Biologic Assignments Flashcards
what is the other name for omalizumab
xolair
what is omalizumab indicated for
xolair- 1) adults and adolescents 12 years and over with moderate-severe persistent asthma and whose symptoms are inadequately controlled with inhaled corticosteroids 2) adults and adolescents 12 and over with chronic idiopathic urticaria after antihistamine failure
how does omalizumab come
xolair-sterile powder for reconstitution and injection
efficacy of xolair
omalizumab-decrease in asthma related hospital admission, unscheduled dr visits and emergency room visits vs placebo
how does xolair work
omalizumab- targets receptor binding on IgE
special administration of omalizumab
xolair-SC-any dose above 150mg must be divided over more than one injection site- patient must be observed for minimum of two hours after each injection. Given q4weeks, or q2weeks if over 90kg
contraindications for xolair, and DI
omalizumab-rash, increased risk infection, heart attacks/failure/abnormal rhythms, fainting, mini stroke, blood clots, no DI
omalizumab pregnancy category
xolair- B
place in therapy for xolair
omalizumab- expensive, inconvenient, only for those 12 and over who are poorly controlled despite high dose steroid- is an appropriate add on with or without oral prednisone. Last line therapy
what is the other name for dinutuximab
unituxin
what is dinutuximab indicated for
unituxin- treatment of high risk neuroblastoma in combination with GM CSF, IL2 and isotretinoin in patients under 5 (peds) who show at minimum a partial response to other therapies
-is used as part of a multimodality regimen that includes surgery, chemo, and radiation
neuroblastoma-who affects and what is it-what drug is this relevant for
unituxin-dinutuximab-mostly children under 5 (suggests preconceptual and gestational link), may originate anywhere in SNS, most commonly presents as mass in abdomen, chest, neck and most commonly adrenal glands. Signs and sx vary with location of tumor. Prognosis often poor due to late detection. Treatment based on risk stratification
talk about risk categories for neuroblastoma- which drug is this relevant for
unituxin-dinutuximab- low to intermediate have good prognosis (treat with observation, surgery, and or chemo), high risk have poor prognosis and have aggressive treatment with chemo, surgery, myeloablative chemo, autologous stem cell rescue, transpolant, radiation, differentiation, and or immunotherapy
what is unituxin (how it works)
dinutuximab- glycosylated IgG mAb that targets the antigen GD2 which is on the surface of neuroblastoma cells and promotes cell growth- drug binds and induces cell lysis of GDs expressing cells
handling, storage and administration of unituxin
dinutuximab- fridge, no light, don’t shake, patient must be checked to ensure hematologic/resp/hepatic/renal adequacy first, added to NaCl. Store in fridge and use within 4 hours of prep. IV infusion over 10-20 hours for 4 consecutive days up to 5 cycles
adverse effects and DI of dinutuximab
unituxin- infusion reactions (prehydrate with NSS and diphenhydramine), neuropathic pain (morphine and or gabapentin or lidocaine), capillary leak syndrome, hypotension, sepsis, neurologic eye disorders, hypokalemia, embryo fetal tox (contraception advised), bone marrow suppression. No DI studies done
what is the brand name for palivizumab
synagis
what is synagis indicated for
palivizumab- prevention of serious lower respiratory tract diseases caused by RSV in children at high risk. Safety and efficacy has been established for children with premature history, infants with bronchopulmonary displasia, and children with congenital heart disease- only for prevention not treatment
what are risk factors for getting RSV, how to prevent it, and what drug is this relevant for
palivizumab-synagis- premature, congenital heart disease, airway abnormalities, down’s syndrome, cleft lip/palate- can assess these patients for prophylactic use of synagis. Can only prevent by washing hands, other than synagis
clinical presentation of RSV, why its worse in kids- what drug is this relevant for?
cold like symptoms that can progress to cough, fast breathing and wheezing in the acute phase (bronchiolitis). Can lead to death from lack of oxygenation or dehydration (more serious in young kids because smaller airways and immature immune system)
treatment for active RSV, what drug is this relevant for?
