertension (PAH).
Pharmacokinetics
Absorption:
Bioavailability:
Not available (prodrug)
Tmax:
1-3 hours (selexipag), 3-4 hours (active metabolite)
FoodEffect:
Food does not affect the AUC of selexipag or its active metabolite, but delays Tmax by 1-2 hours. Can be taken with or without food.
Distribution:
Vd:
11.7 L (selexipag), 16.1 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:
Mainly fecal (93%), minor renal (7%)
Unchanged:
<1% (selexipag), <1% (active metabolite)
Pharmacodynamics
OnsetOfAction:
Gradual, as dose is titrated over weeks to months.
PeakEffect:
Achieved after reaching the maximum tolerated dose, typically weeks to months after initiation.
DurationOfAction:
Approximately 12 hours (due to twice-daily dosing and half-life of active metabolite).
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. 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. 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 persist, contact your doctor for guidance:
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 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. 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 persist, contact your doctor for guidance:
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 jaw pain
- Dizziness or lightheadedness (signs of low blood pressure)
- Unusual bleeding or bruising
- Signs of liver problems (e.g., yellowing of skin/eyes, dark urine, severe nausea/vomiting, abdominal pain)
- Worsening shortness of breath, chest pain, or swelling in legs/ankles (signs of worsening PAH)
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 change 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 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 change 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 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
- Diarrhea
- Flushing
- Hypotension (low blood pressure)
- Dizziness
- Tachycardia (fast heart rate)
What to Do:
Seek immediate medical attention or call a Poison Control Center (1-800-222-1222). Treatment is supportive. Monitor vital signs and provide symptomatic treatment as needed.
Drug Interactions
Major Interactions
- Strong CYP2C8 inhibitors (e.g., Gemfibrozil): Co-administration significantly increases exposure to selexipag and its active metabolite. Reduce selexipag dose to 200 mcg once daily. Max dose 400 mcg once daily.
- Strong UGT1A3 inhibitors (e.g., Atazanavir, Indinavir): May increase exposure to active metabolite. Monitor for adverse effects.
Moderate Interactions
- Moderate CYP2C8 inhibitors (e.g., Clopidogrel, Trimethoprim): May increase exposure to selexipag and its active metabolite. Monitor for adverse effects.
- Strong CYP2C8 inducers (e.g., Rifampin): May decrease exposure to selexipag and its active metabolite, potentially reducing efficacy. Avoid co-administration if possible.
Minor Interactions
- Other CYP inhibitors/inducers (e.g., CYP3A4): Minor impact due to limited metabolism via these pathways.
Monitoring
Baseline Monitoring
Liver Function Tests (LFTs)
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, especially given dose adjustments for severe renal impairment.
Timing: Prior to initiation of therapy.
Blood Pressure and Heart Rate
Rationale: To establish baseline and monitor for hypotension or tachycardia, common side effects.
Timing: Prior to initiation of therapy.
WHO/NYHA Functional Class and 6-Minute Walk Distance (6MWD)
Rationale: To establish baseline disease severity and assess treatment efficacy.
Timing: Prior to initiation of therapy.
Routine Monitoring
Blood Pressure and Heart Rate
Frequency: Regularly during dose titration and periodically thereafter.
Target: Individualized, maintain within acceptable limits.
Action Threshold: Significant hypotension (e.g., symptomatic or SBP <90 mmHg) or persistent tachycardia; consider dose reduction or discontinuation.
Signs and Symptoms of PAH
Frequency: Regularly, especially during dose titration.
Target: Improvement or stabilization of functional class and exercise capacity.
Action Threshold: Worsening symptoms, signs of right heart failure; consider re-evaluation of therapy.
Adverse Effects (e.g., headache, jaw pain, flushing, nausea, diarrhea, myalgia, arthralgia)
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 (very common, especially during titration)
- Jaw pain (common, related to vasodilation)
- Flushing
- Nausea
- Diarrhea
- Vomiting
- Myalgia (muscle pain)
- Arthralgia (joint pain)
- Hypotension (dizziness, lightheadedness)
- Anemia (monitor for signs of fatigue, pallor)
Special Patient Groups
Pregnancy
There are no adequate and well-controlled studies of Uptravi 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:
Potential for embryo-fetal toxicity based on animal data.
Second Trimester:
Potential for embryo-fetal toxicity based on animal data.
Third Trimester:
Potential for embryo-fetal toxicity based on animal data.
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, breastfeeding is not recommended during treatment with Uptravi.
Infant Risk:
Risk of serious adverse reactions (e.g., effects on cardiovascular system, growth) in breastfed infants. L3 (Moderate risk).
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, elderly patients may be more sensitive to the effects of the drug, and dose titration should be done cautiously. Monitor 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 encouraged to tolerate these if possible, as they indicate drug activity.
- Patients should be advised not to abruptly discontinue Uptravi, as this can lead to clinical worsening of PAH.
- Strong CYP2C8 inhibitors (e.g., gemfibrozil) require a significant dose reduction of selexipag. Always check for drug interactions.
- Uptravi is a prostacyclin pathway agent and can be used in combination with other PAH-specific therapies (e.g., ERA, PDE5i) for patients with an inadequate response to monotherapy or dual therapy.
Alternative Therapies
- Prostacyclin Analogs (e.g., Epoprostenol, Treprostinil, Iloprost)
- Endothelin Receptor Antagonists (ERAs) (e.g., Bosentan, Ambrisentan, Macitentan)
- Phosphodiesterase-5 (PDE5) Inhibitors (e.g., Sildenafil, Tadalafil)
- Soluble Guanylate Cyclase (sGC) Stimulators (e.g., Riociguat)
Cost & Coverage
Average Cost:
$10,000 - $15,000+ per 60 tablets (approx. 1 month supply)
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 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 overdose, including the medication taken, the amount, and the time it occurred.