TB Drugs: Flashcards
RIPE (1st line drugs)=
Rifampin/rifapentine
Isoniazid
Pyrazinamide
Ethambutol
Isoniazid (INH) :
MOA
Inhibits bacterial cell wall synthesis
Bactericidal
Indicated in adults and peds for TB treatment and prevention
Contraindicated in patients with acute liver disease
Take on empty stomach
Preg cat C
P450 2C9 inhibitor
Drug interactions: antacids, carbamazepine, phenytoin, ketoconazole, theophylline, valproate, BZDs, warfarin
Isoniazid ARDs:
Peripheral neuropathy most common
Dose-related
Most often in malnourished, diabetes, EtOH
Elevated LFTs
10% - 20% usually within first 3 months of treatment
Sometimes progresses to jaundice and fatal hepatitis
Prodrome: anorexia, N/V, fatigue, malaise, weakness
Pyridoxine (vit B6) deficiency
N/V
Less common: agranulocytosis, SLE-like syndrome, fever
Isoniazid (INH) side effects:
INH
Intestinal upset
Neuropathy
Hepatotoxicity
INH intoxication:
Overdosage N/V, dizziness, speech slurring, vision blurring, hallucinations Respiratory distress CNS depression (stupor to profound coma) Seizures Severe metabolic acidosis hyperglycemia
Rifampin:
Class: Rifamycin MOA: Inhibits DNA-dependent RNA polymerase Bactericidal Highly lipophilic Spectrum: M. tb, N. meningitidis, M. leprae, MRSA, Staph epi. Indications Tuberculosis Meningococcal carriers Not meningitis due to resistance Dose for 2 days Used in kids and adults
Rifampin ADRs:
*Red-orange body fluids GI: heartburn, anorexia, N/V, jaundice, flatulence, cramps, diarrhea, CDAD Thrombocytopenia HA, fever, drowsiness, fatigue, ataxia, dizziness Visual disturbances Dysmenorrhea Hyperuricemia Pruritus, urticaria, rash, Stevens-Johnson, TEN
Rifampin DIs:
STRONG 3A4 inducer Oral contraceptives Warfarin Ketoconazole SMX-TMP INH
Rifapentine:
MOA
inhibits DNA-dependent RNA polymerase in susceptible strains ofM. tuberculosisbut not mammalian cells
Bactericidal
Used with INH for patients 12 yo and older
Not for pregnancy, HIV, kids under 2, resistant M.tb
Induces 3A4, 2C9
Rifapentine:
Hepatotoxicity, hyperbilirubinemia, colored body fluids, CDAD
≥10%: hyperuricemia, pyuria, hematuria, UTI, proteinuria, lymphopenia, neutropenia, anemia, and hypoglycemia
Pyrazinamide:
Nicotinamide (vitamin B3) analog
Indicated for treatment of active TB in adults and children
Contraindicated in gout or severe liver disease
Half-life 9 – 10 hours
Prolonged in renal/liver impairment
Excreted in urine
Pyrazinamide ADRs:
Hyperuricemia Inhibits renal excretion of uric acid Increased LFTs Rash Arthralgias, myalgias
Ethambutol
MOA: inhibits metabolite synthesis, impairing cell metabolism, stopping reproduction
Only useful for mycobacteria
*Used for adjunct treatment of tb
*Not used as monotherapy
Contraindicated in optic neuritis
Drug interactions: Al-containing antacids
Ethambutol ADRs:
Decreased visual acuity, optic neuritis, optic neuropathy,
Patients should report any visual change
Hyperuricemia, arthralgias, GI, confusion, disorientation
Bedaquiline:
First new drug for TB in 40 years Approved 2012 MOA: inhibits mycobacterial ATP synthase *Indicated in combo tx for MDR TB QT prolongation Increased risk of death (11.4%, 4x placebo in once study) Hepatotoxicity CYP 3A4 substrate ADRS: nausea, arthralgia, HA Preg cat B
Tx of LTBI:
LTBI is treated to prevent the development of TB disease
Reduces risk of disease progression
LTBI is treated with multiple medications
Monotherapy no longer recommended
High Priority LTBI Tx:
High risk groups if positive IGRA or TST result of > 5 mm
Recent close contacts of people with infectious TB disease
People living with HIV
People with chest x-ray findings suggestive of previous TB disease
Patients with organ transplants
Other immunosuppressed patients
High Priority LTBI Tx Cont.:
High risk groups if positive IGRA or TST result of > 10 mm:
People who have come to U.S. within last 5 years from countries where TB is common
People who inject drugs
People who live or work in high-risk facilities (prisons, homeless shelters, long-term care, etc)
People who work in mycobacteriology laboratories
People with medical conditions that increase risk of TB disease (DM, CRF, cancer, silicosis, gastric bypass)
Children younger than 4 years old
Infants, children, and adolescents exposed to adults in high-risk groups
Low priority Tx for LTBI:
