Gilenia

Uses

Gilenia is a sphingosine 1-phosphate receptor modulator used to treat patients with the relapsing-remitting form of multiple sclerosis (MS) and studied to manage lung complications of COVID-19.

Gilenia is indicated for the treatment of patients aged 10 and above with relapsing forms of multiple sclerosis, which may include clinically isolated syndrome, relapsing-remitting disease, as well as active secondary progressive disease.

This drug is being studied for administration in patients infected with COVID-19 with a high risk for acute respiratory distress syndrome, or ARDS. As of April 3 2020, this is currently not an approved indication and clinical trials are underway.

Gilenia is also used to associated treatment for these conditions: Relapsing Multiple Sclerosis (RMS), Alternative Treatment

How Gilenia works

Sphingosine‐1‐phosphate (S1P) is an important phospholipid that binds to various G‐protein‐coupled receptor subtypes, which can be identified as S1P1–5R. S1P and the receptors it binds to perform regular functions in the immune, cardiovascular, pulmonary, and nervous system. S1P can be expressed ubiquitously, playing an important role in regulating inflammation. S1P1R, S1P2R, and S1P3R receptors can be found in the cardiovascular, immune, and central nervous systems. S1P4R is found on lymphocytic and hematopoietic cells, while S1P5R expression is found only on the spleen (on natural killer cells) or in the central nervous system.

The active form of the drug, fingolimod phosphate, is a sphingosine 1-phosphate receptor modulator that exerts its mechanism of action in MS by binding to various sphingosine 1-phosphate receptors (1, 3, 4, and 5). It suppresses the exit of lymphocytes from lymph nodes, leading to a lower level of lymphocytes circulating in peripheral circulation. This reduces the inflammation that is associated with MS. The mechanism of action of fingolimod is not fully understood, but may be related to reduced lymphocyte circulation into the central nervous system.

Immune modulating treatment such as fingolimod is not typically employed for SARS-CoV-2 pneumonia. Despite this, with the tissue findings of pulmonary edema and hyaline membrane formation, the timely use of immune modulators such as fingolimod can be considered to prevent acute respiratory distress syndrome (ARDS) associated with COVID-19.

Toxicity

The LD50 of fingolimod in rats ranges from 300-600 mg/kg.

Prescribing information for fingolimod does not mention symptoms or management of an overdose , however, a case report of an intentional overdose with 14mg of fingolimod and 2g phenoxymethylpenicillin resulted in hypotension in bradycardia, resolved by administering atropine. Since fingolimod has been associated with cardiotoxicity, it would be reasonable to expect cardiac effects such as bradycardia and heart block in the case of an overdose.

Food Interaction

• Take with or without food.

Gilenia Hypertension interaction

[Moderate] Hypertension was reported as an adverse reaction in patients on fingolimod.

Blood pressure should be monitored during treatment with this agent as it can increase the blood pressure of patients with hypertension.

Gilenia Drug Interaction

Major: methylprednisolone, ocrelizumab, sotalol, natalizumabModerate: lactobacillus acidophilus, interferon beta-1a, bifidobacterium infantis / lactobacillus acidophilusUnknown: aspirin, amphetamine / dextroamphetamine, dalfampridine, duloxetine, tamsulosin, heparin, pregabalin, vitamin a topical, bioflavonoids, topiramate, oxcarbazepine, cyanocobalamin, cholecalciferol

Gilenia Disease Interaction

Major: CV diseaseModerate: hepatic impairment, hypertension, infections, macular edema, respiratory dysfunction, encephalopathy, MS

Volume of Distribution

The volume of distribution of fingolimod is about 1200±260 L. It is approximately 86% distributed in the red blood cells (RBC).

Elimination Route

Gilenia is slowly but efficiently absorbed in the gastrointestinal tract. AUC varies greatly, depending on the patient, and pharmacokinetic studies demonstrate a range of AUC values for fingolimod. The Tmax of fingolimod ranges between 12-16 hours and its bioavailability is 90-93%. Steady-state concentrations of fingolimod are achieved within 1-2 months after initiation when it is administered in a single daily dose.

Half Life

The half-life of fingolimod and its active metabolite ranges from 6-9 days.

Clearance

Gilenia blood clearance is 6.3±2.3 L/h, according to prescribing information. Another resource mentions it ranges from 6-8 L/h.

Elimination Route

About 81% of an oral dose of fingolimod is excreted in the urine in the form of inactive metabolites. Intact fingolimod and its active metabolite account for less than 2.5% of the dose, and can be found excreted in the feces.

Innovators Monograph

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