NSAIDs and RA Flashcards by Kyle Walker

Q

Celecoxib

A

Celebrex

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Q

Diclofenac

A

Cambia, Voltaren, Zipsor, Zorvolex

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Q

Etodolac

A

Lodine

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Q

Ibuprofen

A

Motrin

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Q

Indomethacin

A

Indocin, Tivorbex

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Q

Meloxicam

A

Mobic

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Q

Nabumetone

A

Relafen

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Q

Naproxen

A

Naprosyn

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Q

Lidocaine Topical Patch

A

Lidoderm

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Q

Therapeutic class of Celecoxib

A

Cyclooxygenase-2 inhibitor/NSAID

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Q

Therapeutic class of Diclofenac

A

NSAID

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Q

Therapeutic class of Etodolac

A

NSAID

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Q

Therapeutic class of Ibuprofen

A

NSAID

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Q

Therapeutic class of Indomethacin

A

NSAID

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Q

Therapeutic class of Meloxicam

A

NSAID

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Q

Therapeutic class of Nabumetone

A

NSAID

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Q

Therapeutic class of Naproxen

A

NSAID

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Q

Therapeutic class of Lidocaine Topical Patch

A

Local anesthetic

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Q

Azathioprine

A

Azamun, Imuran

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Q

Methotrexate

A

Trexall

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Q

Folic Acid

A

FA-8

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Q

Hydroxychloroquine

A

Plaquenil

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Q

Etanercept

A

Enbrel, ERelzi

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Q

Tacrolimus

A

Prograf, Astagraf XL, Envarsus XR

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Therapeutic class of Azathioprine

Immunosuppressant agent

Therapeutic class of Methotrexate

Antimetabolite

Therapeutic class of Folic Acid

Essential B vitamin

Therapeutic class of Hydroxychloroquine

Aminoquinoline

Therapeutic class of Etanercept

Antirheumatic, disease-modifying, TNF-blocking agent

Therapeutic class of Tacrolimus

Calcineurin inhibitor

Celecoxib dosage forms

Capsule - 50 mg, 100 mg, 200 mg, 400 mg

Diclofenac dosage forms

Tablet - 50 mg ER Tablet - 25 mg, 50 mg, 75 mg, 100 mg Capsule - 18 mg, 25 mg, 35 mg Oral Solution - 50 mg powder

Etodolac dosage forms

Tablet - 400 mg, 500 mg ER Tablet - 400 mg, 500 mg, 600 mg Capsule - 200 mg, 300 mg

Ibuprofen dosage forms

Tablet - 100 mg, 200 mg, 400 mg, 600 mg, 800 mg Chewable Tablet - 100 mg Capsule - 200 mg Oral Liquid - 100 mg/5 mL, 50 mg/1.25 mL

Indomethacin dosage forms

Capsule - 20 mg, 25 mg, 40 mg, 50 mg ER Capsule - 75 mg Oral Liquid - 25 mg/5 mL Rectal Suppository - 50 mg

