Disease Modifying Anti-Rheumatic Drugs Flashcards
Methotrexate
(Trexall)
MOA: Inhibition of aminoimidazolecarboxamide ribonucleotide (AICAR) transformylase –> Suppression of inflammatory responses of neutrophils, macrophages, lymphocytes
ADE: N/D, hepatotox, stomatitis, alopecia, SOB, myelosuppression (MYL), Mucosal Ulcers, Dose-related increased hepatic enzymes, Thrombocytopenia
Requires supplementation with folic acid (Leucovorin)
Folic acid 1-3mg/day decreases frequency of toxicities —> Mucositis, nausea, hematologic and LFT elevations
Category X
Caution/Avoid: Scr ≥2.0mg/dL
Monitor pulmonary function –> SOB, cough, HA (Pulmonary toxicity) –> Acute interstitial pneumonitis –> Chest X-ray: Bilateral interstitial infiltrates (D/C MTX if this occurs AND DO NOT re-challenge patient)
DIs: Sulfamethoxazole/trimethoprim (Bactrim) = MAJOR –> Increased bone marrow suppression
Leflunomide
(Arava®)
MOA: Inhibition of dihydroorotate dehydrogenase (pyrimidine synthesis) —> apoptosis
ADE: Hepatotox, N/D, HTN, rash, HA, abdom.pain, Weight gain, alopecia; peripheral neuropathy, Bone marrow toxicity
Category X
Sulfasalazine
(Azulfidine®, Sulfazine®)
MOA: Metabolism to sulfapyridine (by GI bacteria) –> Inhibition of cytokine release (IL-1, -6 , -12 , TNF - alpha)
ADE: N/D, HA, yellow-orange discolor. (body fluids/skin), photo sens. (use SPF), myelosuppression (MYL), rash, itching.
Hydroxychloroquine
(Plaquenil®)
MOA: Suppression of T-lymphocyte responses and decreased leukocyte chemotaxis through stabilization of lysosomal enzymes, oxygen radical trapping.
ADE: N/D, HA, vision changes (eye exams), skin pigmentation
NO myelosuppression , hepatotox. , neprotox
Infliximab
(Remicade) - 3-10 mg/kg @ 0,2, and 6 weeks then q6-8wk; IV infusion (2hours) –> compliance issues
TNF-∝ Antagonist
ADEs: Infusion rxn (rash, N, SOB urticaria, HA, fever, chills), ↑ risk of infection
Combination with methotrexate
Demyelinating syndrome
Indicated: rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, Crohn’s disease
Adalimumab
(Humira) - 40mg SC q2 weeks
TNF-∝ Antagonist
MOA: Blocks interaction of TNF-α with TNF receptors —> Lysis of cells expressing TNF-α
ADEs: injection site reaction (ISR), ↑ risk of infection
Clearance is decreased by concurrent methotrexate (indicated with or without MTX)
Indicated: rheumatoid arthritis, juvenile chronic arthritis, psoriasis, psoriatic arthritis, alklylosing spondylitis
Etanercept
(Enbrel) - 50mg SC q weekly
TNF-∝ Antagonist
*TNF p75 Receptor Fusion Protein
MOA: Binds to both TNF-α and TNF-β
ADEs: Injection site reactions (ISR), ↑ risk of infection
indicated with or without MTX
Indicated for rheumatoid arthritis, juvenile chronic arthritis, psoriasis, psoriatic arthritis, alklylosing spondylitis
Golimumab
(Simponi) - 50mg SC q4 weeks
TNF-∝ Antagonist
MOA: Binds to soluble and membrane-bound TNF-α
ADEs: ISR, ↑ risk of infection
Concomitant MTX decreases clearance
Indicated for rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis
Certolizumab pegol
(Cimzia) - 400mg SC @ 0, 2, 4 weeks then q4 weeks (or 200mg SC q2 weeks)
TNF-∝ Antagonist
MOA: Blocks interaction of TNF-α with TNF receptor (no lysis)
