SLE Pharmacotherapy

which glucocorticoid topical(s) are super potent agents?

augmented betamethasone dipropionate

which glucocorticoid topical(s) are very high potency agents?

clobetasol propionate and halobetasol propionate

which glucocorticoid topical(s) are high potency agents?

betamethasone dipropionate, fluocinonide, halcinonide, and mometasone furoate

which glucocorticoid topical(s) are moderate potency agents?

betamethasone valerate, fluocinolone acetonide (0.025%), triamcinolone acetonide, and hydrocortisone valerate (0.2%)

which glucocorticoid topical(s) are low potency agents?

desonide (0.05%), fluocinolone acetonide (0.01%), and hydrocortisone (0.5-2.5%)

what are the calcineurin inhibitors that are used topically?

pimecromus cream and tacrolimus ointment

which topical option should be used on the face in a short-term capacity only?

low potency glucocorticoids

which topicals can be used on the body long term?

moderate strength corticosteroids

T/F: calcineurin inhibitors have no time limit for use on the face

true

what are glucocorticoids used for in SLE?

used to suppress immune response and therefore inflammatory response

what is the MOA of glucocorticoids?

decreases inflammation by suppression of migration of polymorphonuclear leukocytes and reversal of increased capillary permeability and decreases activity of lymphatic and adrenal system

what are the ADRs of glucocorticoids?

CNS/behavioral effects, GI effects, Ocular effects

what monitoring should be done for patients on glucocorticoids?

signs of adrenal insufficiency

what is the peak time for IR glucocorticoid tablets?

2 hours

what is the half-life of glucocorticoids?

2-3 hours

T/F: the lowest possible dose of glucocorticoids should be used to control symptoms of SLE

true

How are glucocorticoids dosed for SLE flares?

methylprednisolone pulse therapy (250-1000 mg for 1-3 days) followed by an oral taper

how should SLE patients controlled on more than 5 mg of glucocorticoids per day taper off?

taper to less than 5 mg and off prednisone within 6 months

if unable to taper to 0 mg initiate or escalate immunosuppressive therapy

what is the brand name for chloroquine?

Aralen

what is chloroquine used for in SLE?

helps to modulate the immune system and prevent activation of dendritic cells present in disease flare ups

what is the MOA of chloroquine?

inhibit prostaglandin synthesis (known more as an antimalarial agent)

what is the dose for chloroquine?

max dose of 2.3 mg/kg/day

what are the ADRs for chloroquine?

blue-grey skin pigmentation, hypoglycemia, abdominal cramp

what should be monitored in patients using chloroquine?

CBC with differential (baseline, renal function)

what is the peak for chloroquine?

1-2 hours

what is the half-life for chloroquine?

~30 hours

what is the brand name of azathioprine?

Imuran

what is azathioprine’s role in SLE?

blocks purine synthesis which suppresses the immune system response

T/F: azathioprine is the safest drug option for pregnancy in SLE

true

what is the MOA of azathioprine?

imidazolyl derivative of mercaptopurine; metabolites are incorporated into replicating DNA and half replication; also block the pathway for purine synthesis

what is the dosing for azathioprine?

2-3 mg/kg/day in 2 divided doses

what are the BBW for azathioprine?

malignancies such as post-transplant lymphoma and hepatosplenic T-cell lymphoma in patients with inflammatory bowel disease

what are the ADRs for azathioprine?

pancreatitis, liver toxicity, infections

what monitoring is done for azathioprine?

CBC with differential, AST/ALT, creatinine

what is the time to peak for azathioprine?

1-2 hours

what is the half-life for azathioprine?

2 hours

what are the brand names for methotrexate?

Trexall, Rheumatrex

what is methotrexates role in SLE?

inhibits purine and thymidylic acid synthesis decreasing immune response

why is folic acid given with methotrexate?

to decrease side effects.

T/F: methotrexate is more effective than azathioprine

true

what is the MOA for methotrexate?

folate antimetabolite that inhibits DNA synthesis, repair, and cellular replication

what is the dosing for methotrexate?

20-25 mg SQ or PO once weekly

what are the BBW for methotrexate?

embryo-fetal toxicity, bone marrow suppression, serious infections, renal toxicity and increased toxicity with renal impairment, GI toxicity, hepatic toxicity, pulmonary toxicity, HS, and dermatologic rxns

what are the ADRs for methotrexate?

dermatological toxicity, diarrhea, increased liver enzymes.

what monitoring is done for methotrexate?

CBC with differential, AST/ALT monthly for 3 months and then every 3 months thereafter

what is the peak for methotrexate?

0.75-6 hours

what is the half-life for methotrexate?

