TUBERCULOSIS

DEFINITION

Tuberculosis, or TB, is an infectious bacterial disease caused by Mycobacterium tuberculosis, which

most commonly affects the lungs. It is transmitted from person to person via droplets from the throat

and lungs of people with the active respiratory disease.

Tuberculosis is a chronic infection caused by the bacteria Mycobacterium tuberculosis (and

occasionally other variants of Mycobacterium). It usually involves the lungs, but other organs of the

body can also be involved.

Transmission

The bacteria that causes TB, Mycobacterium tuberculosis , is transmitted by droplets when an infected person
coughs or sneezes. It is not spread through kissing or other physical contact. Children nearly always contract
the disease from an infected adult. When people with active pulmonary TB cough, sneeze, speak, sing, or spit,
they expel infectious aerosol droplets 0.5 to 5.0 µm in diameter. A single sneeze can release up to 40,000
droplets.[41] Each one of these droplets may transmit the disease, since the infectious dose of tuberculosis is
very small (the inhalation of fewer than 10 bacteria may cause an infection).[42]People with prolonged,
frequent, or close contact with people with TB are at particularly high risk of becoming infected, with an
estimated 22% infection rate.[43] A person with active but untreated tuberculosis may infect 10–15 (or more)
other people per year.[3] Transmission should occur from only people with active TB – those with latent infection
are not thought to be contagious.[1] The probability of transmission from one person to another depends upon
several factors, including the number of infectious droplets expelled by the carrier, the effectiveness of
ventilation, the duration of exposure, the virulence of the M. tuberculosis strain, the level of immunity in the
uninfected person, and others.[44] The cascade of person-to-person spread can be circumvented by effectively
segregating those with active ("overt") TB and putting them on anti-TB drug regimens. After about two weeks
of effective treatment, subjects with nonresistant active infections generally do not remain contagious to
others.[43] If someone does become infected, it typically takes three to four weeks before the newly infected
person becomes infectious enough to transmit the disease to others. [45]

SYMPTOMS

Tuberculosis (TB) is a disease caused by bacteria called Mycobacterium tuberculosis. The bacteria

usually attack the lungs, but they can also damage other parts of the body. TB spreads through the air

when a person with TB of the lungs or throat coughs, sneezes, or talks. If you have been exposed, you

should go to your doctor for tests. You are more likely to get TB if you have a weak immune system. Symptoms
of TB in the lungs may include

 A bad cough that lasts 3 weeks or longer

 Weight loss
 Loss of appetite
 Coughing up blood or mucus
 Weakness or fatigue
 Fever
 Night sweats

Skin tests, blood tests, x-rays, and other tests can tell if you have TB. If not treated properly, TB can

be deadly. You can usually cure active TB by taking several medicines for a long period of time.

Diagnosis

Tuberculosis is nearly always diagnosed by tuberculin skin tests, although one can also be

diagnosed by chest x rays and analysis of sputum (matter from the respiratory tract) smears and

cultures. The most common tuberculin skin test is the Mantoux test, which consists of injecting a

small amount of protein from the TB bacillus into the forearm. A reddening and swelling of the area

after 24–72 hours signals the presence of TB. A negative result, however, may not necessarily exclude a
diagnosis of TB.

Treatment

The disease is treated with a regimen of strong antibiotics such as Rifampin and Isoniazid for six months to two
years. Because some strains of the disease are unusually drug-resistant, cultures are grown from the patient's
bacteria and tested with a variety of drugs to determine the most effective treatment. In cases of strong drug-
resistant strains, the child may undergo surgery to remove the infected areas.

Infants with TB are usually hospitalized but children and teenagers can generally lead active lives

within two weeks of beginning medication. It is imperative that the mediation prescribed be taken

faithfully. With treatment, the chances of full recovery is good. Although several treatment protocols

for active TB are in wide use by specialists, and protocols sometimes change due to advanced in our

understanding of optimal therapy, they generally share three principles:

1. The regimen must include several drugs to which the organisms are susceptible.
2. The patient must take the medication on a regular basis.
3. Therapy must continue for a sufficient time.

