MS-Rx Flashcards
Tecfidera
Dimethylfumarate
Obtain Prior to Initiation:
Complete blood count (CBC) with lymphocyte count
Liver tests
(serum aminotransferase, alkaline phosphatase, and total bilirubin).
After Initiation:
At 6 months:
Every 6-12 months thereafter, and as clinically indicated.
Repeat as clinically indicated
Dosing:
Start 120 mg BID x 7 days; then 240 mg BID. Check
Among its possible mechanisms, it has been proposed that it inhibits the differentiation of specific immune T-cells (T helper cell 1 and 17) and reduces the recruitment of neutrophils — a type of white blood cell — in inflammation.
Temporary dose reductions to 120 mg twice a day may be considered for individuals who do not tolerate the maintenance dose. Within 4 weeks, the recommended dose of 240 mg twice a day should be resumed
Discontinuation of TECFIDERA should be considered for patients unable to tolerate return to the maintenance dose.
Serious:
Anaphylaxis. Angioedema. PML. Hepatotoxic. Lymphopenia. Flushing.
Vumerity
Diroximel Fumarate
The new Tecfidera. Lower GI side effects. Still has flushing. Avoid with high-fat meal. 231 mg. One BID for one week, then Two BID thereafter. Small low-fat meal okay.
Bafiertam
Monomethyl fumarate
The new new Tecfidera.
No dietary restrictions.
BID. With or without food.
GILENYA
Fingolimod.
Modulator of sphingosine-1 phosphate receptors.
Bonds to these receptors on T- lymphocytes.
Prevents activation. Sequesters them.
Starting: CBC. LFT. (JCV?).
Examine maculae.
Hx. Chickenpox or VZV vaccine/serology.
First dose observation w/ EKG, BP, pulse hourly x 6 hrs.
Contraindication: MI, angina, CHF, SSS, AVB, CVA, TIA.
SFx: first dose bradycardia & AVB. Infections opportunistic. PML. Macular edema, check at month one and three. PRES. FEV 1.
LFT elevations within 9 months, usually return to baselines with discontinuance.
Some fetal risk. BP increases. BCCa. Headaches and somatic aches. URI sx.
Serious:
Infections. PML. Macular edema. Hepatotoxic. Fetal risk. Hypertension. PRES. Low PFT’s.
TRANSFORMS: 52% reduces relapses vs Avonex.
FREED-MS: RRR 54% vs Placebo. & slightly better than placebo at disability progression 82% vs 76% at three yrs were stable/ unprogressed.
Mayzent
Siponimod.
selective sphingosine-1-phosphate receptor modulator for oral use that is used for multiple sclerosis (MS). It is intended for once-daily oral administration.
relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.
Before starting: LFT, (CBC) (ie, within 6 months or after discontinuation of prior therapy). VZV serology.
CYP2C9 1/3 or 2/3 genotype. Dosing titration based on this. Do not use in 3/3 genotype.
HTN?
Delay initiation of treatment in patients with severe active infections until resolved. Cases of fatal cryptococcal meningitis (CM).
No cases of (PML). ; however, they have been observed in patients treated with Gilenya.
Patients without a confirmed history of varicella zoster virus (VZV) or without vaccination should be tested for antibodies. If NEGATIVE, then VZV immunization is recommended.
Use of live vaccines should be avoided
First dose observation for bradycardia.
Observe for HTN.
Ophtho exam for macular edema at start and PRN. Higher risk with DM and uveitis.
Most common adverse reactions (>10%) are headache, hypertension, and transaminase increases.
Serious:
Infections. PML. Macular edema. Hepatotoxic. Fetal risk. Hypertension. PRES. Low PFT’s.
Zeposia
Ozanimod
Modulator of sphingosine-1 phosphate receptors.
Bonds to these receptors on T- lymphocytes.
Prevents activation. Sequesters them.
Starting:
CBC. LFT. And bilirubin (CMP). Option JCV.
EKG.
No significant cardiac history. MI. Angina. CVA. AV block. SSS. CHF. etc.
Once-a-day.
No first-dose observation (7-day titration instead).
No genetic testing (as in Mayzent).
No eye exam ( unless history uveitis or DM).
Hx. Chickenpox or VZV vaccine/serology— then OK.
No history or antibodies— then vaccinate one month prior to start.
Can get infections: HSV. HS meningitis/encephalitis. Cryptococcal. JCV w/similar meds.
Can get HTN at 3 months. Persistent.
Rebound disease with stoppage.
Aubagio.
Teriflunamide.
Exact MOA unknown.
Inhibits proliferation of B and T lymphocytes in periphery.
Rapidly proliferating lymphocytes need to synthesize extra pyrimidines for metabolic demands. Aubagio inhibits mitochondrial DHODH enzyme required for this. ( normal population of resting lymphocytes should not be affected)
Hepatotoxic. Made from leflunomide analogue which is teratogenic. Monitor LFT. Pregnancy or LFT can accelerate elimination with charcoal or cholestyramine.
WBC count reduces, also plates. Hypersensitivity skin reaction. Polyneuropathy. Mononeuropathy. BP increases. Interstitial Lung dz.
