Ponesimod
Ponesimod Uses, Dosage, Side Effects, Food Interaction and all others data.
Ponesimod is a selective sphingosine 1-phosphate receptor 1 modulator indicated in the treatment of relapsing forms of multiple sclerosis in adults. Ponesimod was developed out of a need for a more selective modulator of sphingosine 1-phosphate receptor 1 than fingolimod. Fingolimod's activity at sphingosine 1-phosphate receptor 3 was suspected to be responsible for a portion of it's adverse effects, and so more selective modulators were developed.
Ponesimod was granted FDA approval on 18 March 2021.
Ponesimod is a sphingosine 1-phosphate receptor 1 modulator indicated to treat adults with relapsing forms of multiple sclerosis. It has a long duration of action as it is given once daily. Patients should be counselled about the risk of infections, bradyarrhythmia, atrioventricular conduction delays, decreased respiratory function, liver injury, increased blood pressure, cutaneous malignancies, fetal harm, and macular edema.
| Trade Name | Ponesimod |
| Availability | Prescription only |
| Generic | Ponesimod |
| Ponesimod Other Names | Ponesimod |
| Related Drugs | Gilenya, Tysabri, Vumerity, Copaxone, Tecfidera, Aubagio, Avonex |
| Type | |
| Formula | C23H25ClN2O4S |
| Weight | Average: 460.97 Monoisotopic: 460.1223562 |
| Protein binding | Ponesimod is >99% protein bound in plasma. Though the proteins it binds to have not been identified in literature. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Ponesimod is a sphingosine 1-phosphate receptor modulator indicated to treat relapsing multiple sclerosis.
Ponesimod is indicated to treat adults with relapsing forms of multiple sclerosis, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.
Ponesimod is also used to associated treatment for these conditions: Active secondary progressive Multiple Sclerosis, Relapsing Multiple Sclerosis (RMS), Relapsing Remitting Multiple Sclerosis (RRMS)
How Ponesimod works
The sphingosine 1-phosphate receptor 1 (S1P1R) is expressed on the surface of lymphocytes and detects sphingosine 1-phosphate (S1P) at nanomolar concentrations. S1P is a metabolite of the cell membrane component, sphingomyelin. As sphingomyelin degrades, lymphocytes respond to agonism of S1P1R by concentration gradients of S1P. Lymphocytes leave the lymphoid organs in response to higher concentrations of S1P in blood and lymph. Ponesimod modulates this response by stimulating and internalizing S1P1R on lymphocytes, effectively blinding them to concentration gradients of S1P, reducing the number of lymphocytes in blood. Ponesimod is roughly 650 times more selective for S1P1R than S1P.
Toxicity
Patients experiencing an overdose may present with bradycardia, AV conduction block, and changes in blood pressure. Patients should be monitored for pulse rate and blood pressure, as well as ECGs. Treat patients with symptomatic and supportive measures, which may include atropine for bradycardia. dialysis is not expected to remove a significant amount of drug from blood.
Food Interaction
- Take with or without food. The absorption of ponesimod is not significantly affected by food.
Ponesimod Hypertension interaction
[Moderate] The use of ponesimod may result in a transient decrease in heart rate and atrioventricular (AV) conduction delays, especially during treatment initiation.
This drug is not recommended in patients with a history of cardiac arrest, cerebrovascular disease (e.g., TIA, stroke occurring more than 6 months prior to treatment initiation), uncontrolled hypertension, or severe untreated sleep apnea, since significant bradycardia may be poorly tolerated in these patients.
The use of this drug in patients with a history of recurrent syncope or symptomatic bradycardia should be based on an overall benefit-risk assessment.
Obtain an ECG in all patients to determine whether preexisting conduction abnormalities are present and consult a cardiologist if appropriate.
Monitor closely patients taking concurrent therapy with drugs that decrease heart rate (e.g., beta-blockers, non-dihydropyridine calcium channel blockers, and other drugs that may decrease heart rate).
Hypertension interaction[Moderate] The use of ponesimod may result in increased blood pressure.
Care should be exercised when using this drug in hypertensive patients and those at risk for hypertension.
It is recommended to monitor blood pressure during treatment and manage it according to clinical practices.
Ponesimod Disease Interaction
Moderate: arrhythmia, hypertension, infections, liver dysfunction, pulmonary impairment, vaccination, encephalopathy, macular edema, MS
Volume of Distribution
The volume of distribution of ponesimod at steady state is 160 L.
Elimination Route
A 10mg oral dose of ponesimod is 84% bioavailable. Ponesimod reaches a Cmax of 109 ng/mL, with a Tmax of 4.0 hours, and an AUC of 3872 h*ng/mL.
Half Life
Ponesimod has an elimination half life of 33 hours.
Clearance
The clearance of ponesimod is 3.8 L/h.
Elimination Route
57.3-79.6% of a radiolabelled oral dose is recovered in the feces, with 16-26% as the unmetabolized parent compound and 22% as the M12 metabolite. 10.3-18.4% of an oral dose is eliminated in the urine. 0.6-1.9% of a radiolabelled dose was recovered as expired CO2.
Innovators Monograph
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