Also, treatment recommendations are subject to change depending upon both the characteristics of

the particular organism being treated and newer advances in therapeutic agents. Thus, consultation

on treatment strategies with local public health and infectious disease experts is always advisable.

Isoniazid (INH) is one of the most common drugs used for TB. Inexpensive, effective and easy to take,

it can prevent most cases of TB and, when used in conjunction with other drugs, cure most TB. INH

preventive treatment is recommended for individuals who have:

 close contact with a person with infectious TB

 positive tuberculin skin test reaction and an abnormal chest x-ray that suggests inactive TB
 a tuberculin skin test that converted from negative to positive within the past two years
 a positive skin test reaction and a special medical condition (for example, AIDS or HIV infection or
diabetes) or who are on corticosteroid therapy
 a positive skin test reaction, even with none of the above risk factors (in those under 35)

Prognosis

With treatment, TB infection that is not drug resistant can nearly always be cured as long as patients are
consistent with their medications and considerable lung damage as not already occurred. Drug-resistant TB has
a lower cure rate. Without treatment, the disease will continue to progress; approximately one-half of
untreated TB patients will die of the disease.

Prevention

Stopping the spread of tuberculosis is the most effective way of preventing its incidence among children. All
adults who work with children should be screened regularly. In many communities, children are tested when
they reach their first birthday and then at one-to-three year intervals throughout the school years. The medical
profession is divided on the issue of screening; some physicians believe that the screening should be focused in
areas of common occurrence or within high-risk populations such as foreign-born children. The practice of
relying on parents to report results of the skin testing has also come under criticism from some members of the
medical community.

While a vaccine for TB does exist (Bacille Calmette-Guerin or BCG vaccine), it is not widely available in the
United States and has had conflicting reports about its efficacy. Being inoculated with BCG vaccine does not
always prevent infection wit

NEW DRUDS

The Food and Drug Administration approved a new treatment for multidrug-resistant tuberculosis that can be
used as an alternative when other drugs fail.

The drug, to be called Sirturo, was discovered by scientists at Janssen, the pharmaceuticals unit of Johnson &
Johnson, and is the first in a new class of drugs that aims to treat the drug-resistant strain of the disease.

Tuberculosis is a highly infectious disease that is transmitted through the air and usually affects the lungs but
can also affect other parts of the body, including the brain and kidneys. It is considered one of the world’s most
serious public health threats. Although rare in the United States, multidrug-resistant tuberculosis is a growing
problem elsewhere in the world, especially in poorer countries. About 12 million people worldwide had
tuberculosis in 2011, according to Johnson & Johnson, and about 630,000 had multidrug-resistant TB.

A study in September in The Lancet found that almost 44 percent of patients with tuberculosis in countries like
Russia, Peru and Thailand showed resistance to at least one second-line drug, or a medicine used after another
drug had already failed.

Treating drug-resistant tuberculosis can take years and can cost 200 times as much as treating the ordinary
form of the disease

“This is quite a milestone in the story of therapy for TB,” Dr. Paul Stoffels, the chief scientific officer at Johnson
& Johnson, said in an interview. He said the approval was the first time in 40 years that the agency had
approved a drug that attacked tuberculosis in a different way from the current treatments on the market.
Sirturo works by inhibiting an enzyme needed by the tuberculosis bacteria to replicate and spread throughout
the body.

Sirturo, also known as bedaquiline, would be used on top of the standard treatment, which is a combination of
several drugs. Patients with drug-resistant tuberculosis often must be treated for 18 to 24 months.