Meloxicam dosage forms

Tablet - 7.5 mg, 15 mg Capsule - 5 mg, 10 mg Oral Liquid - 7.5 mg/5 mL

Nabumetone dosage forms

Tablet - 500 mg, 750 mg

Naproxen dosage forms

``` Tablet - 220 mg, 250 mg, 275 mg, 375 mg, 500 mg, 550 mg ER Tablet - 375 mg, 500 mg, 750 mg DR Tablet - 375 mg, 500 mg Capsule - 220 mg Oral Liquid - 125 mg/5 mL ```

Lidocaine Topical Path dosage forms

Topical patch - 5%

Azathioprine dosage forms

Tablet - 50 mg, 75 mg, 100 mg

Methotrexate dosage forms

Tablet - 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg | Oral Liquid - 2.5 mg/mL

Folic Acid dosage forms

Tablet - 0.4 mg, 0.8 mg, 1 mg | Capsule - 0.8 mg, 5 mg, 20 mg

Hydroxychloroquine dosage forms

Tablet - 200 mg

Tacrolimus dosage forms

IR and ER Capsule - 0.5 mg, 1 mg, 5 mg | ER Tablet - 0.75 mg, 1 mg, 4 mg

Etanercept dosage forms

Solution autoinjector: 50 mg/1 mL Solution Prefilled Syringe - 25 mg/0.5 mL, 50 mg/1 mL Powder for Reconstitution - 25 mg

Celecoxib MOA

Inhibits COX-2 enzyme isoform thought to be responsible for the anti-inflammatory effects of NSAIDs

FDA-Approved Indications for Celecoxib

Osteoarthritis: 100 mg BID or 200 mg QD Rheumatoid Arthritis: 100-200 mg BID (adults) 50 mg BID (children >2 years; 10-25 kg), 100 mg BID (children >2 years; >25 kg) Ankylosing spondylitis: 100 mg BID or 200 mg QD - may increase to 400 mg QD if not improved within 6 weeks Acute pain, primary dysmenorrhea: 200 mg BID PRN

Off-Label Uses for Celecoxib

Acute gout: 200 mg BID for 5-7 days

Diclofenac MOA

Nonselective inhibitor of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) and reversibly alters platelet function and prolongs bleeding time

FDA-Approved Indications for Diclofenac

Pain: 18-50 mg TID (IR tablet or capsule only) Dsymenorrhea: 50 mg TID (IR tablets only) Migraine: 50 mg once (powder for reconstitution only) Osteoarthritis: 100 mg ER QD or BID Rheumatoid arthritis: 100 mg ER QD or BID Ankylosing spondylitis: 25 mg QID (DR tablets only) + 25 mg HS PRN

Off-Label Uses for Diclofenac

Gout, acute flare: 50 mg BID for 5-7 days

Etodolac MOA

Nonselective inhibitor of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) and reversibly alters platelet function and prolongs bleeding time

FDA-Approved Indications for Etodolac

General pain: 200-400 mg (IR tablet or capsule); max 1000 mg/d Osteoarthritis and rheumatoid arthritis: 300 mg BID-TID or 400-500 mg BID (IR); 400-1000 mg QD (ER); max 1000 mg/d Juvenile Rheumatoid Arthritis: 400 mg ER QD (6-16 y and 20-30 kg); 600 mg QD (31-45 kg); 800 mg QD (46-60 kg); 1000 mg QD (>60 kg)

Ibuprofen MOA

Nonselective inhibitor of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) and reversibly alters platelet function and prolongs bleeding time

FDA-Approved Indications for Ibuprofen

Fever, Pain, Headache: 5-10 mg/kg q6-8h PRN (children 6 mon. to 12 years); 200-400 mg q4-6h PRN max 1200 mg/d for OTC use (children >12 years and adults) Osteoarthritis or Rheumatoid Arthritis: 1200-3200 mg/d divided in 3-4 divided doses Juvenile rheumatoid arthritis: 30-50 mg/kg/d divided QID - max 2400 mg/d

Indomethacin MOA

Nonselective inhibitor of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) and reversibly alters platelet function and prolongs bleeding time

FDA-Approved Indications for Indomethacin

Ankylosing spondylitis, osteoarthritis, rheumatoid arthritis; 25-50 mg BID-TID max 200 mg/d (IR); 75 mg BID (ER) Acute Pain (mild to moderate): 20 mg TD or 40 mg BID-TID (IR - Tivorbex) Acute Gout Exacerbation: 50 mg PO or PR TID

Meloxicam MOA

Nonselective inhibitor of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) and reversibly alters platelet function and prolongs bleeding time

FDA-Approved Indications for Meloxicam

Osteoarthritis: 7.5 mg QD - max 15 mg/d (tablets/suspension); 5 mg QD, may increase to 10 mg QD (capsules) Rheumatoid arthritis: 7.5 mg QD - max 15 mg/d Juvenile rheumatoid arthritis: 0.125 mg/kg QD max 7.5 mg/d (children >2 years)

Off-Label Uses for Meloxicam

Gout: 15 mg QD for 5-7 days, initiate within 24-48 hours of onset of gout exacerbation

Nabumetone MOA

Nonselective inhibitor of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) and reversibly alters platelet function and prolongs bleeding time

FDA-Approved Indications for Nabumetone

Osteoarthritis and Rheumatoid Arthritis: 1000-2000 mg QD or BID

Off-Label Uses for Nabumetone

Soft tissue injury: 1000-2000 mg QD or BID

Naproxen MOA

Nonselective inhibitor of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) and reversibly alters platelet function and prolongs bleeding time

FDA-Approved Indications for Naproxen

Osteoarthritis and Rheumatoid Arthritis: 250-550 mg BID (IR); 750-1000 mg QD (ER) Acute Gout: 250-275 mg TID (IR); 1000 mg QD (ER) Fever: 200-400 mg q8-12h PRN max 600 mg QD (adults and children >12 years) Pain: 500 mg BID or 250 mg q4-6h

Off-Label Uses for Naproxen

Migraine Treatment: initial 750 mg; may administer an additional 250-500 mg PRN; max 1250 mg/24h Migraine Episode Prevention: 250-500 mg BID, max 1500 mg/d

Lidocaine MOA

Amide-type local anesthetic agent that stabilizes neuronal membranes by inhibiting the ionic fluxes required for the initiation and conduction of impulses. Penetration of lidocaine in patch form into intact skin is sufficient to produce an analgesic effect, but less than the amount necessary to produce a complete sensory block

FDA-Approved Indications for Lidocaine

Postherpetic neuralgia and localized pain: 1-3 patches topically simultaneously for up to 12 hours within a 24-h period (12 on 12 off)

Azathioprine MOA

Incorporated into replicating DNA, also inhibits purine synthesis, both actions halt DNA synthesis

FDA-Approved Indications for Azathioprine

Renal Transplantation: 3-5 mg/kg/d immediately after transplant, then 1-3 mg/kg QD (adults) RA: 1-2.5 mg/kg/d QD or BID (adults)

Off-Label Uses for Azathioprine

Crohn's Disease, Ulcerative Colitis: 1.5-2.5 mg/kg/d (adults) Dermatomyositis/Polymyositis: 50 mg/d initially, titrate by 50 mg/week to a total dose of 2-3 mg/kg/d Eosinophilic Granulomatosis with Polyangitis, lung transplantation, lupus nephritis: 2 mg/kg/d Erythema Multiforme: 100-150 mg/d Heart transplantation: 1-3 mg/kg/d Hepatitis caused by autoimmune system: 50-100 mg QD, may titrate to 2 mg/kg/d Liver transplantation: 1-2 mg/kg QD Psoriasis: 0.5 mg/kg/d, may increase by 0.5 mg/kg/d every 4 weeks until response

Methotrexate MOA

Reversibly inhibits dihydrofolate reductase (DHFR). Dihydrofolates are reduced to tetrahydrofolates by DHFR before they are used in DNA synthesis. Methotrexate interferes with DNA synthesis, repair, and cellular replication

FDA-Approved Indications for Methotrexate

Non-Hodgkin Lymphoma, advanced (Burkitt lymphoma, stages I and II): 10-25 mg/d for 4-8 days for several courses with a 7-10 day rest response Psoriasis, severe: initial 2.5-5 mg q12h x 3 doses/week, may titrate dose to 10-25 mg/week Rheumatoid arthritis, severe: 7.5-15 mg once weekly, may titrate by 5 mg/week every 2-3 weeks to max 20-30 mg/week Juvenile RA, polyarticular course: 10 mg/m^2 once weekly, may titrate to clinical response

Off-Label Uses for Methotrexate

Many cancers: dose varies with cancer, stage, and concurrent chemotherapy

Folic Acid MOA

Required for the conversion of deoxyuridylate to thymidylate, which is a rate-limiting step in DNA synthesis. Folic acid deficiency present clinically as macrocytic anemia when red blood cells are unable to extrude their nucleus

FDA-Approved Indications for Folic Acid

Prevention of neural tube defects: females of childbearing potential 0.4-0.8 mg QD (starting 1 month prior to pregnancy, through 12 weeks of gestation); high risk of pregnancy with neural tube defect, 4 mg QD (starting 3 months prior to pregnancy through 12 weeks of gestation) Prevention of methotrexate and pemetrexed toxicity: 5-27.5 mg weekly

Hydroxychloroquine MOA

Unknown. Effective in treating P. vivax, P. malariae, and susceptible strains of P. falciparum. 200 mg hydroxychloroquine sulfate = 155 hydroxychloroquine base

FDA-Approved Indications for Hydroxychloroquine

Lupus erythematosus: 200-400 mg QD (may divide into 2 doses) Malaria, suppression: 400 mg every week on same day (adults); 5 mg base/kg (children); begin 2 weeks prior to entering an endemic area and continue for 4 weeks after leaving Malaria, uncomplicated: 800 mg followed by 400 mg at 6, 24, 48 h after initial dose (2 g total; adult); 13 mg/kg (not to exceed 800 mg) followed by 6.5 mg/kg (not to exceed 400 mg) at 6, 24, 48 h after initial dose (children) RA, maintenance: 400-600 mg QD, after 4-12 weeks reduce dose to 200-400 mg QD

Etanercept MOA

Recombinant DNA-derived protein composed of tumor necrosis factor receptor linked to the Fc portion of human IgG1. Binds to soluble human TNF-alpha with the p55 and p75 cell surface TNF receptors

FDA-Approved Indications for Etanercept

Ankylosing spondylitis, psoriatic arthritis, RA: 50 mg SQ once weekly or 25 mg SQ twice weekly (adults) Polyarticular juvenile idiopathic arthritis: children > 2 years and < 63 kg - 0.8 mg/kg (max 50 mg) SQ once weekly; >63 kg 50 mg once weekly Plaque psoriasis: 0.8 mg/kg/dose SQ once weekly (max 50 mg; children > 4 years); 50 mg twice weekly SQ for 3 months, then 50 mg SQ once weekly (adults)

Off-Label Uses for Etanercept

Acute graft-versus-host disease: adults 0.4 mg/kg SQ (max 25 mg/dose) twice weekly for 8 weeks

Tacrolimus MOA

Binds to cyclophilin, which inhibits the antigenic response of helper T lymphocytes, which in turn reduces the production of interleukin-2 and suppresses interferon-gamma. Inhibition of the immune response limits inflammation. Immediate-release to extended-release conversion is 1:1

FDA-Approved Indications for Tacrolimus

[Doses titrated based on clinical response, serum levels and tolerability] Cardiac transplant rejection, prophylaxis: 0.075 mg/kg/d PO in 2 divided doses Liver transplant rejection, prophylaxis: adults 0.1-0.15 mg/kg/d PO in 2 divided doses; children 0.15-0.2 mg/kg/d PO in 2 divided doses Renal transplant rejection, prophylaxis: IR 0.2 mg/kg/d PO in 2 divided doses; ER 0.1-0.2 mg/kg/d PO in 1 dose

Off-Label Uses for Tacrolimus

Lung, small bowel, transplant rejection; prophylaxis, graft-versus-host disease, prevention: use liver transplant dose Treatment of graft-versus-host disease in allogeneic stem cell transplant: 0.06 mg/kg PO BID

Celecoxib Kinetics

Absorption: good, food enhances Distribution: Vd = 400 L; 97% protein bound Metabolism: hepatic 97%; CYP2C9 substrate, inhibits CYP2C8 and CYP2D6 Elimination: renal 27%; T1/2 = 11 hours Hepatic Dose Adjustment: moderate = reduce dose Renal Dose Adjustment: CrCl < 30 mL/min - AVOID

Diclofenac Kinetics

