Octec 0.5

White powder in yellow/opaque white capsule no.3 with printed FG and 0.5 in black color.
Each capsule contains Fingolimod hydrochloride 0.56 mg eq. to Fingolimod 0.50 mg.

Pharmacology: Pharmacodynamics: Fingolimod-phosphate, active metabolite of Fingolimod, binds to sphingosine 1-phosphate receptors 1, 3, 4, and 5. Fingolimod-phosphate blocks the lymphocytes' ability to emerge from lymph nodes; therefore, the amount of lymphocytes available to the central nervous system is decreased, which reduces central inflammation.
Pharmacokinetics: Distribution: V_d: ~1,200 L: distributes into red blood cells (86%).
Protein binding: >99.7% (Fingolimod and Fingolimod-phosphate).
Metabolism: Hepatic via CYP4F2 to Fingolimod-phosphate (active) and other metabolites (inactive); CYP2D6, 2E1, 3A4, and 4F12 also contribute to metabolism.
Bioavailability: 93%.
Half-life elimination: 6 to 9 days; prolonged by approximately 50% in patients with moderate or severe hepatic impairment.
Time to peak, plasma: 12 to 16 hours.
Excretion: Urine (~81 % as inactive metabolites); feces (Fingolimod and Fingolimod phosphate; <2.5% of dose).

Fingolimod is indicated as a disease modifying therapy for the treatment of patients with relapsing multiple sclerosis to reduce the frequency of relapses and to delay the progression of disability.

Before initiating Fingolimod therapy: Review medications for current drugs that could slow heart rate or atrioventricular (AV) conduction. Perform a cardiac evaluation in patients with certain preexisting conditions. Perform an ECG before the first dose and at the end of the first-dose observation period.
Review results of a recent CBC.
Within 6 months before initiating Fingolimod treatment, obtain serum transaminases (ALT and AST) and total bilirubin levels.
Review current or past use of antineoplastic, immunosuppressive, or immune-modulating therapies that may have unintended additive immunosuppressive effects.
Test for antibodies to varicella zoster virus. Varicella zoster virus vaccination is recommended for antibody-negative patients before initiating treatment.
Adults: The recommended dose of Fingolimod is one 0.5 mg capsule taken orally once daily. Perform an ECG before the first dose and observe for 6 hours after the first dose and repeat ECG at the end of the first-dose observation period.
Pediatric patients (below the age of 18): The safety and efficacy of Fingolimod in pediatric patients below the age of 18 have not been studied. Fingolimod is not approved in pediatric patients.
Reinitiation of treatment: The same first dose monitoring as for treatment initiation is recommended when treatment is interrupted for: 1 day or more during the first 2 weeks of treatment; more than 7 days during weeks 3 and 4 of treatment; more than 2 weeks after one month of treatment.
If the treatment interruption is of shorter duration than the previously mentioned, the treatment should be continued with the next dose as planned.
Special populations: Renal impairment: Fingolimod was not studied in patients with renal impairment in the multiple sclerosis pivotal studies. Based on clinical pharmacology studies, no dose adjustments are needed in patients with mild to severe renal impairment.
Hepatic impairment: Mild or moderate hepatic impairment (Child-Pugh Class A-B): No dose adjustments are needed, Severe hepatic impairment (Child-Pugh Class C): No dosage adjustment, use with caution and closely monitor.
Administration: Fingolimod can be taken with or without food.
The capsules should always be swallowed intact, without opening them.
Discontinuation: Consider gradual discontinuation, such as a tiered reduction in dosage or alternate-day administration, due to an increased risk for disease exacerbation, especially in patients with lower peripheral total lymphocyte count (TLC) at the time of discontinuation and a higher ratio of TLCs in a short period.

Mild to moderate toxicity: Transient mild bradycardia and atrioventricular (AV) conduction disturbances may develop. Fingolimod may increase the risk of infection and macular edema. Mild elevations in transaminase concentrations may occur.
Treatment is symptomatic and supportive. Transient bradycardia usually does not require intervention. Atropine can reverse the negative chronotropic effect of Fingolimod and may be indicated in clinically significant bradycardia.
Severe toxicity: Symptomatic bradydysrhythmias and AV blocks, dyspnea, severe infections, and hepatic injury.
Treatment is symptomatic and supportive. Atropine is indicated to treat clinically significant bradycardia. Isoproterenol may also be indicated in some patients. Monitor for atrioventricular conduction disturbances or heart block. Treat infections as indicated. Monitor hepatic enzymes for evidence of liver injury.

