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Top Drugs 1 > NSAIDs and RA > Flashcards

NSAIDs and RA Flashcards

1
Q

Celecoxib

A

Celebrex

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2
Q

Diclofenac

A

Cambia, Voltaren, Zipsor, Zorvolex

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3
Q

Etodolac

A

Lodine

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4
Q

Ibuprofen

A

Motrin

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5
Q

Indomethacin

A

Indocin, Tivorbex

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6
Q

Meloxicam

A

Mobic

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7
Q

Nabumetone

A

Relafen

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8
Q

Naproxen

A

Naprosyn

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9
Q

Lidocaine Topical Patch

A

Lidoderm

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10
Q

Therapeutic class of Celecoxib

A

Cyclooxygenase-2 inhibitor/NSAID

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11
Q

Therapeutic class of Diclofenac

A

NSAID

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12
Q

Therapeutic class of Etodolac

A

NSAID

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13
Q

Therapeutic class of Ibuprofen

A

NSAID

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14
Q

Therapeutic class of Indomethacin

A

NSAID

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15
Q

Therapeutic class of Meloxicam

A

NSAID

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16
Q

Therapeutic class of Nabumetone

A

NSAID

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17
Q

Therapeutic class of Naproxen

A

NSAID

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18
Q

Therapeutic class of Lidocaine Topical Patch

A

Local anesthetic

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19
Q

Azathioprine

A

Azamun, Imuran

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20
Q

Methotrexate

A

Trexall

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21
Q

Folic Acid

A

FA-8

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22
Q

Hydroxychloroquine

A

Plaquenil

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23
Q

Etanercept

A

Enbrel, ERelzi

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24
Q

Tacrolimus

A

Prograf, Astagraf XL, Envarsus XR

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25
Q

Therapeutic class of Azathioprine

A

Immunosuppressant agent

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26
Q

Therapeutic class of Methotrexate

A

Antimetabolite

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27
Q

Therapeutic class of Folic Acid

A

Essential B vitamin

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28
Q

Therapeutic class of Hydroxychloroquine

A

Aminoquinoline

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29
Q

Therapeutic class of Etanercept

A

Antirheumatic, disease-modifying, TNF-blocking agent

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30
Q

Therapeutic class of Tacrolimus

A

Calcineurin inhibitor

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31
Q

Celecoxib dosage forms

A

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

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32
Q

Diclofenac dosage forms

A

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

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33
Q

Etodolac dosage forms

A

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

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34
Q

Ibuprofen dosage forms

A

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

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35
Q

Indomethacin dosage forms

A

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

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36
Q

Meloxicam dosage forms

A

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

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37
Q

Nabumetone dosage forms

A

Tablet - 500 mg, 750 mg

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38
Q

Naproxen dosage forms

A 
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
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39
Q

Lidocaine Topical Path dosage forms

A

Topical patch - 5%

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40
Q

Azathioprine dosage forms

A

Tablet - 50 mg, 75 mg, 100 mg

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41
Q

Methotrexate dosage forms

A

Tablet - 2.5 mg, 5 mg, 7.5 mg, 10 mg, 15 mg

Oral Liquid - 2.5 mg/mL

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42
Q

Folic Acid dosage forms

A

Tablet - 0.4 mg, 0.8 mg, 1 mg

Capsule - 0.8 mg, 5 mg, 20 mg

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43
Q

Hydroxychloroquine dosage forms

A

Tablet - 200 mg

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44
Q

Tacrolimus dosage forms

A

IR and ER Capsule - 0.5 mg, 1 mg, 5 mg

ER Tablet - 0.75 mg, 1 mg, 4 mg

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45
Q

Etanercept dosage forms

A

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

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46
Q

Celecoxib MOA

A

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

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47
Q

FDA-Approved Indications for Celecoxib

A

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

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48
Q

Off-Label Uses for Celecoxib

A

Acute gout: 200 mg BID for 5-7 days

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49
Q

Diclofenac MOA

A

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

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50
Q

FDA-Approved Indications for Diclofenac

A

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

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51
Q

Off-Label Uses for Diclofenac

A

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

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52
Q

Etodolac MOA

A

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

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53
Q

FDA-Approved Indications for Etodolac

A

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)