``` Absorption: F = 50% Distribution: Vd = 1.3 L/kg Metabolism: hepatic, multiple CYP Elimination: renal 65%, T1/2 = 2 hours Hepatic Dose Adjustment: NO Renal Dose Adjustment: CrCl < 30 mL - AVOID ```

Etodolac Kinetics

``` Absorption: F = 80% Distribution: Vd = 393 mL/kg (IR), 570 mL/kg (ER); 99% protein bound Metabolism: Hepatic, not CYP Elimination: renal 72%; T1/2 = 6-7 hours Hepatic Dose Adjustment: NO Renal Dose Adjustment: severe = AVOID ```

Ibuprofen Kinetics

Absorption: F=90% Distribution: Vd = 0.1 L/kg; 99% protein bound Metabolism: hepatic, CYP2C19 substrate Elimination: renal 45-80%; T1/2 = 1.8-2.2 hours Hepatic Dose Adjustment: NO Renal Dose Adjustment: severe = AVOID

Indomethacin Kinetics

Absorption: F=90% Distribution: Vd = 0.34-1.57 L/kg; 99% protein bound Metabolism: 40% hepatic Elimination: renal 60%; T1/2 = 4.5 hours Hepatic Dose Adjustment: severe = caution Renal Dose Adjustment: CrCl < 30 mL/min - AVOID

Meloxicam Kinetics

Absorption: F=89% Distribution: Vd = 10-16 L; 99% protein bound Metabolism: hepatic, CYP3A4 substrate Elimination: renal; T1/2 = 15-22 hours Hepatic Dose Adjustment: NO Renal Dose Adjustment: CrCl<20 mL/min = AVOID

Nabumetone Kinetics

Absorption: F = 35%, food increases Distribution: Vd = 5.3-7.5 L/kg; 99% protein bound Metabolism: hepatic to active, not CYP Elimination: renal 80%; T1/2 = 24 hours Hepatic Dose Adjustment: NO Renal Dose Adjustment: Reduce dose by 50% if CrCl<50 mL/min

Naproxen Kinetics

Absorption: F = 95% Distribution: Vd = 0.16 L/kg; >99% protein bound Metabolism: hepatic, not CYP Elimination: renal 95%, fecal 3%, T1/2 = 12-17 hours (age-dependent) Hepatic Dose Adjustment: use at lowest effective dose, reduced dose may be considered Renal Dose Adjustment: CrCl<30 mL/min = AVOID

Lidocaine Kinetics