Class III or IV heart failure within the last 6 months.
Cardiac arrhythmias requiring anti-arrhythmic treatment with Class Ia or Class III antiarrhythmic drugs.
Decompensated heart failure requiring hospitalization within the last 6 months.
Hypersensitivity reaction to Fingolimod or any of the excipients.
Mobitz type II second-degree or third-degree atrioventricular block (history or current), unless the patient has a functional pacemaker.
Myocardial infarction within the last 6 months.
QTc interval at baseline 500 milliseconds or greater.
Sick-sinus syndrome (history or current), unless the patient has a functional pacemaker.
Stroke within the last 6 months.
Transient ischemic attack within the last 6 months.
Unstable angina within the last 6 months.

Cardiovascular: Atrioventricular conduction delays, including transient asystole and fatalities, have been reported; monitoring of therapy initiation in a medical facility is required and medical management may be warranted.
Blood pressure increases and hypertension have been reported; monitoring recommended.
Bradycardia has been reported; some preexisting conditions may cause decreased bradycardia tolerance or serious rhythm disturbance after the first dose; monitoring of therapy initiation in a medical facility is required and medical management may be warranted.
Patients with preexisting cardiovascular conditions, cerebrovascular disease, baseline QT-interval prolongation, or risk factors for QT prolongation require overnight monitoring of therapy initiation in a medical facility because bradycardia or rhythm disturbances may occur.
Avoid use of live attenuated vaccines during and for 2 months after treatment.
Concomitant use with agents that slow heart rate or atrioventricular conduction (eg, diltiazem, verapamil, digoxin, beta blockers) requires overnight ECG monitoring following the first dose of Fingolimod in a medical facility as severe bradycardia or heart block may occur.
Dermatologic: Basal cell carcinoma, Merkel cell carcinoma, and melanoma have been reported. Limit exposure to sunlight and ultraviolet light; monitoring recommended and prompt evaluation required.
Cutaneous T-cell lymphoma, including mycosis fungoides, has been reported.
Hematologic: Lymphocyte count decreases have been reported and may persist for 2 months following discontinuation of therapy; additive immunosuppressant effects may be expected when other immunosuppressant agents are given during this period; monitoring recommended and suspension of treatment should be considered if serious infection develops.
Hepatic: Liver enzyme elevations have been reported; monitoring recommended and discontinuation may be required.
Severe hepatic impairment increases risk of adverse events; monitoring recommended.
Clinically significant liver injury and cases of active liver failure requiring liver transplant have been reported; monitoring recommended and discontinuation may be required.
Immunologic: Do not initiate treatment in patients with active acute or chronic infection.
Disseminated varicella zoster and herpes simplex infections, including cases of encephalitis and multiorgan failure, have been reported.
Cryptococcal infections (eg, cryptococcal meningitis, disseminated cryptococcal infections) including fatal cases of cryptococcal meningitis have occurred; if suspected, prompt diagnostic evaluation and management required.
Immunosuppression, during therapy and persisting for 2 months after discontinuation, increases risk of serious infection; additive immunosuppressant effects may be expected when other immunosuppressant agents are given during this period; monitoring recommended and treatment interruption may be warranted.
Switching from immune-modulating or immunosuppressive medication to Fingolimod; consider the duration of action to avoid risk of additive immunosuppressive effects.
Test for presence of varicella zoster virus (VZV) antibodies prior to initiation in patients with a negative history for chickenpox or without VZV vaccination; vaccination is recommended for antibody-negative patients 1 month prior to Fingolimod initiation.
Human papilloma virus (HPV) infections, including papilloma, dysplasia, warts, and HPV-related cancer, have been reported; consider vaccination prior to therapy and follow standard of care for cancer screening.
Hypersensitivity reactions including rash, urticaria, and angioedema upon treatment initiation have been reported.
Lymphoma, including T-cell and B-cell types and CNS lymphoma, has been reported.
Infections: Serious, life-threatening, and fatal infections with opportunistic pathogens including viruses, herpes, fungi, and bacteria have been reported; if suspected, prompt diagnostic evaluation and management required.
Musculoskeletal: Kaposi's sarcoma has been reported; if suspected, prompt diagnostic evaluation and management required.
Neurologic: Multiple sclerosis relapses with tumefactive demyelinating lesions on imaging have been observed during and after therapy discontinuation; most cases have occurred within the first 9 months of therapy and has also been reported during the first 4 months following discontinuation.
Progressive multifocal leukoencephalopathy has been reported, including cases in patients who were not immunocompromised and had no prior exposure to immunosuppressant drugs, including natalizumab. MRI findings and JCV DNA detection in cerebrospinal fluid may be apparent before clinical signs or symptoms; discontinue use and perform diagnostic evaluation if suspected.
Severe increase in disability accompanied by multiple new lesions on MRI has been reported following drug discontinuation and generally occurs within 12 weeks of discontinuation, but may occur for up to 24 weeks following discontinuation. Patients may not regain function status attained prior to drug discontinuation; monitoring is recommended and treatment may be necessary.
Posterior reversible encephalopathy syndrome has been reported and may progress to ischemic stroke or cerebral hemorrhage; delayed diagnosis and treatment may result in permanent neurologic damage, discontinue use immediately if suspected.
Ophthalmic: Macular edema has been reported, the risk is dose-dependent and increased in patients with preexisting uveitis or diabetes mellitus; monitoring recommended; discontinuation may be required.
Reproductive: Drug may cause fetal harm; use of effective contraception during and for 2 months after treatment is recommended. For women planning to become pregnant, discontinue use 2 months prior to conception.
Respiratory: Dose-dependent decreases in respiratory function have been reported, including a reduction in FEVl and diffusion lung capacity for carbon monoxide (DLCO); monitoring may be warranted.

