MSK Pharmacotherapeutics Flashcards
List the drugs / classes available for osteoporosis
Bisphosphonates
Denosumab
Teriparatide
Romosozumab
Raloxifene
Calcitonin
When should osteoporosis be treated?
- Fragility fracture (#)
- No # but DXA <= -2.5
- DXA -1 to -2.5 but FRAX indicates high risk (>3% hip or >20% major osteoporotic #)
How is the t-score and z-score of the DXA used?
T-score
- <= -2.5: osteoporosis
- -1 to -2.5: osteopenia
- >-1: normal
Z-score: <=-2 indicates coexisting problem that contribute to osteoporosis (exclude secondary causes)
What is the first line treatment for osteoporosis?
Bisphosphonates
When is oestrogen recommended for osteoporosis?
Younger women with estrogen deficiency
Women who need estrogen replacement for other reasons
What are the doses for alendronate, risedronate and zoledronic acid?
Alen: 70mg / week
Rise: 35mg / week
Zole: 5mg / year
What are the contraindications for bisphosphonates?
HypoCa
Gastric issues (PO)
CrCl < 35 (IV), CrCL < 30 (PO)
Inability to sit upright for > 30 mins
aspiration risk
Outline the monitoring for efficacy of bisphosphonates (PO and IV are different)
both IV and PO: use for 2 years, then do BMD –> if responsive
PO: 5 years (10 years if high risk of #)
IV: 3 years (6 years if high risk of #)
Outline the drug holiday algorithm for bisphosphonates
stop, then reassess after 2 years
if BMD drops by >4-5% or treatment criteria met –> restart
What are the safety monitoring parameters for bisphosphonates?
ONJ (dental hygiene, smoking cessation, no dental procedures), atypical fracture (monitor for hip / groin pain)
What is the dosing regimen for denosumab?
SC 60mg Q 6 months
At which CrCL should denosumab be used with caution?
<10
What are the calcium and vit D considerations with denosumab?
check if enough before initiating
Vit D > 20-30 but less than 50-100
monitor SCr, Ca, Vit D
What is the dosing regimen for teriparatide?
SC 20mg OD
What is a common S/E of teriparatide?
postural hypotension
When is teriparatide contraindicated?
CrCL < 30, paget’s disease, history of bone radiation, hyperCa
How long can teriparatide be used?
< 2 years
What is the dosing regimen for romosozumab?
SC 210mg Q monthly
2x 105mg injections given 1 after another
What are the C/I for romosozumab?
Hx of CV event or stroke
How long can romosozumab be used?
1 year
What is the dosing regimen for raloxifene?
PO 60mg OD
When is raloxifene C/I?
CrCl<30, hx of VTE, hepatic impairment
Does raloxifene cause hot flushes and blood clots?
no hot flushes
risk of VTE, stroke
What are some non-pharmacologicals for osteoporosis?
Exercises: weight bearing, muscle strengthening, balance
Smoking cessation
limit coffee alcohol
Reduce fall risk (check eyes, footwear, home improvement, drugs)
Vit D and Ca
What is the dose of vit D supplement?
800 IU / day
What are some DDI with vit D?
rifampin, ASM (PHY, CBZ, VPA), cholestyramine, orlistat, Al
What are some DDI with calcium?
PPI, fibre, Iron, tetracycline, FQ, bisphosphonates, thyroid meds)
What is the first line treatment for mod-severe disease activity RA?
MTX
What is the maximum duration of NSAID use for OA patient with CrCl < 60?
5-7 days
At which CrCL are NSAIDs contraindicated?
15
In what conditions are NSAIDs contraindicated / cautioned?
C/I: Uncontrolled asthma, severe renal impairment, active GI bleed, pregnant
Caution: mod renal impairment, Hx of GI bleed, hypertension
What is the treatment progression for low disease activity RA?
hydroxychloroquine > sulfasalazine > MTX > leflunomide
What is the dosing regimen of methotrexate in RA?
Initial: 7.5mg / week, then folic acid 5mg the day after
Titration: increase by 2.5 - 5mg every 4-12 weeks
Target dose: 15mg / week
Max dose: 25mg / week
What is the dosing regimen of sulfasalazine in RA?