``` Absorption: F = 3% (intact skin) Distribution: N/A Metabolism: N/A/ Elimination: N/A Hepatic Dose Adjustment: severe = reduce number of patches, longer "off" time Renal Dose Adjustment: NO ```

Azathioprine Kinetics

``` Absorption: well absorbed Distribution: 30% protein bound Metabolism: hepatic by TPMT Elimination: renal; T1/2 = 2 hours Hepatic Dose Adjustment: NO Renal Dose Adjustment: CrCl 10-50 mL/min = reduce dose to 75%; CrCl < 10 mL/min = reduce dose to 50% ```

Azathioprine Kinetics

``` Absorption: well absorbed Distribution: 30% protein bound Metabolism: hepatic by TPMT Elimination: renal; T1/2 = 2 hours Hepatic Dose Adjustment: NO Renal Dose Adjustment: CrCl 10-50 mL/min = reduce dose to 75%; CrCl < 10 mL/min = reduce dose to 50% ```

Azathioprine Kinetics

``` Absorption: well absorbed Distribution: 30% protein bound Metabolism: hepatic by TPMT Elimination: renal; T1/2 = 2 hours Hepatic Dose Adjustment: NO Renal Dose Adjustment: CrCl 10-50 mL/min = reduce dose to 75%; CrCl < 10 mL/min = reduce dose to 50% ```

Azathioprine Kinetics

``` Absorption: well absorbed Distribution: 30% protein bound Metabolism: hepatic by TPMT Elimination: renal; T1/2 = 2 hours Hepatic Dose Adjustment: NO Renal Dose Adjustment: CrCl 10-50 mL/min = reduce dose to 75%; CrCl < 10 mL/min = reduce dose to 50% ```

Azathioprine Kinetics

``` Absorption: well absorbed Distribution: 30% protein bound Metabolism: hepatic by TPMT Elimination: renal; T1/2 = 2 hours Hepatic Dose Adjustment: NO Renal Dose Adjustment: CrCl 10-50 mL/min = reduce dose to 75%; CrCl < 10 mL/min = reduce dose to 50% ```

Azathioprine Kinetics

``` Absorption: well absorbed Distribution: 30% protein bound Metabolism: hepatic by TPMT Elimination: renal; T1/2 = 2 hours Hepatic Dose Adjustment: NO Renal Dose Adjustment: CrCl 10-50 mL/min = reduce dose to 75%; CrCl < 10 mL/min = reduce dose to 50% ```

Methotrexate Kinetics

Absorption: dose dependent, < 40 mg/m^2, F = 42%; doses > 40 mg/m^2 F = 17% Distribution: Vd = 0.4-0.8 L/kg; 50% protein bound Metabolism: intracellular polyglutamation, excreted by OATP181 Elimination: renal 48-100%, dose dependent; T1/2 = 4-10 hours Hepatic Dose Adjustment: bilirubin = 3.1-5 mg/dL = reduce dose by 25%; bilirubin > 5 mg/dL = AVOID Renal Dose Adjustment: CrCl = 10-50 mL/min, reduce dose by 50%; CrCl < 10 mL/min: avoid

Folic Acid Kinetics

Absorption: F = 76-93% Distribution: stored in the liver and most tissues Metabolism: metabolized in the liver to active metabolite, 5-methyltetrahydrofolate Elimination: renal 30% Hepatic and Renal Dose Adjustment: NO

Hydroxychloroquine Kinetics

Absorption: F=74% Distribution: concentration in red blood cells is 5 times higher than plasma Metabolism: 40% by unknown enzymes Elimination: renal 16-25%; T1/2 = 40 days Hepatic Dose Adjustment: severe = AVOID Renal Dose Adjustment: severe = AVOID

Etanercept Kinetics

``` Absorption: F = 60% Distribution: Vd = 1.78-3.39 L/m^2 Metabolism: Not metabolized Elimination: T1/2 = 102 hours Renal and Hepatic Dose Adjustment: NO ```

Tacrolimus Kinetics

Absorption: F = 14-32%, food decreases Distribution: Vd = 5-65 L/kg; 99% protein bound Metabolism: extensive hepatic; substrate of CYP3A4 P-glycoprotein, P-gp, inhibitor Elimination: renal <1%; T1/2 = 11 hour Hepatic Dose Adjustment: use doses at the lower end of the dosing range Renal Dose Adjustment: use doses at the lower end of the dosing range

Celecoxib Drug Interactions - Kinetic

2C9 Inducer/Inhibitors 2D6 Substrates Warfarin (2C9 competition)

Diclofenac Drug Interactions - Kinetic

Most CYP Inducers/Inhibitors Cholestyramine (absorption) Warfarin (2C9 competition)

Etodolac Drug Interactions - Kinetic

Warfarin (2C9 competition)

Meloxicam Drug Interactions - Kinetic

Cholestyramine (absorption)

Methotrexate Drug Interactions - Kinetic

OATP181 Inhibitor (+ eltrombopag: AVOID/reduce methotrexate) Aspirin, dantrolene, loop diuretics, NSAIDs, penicillins, PPIs, salicylates, trimethoprim, sulfisoxazole (methotrexate competes for renal tubular secretion, increasing methotrexate toxicity - VOID ALL ESPECIALLY NSAIDS)

Tacrolimus Drug Interactions - Kinetics

3A4 Inducer/Inhibitor | P-gp Substrates

Azathioprine Drug Interactions - Kinetics

Xanthine oxidase inhibitors (AVOID with allopurinol/febuxostat)

NSAID Drug Interactions - Pharmacodynamic