Adverse events have been observed in animal studies. Elimination of Fingolimod takes approximately 2 months; to avoid potential fetal harm, women of childbearing potential should use effective contraception to avoid pregnancy during and for 2 months after discontinuing treatment.
It is not known if Fingolimod is excreted in breast milk. Due to the potential for serious adverse reactions in the nursing infant, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of treatment to the mother.

Common: Gastrointestinal: Abdominal pain, Diarrhea.
Hepatic: Increased liver enzymes, Injury of liver.
Immunologic: Influenza.
Musculoskeletal: Backache, Pain In Extremity.
Neurologic: Headache.
Respiratory: Cough, Sinusitis.
Rare but serious or life-threatening: Cardiovascular: Atrioventricular block, Bradyarrhythmia.
Dermatologic: Basal cell carcinoma-primary, Malignant melanoma, Primary cutaneous T-cell lymphoma.
Hematologic: Lymphocytopenia (Severe).
Immunologic: Cryptococcosis, Herpes virus infection, Human papilloma virus infection, Infectious disease.
Neurologic: Cryptococcal meningitis, Posterior reversible encephalopathy syndrome, Primary localized cutaneous nodular amyloidosis, Progressive multifocal leukoencephalopathy.
Ophthalmic: Macular retinal edema.

Avoid concomitant use of Fingolimod with: Bretylium may result in increased risk of bradycardia or heart block.
Avoid concomitant use of Fingolimod with: Levomethadyl may result in increased risk of QT interval prolongation and Torsade de Pointes.
Avoid concomitant use of Fingolimod with: Dofetilide, amiodarone, ibutilide, disopyramide, quinidine, procainamide, sotalol may result in increased risk of QT interval prolongation, bradycardia, or heart block. 
Avoid concomitant use of Fingolimod with: Mesoridazine, ziprasidone, saquinavir, sparfloxacin, bepridil, piperaquine, terfenadine, thioridazine, pimozide, dronedarone, cisapride and other QT prolonging drugs may result in increased risk of QT-interval prolongation.
Fingolimod may increase the levels/effects of: Antiarrhythmic agents (class la); Antiarrhythmic agents (class III); Bradycardia-causing agents; ceretinib; Higher risk QTc prolonging agents; ivabradine; lacosamide; leflunomide; Moderate risk QTc-prolonging agents; natalizumab; tofacitinib; Vaccines (live); zoster vaccine.
The levels/effects of Fingolimod may be increased by: Beta-blockers; bretylium; denosumab; diltiazem; esmolol; Immunosuppressants; ketoconazole (systemic); mifepristone; pimecrolimus; roflumilast; tacrolimus (topical); trastuzumab; verapamil.
Fingolimod may decrease the levels/effects of: BCG (intravesical); Coccidioides immitis skin test; nivolumab; Sipuleucel-T; Vaccines (inactivated); Vaccines (live); zoster vaccine.
The levels/effects of Fingolimod may be decreased by: Carbamazepine; echinacea.

Store below 30°C.

Immunosuppressants

L04AE01 - fingolimod ; Belongs to the class of sphingosine-1-phosphate (S1P) receptor modulators. Used as immunosuppressants.

S