- March 15, 2022
- Newsletter
- 617-430-5616
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Brand Name :
Uptravi
Synonyms :
selexipag
Class :
Prostacyclin Agonists, PAH
Dosage Forms & Strengths
tablet
1600mcg
1400mcg
1200mcg
1000mcg
800mcg
600mcg
400mcg
200mcg
reconstituted lyophilized powder for injection
1800mcg/vial
Each vial reconstituted: 225 mcg/mL
pulmonary Arterial Hypertension
Orally
200 mcg orally twice a day initially
may Increase dosage by 200 mcg twice a day, generally weekly, to maximal tolerable dose; should not exceed more than 1600 mcg twice a day.
Reduce dosage if untolerable.
orally to Intravenous conversion
for patients temporarily not able to administer orally
Current dosage 1600 mg orally twice a day: Give 1800 mg intravenously twice a day
Current dosage 1400 mg orally twice a day: Give 1575 mg intravenously twice a day
Current dosage 1200 mg orally twice a day: Give 1350 mg intravenously twice a day
Current dosage 1000 mg orally twice a day: Give 1125 mg intravenously twice a day
Current dosage 800 mg orally twice a day: Give 900 mg intravenously twice a day
Current dosage 600 mg orally twice a day: Give 675 mg intravenously twice a day
Current dosage 400 mg orally twice a day: Give 450 mg intravenously twice a day
Current dosage 200 mg orally twice a day: Give 225 mg intravenously twice a day
Safety & efficacy were not established
Refer to adult dosing regimen
NSAIDs may enhance the anticoagulant effect of Heparin
NSAIDs may enhance the anticoagulant effect of Heparin
NSAIDs may enhance the anticoagulant effect of Heparin
NSAIDs may enhance the anticoagulant effect of Heparin
NSAIDs may enhance the anticoagulant effect of Heparin
may decrease the levels of serum concentration of hormonal contraceptives
may decrease the levels of serum concentration of hormonal contraceptives
may decrease the levels of serum concentration of hormonal contraceptives
may decrease the levels of serum concentration of hormonal contraceptives
may enhance the concentration when combined with serum of selexipag
may enhance the concentration when combined with serum of selexipag
may enhance the concentration when combined with serum of selexipag
may enhance the concentration when combined with serum of selexipag
may increase the serum concentration of colchicine
may diminish the serum concentration
may enhance serum concentrations of CYP3A4 inducers
may diminish the serum concentration of CYP3A4 inducers
may diminish the serum concentration when combined with abiraterone acetate
may diminish serum concentrations when combined with aripiprazole lauroxil
may diminish the serum concentration when combined with brexpiprazole
may diminish the concentration of serum when combined with selexipag
they decrease the concentration of doravirine in the serum
they decrease the concentration of rilpivirine
may enhance the serum concentration
may enhance the serum concentration of CYP2C8 inhibitors
may reduce the level of serum concentration of abemaciclib
may diminish serum concentrations of CYP3A4 inducers
may diminish the serum concentration when combined with tolvaptan
may have an increased vasodilatory effect when combined with vasodilators
may have an increased vasodilatory effect when combined with vasodilators
may have an increased hypotensive effect when combined with riociguat
may enhance the hypotensive effect of Blood Pressure Lowering Agents
may enhance the hypotensive effect of Blood Pressure Lowering Agents
may enhance the hypotensive effect of Blood Pressure Lowering Agents
may enhance the hypotensive effect of Blood Pressure Lowering Agents
may enhance the hypotensive effect of Blood Pressure Lowering Agents
thrombolytic Agents may enhance the adverse/toxic effect of prostacyclin Analogues
may enhance the adverse/toxic effect of anticoagulants
may enhance the adverse/toxic effect of anticoagulants
may enhance the adverse/toxic effect of anticoagulants
may enhance the adverse/toxic effect of anticoagulants
may enhance the adverse/toxic effect of anticoagulants
may have an increased antiplatelet effect when combined with antiplatelet agents
may have an increased antiplatelet effect when combined with antiplatelet agents
may have an increased antiplatelet effect when combined with antiplatelet agents
may have an increased antiplatelet effect when combined with antiplatelet agents
may have an increased antiplatelet effect when combined with antiplatelet agents