Headache. Diarrhea alopecia. Nausea.
Cytostatic
Tysabri
Natalizumab
For: RRMS. CIS. SPMS. First line.
Monoclonal antibody against adhesion molecule a4-integrin. Prevents leukocyte entry into CNS.
Reduces exacerbations by 65%, quiets the MRI, slows disability progression.
Infusion every 4 weeks, possibly every 6.
1/1000 PML overall, stratified:
Prior immunosuppressant
After 2 years use.
Positive JCV.
Anaphylaxis in 1/50. Do not retry Rx.
Increased risks: VZV, HSV, meningo-encephalitis.
Acute retinal necrosis (from HSV).
Acute liver injury/ necrosis.
PNA. UTI. GI.
Mavenclad
Cladribine.
Oral tablet, 10 mg.
Second line therapy.
For RR and SPMS.
Weight-based dose:
4-5 days, wait 23-27 days, then another 4-5 days.
Repeat one year later.
No more Mavenclad for next two years.
Prepackaged doses are dispensed for each 4-5 —day cycle.
Prior to start: Cancer screen. B-HCG. CBC: WBC must be WNL for first course; >800 for second; may delay second course up to 6 mos.
Prodrug activated in cells by phosphorylation. Accumulates in the DNA of T and B lymphocytes; inhibits DNA synthesis and repair.
Cytotoxic. Temporarily reduces T and B lymphocytes without continuous suppression.
24-hr t1/2; eliminated after one week. Lymphocytes recover over several months. Total lymphocyte nadir in 8-10 weeks, usually mild to moderate, 25% get below 500.
Malignancies: No in current CA. Follow standard cancer screenings after.
Infections: HZV. TB. Hep. B. Pyelo. No live vaccines.
Liver injury. Teratogenic.
Common Rxns: URI. Headache. Lymphopaenia.
Boxed:
Malignancies. Teratogenic.
HZV. Pyelo. Hepatic. Myelotoxic.
Ocrevus
Ocrelizumab.
First line: RRMS. SPMS. PPMS.
Initial dose:
300 mg one week;
300 mg 2 weeks later.
Maintenance: 600 mg every 6 months.
Targets Anti-CD20-expressing B-cells.
Prior: Hepatitis B panel ( no for active dz). Up to date on all vaccinations. Consider shingles? Consider mammo.
Infections: Hep. B. Herpes. URI. Bronchitis.
Malignancies: maybe breast. Standard screen.
Lemtrada
Alemtuzumab.
Second line. Third line.
For: RRMS. SPMS. Not CIS.
Year one: five infusion days.
Year two: three infusion days.
PRN’s: three infusion days >/= one year apart.
Prior to start:
Complete any necessary immunizations at least 6 weeks prior.
Chickenpox, or VZV serology, or vaccinate.
No active infections.
Avoid foods with Listeria; or heat high.
Binds to CD52 receptors on T and B lymphocytes, depleting them.
Serious/fatal infusion reactions.
Autoimmune: Thrombocytopenia. Glomerular basement membrane disease. Dyscrasias.
most common adverse reactions (incidence ≥10% and >interferon beta-1a) with LEMTRADA vs interferon beta-1a were: rash (53% vs 6%), headache (52% vs 23%), pyrexia (29% vs 9%), nasopharyngitis (25% vs 19%), nausea (21% vs 9%), urinary tract infection (19% vs 8%), fatigue (18% vs 13%), insomnia (16% vs 15%), upper respiratory tract infection (16% vs 13%), herpes viral infection (16% vs 3%), urticaria (16% vs 2%), pruritus (14% vs 2%), thyroid gland disorders (13% vs 3%).
Risk of of malignancies, including thyroid cancer, melanoma, and lymphoproliferative disorders. Perform baseline and yearly skin exams.
Thyroiditis.
Stroke and cervical artery dissections.
Copaxone
Glatiramer
Glatopa
Immunoactive mixture of synthesized polypeptides consisting of 4 naturally occurring amino acids.
Exact mechanism of action is unknown. Resembles myelin basic protein (MBP). It is hypothesized that the T cells produced in response to Copaxone can suppress the immune attack on myelin, preventing demyelination and axonal damage.
2-16%. (Fewer on the 40mg) got: flushing, chest pain, palpitations, tachycardia, anxiety, dyspnea, throat constriction, and urticaria.
Site reactions, including dimpling of skin.
Betaseron
Multiple complex mechanisms action.
Increases experssion and concentration of anti-inflammatory agents. Downregulates proinflammatory cytokines.
May reduce migration of proinflammatory white cells across BBB.
Increase nerve growth factor.
Kesimpta.
Ofatumumab
Monoclonal anti-B cell.
Monthly SQ pen.
Once a week for three weeks, skip one week, then monthly.
CIS, RRMS, SPMS. Not PPMS.
No active hepatitis B.
Hepatitis B virus screening and diagnosis (triple panel).
LabCorp # 144473
Start Labs:
CBC. ESR.
LFT BUN/creat. VZV serology (Quest: VZV antibodies. 34128). TB Quantiferon Gold (or PPD). Stratify JCV index (Quest: 91665).
Consider hypercoagulability profile.