synagis aka palivizumab-no specific treatment besides supportive care, but trialed treatments include Antivirals (no effect), corticosteroids (small improvement if asthma), bronchodilators (not beta agonists, only continued in children with a reduction of wheezing shown), supportive care (hydration, humidifier, suction, may need supplemental oxygen or mechanical ventilation).
how palivizumab works
synagis-antibody to F glycoprotein of RSV (usually mediates fusion of virus to host cell membrane and to each other)- drug stops this and inhibits viral penetration into host cell as well
effectiveness of synagis
palivizumab- reduces RSV hospitalization for premature infants (80% in those without chronic lung disesase, 40% in those with, and 45% in congenital heart disease, but no effect for cystic fibrosis)
SE and CI (including preg) for palivizumab
synagis- AE fever, rash. CI in preg, patients with thrombocytopenia or any coagulation disorder
how to administer synagis, is it covered?
palivizumab- IM into anterolaterial thigh (not gluteal due to risk for siatic nerve damage), volumes greater than 1mL should be in divided doses. Give 15mg.kg.month for duration of RSV season. Covered in SK if child meets criteria
other name for inflectra
infliximab
what is infliximab
a disease modifying anti rheumatic drug (DMARD) for RA
treatment options for RA (include first line), what drug is this relevant for?
inflectra-infliximab- NSAIDs, glucocorticoids (prednisone), analgesics, DMARDs (methotrexate, leflunomide, hydroxychloroquine, cyclosporine, azathioprine), and biologics (abatacept, rituximab, certolizumab, etanercept, golimumab, tocilizumab, adilimumab) **Methotrexate is first line
how are inflectra and remicade related
both infliximab, but biosimilars. No significant differences in PK, efficacy, or time to onset
how does inflectra work
infliximab- binds to TNF alpha which impacts inflammatory processes (like cytokine production)
what is infliximab used for
inflectra- most commonly moderate to severe RA, but also ankylosing spondylitis, crohn’s, moderate to seere plaque psoriasis, psoriatic arthritis, and UC
how is inflectra administered
infliximab- IV at weeks 0.2.6 then q8w (3mg/kg for RA, 5mg/kg for others)
adverse reactions and CI for infliximab
inflectra AE- related to infusion process, infection, N/D, abdominal pain, increased liver enzymes (AE incidence similar with remicade), CI in severe heart failure or infections. DI= other biologics or live vaccines, and potentially cyp450 substrates
efficacy of infliximab, is it covered
inflectra- comparable or superior to other therapies for inflammatory conditions. Superior to othe DMARDs (like methotrexate). EDS coverage for remicade (if failed methotrexate and leflunomide), in 2014 inflectra recommended to be listed as well,
what is the other name for adalimumab
humira
administration of humira
adalimumab- SC
how does adalimumab work?
humira- for Crohn’s- IgG antibody that targets inflammatory mediators (especially TNF alpha- targets both soluble and transmembrane forms of it) to prevent binding will cell surface receptors
what is adalimumab indicated for
humira- treatment of RA, psoriatic arthritis, polyarticular juvenile idiopathic arthritis, plaque psoriasis, Crohn’s, UC, ankylosing spondylitis
-moderate to severe Crohns as second line if steroids did not induce remission or if intolerant to infliximab
efficacy of humira
adalimumab- superior to placebo in inducing remission for moderate to severe crohns disease who are naive to TNF antagonist therapy. Can induce and maintain remission and often used in combination with 6mercapto, azathiprine or methotrex. If ahve already tried infliximab efficacy may be reduced
how to administer humira
adalimumab- SC from prefiled syringe or pen-4 injections on day 1, 2 injections in two weeks, then maintenance of 1 injection (40mg) every two weeks after. Must be assessed after induction dose and ever 6 months by a specialist thereafter
AE of adalimumab and DI, pregnancy
Common SE, but CI if have active severe infection (sepsis, TB, etc) or heart failure, category B in pregnancy
coverage of Humira
adalimumab- EDS if refractory or other contraindications to several other medications
what is metastatic breast cancer often referred to as, what are risk factors, what drug is this relevant for?