3-10 hours

what is the brand for anakinra

Kineret

what is anakinra’s role in SLE?

helps to block IL-1 pathway and decrease immune response

adjunctive or alternative to immunosuppressants and used to lower steroid need

T/F: anakinra is not indicated for LN or CNS involvement in SLE

true

what is the MOA of anakinra?

antagonist of the IL-1 receptor — endogenous IL-1 is induced by inflammatory stimuli and mediates a variety of immunological responses

what is the dose for anakinra?

100 mg SQ or IV daily

what are the ADRs for anakinra?

increase liver enzymes, hyperkalemia, hypernatremia

what is monitored for anakinra?

CBC with differential monthly for 3 months then every 3 months for 3 months then every 6 months

what is the peak for anakinra?

3-7 hours

What is the half-life for anakinra?

4-6 hours

what is the brand name of antifrolumab?

Saphnelo

what is the role of anifrolumab in SLE?

helps to block the inflammatory process and immune functions of IgG1

what is the dose of anifrolumab?

300 mg IV infusion every 4 weeks

what is the BBW for anifrolumab?

None (concern for malignancies)

what are the ADRs for anifrolumab?

antibody development, infection, HS rxns

which vaccine should be given prior to starting anifrolumab?

Zoster vaccine

what is the brand name of Belimumab?

Benlysta

what is Belimumab’s role in SLE?

decrease the ability for autoreactive B-cells to mature and cause damage

alternative or adjunctive to immunosuppressants used to lower steroid need

how long does it take to see results from belimumab?

2-4 months

what is the MOA of Belimumab

IgG1-lambda monoclonal antibody that prevents the survival of B lymphocytes by blocking the binding of soluble human B lymphocyte stimulator protein (BLyS) to receptors on B lymphocytes

what is the dosing of Belimumab?

IV dosing: 10 mg/kg/dose q2 weeks for 3 doses then q4 weeks

SQ dosing: 200 mg weekly

ADRs for Belimumab

diarrhea, nausea, infections, PML

what monitoring is done for Belimumab?

HS rxns and new or worsening depression or suicidal ideation

what is the peak for Belimumab SQ?

2.6 days

what is the half-life for Belimumab SQ?

18.3 days

what is the brand name of colchicine?

Colcrys

what is colchicine’s role in SLE?

used as a steroid sparing agent

what is the MOA for colchicine?

disrupts cytoskeletal functions by inhibiting B-tubulin polymerization into microtubules, preventing activation, degranulation, and migration of neutrophils

what is the dosing for colchicine

0.6 - 1.2 mg daily

what are the ADRs for colchicine?

GI effects, myalgia, CYP3A4 inhibitors

what monitoring is done for colchicine?

eye screening baseline then every 4-6 months EKG at baseline and as needed

what is the peak for colchicine?

0.5 - 3 hours

what is the half-life of colchicine?

27-31 hours

what is the brand name of cyclophosphamide?

Frindovyx

T/F: cyclophosphamide is a prodrug that must be activated by liver enzymes

true

what is the MOA of cyclophosphamide

Is an alkylating agent that prevents cell division by cross-linking DNA strands and decreasing DNA synthesis. It is a cell cycle phase nonspecific agent. Also possesses potent immunosuppressive activity

what is the dosing for cyclophoshamide?

750 - 1000 mg/m2 IV monthly for 6 months

what are the ADRs of cyclophosphamide?

bone marrow suppression, hepatoxicity, pulmonary toxicity — can cause permanent infertility

what monitoring is done for cyclophosphamide?

CBC with differential and creatine weekly for 4 weeks, then monthly urine pregnancy test prior to each infusion, and urinalysis every 6 months following course

what is the peak for cyclophosphamide?

~1 hour

what is the half-life for cyclophosphamide?

6-8 hours

what are the brand names for cyclosporine?

Gengraf, Neoral, Sandimmune

T/F: cyclosporine should be handled and prescribed by an experienced physician

true

what is the MOA of cyclosporine?

inhibition of production and release of interleukin II and inhibits interleukin II-induced activation of resting T-lymphocytes

what is the dose of cyclosporine?

3-5 mg/kg/day by mouth in 2 divided doses

what are the BBW for cyclosporine?

HTN, nephrotoxicity, immunosuppression

what are the ADRs for cyclosporine?

infections, diabetes, neurotoxicity

what is monitored for cyclosporine?

creatine, potassium, magnesium, every 2 weeks for 12 weeks then monthly. CBC with differential, AST/ALT monthly for 3 months then every 3 months. Lipid every 6 months

what is the peak for cyclosporine?

2-6 hours

what is the half-life for cyclosporine?

8.4 hours

what is the brand name of dapsone?

Aczone

which medication is associated with methemoglobinemia and G6PD deficiency?

dapsone

what is dapsone used for in SLE?

refractory skin disease

what is the MOA of dapsone

inhibits neutrophil movement and the lack of the ability to initiate inflammatory processes