may have an increased adverse effect when combined with anticoagulants
may have an increased adverse effect when combined with anticoagulants
may have an increased adverse effect when combined with anticoagulants
may have an increased adverse effect when combined with anticoagulants
may have an increased adverse effect when combined with anticoagulants
may have an increased hypotensive effect when combined with anti-hypertensive agents
may have an increased hypotensive effect when combined with anti-hypertensive agents
may have an increased hypotensive effect when combined with anti-hypertensive agents
may have an increased hypotensive effect when combined with anti-hypertensive agents
may have an increased hypotensive effect when combined with anti-hypertensive agents
may have an increased adverse effect when combined with prostacyclin analogues
may enhance the serum concentration of CYP3A4 inhibitors
may reduce the therapeutic effect of prostaglandins
may reduce the therapeutic effect of prostaglandins
may reduce the therapeutic effect of prostaglandins
may reduce the therapeutic effect of prostaglandins
may reduce the therapeutic effect of prostaglandins
they decrease the concentration of active metabolites of roflumilast in the serum
may increase the serum concentration
may increase the hypotensive effect of antihypertensives
may decrease the serum concentration
may decrease the level of serum concentration of pretomanid
may decrease the serum concentration of estazolam
may decrease the serum concentration of estrogen derivatives
bazedoxifene/conjugated estrogens
may decrease the serum concentration of estrogen derivatives
may decrease the serum concentration of estrogen derivatives
may decrease the serum concentration of estrogen derivatives
may decrease the serum concentration of estrogen derivatives
may enhance the toxic effect of anti-coagulants
may decrease the therapeutic effect of Nonsteroidal Anti-Inflammatory Agents
may increase the hypotensive effect of calcium channel blockers
may increase the hypotensive effect of calcium channel blockers
lisinopril/hydrochlorothiazide
may increase the hyperkalemic effect of Angiotensin-converting enzyme inhibitors
lisinopril/hydrochlorothiazide
may increase the hypotensive effect of blood pressure-lowering agents
eprosartan/hydrochlorothiazide
may increase the hypotensive effect of blood pressure-lowering agents
may increase the hypotensive effect of blood pressure-lowering agents
may diminish the serum concentration of CYP3A4 inducers
may enhance the serum concentration when combined with CYP3A4 substrates
may enhance serum concentrations when combined with doxercalciferol
may diminish the serum concentration when combined with nimodipine
may increase the antiplatelet effect of antiplatelet agents
may have an increased hypotensive effect when combined with antihypertensive agents
may have an increased hypotensive effect when combined with antihypertensive agents
may have an increased hypotensive effect when combined with antihypertensive agents
may have an increased hypotensive effect when combined with antihypertensive agents
may have an increased hypotensive effect when combined with antihypertensive agents
may increase the hypotensive effect of Blood Pressure Lowering Agents
may increase the hypotensive effect of Blood Pressure Lowering Agents
may increase the vasodilatory effect
may increase the vasodilatory effect
may increase the vasodilatory effect
may increase the vasodilatory effect
may increase the vasodilatory effect
may increase the anticoagulant effect of heparin
may increase the anticoagulant effect of heparin
may increase the anticoagulant effect of heparin
may increase the anticoagulant effect of heparin
may increase the anticoagulant effect of heparin
may increase the hypotensive effect of Blood Pressure Lowering Agents
Actions and spectrum:
selexipag is a selective prostacyclin receptor agonist with vasodilatory and anti-proliferative effects. It acts on the prostacyclin receptor (IP receptor) to increase the production of cyclic adenosine monophosphate (cAMP) in vascular smooth muscle cells.
This leads to vasodilation, inhibition of platelet aggregation, and suppression of smooth muscle cell proliferation. selexipag is primarily used for the treatment of pulmonary arterial hypertension (PAH) to improve exercise capacity and delay disease progression. It has a broad spectrum of action, targeting multiple components involved in PAH pathophysiology.