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54
Q

Ibuprofen MOA

A

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

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55
Q

FDA-Approved Indications for Ibuprofen

A

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

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56
Q

Indomethacin MOA

A

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

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57
Q

FDA-Approved Indications for Indomethacin

A

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

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58
Q

Meloxicam MOA

A

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

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59
Q

FDA-Approved Indications for Meloxicam

A

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)

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60
Q

Off-Label Uses for Meloxicam

A

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

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61
Q

Nabumetone MOA

A

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

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62
Q

FDA-Approved Indications for Nabumetone

A

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

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63
Q

Off-Label Uses for Nabumetone

A

Soft tissue injury: 1000-2000 mg QD or BID

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64
Q

Naproxen MOA

A

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

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65
Q

FDA-Approved Indications for Naproxen

A

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

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66
Q

Off-Label Uses for Naproxen

A

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

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67
Q

Lidocaine MOA

A

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

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68
Q

FDA-Approved Indications for Lidocaine

A

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

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69
Q

Azathioprine MOA

A

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

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70
Q

FDA-Approved Indications for Azathioprine

A

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)

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71
Q

Off-Label Uses for Azathioprine

A

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

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72
Q

Methotrexate MOA

A

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

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73
Q

FDA-Approved Indications for Methotrexate

A

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

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74
Q

Off-Label Uses for Methotrexate

A

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

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75
Q

Folic Acid MOA

A

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

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76
Q

FDA-Approved Indications for Folic Acid

A

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

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77
Q

Hydroxychloroquine MOA

A

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

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78
Q

FDA-Approved Indications for Hydroxychloroquine

A

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

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79
Q

Etanercept MOA

A

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

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80
Q

FDA-Approved Indications for Etanercept

A

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)

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81
Q

Off-Label Uses for Etanercept

A

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

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82
Q

Tacrolimus MOA

A

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

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83
Q

FDA-Approved Indications for Tacrolimus

A

[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

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84
Q

Off-Label Uses for Tacrolimus

A

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

85
Q

Celecoxib Kinetics

A

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

86
Q

Diclofenac Kinetics

A 
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
87
Q

Etodolac Kinetics

A 
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
88
Q

Ibuprofen Kinetics

A

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

89
Q

Indomethacin Kinetics

A

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

90
Q

Meloxicam Kinetics

A

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

91
Q

Nabumetone Kinetics

A

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

92
Q

Naproxen Kinetics

A

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

93
Q

Lidocaine Kinetics

A 
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
94
Q

Azathioprine Kinetics

A 
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%
94
Q

Azathioprine Kinetics

A 
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%
94
Q

Azathioprine Kinetics

A 
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%
94
Q

Azathioprine Kinetics

A 
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%
94
Q

Azathioprine Kinetics

A 
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%
94
Q

Azathioprine Kinetics

A 
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%
95
Q

Methotrexate Kinetics

A

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

96
Q

Folic Acid Kinetics

A

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

97
Q

Hydroxychloroquine Kinetics

A

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

98
Q

Etanercept Kinetics

A 
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
99
Q

Tacrolimus Kinetics

A

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

100
Q

Celecoxib Drug Interactions - Kinetic

A

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

101
Q

Diclofenac Drug Interactions - Kinetic

A

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

102
Q

Etodolac Drug Interactions - Kinetic

A

Warfarin (2C9 competition)

103
Q

Meloxicam Drug Interactions - Kinetic

A

Cholestyramine (absorption)

104
Q

Methotrexate Drug Interactions - Kinetic

A

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)

105
Q

Tacrolimus Drug Interactions - Kinetics

A

3A4 Inducer/Inhibitor

P-gp Substrates

106
Q

Azathioprine Drug Interactions - Kinetics

A

Xanthine oxidase inhibitors (AVOID with allopurinol/febuxostat)