Initial: 500mg OD/BD
Target: 1g BD
Max: 3g a day
What is the dosing regimen of hydroxychloroquine in RA?
200-400mg in 1-2 divided doses
Max: 5mg/kg/day
What is the dosing regimen of leflunomide in RA?
Loading: 100mg OD for 3 days
Maintenance: 20mg OD
Can leflunomide be used in pregnancy?
No
Which RA DMARDs should be used with caution in pt with G6PD deficiency?
Sulfasalazine, hydroxychloroquine
What are the S/E of MTX?
Increase in transaminases, myelosuppression, SJS/TEN
What are the contraindications of sulfasalazine?
sulfa allergy, G6PD
What are the contraindications of hydroxychloroquine?
Preexisting retinopathy, G6PD (do an eye exam)
What are the contraindications of leflunomide?
ALT > 2x ULN
What is the max number of bDMARDs and tsDMARDs that can be taken together?
1
Which bDMARD cannot be used in heart failure and severe infection?
TNF-alpha
Prior to initiation of bDMARDs / tsDMARDs, what screening should be done?
Screening: TB, HepB/C
Vaccination: HepB, pneumococcal, flu, chicken pox
Labs: CBC, LFTs, Lipids, SCr
What should be done if RA is not on target with MTX?
- Add b/tsDMARD
- triple therapy: add hydroxychloroquine, sulfasalazine
How should discontinuation of treatment be done when RA is at target?
not abruptly, as it increases chance of flares
In RA triple therapy (MTX, sulfasalazine, hydroxychloroquine), which should be discontinued first?
sulfasalazine
In RA treatment with MTX and bDMARD/tsDMARD, which should be discontinued first?
MTX
Briefly, what is the role of glucocorticoids in RA?
- bridging
- IA GC into joints (q3 monthly, not more than 2-3 times / year / joint)
How should glucocorticoids be used to bridge therapy for DMARD? (inc drug, dose, duration)
low dose GC, eg PO Prednisolone <7.5mg / day up to 3 months
How should the dose of methotrexate be adjusted in renal impairment?
CrCL < 50: reduce by 50%
CrCL < 30: contraindicated
What are the side effects of leflunomide?
increase in transaminases, alopecia, myelosuppression
Within how many hours should colchicine be started for an acute gout flare?
24-36 hours
What are the 2 dosing regimens for colchicine?
- 1mg loading dose then 0.5mg 1 hour later
- 0.5mg BD-TDS
What are the common side effects of colchicine?
N/V/D
What should be done with colchicine dose in renally impaired patients?
Dose should be reduced
For urate lowering therapy, what are the uric acid targets for both tophaceous and non-tophaceous gout?
tophi: <5 mg/dL
non-tophi: <6 mg/dL
What is the criteria to begin urate lowering therapy?
- > =2 flares in a year
- tophi
- gouty arthropathy
- Hx of kidney stones
What is the dosing regimen for allopurinol (include renal dosing)?
Initiate: <=100mg / day (<50 in CKD stage 3)
Titration: increase by 50-100mg every 2-8 weeks
Maintenance: >300mg / day (same for renal)
Max: 800-900 mg / day
What are the risk factors for SCAR from allopurinol?
Renal impairment
Agent - concom diuretics
Starting dose too high
HLA-B*58:01
Escalation of dose too fast
Seniority
What are the early signs of allopurinol induced SCAR?
flu-like Sx, red eyes, rash, mouth ulcers
What is the typical duration of SCAR occurrence from allopurinol?
3 months
What is the dosing regimen for fexobustat?
initiate: <=40mg/day
titration: 80mg / day if treatment not at target after 2-4 weeks
Are allopurinol and fexobustat renally or hepatically cleared?
allopurinol: renal
fexobustat: hepatic
In what medical conditions should fexobustat be used with caution and why?
CHF, Chronic heart disease (because increase risk of MACE)
What is the dosing regimen of probenecid?
250mg BD x 1 week, then 500mg BD
Increase 500mg BD every 4 weeks if not well controlled, max is 2g / day
At what CrCL does probenecid become less effective?
50
What is the contraindication for probenecid?
urolithiasis
What non-pharmacological counselling point should be given to patients on probenecid?
Drink water