ADEs: ISR, ↑ risk of infection
Indicated for rheumatoid arthritis and Crohn’s disease
TNF-α Inhibitors Tox. and Monitoring - class effect
BBW:
Infections (including fungal and opportunistic); malignancy and TB; multiple sclerosis, hepatitis B (HBV) and C (HCV); heart failure; drug induced lupus
Toxicities
- Reactivation of latent tuberculosis
- Increased incidence of bacterial/fungal/viral infections
- Avoid patients with chronic heart failure
- Increased risk of malignancies (lymphoma)
Monitoring
- TB screening
- CBC, ESR, CRP, RF, joint counts, steroid use
- Vaccines- Influenza and pneumococcal (No LIVE)
- Signs of infection- counseling not to delay care
- Skin checks — SPF use
- Cancer screenings
Abatacept
(Orencia) - 500mg (100kg), IV (over 30mins) @ 0, 2, 4 then q 4weeks
125 mg SC q week after loading dose
T-cell Modulator - CTLA-4 Ig human fusion protein
MOA: Binds to CD80/86 protein (Antigen-presenting cell) —> Blocks T-cell activation
ADEs: Injec.site rxn, HA, dizziness, cough, nasopharynx.
Monitor: Screen for TB (Reactivation of tuberculosis), Signs of infection, respiratory w/ COPD pts. (lowest risk of infection)
Indicated for rheumatoid arthritis and juvenile idiopathic arthritis
Rituximab
(Rituxan) - 1,000mg IV infusion(~6hrs) twice, given 2wks apart = 1 cycle
B-cell Modulator
MOA: CD20 (B-cells, B-cell lymphomas)
ADEs: Infusion rxn (rash, N, SOB, urticaria, HA, fever, chills) Methylprednisone 100mg 30mins prior & Benadryl
Monitoring: Signs of infection, post infusion rxn,
Progressive multifocal leukoencephalopathy (PML)- neurology s/sx
BBW: Infusion related rxn; cutaneous rxn; HBV; progressive multifocal leukoencephalopathy (PML); infections; response to vaccines?
Tocilizumab
(Actemra) - 4-8mg/kg IV infusion (over 1 hr) q 4weeks;
100kg: weekly
IL-6 inhibitor
MOA: Binds to soluble and membrane bound IL-6 —> Decreased B-Cell differentiation and Decreased T-Cell activation
ADEs: Infus. rxn, ↑ risk of infection, ↑ lipids/ liver enzymes, GI sx (Gastrointestinal perforation)
Monitoring: ↑ risk of infection ANC, LFTs, platelets, lipids, GI symptoms; drug intx
BBW: Infections; TB; infusion rxn; liver enzymes; cholesterol; neutropenia; thrombocytopenia; CYP 3A4 inducer
Tofacitinib
(Xeljanz)
MOA: Janus kinase (JAK) inhibitor
- Inhibits the intracellular activation to prevent release of pro-inflammatory cytokines
- Inhibition of Janus Kinase 3 (JAK3) mostly
Dosing: 5mg PO BID with or without MTX or other non-biologic DMARDs
Should NOT be used in combination with
TNFi, abatacept (Orencia), anakinra (Kineret), tocilizumab (Acetmra), rituximab (Rituximab) or potent immunosuppressive therapies (azathioprine or cyclosporine)
- Dose reduce to 5mg PO QD with: CYP3A4 potent or moderate inhibitors or CYP2C19 potent inhibitors
Initial side effects: HA, N/D, HTN
Sustained side effects: ↑ Risk of infections, ↑LFTs, ↑LDL, ↑HDL ↑ Scr, ↑ anemia, ↑ neutropenia, ↑lymphopenia
BBW: Infections (including fungal and opportunistic); malignancy and TB; liver enzymes; cholesterol; neutropenia; reduce dose in renal/hepatic insufficiency and in combo with 3A4 inhibitors