advanced or stage 4, herceptin (trastuzumab); when cancer of the breasts spreads to distant sites, risks=over 40, nulliparity, early onset menses, late age menopause, OCP/hormone replacement, family hx (breast or ovarian)
symptoms of metastatic breast cancer, prognosis, what drug is this relevant for?
herceptin (trastuzumab)- depends on site of metastases, but common bone pain, trouble breathing, enlarged abdomen, jaundice, changes in mental status. All cases have neglected breast mass. Survival 23 months, bone only live longer. Untreated 9-12 months
treatment of metastatic breast cancer, what drug is this relevant for?
herceptin, trastuzumab; endocrine therapy, biological therapy or chemo. DOC depends on specific tumor and which sites affected (esp presence of HER2). Rare to cure, goal to prolong life
how does trastuzumab work?
herceptin- binds HER2 to inhibit proliferation of cells and induce apoptosis (mediates antibody dependent cellular cytotoxicity) (decreases number of cells entering S phase leading to downregulation of HER 2 receptors on cancer cells)
how to administer herceptin
trastuzumab- have cardiac fx tested first. IV infusion NOT push or bolus (28 day BUD after reconstitution) weekly basis or q3weeks. Loading dose and maintenance. Can show pulmonary tox within 24 hours (if dyspnea or hypotension, stop infusion). Dosed mg/kg
indication for trastuzumab
herceptin- monotherapy for MBC with HER2 positive tumors who have had at least 2 prior chemo regimens, including anthracycline and taxane, unless those were unsuitable for patient and or hormone therapy that has failed or was unsuitable. Can be combo therapy with paclitaxel for patients who have not received chemo and anthracycline was unsuccessful
-all aptients HERs positive with MBC should receive it, with or without chemo, and offered early to all patients
efficacy of herceptin
trastuzumab- synergy with chemo, first line if MBC starts to progress with chemo, less SE than chemo (no N/V, bone or hair loss), all trials show more effective (improves overall survival) than other therapies alone
AE, CI, preg, DI of trastuzumab
herceptin- increased risk cardiac toxicities, cardiomyopathy, infusion related, H/A, dizzy, rash, N/V/D, infection, back pain, weakness. **can be mistaken for trastuzumab emtansine (Kadcyla) so both meds should always include trade and generic names (can use this as 2nd line if trastuzumab fails). Preg cat D. DI=anthracyclines (worsen cardiotoxic effects)
cost of herceptin
trastuzumab- no cost to patient if meet criteria
low risk geneotypes of HPV, what drug is this relevant for?
6,11 (gardasil), warts can resolve spontaneously in 1-2 years, reinfection is common
high risk genotypes for HPV, what drug is this relevant for?
16,18 (gardasil), warts can resolve spontaneously in 2-3 years but can cause persistent infection associated with anogenital cancers. Risk of cervical cancer is high, but to cause must have HPV and host immune defenses/genetic factors, HPV genotypes etc
how to administer and store gardasil
cloudy liquid stored in fridge away from light and not frozen, not out of fridge for more than 72 hours. Observe patient for 15 minutes after. IM either deltoid or anterolateral area of thigh. 3 doses; 1, 2 2 months later, and 3 six months after first dose.
indication for gardasil, funding
funded for girls born after Jan 1 1996, prevention (1’=prevent, 2’=reduce complications-limited value, not effective in preventing transmission, 3’=decrease chronic disability due to warts and cancer). **for females age 9-26 to prevent anal cancer and anal intraepithelial neoplasia, and for females age 9-45 to prevent cervical, vulvar, vaginal cancer and genital warts. Males 9-26 anal cancer and intraepithelial neoplasia and genital warts.