107
Q

NSAID Drug Interactions - Pharmacodynamic

A 
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)
108
Q

Azathioprine Drug Interactions - Pharmacodynamic

A

Azathioprine + any immunosuppressant - AVOID

109
Q

Etanercept Drug Interactions - Pharmacodynamic

A

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

110
Q

Methotrexate Drug Interactions - Pharmacodynamic

A

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

111
Q

Monitor Lithium concentration when taken with these drugs

A
  1. Celecoxib
  2. Ibuprofen
  3. Indomethacin
112
Q

Other Drug Interactions - NSAIDS + Cyclosporine/Tacrolimus

A

Monitor concentrations

113
Q

Other drug interactions - NSAIDs + Sulfonylureas

A

Increased hypoglycemia

114
Q

Other drug interactions - Azathioprine + Vaccines

A

Decreased vaccine efficacy, complete vaccines 2 weeks prior to starting

115
Q

Contraindicated Drugs with Live Vaccines

A
  1. Methotrexate
  2. Etanercept - wait 3 months after stopping
  3. Tacrolimus
116
Q

Other Drug Interactions with Hydroxychloroquine

A

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

117
Q

Other Drug Interactions with Tacrolimus

A

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

118
Q

NSAIDs Black Box Warning

A
  1. CV thrombotic events
  2. Serious GI bleeding and perforation
  3. CABC (coronary artery bypass graft)
119
Q

NSAIDs Contraindications

A
  1. Concurrent ketorolac, pentoxifylline use
  2. Asthma, allergic-type reaction following other NSAIDs use
  3. Treatment of perioperative pain (around surgery)
120
Q

NSAIDs in Pregnancy and Lactation

A

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

121
Q

NSAIDs and BEERs

A 
Celecoxib - avoid sometimes
Diclofenac - avoid chronic
Etodolac - avoid chronic
Ibuprofen - avoid chronic 
Indomethacin - AVOID
Nabumetone - avoid chronic
Naproxen - avoid chronic
122
Q

Other Contraindications with Celecoxib

A

Hypersensitivity to sulfonamides

123
Q

Lidocaine in Pregnancy/Lactation

A

Pregnancy: compatible
Lactation: probably compatible

124
Q

Azathioprine in Pregnancy/Lactation

A

Pregnancy: risk in 3rd trimester
Lactation: probably compatible

125
Q

Contraindications with Azathioprine

A

Pregnancy (for rheumatoid arthritis), prior alkylating therapy

126
Q

Azathioprine Black Box Warning

A

Malignancy

127
Q

Methotrexate in Pregnancy/Lactation

A

Contraindicated

128
Q

Contraindications with Methotrexate

A

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

129
Q

Methotrexate Black Box Warning

A

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

130
Q

Folic Acid in Pregnancy/Lactation

A

Compatible

131
Q

Hydroxychloroquine in Pregnancy/Lactation

A

Probably compatible

132
Q

Contraindications with Hydroxychloroquine

A

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

133
Q

Etanercept in Pregnancy/Lactation

A

Pregnancy: Low risk
Lactation: compatible

134
Q

Etanercept Black Box Warning

A

Serious infections, malignancies

135
Q

Contraindications with Etanercept

A

Sepsis

136
Q

Tacrolimus in Pregnancy/Lactation

A

Pregnancy: Low risk
Lactation: Compatible

137
Q

Tacrolimus Black Box Warning

A

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

138
Q

Contraindications with Tacrolimus

A

Concurrent Ziprasidone use

139
Q

Do Not Crush

A 
Diclofenac XR
Etodolac XR
Indomethacin XR
Naproxen ER and DR
Azathioprine
140
Q