Even as it announced the approval, however, the F.D.A. also issued some words of caution.
“Multidrug-resistant tuberculosis poses a serious health threat throughout the world, and Sirturo provides
much-needed treatment for patients who have don’t have other therapeutic options available,” Edward Cox,
director of the office of antimicrobial products in the F.D.A.’s center for drug evaluation and research, said in a
statement. “However, because the drug also carries some significant risks, doctors should make sure they use it
appropriately and only in patients who don’t have other treatment options.”

The consumer advocacy group Public Citizen opposed approval in a letter to the F.D.A. in mid-December, saying
that the results of a limited clinical trial showed that patients using bedaquiline were five times as likely to die
than those on the standard drug regimen to treat the disease.

“Given that bedaquiline belongs to an entirely new class of drugs, it is entirely feasible that death in some cases
was due to some unmeasured toxicity of the drug,” the letter said.

Sirturo carries a so-called black box warning for patients and health care professionals that the drug can affect
the heart’s electrical activity, which could lead to an abnormal and potentially fatal heart rhythm. The warning
also notes deaths in patients treated with Sirturo. Nine patients who received Sirturo died compared with two
patients who received a placebo. Five of the deaths in the Sirturo group and all of the deaths in the placebo arm
seemed to be related to tuberculosis, but no consistent reason for the deaths in the remaining Sirturo-treated
patients could be identified.

Doctors Without Borders and the Bill and Melinda Gates Foundation, both active in the fight against
tuberculosis and other global diseases, applauded the F.D.A.’s decision.

Jan Gheuens, interim director of the TB Program for the Gates Foundation, called it a “long-awaited event” and
said the fight against TB had not benefited from new drugs in the way H.I.V. had. Beyond the benefits of the
drug itself, he said the quick approval process could be a model for other drugs sorely needed in the developing
world.

He also suggested, however, that more trials should be conducted to get a better understanding of the side
effects that led to the black box warning.

The F.D.A. approved bedaquiline under an accelerated program that allows the agency to conditionally approve
drugs that are viewed as filling unmet medical needs with less than the usual evidence that they work. The
drug’s approval was based on studies that showed it killed bacteria more quickly than a control group taking
the standard regimen, but it did not measure whether in the end patients actually fared better on bedaquiline.
Johnson & Johnson will conduct larger clinical trials to investigate whether the drug performs as predicted.

In a statement responding to Public Citizen’s letter, a spokeswoman for Johnson & Johnson said the company
was committed to supporting appropriate use of Sirturo and would “work to ensure Sirturo is used only where
treatment alternatives are not available.”
Dr. Stoffels said the hope was that other new tuberculosis drugs would also be approved that, when used in
combination with bedaquiline, could shorten and simplify the current standard of treatment. “That is still a long
time away,” he acknowledged, but “this is a first step in a new regimen for TB.”