Frequency defined
1-10%
Anemia (8%)
Decreased hemoglobin (8.6%)
Decreased appetite (6%)
>10%
Diarrhea (42%)
Nausea (33%)
Pain in extremities (17%)
Flushing (12%)
Rash (11%)
Headache (65%)
Jaw pain (26%)
Vomiting (18%)
Myalgia (16%)
Arthralgia (11%)
Frequency not defined
Vascular disorders: hypotension
Reduced TSH (till −0.3 MU/L from the baseline of about 2.5 MU/L)
Black Box Warning:
selexipag has a black box warning regarding the risk of embryo-fetal toxicity. selexipag is contraindicated in pregnancy and not to be used in pregnant and lactating women. It is essential for women of childbearing potential to use effective contraception while taking selexipag.
Contraindication/Caution:
Contraindication:
Caution:
Comorbidities:
Pregnancy consideration: N/A
Lactation: N/A
Pregnancy category:
Pharmacology:
selexipag is a selective prostacyclin receptor agonist that acts as a vasodilator and inhibits the platelet aggregation. It is specifically designed to target the prostacyclin receptor (IP receptor) found on vascular smooth muscle cells and platelets.
Upon administration, selexipag is rapidly converted into its active metabolite, ACT-333679, through hydrolysis by carboxylesterases. ACT-333679 then binds to the IP receptor, activating the cyclic adenosine monophosphate (cAMP) pathway, leading to vasodilation and systemic arterial vascular beds.
The vasodilatory effects of selexipag are primarily exerted on the pulmonary vasculature, reducing pulmonary vascular resistance, and improving exercise capacity in patients with pulmonary arterial hypertension (PAH). It also inhibits platelet aggregation, thereby reducing the risk of thrombosis.
Pharmacodynamics:
The pharmacodynamics of selexipag involve its selective activation of the prostacyclin (IP) receptor. By binding to this receptor, selexipag and its active metabolite, ACT-333679, stimulate the production of cyclic adenosine monophosphate (cAMP) in vascular smooth muscle cells and platelets.
The activation of the IP receptor and subsequent increase in cAMP levels lead to various effects, including vasodilation of pulmonary and systemic arterial vascular beds, inhibition of platelet aggregation, and suppression of smooth muscle cell proliferation.
Pharmacokinetics:
Absorption
selexipag is administered orally and is rapidly absorbed from the gastrointestinal tract. It undergoes first-pass metabolism in the liver, primarily by the action of cytochrome P450 enzymes, before reaching systemic circulation. The absolute bioavailability of selexipag is low, estimated to be around 15%.
Distribution
selexipag is highly bound to plasma proteins, particularly albumin. It has a large volume of distribution, indicating extensive tissue distribution. The drug crosses the blood-brain barrier poorly.
Metabolism
selexipag is metabolized primarily by cytochrome P450 enzymes, CYP2C8 and to a lesser extent CYP3A4. It is metabolized to its active metabolite, ACT-333679, which exhibits pharmacological activity like selexipag. The active metabolite undergoes further metabolism before being eliminated.
Elimination and excretion
The elimination of selexipag and its metabolites occurs through the feces, with minimal renal excretion. The drug has a long elimination half-life, estimated to be 7-9 hours for selexipag and 9-11 hours for ACT-333679.
Administration:
selexipag is available in tablet form for oral administration. The recommended starting dose of selexipag is typically 200 micrograms (mcg) twice daily. The dose is gradually increased based on the individual patient’s tolerability and response.
The dose titration is done in increments of 200 mcg, with the target maintenance dose ranging from 1,600 mcg to 2,000 mcg twice daily. It is important to take selexipag with food to minimize the potential for stomach-related side effects. The tablets should be administered whole and not crushed, chewed, or divided.
Patient information leaflet
Generic Name: selexipag
Pronounced: [ se-LEX-i-pag ]
Why do we use selexipag?
selexipag is primarily used to treat pulmonary arterial hypertension. It is characterized with high blood pressure in the arteries, leading to shortness of breath, fatigue, and chest pain. selexipag helps to dilate and relax the blood vessels in the lungs, reducing the workload on the heart and improving exercise capacity in patients with PAH.
selexipag is specifically indicated for the long-term treatment of PAH in patients who are not candidates for other forms of PAH therapy or who have not responded adequately to other PAH treatments. It can be used as a monotherapy or as a combination with other PAH medications.