fingolimod (fin-go-li-mod) Gilenya

 Indications

Treatment of relapsing forms of multiple sclerosis.

Action

Converted by sphingosine kinase to the active metabolite

fingolimod-phosphate, which binds to sphingosine 1–

phosphate receptors, resulting inpmigration of lymphocytes

into peripheral blood. This mayplymphocyte migration

into the CNS. Therapeutic Effects:pfrequency

of relapses/delayed accumulation of disability.

Pharmacokinetics

Absorption: Well absorbed (93%) following oral

administration.

Distribution: Extensively distributed to body tissues;

86% of parent drug distributes into red blood cells; active

metabolite uptake 17%.

Metabolism and Excretion: Converted to its active

metabolite, then metabolized mostly by the CYP450

4F2 enzyme system, with further degradation by other

enzyme systems. Most inactive metabolites excreted in

urine (81%); 2.5% excreted as fingolimod and fingolimod-

phosphate in feces.

Protein Binding: 99.7%.

Half-life: 6–9 hr.

TIME/ACTION PROFILE

ROUTE ONSET PEAK DURATION

PO unknown 1–2 mo* 2 mo†

*Time to steady state blood levels, peak blood levels after a

single dose at 12–16 hr.

†Time for complete elimination.

Contraindications/Precautions

Contraindicated in: Hypersensitivity; MI, unstable

angina, stroke, TIA, or class III or IV HF within previous

6 mo; 2nd- or 3rd-degree heart block or sick sinus syndrome

(in the absence of a pacemaker); QT interval

500 msec; Concurrent use of class Ia or III antiarrhythmics;

Active acute/chronic untreated infections;

Lactation: Breast feeding should be avoided.

Use Cautiously in: Concurrent use of beta blockers,

diltiazem, verapamil, or digoxin (qrisk of bradycardia/

heart block); History of ischemic heart disease,

MI, HF, cerebrovascular disease, uncontrolled hypertension,

AV block, bradycardia, syncope, cardiac arrest,

or severe sleep apnea (qrisk of bradycardia/heart

block); Severe hepatic impairment (qblood levels and

risk of adverse reactions); Diabetes mellitus/history of

uveitis (qrisk of macular edema); Negative history for

chickenpox or vaccination against varicella zoster virus

vaccination; Geri: Risk of adverse reactions may beq

consider age-relatedpin cardiac/renal/hepatic function,

chronic illnesses, and concurrent drug therapy;

Pedi: Safety and effectiveness not established; OB: Use

only if potential benefit justifies potential risk to fetus.

Adverse Reactions/Side Effects

CNS: POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME

(PRES), PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY

(PML), headache. EENT: blurred vision, eye

pain, macular edema. Resp: cough,ppulmonary

function. CV: ASYSTOLE, BRADYCARDIA, HEART BLOCK, QT

INTERVAL PROLONGATION, hypertension, syncope.

Derm: basal cell carcinoma. GI: diarrhea,qliver enzymes.

Hemat: leukopenia, lymphopenia. MS: back

pain. Misc: INFECTION (including bacterial, viral and

fungal), HYPERSENSITIVITY REACTION (including rash, urticaria,

and angioedema).

Interactions

Drug-Drug: Concurrent use of class Ia or class III

antiarrhythmics mayqrisk of serious arrhythmias;

careful monitoring recommended. Concurrent use of

beta blockers, diltiazem, verapamil, or digoxin

mayqrisk of bradycardia; careful monitoring recommended.

Concurrent use of ketoconazole mayq

blood levels and risk of adverse reactions.qrisk of immunosuppression

with antineoplastics, immunosuppressants,

or immune modulating therapies.

Live-attenuated vaccinesqrisk of infection.

Route/Dosage

PO (Adults): 0.5 mg once daily.

Availability

Capsules: 0.5 mg.