November 7, 2014

Drug Name Active Ingredient Dosage Form/Route Sponsor Submission

Type

Belsomra suvorexant Tablet;Oral Merck Sharp Labeling

Dohme Revision

Foscavir foscarnet sodium Injectable;Injection Clinigen Labeling

Hlthcare Revision

Iprivask desirudin recombinant Injectable;Subcutaneous Marathon Labeling

Pharms Llc Revision

Otrexup methotrexate Solution;Subcutaneous Antares Manufacturing

Pharma Inc Change or
Addition

Sucraid sacrosidase Solution;Oral Qol Medcl Manufacturing

Change or
Addition

November 5, 2014

Drug Name Active Ingredient Dosage Form/Route Sponsor Submission

Type

Cerdelga eliglustat tartrate Capsule;Oral Genzyme Corp Manufacturing

Change or
Addition

Cyramza ramucirumab Injectable;Injection Eli Lilly and Co Efficacy

Supplement
 with Clinical
Data to Support

Levoxyl levothyroxine sodium Tablet;Oral King Pharms R Manufacturing

and D Change or
Addition

Lopid gemfibrozil Capsule;Oral Pfizer Pharms Labeling

Revision

Lopid gemfibrozil Tablet;Oral Pfizer Pharms Labeling

Revision

Olysio simeprevir sodium Capsule;Oral Janssen Prods Efficacy

Supplement
with Clinical
Data to Support

Pennsaid diclofenac sodium Solution;Topical Mallinckrodt Inc Labeling

Revision

Protonix Iv pantoprazole sodium Injectable;Iv Wyeth Pharms Manufacturing

(Infusion) Inc Change or
Addition

Seasonale ethinyl estradiol; Tablet;Oral Teva Branded Manufacturing

levonorgestrel Pharm Change or
Addition

Zithromax azithromycin For Suspension;Oral Pfizer Manufacturing

Change or
Addition

November 4, 2014

Drug Name Active Ingredient Dosage Form/Route Sponsor Submission

Type
Abstral fentanyl citrate Tablet;Sublingual Galena Labeling
Biopharma Revision

Docetaxel docetaxel Injectable;Injection Sandoz Labeling

Revision

Valganciclovir valganciclovir Tablet;Oral Endo Pharms Approval

Hydrochloride hydrochloride Inc

Valganciclovir valganciclovir Tablet;Oral Dr Reddys Labs Approval

Hydrochloride hydrochloride Ltd

November 3, 2014

Drug Name Active Ingredient Dosage Form/Route Sponsor Submission

Type

Furadantin nitrofurantoin Suspension;Oral Shionogi Inc Manufacturing

Change or
Addition

Kyprolis carfilzomib Powder;Intravenous Onyx Pharms Manufacturing

Change or
Addition

Levitra vardenafil hydrochloride Tablet;Oral Bayer Hlthcare Manufacturing

Change or
Addition

Lunesta eszopiclone Tablet;Oral Sunovion Manufacturing

Pharms Inc Change or
Addition

Marqibo Kit vincristine sulfate Injectable, Talon Therap Manufacturing

Liposomal;Intravenous Change or
Addition
Northera droxidopa Capsule;Oral Lundbeck Na Manufacturing
Ltd Change or
Addition

Telmisartan telmisartan Tablet;Oral Sandoz Approval

Important drug interactions with Rifampicin

TABLE 1
Drugs Rifampicin interaction Management

ANTIHYPERTENSIVES
Diuretics
No interactions found Safe option
Thiazides
Spironolactone
Furosemide
Calcium channel Monitor response closely and increase
Rifampicin markedly reduces the levels
blockers dose of calcium channel blocker if
of calcium channel blockers by
Nifedipine Amlodipine needed2
increasing the metabolism of these
Verapamil
drugs in the gastrointestinal wall2

β-Blockers 3 β-blockers that undergo extensive liver

Rifampicin reduces levels
Propranolol of -blockers by enzyme induction.
Carvedilol (↓AUC of carvedilol by about 70%)3
metabolism (e.g. propranolol) would be
expected to be affected by the enzyme
inducing effects of rifampicin
Those -blockers mainly lost unchanged
in the urine (e.g. atenolol) would not be
expected to be affected2,3
Monitor patient response (blood
pressure, signs/symptoms of hepatic
dysfunction) and adjust -blocker
dosage as needed3

ACE inhibitors Two isolated reports of interaction with Monitor for continuing blood pressure
Captopril enalapril, with minor clinical E control after the addition or
Enalapril relevance2 withdrawal of rifampicin, adjusting the
Lisinopril ACE inhibitor dose if needed to regain
control 3

ANALGESICS Increased clearance of paracetamol Clinical importance awaits further

Paracetamol in 2 patients study2
NSAIDS Small study showed decreased May need ↑ dosage of diclofenac,
Diclofenac levels of diclofenac 2 more study needed2 Ibuprofen
Ibuprofen No interaction found with aspirin, and aspirin are safer options
Aspirin ibuprofen

Tramadol No interactions found

Opioids
Morphine Rifampicin reduces opioid levels2,3 Monitor for adequate pain control
Codeine Doses of opioids may need to be
increased and re-evaluated when
rifampicin is discontinued3