``` Bleed Risk/GI Toxicity: 1. Aspirin 2. SSRIs 3. Low MW heparin 4. Pentoxifylline 5. Ketorolac (ibuprofen and indomethacin) Renal 1. Pemetrexed - AVOID 2. ACE inhibitors/ARBs 3. Beta blockers 4. Loop and thiazide diuretics 5. Rivaroxaban, apixaban, dabigatran (naproxen) ```

Azathioprine Drug Interactions - Pharmacodynamic

Azathioprine + any immunosuppressant - AVOID

Etanercept Drug Interactions - Pharmacodynamic

Etanercept + any other anti-TNF agents or immunosuppressants = AVOID

Methotrexate Drug Interactions - Pharmacodynamic

Leucovorin (folate analog) - counteracts methotrexate = AVOID, unless using as rescue agent

Monitor Lithium concentration when taken with these drugs

1. Celecoxib 2. Ibuprofen 3. Indomethacin

Other Drug Interactions - NSAIDS + Cyclosporine/Tacrolimus

Monitor concentrations

Other drug interactions - NSAIDs + Sulfonylureas

Increased hypoglycemia

Other drug interactions - Azathioprine + Vaccines

Decreased vaccine efficacy, complete vaccines 2 weeks prior to starting

Contraindicated Drugs with Live Vaccines

1. Methotrexate 2. Etanercept - wait 3 months after stopping 3. Tacrolimus

Other Drug Interactions with Hydroxychloroquine

Increases digoxin level - AVOID Fenofibrates = increased risk of cholelithiasis - AVOID Increases metoprolol = AVOID

Other Drug Interactions with Tacrolimus

Hyperkalemia: AVOID Amiloride, potassium-sparing diuretics Nephrotoxicity: AVOID Aminoglycosides, amphotericin, cisplatin, ganciclovir QT prolongation: Ziprasidone CONTRAINDICATED, avoid all others or monitor very closely

NSAIDs Black Box Warning

1. CV thrombotic events 2. Serious GI bleeding and perforation 3. CABC (coronary artery bypass graft)

NSAIDs Contraindications

1. Concurrent ketorolac, pentoxifylline use 2. Asthma, allergic-type reaction following other NSAIDs use 3. Treatment of perioperative pain (around surgery)

NSAIDs in Pregnancy and Lactation

Pregnancy: human data suggest risk in 1st and 3rd trimesters Lactation: most are probably compatible, Ibuprofen is definitely compatible, Etodolac and Nabumetone are possibly toxic

NSAIDs and BEERs

``` Celecoxib - avoid sometimes Diclofenac - avoid chronic Etodolac - avoid chronic Ibuprofen - avoid chronic Indomethacin - AVOID Nabumetone - avoid chronic Naproxen - avoid chronic ```

Other Contraindications with Celecoxib

Hypersensitivity to sulfonamides

Lidocaine in Pregnancy/Lactation

Pregnancy: compatible Lactation: probably compatible

Azathioprine in Pregnancy/Lactation

Pregnancy: risk in 3rd trimester Lactation: probably compatible

Contraindications with Azathioprine

Pregnancy (for rheumatoid arthritis), prior alkylating therapy

Azathioprine Black Box Warning

Malignancy

Methotrexate in Pregnancy/Lactation

Contraindicated

Contraindications with Methotrexate

Pregnancy, nursing, pre-existing blood dyscrasias with patients treated for psoriasis and rheumatoid arthritis

Methotrexate Black Box Warning

Bone marrow suppression, renal impairment, hepatotoxicity, pneumonitis, GI toxicity, secondary malignancy, tumor lysis syndrome, dermatologic toxicity, opportunistic infections, radiotherapy, hypersensitivity, pregnancy

Folic Acid in Pregnancy/Lactation

Compatible

Hydroxychloroquine in Pregnancy/Lactation

Probably compatible

Contraindications with Hydroxychloroquine

Retinal or visual field changes from prior hydroxychloroquine, long-term use in children

Etanercept in Pregnancy/Lactation

Pregnancy: Low risk Lactation: compatible

Etanercept Black Box Warning

Serious infections, malignancies

Contraindications with Etanercept

Sepsis

Tacrolimus in Pregnancy/Lactation

Pregnancy: Low risk Lactation: Compatible

Tacrolimus Black Box Warning

Risk of infection, risk of malignancies, increased mortality in female transplant patients with Astagraf XL (not approved for liver transplant)

Contraindications with Tacrolimus

Concurrent Ziprasidone use

Do Not Crush

``` Diclofenac XR Etodolac XR Indomethacin XR Naproxen ER and DR Azathioprine ```