Individuals without any risk factors generally should not be tested for TB infection
However, individuals with no risk factors who are tested and have a positive IGRA or TST result of >15 mm should be evaluated for LTBI treatment
LTBI Tx Reginmens:
Preferred regimen is 9 mos daily isoniazid (INH)
Reduces lifetime infection risk from 10% to 1%
LTBI TX regimens cont.:
Successful treatment Adherence to regimen INH-susceptible TB No reinfection from exogenous source Usually dosed 300 mg po daily Can dose 900 mg BIW with DOT Give pyridoxine 10 – 50 mg daily to decrease incidence of peripheral neuropathy
Rifampin LGTI regimen:
Rifampin (RIF) is recommended for people who
Cannot tolerate INH
Have been exposed to INH-resistant TB
RIF should be given daily for 4 months
RIF should not be used with certain combinations of anti-retroviral (ARV) therapy
In some cases, rifabutin may be substituted when RIF cannot be used
Tx of LTBI in pregnant women:
For most pregnant women, LTBI treatment can be delayed until after delivery, unless they have certain medical conditions
INH has not been shown to have harmful effects on the fetus
Immediate treatment should be considered if woman is living with HIV, has another immunocompromising condition, or is a recent TB contact
Preferred LTBI treatment regimen is 9 months of INH with a vitamin B6 supplement
LTBI HIV Tx:
Individuals living with HIV should be treated with 9-month regimen of INH
RIF should not be used for people living with HIV who are being treated with certain combinations of ARV
In some cases, rifabutin may be given
Pt eval before prescribing:
Patient has ever had adverse reactions to LTBI drugs
Patient is currently on medications that may interact with LTBI drugs
Because of the interaction between TB and HIV, all patients should be recommended to undergo HIV screening and be offered an HIV test
Goals of active TB tx:
Cure patient, minimize risk of death/disability, prevent transmission to others
Provide safest, most effective therapy in shortest time
Prescribe multiple drugs to which the organisms are susceptible
Never treat with a single drug or add single drug to failing regimen
Ensure adherence and completion of therapy
adherence:
Clinician responsible for completion of therapy
DOT=
DOT is preferred management strategy for all patients
Can reduce acquired drug resistance, treatment failure, and relapse
Nearly all regimens can be intermittent if given as DOT
DOT reduces total number of doses and encounters
For drug-resistant TB, use daily regimen and DOT
Directly Observed Therapy (DOT)
intitial tx phase:
First 8 weeks of treatment
Most bacilli killed during this phase
4 drugs used
Continuation Tx phase:
After first 8 weeks of TB disease treatment Bacilli remaining after initial phase are treated with at least 2 drugs
Relapse Tx:
Occurs when treatment is not
continued for long enough
Surviving bacilli may cause TB
disease at a later time
standard 4 drugs for initial phase:
Initial phase: standard four drugs (INH, RIF, PZA, EMB) for 8 weeks
drug-resistant TB:
Caused by organisms resistant to one or more TB drugs
Transmitted same way as drug-susceptible TB, and no more infectious
Delay in detecting drug resistance may prolong period of infectiousness because of delay in starting correct treatment
MDR TB:
caused by bacteria resistant to isoniazid and rifampin
XDR TB:
caused by organisms resistant to isoniazid and rifampin, plus fluoroquinolones and ≥1 of the 3 injectable second-line drugs
types of drug resistance:
Primary resistance develops in persons initially infected with resistant organisms
Secondary (acquired) resistance develops during TB therapy
Factors that increase chance of patient having or developing drug-resistant TB:
Patient has spent time with someone with active drug-resistant TB disease
Patient does not take all of their medicine or doesn’t take their medicine regularly
Patient develops active TB disease after having taken TB medicine in the past
Patient comes from area of the world where drug-resistant TB is common
Monitoring Adverse Reactions
Patients should have baseline blood and vision tests to detect problems that may complicate treatment
Children only need vision tests, unless there are other medical conditions that may complicate treatment