ANTIFUNGALS
Itraconazole
Ketoconazole

CONTRACEPTIVES
Oral contraceptives (OC) Very unreliable contraceptive choice
Ethinylestradiol Rifampicin reduces effectiveness by when given with rifampicin
Levonorgestrel enzyme induction and by intestinal Breakthrough bleeding and spotting
Norgestrel flora alteration, which in turn, alters commonly occur and conception and
the enterohepatic circulation of the pregnancy may
drug3 not be prevented2 Should NOT be
administered concomitantly

Progestogen-only
injectable contraceptives
Medroxyprogesterone acetate
Norethisterone enanthate
Rifampicin reduces fectiveness by
enzyme induction 3
Safer alternative — injectable form
Interaction may be overcome by
shortening
the interval between injections to 8
weeks
for medroxyprogesterone acetate and
to
6 weeks for norethisterone enanthate4

TABLE 2

ARV AGENTS
Didanosine (ddI)
Efavirenz (EFV)
No interactions found
Rifampicin reduces EFV Rifampicin can be used with EFV
levels by enzyme induction 3 without dosage modification5

Lamivudine No interactions found

Lopinavir- Rifampicin reduces ritonavir levels by Monitoring of liver function advised

ritonavir enzyme induction3 Adults: add ritonavir 300 mg every 12
(Kaletra) ↑ ALT/AST 2 hours to usual Kaletra dose, while
patient is on
rifampicin and for 1 month after

Nevirapine (NVP) Rifampicin reduces NVP levels by
enzyme induction3
Stavudine No interactions found
Zidovudine Rifampicin increases the clearance
of AZT2,3,7
ANTI-EPILEPTICS
Carbamazepine One case report of increased level
and toxicity of carbamazepine when
isoniazid and rifampicin are given
together, probably by inhibition of
carbamazepine metabolism2,3
Phenytoin Rifampicin markedly reduces
phenytoin serum levels by enzyme
induction2
When rifampicin is used in
combination with isoniazid the
phenytoin clearance is not
increased as much as when
rifampicin is given alone with
phenytoin3
Valproic acid Rifampicin may decrease valproate
levels by increasing clearance3
TABLE 3 Isoniazid (INH) drug interactions
Antacids Absorption of INH is reduced by
concurrent use of aluminium
hydroxide 2,4
Carbamazepine Serum levels of carbamazepine are
completion of TB therapy6
Children: swap from Kaletra to
ritonavir only
Alternative: If over 3 years old and
over 10 kg, switch to efavirenz If under
3 years old or under 10 kg, switch to
ritonavir if appropriate
Dosage alterations may NOT be
necessary with concurrent use, but be
alert for any evidence of a reduced
response to AZT2,3,7
Monitor the patient for signs of
carbamazepine toxicity, including
ataxia, nystagmus, diplopia,
headache, vomiting, apnoea, seizures
and coma3
Monitor phenytoin levels and increase
the dosage appropriately if rifampicin
is started ALONE
Decrease the dosage if rifampicin is
stopped If rifampicin and isoniazid are
given ONCOMITANTLY, the outcome
may depend on the isoniazid
acetylator status of the patient
Fast acetylators will probably also
need an increased phenytoin dosage
Slow acetylators may need a smaller
phenytoin
dosage if toxicity is to be avoided
All patients should be monitored
very closely as the outcome is
unpredictable2
Monitor valproate levels and the
patient for seizure control. An
adjustment in the dosage
may be necessary 3
Give INH at least 1 hour before the
antacid. Although didanosine tablets
contain antacids in the formulation it
has been shown that it is too little to
affect the bioavailability of INH if given
concurrently
Toxicity of carbamazepine can occur if
 markedly and rapidly increased 2,4 dosage is not reduced appropriately.
Concurrent use
should not be undertaken unless the
effects can be closely monitored and
suitable downward
dosage adjustments made

