Fingolimod

BRAND NAMES:

Tascenso – It contains the active ingredients of Fingolimod. It is available in the form of oral disintegrating tablets used to treat multiple sclerosis.

Gilenya – It contains the active ingredients of Fingolimod. It is available in the form of capsules.

MECHANISM OF ACTION:

Fingolimod is an oral medication that treats multiple sclerosis by binding to sphingosine-1-phosphate receptors on lymphocytes. This binding stops lymphocytes from leaving lymph nodes, reducing the number of lymphocytes in the blood and preventing them from crossing the blood-brain barrier. This can help prevent autoantibodies from attacking the myelin that protects nerves in the brain and spinal cord.

PHARMACOKINETICS:

Absorption: Fingolimod has an oral bioavailability of 93%, unaffected by food intake. The drug achieves a study state within 8 to 36 hours after administration with a half-life ranging from 6 to 9 days.

Distribution: Approximately 86% of fingolimod is distributed via red blood cells, with a volume of distribution of approximately 1200±260L.

Metabolism: Fingolimod undergoes metabolism via 3 different pathways. The first pathway involves reversible phosphorylation catalyzed by lipid phosphate phosphohydrolases and specific sphingosine 1- 1-phosphate phosphatase. The second pathway includes fingolimod hydroxylation and oxidation by enzymes such as CYP4F2 and other CYP4F enzymes aimed at neutralizing carboxylic acid metabolites excreted by the kidneys. The third metabolic pathway leads to the formation of nonpolar ceramides by dihydroceramide synthase, contributing to the least concentration in the blood.

Excretion: Fingolimod is primarily excreted in urine with the most common metabolic products being the butanoic acid metabolites. Fingolimod and fingolimod phosphate comparing less than 2.5% of the dose are detectable in both blood and feces.

PHARMACODYNAMICS:

During therapy commencement, fingolimod induces a transitory drop in heart rate and AV conduction. It has the potential to increase the QT interval. In multiple sclerosis, fingolimod binds to sphingosine receptors, decreasing neuroinflammation. In COVID-19, it may minimize lung inflammation and improve patients' clinical results.

DOSAGE AND ADMINISTRATION:

• Fingolimod is available in capsules with the strengths of 0.25 mg and 0.5 mg.
• Fingolimod is available in oral disintegrating tablets with strengths of 0.25mg.
• Fingolimod formulations are available as oral capsules in strengths of 0.25 mg and 0.54 mg. Food consumption does not affect drug administration.

DRUG INTERACTION:

Drug interaction with fingolimod may include

•  Medicines that suppress or support the immune system – Natalizumab, Mitoxantrone, Teriflunomide

•  Medicines that slow the heartbeat- Atenolol

•  Medicines for irregular heartbeat- Quinidine, Disopyramide, and Amiodarone

•  Medicines used to treat Epilepsy- Phenytoin, Carbamazepine

•  HIV drugs- Efavirenz

•  Corticosteroid medications- Methylprednisolone

CONTRAINDICATIONS:     

Fingolimod is contraindicated in patients who have had a cardiovascular event within the last 6 months, such as a myocardial infarction, unstable angina, stroke, transient ischaemic attack, or class III/IV heart failure necessitating hospitalization. Furthermore, patients with a history of Mobitz type II heart block, third-degree AV block, or sick sinus syndrome should avoid fingolimod unless they have a functioning pacemaker. If patients have a hypersensitive reaction to fingolimod, the medical team should promptly halt the medication and take appropriate precautions to ensure the patient's safety..

SIDE EFFECTS:

Common side effects of Fingolimod include

•  Headache

•  Tired feeling

•  Influenza

•  Stuffy nose

•  Sinus pain

•  Diarrhea

•  Back pain

•  Cough

Serious side effects include

•  Shinny nodules on the skin

•  Sores that do not heal

•  Blurred vision

•  Eye pain

•  A blind spot in the center of the vision

•  Blood vessel problems in the brain

•  Heart problems

•  Liver problems

OVERDOSE:

Overdose symptoms of fingolimod may include

•  Chest pain

•  Confusion

•  Dizziness

•  Fainting

•  Shortness of breath

•  Tiredness

•  Feeling like your heart is skipping beats

TOXICITY:

In one case report, an intended overdose of 14mg fingolimod and 2gr phenoxymethylpenicillin resulted in bradycardia, which was treated with atropine. Fingolimod has been linked to cardiotoxicity. An overdose could cause cardiac consequences such as bradycardia and heart block.

STORAGE:

Store safely away from children. Maintain at room temperature between 20 and 25 degrees Celsius (68 and 77 degrees Fahrenheit). Protect against moisture content.