Common Adverse Effects of Celecoxib

HTN, headaches, GI distress, diarrhea

Less Common Adverse Effects of Celecoxib

AMI, bronchospasm

Rare but Serious Adverse Effects of Celecoxib

SJS, GI ulcers and bleeding, thrombosis, elevated liver functions

Common Adverse Effects of Diclofenac

Headaches, GI distress

Less Common Adverse Effects of Diclofenac

GI ulcers

Rare but Serious Adverse Effects of Diclofenac

SJS, GI bleeding, thrombosis, elevated liver functions, acute renal failure, MI, aplastic anemia, hemolytic anemia

Etodolac - Less Common Adverse Effects

Edema, itching, rash, GI distress, dizziness, tinnitus, ototoxicity

Etodolac - Rare but Serious Adverse Effects

SJS, GI bleeding, thrombosis, elevated liver functions, acute renal failure, MI, aplastic anemia, hemolytic anemia

Ibuprofen - Less Common Adverse Effects

Edema, itching, rash, GI distress, dizziness, tinnitus, ototoxicity

Ibuprofen - Rare but Serious Adverse Effects

SJS, GI bleeding, thrombosis, elevated liver functions, acute renal failure, MI, aplastic anemia, hemolytic anemia

Indomethacin - Common Adverse Effects

Headache

Indomethacin - Less Common Adverse Effects

Edema, itching, rash, GI distress, dizziness, tinnitus, ototoxicity

Indomethacin - Rare but Serious Adverse Effects

SJS, GI bleeding, thrombosis, elevated LFTs, acute renal failure, heart failure, aplastic anemia

Meloxicam - Common Adverse Effects

GI distress

Meloxicam - Less Common Adverse Effects

Edema, itching, rash, dizziness, tinnitus, ototoxicity

Meloxicam - Rare but Serious Adverse Effects

Stevens-Johnson syndrome, GI bleeding, elevated LFT, acute renal failure, congestive heart failure, aplastic anemia

Nabumetone - Common Adverse Effects

Elevated LFTs, dyspepsia, abdominal pain, diarrhea

Nabumetone - Less Common Adverse Effects

Edema, itching, rash, dizziness, tinnitus, ototoxicity, vomiting

Nabumetone - Rare but Serious Adverse Effects

Stevens-Johnson syndrome, GI bleeding, thrombosis, acute renal failure, congestive heart failure, aplastic anemia

Naproxen - Less Common Adverse Effects

Edema, itching, rash, GI distress, dizziness, tinnitus, ototoxicity

Naproxen - Rare but Serious Adverse Effects

Stevens-Johnson syndrome, GI bleeding, thrombosis, elevated LFTs, acute renal failure, congestive heart failure, aplastic anemia

Lidocaine - Common Adverse Effects

Skin irritation, somnolence

Lidocaine - Less Common Adverse Effects

Hypotension, nausea, vomiting, confusion, dizziness, headache, paresthesia, constipation, tremor

Lidocaine - Rare but Serious Adverse Effects

Cardiac arrest, cardiac dysrhythmia, seizure, methemoglobinemia

Azathioprine - Common Adverse Effects

Nausea, leukopenia, infection

Azathioprine - Less Common Adverse Effects

Diarrhea, malaise, myalgia, increased LFTs

Azathioprine - Rare but Serious Adverse Effect

Neoplasia, pancreatitis

Methotrexate - Common Adverse Effects

Myelosuppression, nausea, vomiting, alopecia, stomatitis, photosensitivity, rash

Methotrexate - Less Common Adverse Effects

Elevated LFTs, diarrhea

Methotrexate - Rare but Serious Adverse Effects

Acute renal failure, liver failure, interstitial lung disease, Stevens-Johnson syndrome, secondary malignancies (lymphomas), opportunistic infections

Folic Acid - Common Adverse Effects

Loss of appetite

Folic Acid - Less Common Adverse Effects

Confusion, irritation

Folic Acid - Rare but Serious Adverse Effects

Anaphylaxis

Hydroxychloroquine - Less Common Adverse Effects

Acute renal failure, liver failure, interstitial lung disease, Stevens-Johnson syndrome, secondary malignancies (lymphomas), opportunistic infections

Hydroxychloroquine - Rare but Serious Adverse Effects

Arrhythmias, cardiomyopathy, Stevens-Johnson syndrome, agranulocytosis, seizures, retinopathy, psychosis

Etanercept - Common Adverse Effects

Headache, skin rash, infections antibody development, injection site reactions

Etanercept - Less Common

Dizziness, nausea

Etanercept - Rare but Serious Adverse Effects

Serious infections, reactivation of latent infections, malignancies, heart failure

Tacrolimus - Common Adverse Effects

Chest pain, HTN, alopecia, diabetes, hyperglycemia, hyperkalemia, hypomagnesemia, hyperlipidemia, constipation, diarrhea, nausea, anemia, leukopenia, thrombocytopenia, infection, arthralgia, dizziness, headache, insomnia, neuropathy, myoclonus, seizure, nephrotoxicity, dyspnea, pleural effusions

Tacrolimus - Less Common Adverse Effects

Pruritis, elevated LFTs

Tacrolimus - Rare but Serious Adverse Effects

Cardiomegaly, arrhythmia, Stevens-Johnson syndrome, increased risk of cancer, pancreatitis, acute renal failure

NSAIDs - Drug Monitoring

Efficacy: decreased pain and improved range of motion Toxicity: CBC, LFTs, SCr, BP, fecal occult blood tests if chronic use. Seek medical attention if severe skin rash, black tarry stools, chest pains, yellowing of eyes or skin, weight gain, edema or change in urination

Lidocaine Patch - Drug Monitoring

Efficacy: relief from pain Toxicity: Application of too many patches, for too long a period of time, and/or without adequate drug-free period may increase toxicity; application to broken skin or covering with occlusive dressing may lead to toxicity, particularly cardiac dysrhythmia.