SE and CI for gardasil
contains yeast and polysorbate- if sensitive, don’t take. CI if other immunosuppressants. Avoid in pregnancy. Local reactions fever and H/a=SE
other name for evolocumab
repatha
what is repatha for (indication)
evolocumab-all other options must be tried first, adjunct usually not monotherapy. dyslipidemia: adjunct to diet and maximally tolerated statin therapy or other LDL lowering therapies in adults with familial hypercholesterolemia or clinical atherosclerotic CVD who require additional LDL lowering
how does evolocumab work
repatha-human IgG antibody targetting PcSK9; inhibits its binding to LDL receptors therefore increasing LDL receptors to clear LDL and lowers blood LDL levels
how to administer repatha
evolocumab- inject into ab, thigh or upper arm, store in fridge (room temp use within 30 days), dosed 140 q2w or 420 monthly
AE CI and DI of evolocumab
repatha- nasopharyngitis is most common, increase in clearance when coadministered with statins but no statin adjustment necessary
price of repatha
evolocumab- not on formulary
other name for vedolizumab
entyvio
how does entyvio works
integrin receptor antagonist that blocks interaction with MAdCAM1 (expressed mainly on GI cells)
how is vedolizumab administered
entyvio- IV infusion over 30 minutes at weeks 0,2,6 and every 8 weeks thereafter
adverse effects, CI and DI of vedolizumab
entyvio- SE=nasopharyngitis, H/A, arthralgia, N, pyrexia, faitgue, cough, during preg greater chance of AE in 2nd and 3rd trimester, CI if severe infection, DI with natalizumab and TNF blockers (increase risk of infection and PML)
how does denosumab work
prolia/xgeva: binds RANK ligands to prevent interaction with the RANK receptor- prevents osteoclasts from forming
what should patients with osteoporosis do as first line therapy, what drug is this relevant for?
denosumab- take vitamin D, increase phosphorus and PTH, or bisphosponates along with getting bone mineral density q1-2 years. Bisphosphantes are first line, the SERMS, calcitonin and PTH. Denosumab is last line.
what causes osteoporosis
RANK ligand binding to RANK receptors on osteoclasts allowing for their formation- they absorb and remove bone
administration of denosumab
prolia/xgeva: store in fridge or room temp up to 14 days, SC injection, concentration peaks in 10 days and slowly declines for 4-5 months, half life 25 days, repeat injection q6months. MUST take vitamin D and calcium throughout therapy
indication for denosumab
prolia/xgeva: to increase bone mass in men and postmenopausal women with osteoporosis, and at high risk of bone fracture who are resistant to other available therapies. Also men receiving androgen deprivation therapy for non metastatic prostate cancer, and women receiving aromatase inhibitor therapy for non metastatic breast cancer
efficacy of denosumab
prolia/xgeva: reduced risk of vertebral fracture in post postmenopausal women and high risk patients, non inferior in DECIDE and STAND trials between 60mg of it and 70 mg alendronate orally but small statistically significant increased in BMD T scores at lumbar spine, total hip and femoral neck sites within 12 month period
AE, CI, DI and cost of denosumab
prolia/xgeva: SE= weakness, fatigue, GI, hypophosphatemia (but unique to Xgeva not Prolia which had overall less SE- back/extremity and muscle pain were linked to it), serious=osteonecrosis of jaw and cellulitis, hypocalcemia (more likely with kidney dysfx). CI in preexisting hypocalcemia (correct first). CI in preg (D and X). DI- immunosuppressive drugs. EDS coverage (postmenopausal women, can’t take bisphosphonate or not responding, 2 of over 75/BMD less tahn 2.5, prior fragility fractures)
other name for denosumab
2! Prolia and Xgeva
other name for imiglucerase
cerezyme
what is imiglucerase used to treat
cerezyme- gaucher’s disease (genetic autosomal recessive glucocerebrocidase deficiency (no conversion to ceramide and glucose) leading to accumulation of glucocerebrocidase (fatty substance) in macrophages causing cells to increase in size (Gaucher cells) that over time will accumulate in bone marrow and organs resulting in signs and sx (depending on where cells accumulate)
3 types of gaucher’s disease, what drug is this relevant for?
cerezyme (imiglucerase)-1- non neurologic (90%), 2- usually 3-6 months of afe, mostly neurologic, 3- less severe neurologic. Type 1 and 3 can expect normal life, 2 usually die in early childhood (2-5). All types are progressive and if not treated become worse over time possibly resulting in death
what is the drug of choice for gauchers disease
cerezyme (imiglucerase)- a glucocerebrosidase replacement therapy. Substrate reduction therapy is second line (Miglustat). Other body systems must be treated as well with analgesics and antiinflam.
