Pharm - Tb Flashcards
A person w/ latent Tb infection:
- usually has skin test/blood test results indicating Tb
- normal CXR and neg. sputum test
- Tb bacteria in body that are alive but inactive
- does not feel sick
- cannot spread to others
- needs tx for latent infection to prevent dz
DOT (directly observed therapy)
someone has to watch the person take treatment
What are the 4 drugs used to treat latent Tb?
- Isoniazid (INH)
- Rifampin
- INH w/ rifapentine
- ING w/ rifampin
mechanism of action for INH
- selective for mycobacteria
- causes cell dath by inhibiting enzymes associated w/ mycolic acid sysnthesis, an essential component of bacterial cell wall
- bactericidal
spectrum of activity of INH
- active against intracellular and extracellular mycobacterium tb
- at therapuetic levels isoniazid is bactericidal against actively growing intra and extracell mycobacterium tb
indications for the treatment of INH
- latent Tb infection
- active Tb
contraindications for the treatment of INH
- hypersensitivity reaction sto isoniazid
- hx of drug-induced hepatitis
- actue liver dz
- Hx of hepatic injury secondary to INH
- Hx of sever adverse rxn to INH
Duration of INH tx of latent Tb
- 9 mos recommended
- 6 mos can be considered to reduce cost and improve adherence
drug interactions with INH
- phenytoin (anticonvulsant) - INH could increase serum concentration
- carbamazepine (anticonvulsant) - INH could increase hepatotoxic effects
- always check w/ pharmacist for interactions
monitoring parameters of INH
- baseline and periodic LFTs (ALT AST)
- sputum cultures monthly (until 2 consecutive negatives)
- monitor for prodromal signs of hepatitis (fatigue, anorexia, nausea, upper quadrant pain)
hepatitis associated w/ INH
- *most important side effect
- can be fatal
- can occur after months of tx
- risk is age related
- incidence is 1 in 1000
- most likely to occur in those who drink alcohol
Peripheral neuropathy occurs in about 2% of INH patients; what can be done to prevent it?
pyridoxine supplementation
mechanism of action of rifampin
- *red flags should go up in brain when you see this drug**
- binds to DNA-dependent bacterial RNA polymerase
- blocks RNA transcription and protein synthesis
spectrum of activity of rifampin
- intracellular penetration is high so it’s useful for tx of intracellular pathoens
- primary use is for latent and active Tb
- bactericidal against most
indications for the tx of rifampin
-management of active and latent tb in combo w/ other agents
contraindications for use of rifampin
- hypersensitivity to rifampin
- concurrent use of antiretroviral or protease inhibitors
most common ADRs in rifampin
- rash
- GI distress
- increased LFTs (hepatitis is rare)
- flu-like syndrome
- orange-red discoloration of body fluid
- CBC changes like thrombocytopenia, leukopenia, anemia
most notable ADRs in rifampin
- red/orange disocoloration of urine, feces, saliva, sweat, tears and CSF
- advise pts
- drug is relatively well tolerated
what is significant about the function of rifampin?
- it is a potent CYP3A4 inducer
- so decreases concentration of many drugs
- and has LOTS of drug interactions
- **red flag reminder
use of rifampin during pregnancy or in breastfeeding mothers
- it crosses the placenta
- d/t risk of tb in fetus, tx is recomended when risk of tb in mother is moderate to high
- its excreted in breast milk
- d/t potential for serious ADRs to nursing infant its recommended to stop nursing or stop drug
indications for use of rifapentine (Priftin)
-tx of LTBI and active tb
contraindications of rifapentine
- hypersensitivity to rifapentine, other rifamycins or any component in the formulation
- not effective in tx of latent tb in children <2
- infection w/ INH or rifampin resistant tb
- tb w/ HIV infection d/t increased risk of aquired rifampin resistance
- pregnant or breast feeding women
ADRs associated w/ rifapentine
- GI: n/v
- hepatotoxicity
- elevated uric acid levels and LFTs
- orange/red discoloration of body fluid
- flu-like syndrome
- hypotension and syncope associated w/ once weekly dosing
What is the preferred tx regimen for latent tb?
- INH for 9 mos self administered
- Weekly INH and rifapentine for 3 mos given by DOT
What is the alternative tx regimen for latent tb?
- INH for 6 mos
- INH plus rifampin for 3 mos
- Rifampin daily for 4 mos is an alternative for INH resistant infections
What is the drug of choice for treatment of latent tb during pregnancy?
- ioniazid (5mg/kg/day up to 300 mg daily) for 9 mos
- can have minor interuptions as long as 270 doses are completed in 12 mos
- pyridoxine supplementation
Alternative: rifampin daily for 4 mos
What is the drug of choice in children for the tx of latent tb?