Azathioprine - Drug Monitoring

Efficacy: absence of rejection, improved symptoms Toxicity: CBC, TPMT genotyping, LFTs, monitor for development of cancers

Methotrexate - Drug Monitoring

Efficacy: Resolution of symptoms of psoriasis. Decreased pain and improved range of motion in rheumatoid arthritis. Shrinkage or disappearance of tumor. Methotrexate levels may be monitored and used to adjust leucovorin Toxicity: Baseline and periodic CBC, SCr, LFTs, negative pregnancy test. Seek medical attention if severe mouth ulcerations, fever >101.5°F, shortness of breath, changes in urination, yellowing of eyes or skin, unusual bruising or bleeding

Folic Acid - Drug Monitoring

Efficacy: Baseline and periodic CBC, SCr, LFTs, negative pregnancy test. Seek medical attention if severe mouth ulcerations, fever >101.5°F, shortness of breath, changes in urination, yellowing of eyes or skin, unusual bruising or bleeding. Toxicity: Seek medical attention if severe shortness of breath, skin rash, or hives

Hydroxychloroquine - Drug Monitoring

Efficacy: Rheumatoid arthritis: decreased pain and improved range of motion. Lupus: decreased joint pain, decrease in butterfly rash, improved energy. Toxicity: Seek medical attention if heart palpitations, severe rash, unusual bruising or bleeding, or difficulty seeing or changes in visual fields. Baseline and periodic eye exams.

Etanercept - Drug Monitoring

Efficacy: improvement in symptoms and physical functioning Toxicity: screen patients for active or latent infections prior to use (hepatitis C, hepatitis B, herpes tuberculosis, etc.), CBC, renal functions, LFTs

Tacrolimus - Drug Monitoring

Efficacy: Lack of signs of rejection (elevation in SCr for renal transplant, LFTs for liver transplant). Tacrolimus trough whole blood concentrations (target 5-20 ng/mL). Toxicity: Monitor electrolytes, FPG, BP and SCr, BUN, lipids, and CBC. Itching or hives, swelling of face, hands, mouth facial or throat, chest tightness, trouble breathing, blistering, peeling, or red skin rash, chest pain, change in urination, unusual bruising or bleeding, severe abdominal pain.

Celecoxib - Counseling and Pearls

Counseling: may take with food or milt to decrease GI upset, may open capsule and pour into a teaspoon of applesauce Pearls: Elderly patients are at increased risk of GI ulceration. Patients with underlying cardiac dysfunction are at increased risk for cardiovascular effects. Celecoxib has less risk of GI effects than other NSAIDs, but increased cardiovascular toxicity. Use the lowest dose for the shortest period of time to avoid adverse effects.

Diclofenac - Counseling and Pearls

Counseling: take with food or milk to decrease GI upset Pearls: Elderly patients are at increased risk of GI ulceration. Patients with underlying cardiac dysfunction are at increased risk of cardiovascular events. Use lowest dose for shortest period of time to minimize toxicity. Available in both sodium and potassium salts, in combination with misoprostol, and in parenteral, ophthalmic, and topical products. Medication guide required at dispensing

Diclofenac - Counseling and Pearls

Counseling: take with food or milk to decrease GI upset Pearls: Elderly patients are at increased risk of GI ulceration. Patients with underlying cardiac dysfunction are at increased risk of cardiovascular events. Use lowest dose for shortest period of time to minimize toxicity. Available in both sodium and potassium salts, in combination with misoprostol, and in parenteral, ophthalmic, and topical products. Medication guide required at dispensing

Etodolac - Counseling and Pearls

Counseling: take with food or milk to decrease GI upset Pearls: Elderly patients are at increased risk of GI ulceration. Use lowest effective dose for shortest possible duration; after observing initial response, adjust dose and frequency to meet individual patient’s needs.

Ibuprofen - Counseling and Pearls

Counseling: Take with food or milk to decrease GI upset. Counsel heart failure patients post discharge on NSAIDs avoidance due to fluid retention, edema leading to exacerbations. Pearls: Elderly patients are at increased risk of GI ulceration. NSAIDs are associated with an increased risk of adverse cardiovascular thrombotic events, including fatal MI and stroke. Use the lowest effective dose for the shortest possible duration; after observing initial response, adjust dose and frequency to meet individual patient’s needs. NSAIDs are also associated with renal adverse events, especially in patients with preexisting CKD, nephrotic syndrome, liver disease, and patients who are volume depleted. Various OTC ibuprofen products are available; caution patients not to duplicate dosing with multiple ibuprofen products.

Indomethacin - Counseling and Pearls

Counseling: Take with food or milk to decrease GI upset. Counsel heart failure patients post discharge on NSAIDs avoidance due to fluid retention, edema leading to exacerbations. Pearls: Elderly patients are at increased risk of GI ulceration. NSAIDs are associated with an increased risk of adverse cardiovascular thrombotic events, including fatal MI and stroke. Use the lowest effective dose for the shortest possible duration; after observing initial response, adjust dose and frequency to meet individual patient needs. NSAIDs are also associated with renal adverse events, especially in patients with preexisting CKD, nephrotic syndrome, liver disease, and patients who are volume depleted. Caution patients not to duplicate therapy with multiple NSAID products. Indomethacin is effective for stopping premature labor and delaying delivery for several weeks but should be used with caution as it may cause harm to the infant. IV formulation also available. Used in the treatment of hemodynamically significant patent ductus arteriosus in premature infants. Medication guide required at dispensing

Meloxicam - Counseling and Pearls

Counseling: Take with food or milk to decrease GI upset. For suspension, shake gently before using. Avoid use around 20 wk gestation Pearls: Elderly patients are at increased risk of GI ulceration. Use lowest effective dose for shortest possible duration; after observing initial response, adjust dose and frequency to meet individual patient’s needs.