Cerezyme is indicated for treatment of type 1 and 3 gauchers disease and over age of 2 (safety and efficacy not established under 2)
administration of imiglucerase
cerezyme- reconstituted then given by IV over 1-2 hours. Doses are based on weight and disease severity. Most benefit with 30-60units/kg q2w
SE, DI, cost of cerezyme
imiglucerase- less than 15% of people report SE (general, including rapid HR), about 15% develop immune reaction through IgG within 6 months (high risk of anaphylactic reaction and substrate reduction therapy with Miglustat should be used instead), safe in preg (caution in nursing), not covered
drugs with highest level of evidence for migraines
topiramate and onabotulinumtoxinA (botox)
drugs with lower quality evidence for migraines
sodium valproate, gabapentin, tizanidine, amytriptyline. Other options are antiepileptics, non cardioselective BBs (propranolol), CCB, lithium, seratonin antagonists, SNRI, TCAs
how does botox work
acts on presynaptic neurons by blocking exocytosis of ACh therefore prohibiting action potentials
administration of Botox
IM, intradermal or intradetrusor, each vial has BTX A complex + human serum albumin + NaCl, 31 injections every 12 weeks
indications for Botox
blepharospasm, stabismus, cervical dystonia, focal spasticity, equinus foot (pediatric cerebral palsy), primary hyperhidrosis of axillae (uncontrolled sweating of armpit), bladder dysfunction, CHRONIC MIGRAINE prophylaxis (15 or more days per month lasting four hours or longer (not for episodic migraines) for 18 and over
AE, CI, DI, cost of botox
preg cat C, AE occur in one week may last several months (HTN, H/A, neck pain, blepharoptosis, etc), DI- drugs that interfere with neuromuscular transmission (aminoglycosides, tetracyclines, spectinomucin, polymixins, lincomycin, quinidine, magnesium sulfate, anticholinesterases), EDS in SK but NOT for chronic migraine
what is the other name for belimumab
benlysta
what is belimumab for, classic sx of this disease
benlysta- lupus (AI, inflam of tissue and organs and alterations of T and B lymphocytes- immune complexes accumulate in body and cause tissue damage). Sx are non specific can be flu like, hair loss, changes in finger color in fold, high BP, joint pain, inflammation, rash on upper cheeks and bridge of nose, unusual reaction to sun, scaly rash, small painless sores inside mouth and nose, etc. CLASSIC TRIAD= fever, joint pain, butterfly rash on cheeks and nose bridge. Severity depends on organs affected, no cure
non pharm treatment for lupus, what drug is this relevant for?
belimumab, benlysta: sunscreen, smoking cessation, weight control, exercise, other therapies based on condition (heart, bone, etc). Diet high in omega 3 may reduce disease severity
standard pharm tx for lupus, what drug is this relevant for? What if you are refractory to standard treatment?
belimumab, benlysta: NSAIDs, antimalarial (hydroxychloroquine), glucocorticoid (prednisone), immunosuppressants (azathioprine, methotrex, mycophenolate). If refractory to standard treatment can consider stem cell transplant.