- INH (10-15 mg/kg daily) for 9 mos
- alternative: 20-30 mg/kg twice a week w/ DOT
- monitor frequently
- in children >2: INH plus rifapentine can be used
- for children intolerant to INH or w/ resistant organism: rifampin
What is the drug of choice for tx of latent Tb in HIV infected pts?
- preferred tx in resource rich setting: INH 300mg daily for 9 mos
- in resource-limited settings: minimum of 6 most of INH up to 36 mos of tx
What drugs are used in the treatment of drug-resistant latent tb?
- for people exposed to single-drug INH or rifampicin, the other drug should be administered as a single agent
- for people exposed to MDR-Tb:
- fluoroquinolone alone (levo or moxi)
- fluoroquinolone plus ethambutol or ethionamide
- 6-12 mos
What is the approach to treatment interruptions in pts w/ latent tb?
-the earlier and longer the interruption, the more serious the impact, and greater need to restart therapy from beginning
If pt is on a 6-9 mo. regimen of INH and misses more than 3 mos of therapy, what do you do?
-reinstitute treatment from beginning
For pts treated w/ a 3-4 mo. regimen and miss more than 2 mos of therapy, what do you do?
-treatment should be reinstated from beginning
What is the treatment of active Tb during the intensive/initial phase?
- 4 drugs: INH, rifampin, pyrazinamide, ethambutol)
- usually 2 mos (varying schedule)
- drug-susceptibility testing should be done on all initial isolates to use as guide for tx
mechanism of action of pyrazinamide (PZA)
- metabolized to pyrazinoic acid (active form)
- exact MOA is unknown - greatest activity against dormant or semi dormant orgs w/i macrophages
- bacteriostatic
- when used in combo w/ INH and rifampin, has a sterilizing effect
- not used as monotherapy b/c rapid development of resistance
spectrum of activity of PZA
- most commonly used for tx of active tb during initial phase of therapy
- in combo w/ other agents
- relatively narrow spectru
ADRs associated w/ PZA
- GI
- arthralgias (very high incidence)*
- uric acid elevations*
- hepatotoxicity*
- photosensitive dermatitis
- hematologic
mechanism of action of ethambutol (EMB)
- inhibits arabinosyl transferase leading to impaired mycobacterial cell wall synthesis
- bacteriostatic
ADRs associated with ethambutol
- **retrobulbar neuritis: optic neuropathy; change in visual acuity and/or color blindess
- hematologic
- GI
- CNS
- skin rash
Describe the treatment of active tb during the continuation phase
- administered for 4 (most pts) or 7 months (for those who require longer)
- in most cases consists of INH and Rifampin
What patient might require the longer continuation phase?
- those w/ cavitary pulmonary tb on initial CXR and positive sputum culture after 2 mos of tx in initial phase
- those whose initial phase did not inlcude pyrazinamide (pregnancy)
What is the approach to treatment interruptions in pts w/ active tb?
- completion of tx is determined by duration of therapy AND total number of doses administered
- duration:
- all doses should be delivered in 3mos
- continuation phase doses should be delivered w/i 6 mos or 9 mos depending on course
- if # of doses can’t be administered in time frame, have to determine if tx needs restarted or prolonged
- in general, continuous tx is MORE important in initial phase
what is another adverse effect that all drugs can cause?
- rash
- petechial rash in pt taking rifampin could indicate hypersentitivity
- if thrombocytopenia then stop drug and monitor platelets
What are the VERY important counseling points in the tx of Tb?
- adherence is key
- GI upset - take w/ food or at bedtime
- educate pts about sx of hepatitis
- report visual changes
- report petechial rashes
describe the tx of HIV infected patients w/ active Tb
- generally have poorer prognosis
- don’t use twice weekly therapy if CD4 cts <100 (once weekly is contraindicated)
- if currently being treated w/ ART, rifabutin should be used
- if diagnosed w/ HIV and Tb simultaneously, tx for tb first and ART 2-4 weeks later
describe the tx of pregnant or breastfeeding patients w/ active Tb
- initial tx: INH, rifampin and ethambutol for 2 mos followed by INH and rifampin for 7 mos
- not much data on PZA in pregnancy
- give pyridoxine supplementation
- avoid aminoglycosides
- use cation w/ ethionamide and fluoroquinolones
- latent tb therapy can be deferred to 2nd trimester
- most antimycobacterial agents are excreted in breastmilk but appear to be safe
describe the tx of children patients w/ active Tb
- similar tx regimens to adults
- total therapy often extended to 9mos
- 3 drug initial regimen is permissible
- rifapentine and ethambutol not considered safe
- same max doses applied as in adults