Oral contraceptives One or two cases of failure have The risk of failure appears to be low
been reported 2

Paracetamol Potential toxicity of paracetamol 2 Normal daily analgesic dosages of 4 g

may not be safe. It is prudent to warn
patients to limit
their use of paracetamol because it
seems that some individuals risk
possible paracetamolinduced
liver toxicity, even with normal doses.
More study is needed to clarify the
situation2

Phenytoin ↑ levels of phenytoin with INH alone 2 Slow metabolisers of INH may develop
phenytoin toxicity if the dosage of
phenytoin is not reduced
appropriately. If both rifampicin and
INH are given, serum phenytoin levels
may
fall in patients who are fast acetylators
of INH, but may occasionally rise in
slow acetylators

Theophylline Plasma level of theophylline may be Monitor levels

increased 4

Interactions may be either pharmacokinetic or pharmacodynamic.

PHARMACOKINETIC DRUG-DRUG INTERACTIONS

Pharmacokinetic interactions are divided into those that affect:
• drug absorption
• drug binding
• drug metabolism
• excretion
• transport systems.1,2
The result of pharmacokinetic drug-drug interactions may be an increase or decrease in the concentration of
the drug at the site of action.1,2 The mechanism most relevant to tuberculosis drug interactions is drug
metabolism, which is explained in more detail below.

Drug metabolism interactions

Drugs are metabolised by two types of reactions: phase Iand II reactions that involve oxidation,
reduction or hydrolysis in which drugs are turned into more polar compounds, and phase III reactions that
involve coupling drugs with some other substance (e.g. glucuronic acid) to make (usually) inactive compounds.
These reactions make drugs more easily excretable. Drug metabolism interactions can increase or decrease the
amount of drug available by inhibition or induction of metabolism.1,2
Enzyme induction
Enzyme induction frequently affects phase I oxidation, which requires the presence of the reduced form of
nicotinamide adenine dinucleotide phosphate (NADPH) and the haem-containing protein cytochrome P450.
Enzyme inducers increase the activity of the microsomal enzymes (cytochrome P450 isoenzymes), increasing
the rate of metabolism and excretion. As a result, larger doses of drugs metabolised by these enzymes are
needed.1,2 Enzyme induction interactions are delayed in both starting and stopping, taking from days to up to
3 weeks to develop fully, and may persist for a similar length of time after the inducing drug is stopped. It is
possible to accommodate the interaction by simply raising the dosage of the drug affected, but this requires
good monitoring and there are risks when the inducing drug is stopped without
remembering to reduce the dosage of the previously affected drug. Examples of enzyme-inducing drugs are
barbiturates, carbamazepine, nevirapine, phenytoin, rifampicin and tobacco
smoke.1,2

PHARMACODYNAMIC INTERACTIONS
Pharmacodynamic interactions are those where the effects of one drug are changed by the presence of another
drug at its site of action, without alterations in the concentrations of
either drug. Sometimes one drug competes directly with another for particular receptors, but often the reaction
is more indirect and involves the interference with physiological mechanisms,
making pharmacodynamic interactions more difficult to classify than pharmacokinetic
interactions. There are 4 basic subdivisions:

• additive or synergistic interactions and combined toxicity

• antagonistic or opposing interactions
• interactions due to changes in drug transport mechanisms
• interactions due to disturbances in fluid and electrolyte balance.1,2

Interactions with tuberculosis drugs

First-line agents for the treatment of tuberculosis include rifampicin, isoniazid, ethambutol pyrazinamide and
streptomycin.3,4 This article focuses on the pharmacokinetic drug interactions
with these first-line agents. It is impossible to remember all clinically important drug interactions, but when one
considers the drugs used for the treatment of tuberculosis, the important interactions are almost exclusively
caused by rifampicin. Rifampicin is a potent liver enzyme
inducer that increases the activity of the microsomal enzymes so that the pace of metabolism and excretion of
other drugs metabolised by the same enzyme system is increased.