indication for benlysta
belimumab:active, autoantibody positive SLE currently on standard therapy (avoid in severe lupus nephritis/CNS and with concomitant biologic or IV cyclophosphamide)
how to administer belimumab
benlysta- 10mg/kg IV q2weeks x 3 (initially), then q4weeks maintenance- infusion over 1 hour (must administer with HC professional as hypersensitivity reactions can occur up to 4 hours after. Premed with antihistamine sometimes
how does belimumab work
benlysta-targetting B cells; binds B lymphocyte stimulators, leads to cell death and B cells not differentiating into plasma cells that produce immunoglobulins. Occurs within 8 weeks, clinical effect seen in 16
efficacy of benlysta
belimumab- no studies as monotherapy, but is effective in providing support so patients can decrease immunosuppressant doses and minimize their SE
AE, DI, CI and cost of benlysta
belimumab- SE common ones, PML can happen rarely, copay assistance program or can contact company for help paying, no DI checked
what is the other name for lemtrada
alemtuzumab
what is alemtuzumab used for
lemtrada- MS- progressive disease- destruction of myelin and degeneration and lossof axons in CNS- thought to be immune mediated. Environment (sunlight and viral) and genetics likely play role. Sx vary depending on location and degree of damage.
4 types of MS, what drug is this relevant for?
alemtuzumab, lemtrada: 1)RRMS-relapse remitting MS (most common- relapses followed by remissions during which no disease progression) (disease modifying therapies only show benefit here) 2) SPMS-secondary progressive MS 3)PPMS- primary progressive MS 4) PRMS- progressive relapsing MS
standard first line treatment for MS, what drug is this relevant for?
alemtuzumab, lemtrada: interferon beta or glatiramer acetate. Short period high dose CS often used. Fampridine improves walking ability. MAb, dimethyl fumarate and fingolimod are other tx options.
indication for almetuzumab
lemtrada- RRMS who have had inadequate response to two or more medications indicated for its treatment (not for progressive MS or clinically isolated syndtome)
how is lemtrada administered
almetuzumab- four hour IV, need pre med with CS for 3 days before dose. 2 courses: 12 mg for 5 days, then 12 mg for 3 days 12 months later. Antiviral prophylaxis is given on first day of treatment and continued until 2 months after completion of second course. Total duration is 24 months. Lab tests to monitor for signs of AI disease should be done periodically and for at least 2 years after tx done
efficacy of lemtrada
alemtuzumab- statistically sig reduction in relapse rates and accumulation of disability over 2 years
CI, SE, DI, cost of alemtuzumab
lemtrada- CI HIV, TB, severe infections, malignancies, concurrent antineoplastic or immunosuppressive, history of PML. 1 in 5 patients get common SE- infusion related, infections, H/A, rash, nasopharyngitis, thyroid AE, fever, N. DI- don’t combine with other immunotherapy or MAb, cloxapine, dipyrone, echinacea, roflumilast vaccine. Not covered. Don’t get immunized with live vaccine during or recently following tx (complete all 6 weeks prior to lemtrada). No studies in under 18 or over 65, preg cat C (contraception recommended four months after treatment course both men and women.
other name for bevacizumab
Avastin
what is avastin for
metastatic colorectal cancer, locally advnaced non small cell lung cancer, and glioblastoma**
what is glioblastoma, what drug is this relevant for?
avastin, bevacizumab: aka astrocytoma, CNS cancer of glial cells, most fatal primary brain cancer in humans, diagnosed best by MRI, sx range from H/A/dizzy/N to seizures/vision loss/stroke sx, cerebral edema can produce more complications (use high dose CS for that)
standard treatment for glioblastoma
total removal, followed by initiation of temozolomide in combo with radiotherapy
how does bevacizumab work
avastin- angiogenesis inhibitor by binding vascular endothelial growth factor (VEGF) to prevent its binding Flt-1 and KDR receptors on endothelial cells therefore inhibiting blood vessel proliferation
efficacy of avastin
bevacizumab- may prolong progression free survival time (time until tumor growth) in recurrant glioblastoma, but does not improve overall survival
administration of bevacizumab
avastin- IV infusion every 2 weeks starting at 90 minutes, 60 minutes if well tolerated, then 30 minutes if well tolerated.
AE, SE, DI, cost of avastin
bevacizumab- most common AE is bleeding (hemmorhage, hemoptysis, thromboembolisms, HTN crisis, GI perforations, CHF), necrotising fasciitis, severe eye inflammation causing blindness. Doesn’t likely interact with drugs commonly administered with but no studies done. DI with irinotecan and sunitinib malate. Not covered