Common Adverse Effects of Celecoxib

A

HTN, headaches, GI distress, diarrhea

141
Q

Less Common Adverse Effects of Celecoxib

A

AMI, bronchospasm

142
Q

Rare but Serious Adverse Effects of Celecoxib

A

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

143
Q

Common Adverse Effects of Diclofenac

A

Headaches, GI distress

144
Q

Less Common Adverse Effects of Diclofenac

A

GI ulcers

145
Q

Rare but Serious Adverse Effects of Diclofenac

A

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

146
Q

Etodolac - Less Common Adverse Effects

A

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

147
Q

Etodolac - Rare but Serious Adverse Effects

A

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

148
Q

Ibuprofen - Less Common Adverse Effects

A

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

149
Q

Ibuprofen - Rare but Serious Adverse Effects

A

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

150
Q

Indomethacin - Common Adverse Effects

A

Headache

151
Q

Indomethacin - Less Common Adverse Effects

A

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

152
Q

Indomethacin - Rare but Serious Adverse Effects

A

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

153
Q

Meloxicam - Common Adverse Effects

A

GI distress

154
Q

Meloxicam - Less Common Adverse Effects

A

Edema, itching, rash, dizziness, tinnitus, ototoxicity

155
Q

Meloxicam - Rare but Serious Adverse Effects

A

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

156
Q

Nabumetone - Common Adverse Effects

A

Elevated LFTs, dyspepsia, abdominal pain, diarrhea

157
Q

Nabumetone - Less Common Adverse Effects

A

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

158
Q

Nabumetone - Rare but Serious Adverse Effects

A

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

159
Q

Naproxen - Less Common Adverse Effects

A

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

160
Q

Naproxen - Rare but Serious Adverse Effects

A

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

161
Q

Lidocaine - Common Adverse Effects

A

Skin irritation, somnolence

162
Q

Lidocaine - Less Common Adverse Effects

A

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

163
Q

Lidocaine - Rare but Serious Adverse Effects

A

Cardiac arrest, cardiac dysrhythmia, seizure, methemoglobinemia

164
Q

Azathioprine - Common Adverse Effects

A

Nausea, leukopenia, infection

165
Q

Azathioprine - Less Common Adverse Effects

A

Diarrhea, malaise, myalgia, increased LFTs

166
Q

Azathioprine - Rare but Serious Adverse Effect

A

Neoplasia, pancreatitis

167
Q

Methotrexate - Common Adverse Effects

A

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

168
Q

Methotrexate - Less Common Adverse Effects

A

Elevated LFTs, diarrhea

169
Q

Methotrexate - Rare but Serious Adverse Effects

A

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

170
Q

Folic Acid - Common Adverse Effects

A

Loss of appetite

171
Q

Folic Acid - Less Common Adverse Effects

A

Confusion, irritation

172
Q

Folic Acid - Rare but Serious Adverse Effects

A

Anaphylaxis

173
Q

Hydroxychloroquine - Less Common Adverse Effects

A

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

174
Q

Hydroxychloroquine - Rare but Serious Adverse Effects

A

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

175
Q

Etanercept - Common Adverse Effects

A

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

176
Q

Etanercept - Less Common

A

Dizziness, nausea

177
Q

Etanercept - Rare but Serious Adverse Effects

A

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

178
Q

Tacrolimus - Common Adverse Effects

A

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

179
Q

Tacrolimus - Less Common Adverse Effects

A

Pruritis, elevated LFTs

180
Q

Tacrolimus - Rare but Serious Adverse Effects

A

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

181
Q

NSAIDs - Drug Monitoring

A

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

182
Q

Lidocaine Patch - Drug Monitoring

A

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.

183
Q

Azathioprine - Drug Monitoring

A

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

184
Q

Methotrexate - Drug Monitoring

A

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

185
Q

Folic Acid - Drug Monitoring

A

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

186
Q

Hydroxychloroquine - Drug Monitoring

A

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.

187
Q

Etanercept - Drug Monitoring

A

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

188
Q

Tacrolimus - Drug Monitoring

A

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.

189
Q

Celecoxib - Counseling and Pearls

A

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.

190
Q

Diclofenac - Counseling and Pearls

A

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

191
Q

Diclofenac - Counseling and Pearls

A

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

192
Q

Etodolac - Counseling and Pearls

A

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.

193
Q

Ibuprofen - Counseling and Pearls

A

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.

194
Q

Indomethacin - Counseling and Pearls

A

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

195
Q

Meloxicam - Counseling and Pearls

A

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.

196
Q

Nabumetone - Counseling and Pearls

A

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.

197
Q

Naproxen - Counseling and Pearls

A

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.

198
Q

Lidocaine Topical Patch - Counseling and Pearls

A

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.

199
Q

Azathioprine - Counseling and Pearls

A

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.

200
Q

Methotrexate - Counseling and Pearls

A

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.

201
Q

Folic Acid - Counseling and Pearls

A

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.

202
Q

Hydroxychloroquine - Counseling and Pearls

A

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

203
Q

Etanercept - Counseling and Pearls

A

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

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Q

Tacrolimus - Counseling and Pearls

A

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

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