Nabumetone - Counseling and Pearls

Counseling: Take with food or milk to decrease GI upset. Pearls: Elderly patients are at increased risk of GI ulceration. Patients with underlying cardiac dysfunction are at increased risk of cardiovascular effects. Use lowest dose for shortest duration to minimize toxicity.

Naproxen - Counseling and Pearls

Counseling: Take with food or milk to decrease GI upset. Pearls: Elderly patients are at increased risk of GI ulceration. Patients with underlying cardiac dysfunction are at increased risk of cardiovascular effects. Use lowest dose for shortest duration to minimize toxicity. Naproxen is also available OTC as a 220 mg tablet. If taken as OTC for fever, do not take longer than 10 d unless directed by physician.

Lidocaine Topical Patch - Counseling and Pearls

Counseling: Instruct patients on the appropriate application process. Leave patches on skin for no >12 h within a 24-h period. Caution patients to administer only as directed, to intact skin, without covering with occlusive dressing or tight clothes. Pearls: Patches may be cut into smaller sizes prior to removal of release liner to refine dose to meet patients’ needs. Patients should be instructed to fold used patches after removal so that the adhesive side sticks to itself and safely discard used patches or pieces of cut patches where children and pets cannot get to them. Accidental ingestion of used patches can lead to serious adverse effects. Lidocaine also available in a wide range of other dosage forms, including topical ointments, lotions, gels and creams, injectables, and oral sprays and gels.

Azathioprine - Counseling and Pearls

Counseling: Take with food. Long-term use may increase your risk of cancer, including lymphoma. Be aware of symptoms of lymphoma (new mass, fatigue, easy bruising) and report to HCP. Requires regular blood tests to assess for lowered blood counts. May increase your risk of infections. Pearls: Azathioprine rarely used for renal transplantation; mycophenolic acid derivatives are considered first line. May be used if patients are intolerant. Chronic immunosuppression increases the risk of infections, including reactivation of latent infections. Check serologies (hepatitis C, HSV) and consider prophylaxis prior to initiating therapy.

Methotrexate - Counseling and Pearls

Counseling: Emphasize appropriate dosing schedule (weekly vs daily). Avoid pregnancy while taking (male and female). Causes nausea and vomiting; ensure patients have antiemetics and know how to take them. Avoid sun exposure. May take with food. Pearls: Baseline and regular CBC w/diff, platelet, LFTs, and renal monitoring are mandatory. High-dose methotrexate requires urine alkalinization with sodium bicarbonate infusions to enhance methotrexate excretion and requires leucovorin administration started 24 h after methotrexate to rescue normal cells. Elimination is reduced in patients with ascites and/or pleural effusions related to third spacing, resulting in prolonged half-life and toxicity. Concomitant methotrexate administration with radiotherapy may increase the risk of soft tissue necrosis and osteonecrosis. Numerous dosing regimens are used; do not confuse daily and weekly dosing strategies. Avoid use of “MTX” as an error prone abbreviation. To reduce stomatitis when used for rheumatoid arthritis, supplementation with folic acid (1 mg po daily) should be given on days methotrexate is not given. Should only be used by providers with knowledge and experience of antimetabolite therapy.

Folic Acid - Counseling and Pearls

Counseling: May require several weeks for maximum effect. Avoid alcohol as it inhibits the absorption of folic acid. Pearls: Drugs that interfere with folate metabolism (methotrexate, hydroxyurea, pemetrexed) will cause an elevated MCV in the absence of vitamin B deficiency. Folic acid is given to women intending to become pregnant and in the early months of pregnancy to reduce the risk of neural tube defects and other birth defects (imperforate anus, cleft lip). Patients on pemetrexed receive folic acid to reduce pemetrexed toxicity. Enriched flour, bread, corn meal, pasta, rice, and other grain products have added folic acid to help decrease the risk of neural tube defects by increasing folic acid intake. Other foods that contain folic acid include dark green leafy vegetables, citrus fruits and juices, and lentils.

Hydroxychloroquine - Counseling and Pearls

Counseling: If taking weekly, take on same day each week. Take with food or milk. Pearls: If serious adverse effects or overdose occurs, ammonium chloride (8 g daily in divided doses for adults) may be administered 3-4 d a week for several months to increase the renal excretion of hydroxychloroquine. The onset of action of hydroxychloroquine for rheumatoid arthritis is up to 6 wk. Malaria acquired in Central America and the Middle East remains susceptible to hydroxychloroquine. For disease acquired in all other regions, widespread resistance to hydroxychloroquine requires treatment with alternative agents which are only available (in the United States) through the CDC

Etanercept - Counseling and Pearls

Counseling: Store in the refrigerator, but do not freeze and do not use if frozen even if it has thawed. Keep in carton to protect from light. Follow injection instructions you were taught. Do not shake. Discard syringe in sharps container. Rotate injection sites. Contact HCP if shortness of breath, infections, signs of cancer. Pearls: For rheumatoid arthritis, usually used in combination with methotrexate in patients with inadequate response. No strong evidence for improved efficacy or decreased toxicity between anti-TNF agents. Choice often based on route of administration and schedule. Some formulations may contain latex. Biosimilar (etanercept-szzs, Erelzi) was approved by the FDA in 2016 and is available in Canada and the European Union, but ongoing legal challenges are delaying launch in the United States

Tacrolimus - Counseling and Pearls

Counseling: Take on an empty stomach. Avoid alcohol, grapefruit, and grapefruit juice. Many medications, OTC medications, and foods interact with tacrolimus. Monitor carefully. Pearls: Tacrolimus is more effective in preventing acute rejection than cyclosporine for patients with liver and kidney transplants. When changing between brand and generic forms, monitor tacrolimus levels. Injectable formulation also available. Topical formulation, used for dermatitis, also available