Uptravi 1400mcg 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 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 to you 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 well.
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 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 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 to you 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 well.
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 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 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. If it's close to your next dose, skip the missed dose. Do not take two doses at once. If you miss doses for 3 or more days, contact your doctor as you may need to restart at a lower dose.
- Report any new or worsening side effects to your doctor.
- Avoid grapefruit juice as it may interact with the medication (though not a major interaction, generally good advice for CYP3A4 substrates).
Available Forms & Alternatives
Dosing & Administration
Adult Dosing
Standard Dose:
Initial dose: 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. Doses should be taken approximately 12 hours apart.
Dose Range:
200 - 1600 mg
Condition-Specific Dosing:
missedDose:
If a dose is missed for 3 or more days, restart at a lower dose and re-titrate.
concomitantMedications:
Consider dose adjustment when co-administered with strong CYP2C8 inhibitors or inducers.
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 dose adjustment required for patients with severe renal impairment (CrCl < 30 mL/min) not on dialysis. Limited data in patients on dialysis.
Dialysis:
Not established. Use with caution. Consider starting at 200 mcg once daily and titrating slowly.
Hepatic Impairment:
Mild:
No dose adjustment required (Child-Pugh A).
Moderate:
Initial dose: 200 mcg once daily. Titrate cautiously in increments of 200 mcg once daily at weekly intervals (Child-Pugh B).
Severe:
Avoid use (Child-Pugh C). If use is unavoidable, consider 200 mcg once daily and titrate very cautiously.
Pharmacology
Mechanism of Action
Selexipag is an orally available, selective prostacyclin IP receptor agonist. It is a prodrug that is rapidly hydrolyzed by carboxylesterase 1 to its active metabolite, ACT-333679. The active metabolite is a potent and selective agonist for the prostacyclin receptor, which mediates vasodilation, inhibition of platelet aggregation, and antiproliferative effects. Activation of the IP receptor leads to increased intracellular cyclic AMP (cAMP), which relaxes vascular smooth muscle cells and inhibits their proliferation.
Pharmacokinetics
Absorption:
Bioavailability:
Not available (prodrug)
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:
Approximately 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:
Less than 1% (selexipag), less than 1% (active metabolite)
Pharmacodynamics
OnsetOfAction:
Not precisely defined for clinical effect, but pharmacodynamic effects (e.g., vasodilation) occur within hours.
PeakEffect:
Not precisely defined for clinical effect, but plasma concentrations of active metabolite peak at 3-4 hours.
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 immediately or seek emergency 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 unusual 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 immediately or seek emergency 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 unusual 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 headache that does not go away
- Severe jaw pain
- Persistent or severe nausea, vomiting, or diarrhea
- Signs of low blood pressure (dizziness, lightheadedness, fainting)
- Unusual bleeding or bruising
- Signs of liver problems (yellowing of skin/eyes, dark urine, severe stomach pain)
- 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, 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 in combination with your other 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, 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 in combination with your other 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 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 headache
- Nausea
- Vomiting
- Diarrhea
- Flushing
- Hypotension
- Dizziness
What to Do:
In case of overdose, seek immediate medical attention or call a Poison Control Center (1-800-222-1222). Treatment is supportive. Monitor vital signs and manage symptoms as appropriate.
Drug Interactions
Major Interactions
- Strong CYP2C8 inhibitors (e.g., Gemfibrozil): Concomitant use significantly increases exposure to the active metabolite. Avoid co-administration. If unavoidable, consider reducing selexipag dose to 200 mcg once daily.
Moderate Interactions
- Strong CYP2C8 inducers (e.g., Rifampin): Concomitant use significantly decreases exposure to the active metabolite, potentially reducing efficacy. Avoid co-administration.
- Strong CYP3A4 inhibitors (e.g., Ketoconazole, Itraconazole, Ritonavir, Clarithromycin): May increase exposure to selexipag and its active metabolite, but generally not considered clinically significant enough to warrant dose adjustment.
- Strong CYP3A4 inducers (e.g., Carbamazepine, Phenytoin, St. John's Wort): May decrease exposure to selexipag and its active metabolite, but generally not considered clinically significant enough to warrant dose adjustment.
Minor Interactions
- Warfarin: No clinically significant pharmacokinetic interaction observed.
Monitoring
Baseline Monitoring
Liver Function Tests (LFTs)
Rationale: To establish baseline and identify pre-existing hepatic impairment, which requires dose adjustment.
Timing: Prior to initiation of therapy.
Renal Function (eGFR/CrCl)
Rationale: To establish baseline and identify severe renal impairment, which may require cautious use.
Timing: Prior to initiation of therapy.
Blood Pressure and Heart Rate
Rationale: To establish baseline and monitor for potential hypotensive effects.
Timing: Prior to initiation of therapy.
Routine Monitoring
Symptoms of PAH (e.g., dyspnea, fatigue, exercise capacity)
Frequency: Regularly during dose titration and throughout therapy.
Target: Improvement or stabilization of symptoms.
Action Threshold: Worsening symptoms may indicate inadequate response or disease progression, requiring re-evaluation of therapy.
Blood Pressure and Heart Rate
Frequency: During dose titration and periodically thereafter.
Target: Maintain within acceptable limits, avoiding symptomatic hypotension.
Action Threshold: Symptomatic hypotension or significant drop in BP may require dose reduction or discontinuation.
Adverse Reactions (e.g., headache, jaw pain, nausea, diarrhea, flushing, myalgia, arthralgia)
Frequency: Regularly, especially during dose titration.
Target: Tolerable level of side effects.
Action Threshold: Intolerable side effects may necessitate dose reduction or slower titration.
Symptom Monitoring
- Headache
- Jaw pain
- Nausea
- Vomiting
- Diarrhea
- Flushing
- Myalgia
- Arthralgia
- Hypotension
- Dizziness
- Anemia
- Rash
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 (reduced fetal weight, skeletal variations) at exposures higher than clinical. Risk in humans unknown.
Second Trimester:
Risk in humans unknown.
Third Trimester:
Risk in humans unknown.
Lactation
It is unknown 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 selexipag.
Infant Risk:
Potential for serious adverse reactions (e.g., effects on cardiovascular system, growth) in breastfed infants. Avoid breastfeeding.
Pediatric Use
Safety and effectiveness in pediatric patients have not been established. Not recommended for use in children.
Geriatric Use
No specific dose adjustment is required based on age. However, elderly patients may be more sensitive to the effects of the drug, particularly hypotension. Monitor closely for adverse reactions.
Clinical Information
Clinical Pearls
- Selexipag is a prodrug; its active metabolite (ACT-333679) is responsible for the pharmacologic activity.
- Dose titration is crucial for tolerability and efficacy. Patients should be educated on the importance of gradual dose increases and managing transient side effects.
- Common side effects (headache, jaw pain, nausea, diarrhea, flushing) are typically dose-dependent and tend to decrease over time with continued therapy.
- Avoid concomitant use with strong CYP2C8 inhibitors (e.g., gemfibrozil) due to significantly increased exposure to the active metabolite, which can lead to severe adverse effects. If unavoidable, a significant dose reduction is necessary.
- Avoid concomitant use with strong CYP2C8 inducers (e.g., rifampin) due to significantly decreased exposure to the active metabolite, which can lead to loss of efficacy.
- Patients with moderate hepatic impairment (Child-Pugh B) require a lower starting dose and slower titration. Use is contraindicated in severe hepatic impairment (Child-Pugh C).
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:
Approximately $10,000 - $15,000+ per 60 tablets (monthly supply)
Insurance Coverage:
Specialty Tier (Tier 3 or 4), often requiring 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 emergency 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.