Table Iand II lists the important drug interactions with rifampicin and Table III the interactions involving
isoniazid, an enzyme inhibitor. Ethambutol and pyrazinamide have few significant drug interactions.
Ethambutol together with pyrazinamide and thiazide diuretics has the potential to elevate serum urate levels.
Pyrazinamide may interact with allopurinol and probenecid as pyrazinamide inhibits the urate clearance.
Dosage adjustments of these agents may be necessary.2-4nWhen using streptomycin one should be aware of
the potential for increased risk of oto- or nephrotoxicity with other ototoxic or nephrotoxic drugs. Streptomycin
(and other aminoglycosides) possess neuromuscular blocking activity. Appropriate measures should be taken to
accommodate the increased neuromuscular blockade and the prolonged and potentially
fatal respiratory depression that can occur with anaesthetics and conventional neuromuscular blocking drugs
of any kind.2,4 Quinolone antibacterials (second-line tuberculosis agent) should generally be avoided in
patients with epilepsy as quinolone antibacterials very occasionally
cause convulsions.2,4

Other interactions to be aware of with quinolones are:

• reduced clearance of theophylline, leading to increased serum levels

• increased anticoagulant effect of warfarin (prothombin time should be monitored)
• concurrent use of sucralfate, antacids containing aluminium, calcium or magnesium, or oral iron, zinc or
magnesium supplements may reduce absorption of the quinolones
• although the mechanism is not fully understood, the serum levels of ciprofloxacin are markedly
reduced if given at the same time as didanosine, probably because of the interaction with the antacid buffers in
the didanosine formulation.

Drug-drug interactions are only one of the many factors that can alter a patient’s response to therapy, but
when unexpected effects are seen, a drug interaction should be suspected.
Taking careful drug histories is important, because patients may be taking over-the-counter drugs or herbal
preparations. Care must be exercised when major changes are made in a drug
regimen and drugs that are not necessary must be discontinued. When an interaction is discovered, it is
possible that the interacting drugs may be used effectively with adjustment of dosage or other therapeutic
modifications.1

Adverse Events of First-line TB

Drugs
Side Effects

Toxicities

SIDE EFFECTS
• Unpleasant reaction
• Not damaging to health
• Does not usually require changes in therapy:
-gas
-bloating
-discoloration of body
fluids
-photosensitivity
-irritability

TB Drug Toxicities

• More severe than side effects

• May be life threatening
• May require changes in dosage or discontinuation of the drug(s)
• May require additional treatment hospitalization

Isoniazid—Side Effects
• GI Intolerance:
-Nausea, abdominal pain common
-Vomiting less common
• Steps to ameliorate:
-Co-administer with food (small snack)
-Pre-medicate with antinausea medications (promethazine, pepcid)
-Reassurance
• Peripheral neuropathy:
-dose-related
-<0.2% of patients will have
-symptoms include burning, tingling, numbness of fingers/toes (usually toes first)
-usually occurs in “stocking glove” distribution
-can be managed by starting/increasing B6 dose •
Rash:
-Mild rash or itching pre-medicate with Benadryl
-Erythematous rash with fever and/or mucous membrane involvmembrane involvement
stop all medications
 rule out anaphylaxis
rule out Steven-Johnson Syndrome
• If rash improves, can restart medications sequentially
• Hepatitis
-10-20% of persons who take isoniazid will develop asymptomatic LFT increase
• Patients can be asymptomatic
• Fatigue, nausea, abdominal pain, vomiting common
• Jaundice

Rifampin—Side Effects
• GI side effects
• Orange urine/body fluids (sweat)
-harmless but may stain contact lenses, clothing
-need to let patients know beforehand
• Hepatitis:
-occurs in about 0.6% of patients with rifampin alone
-Managed similarly to isoniazid
• Flu-like syndrome:
-Fevers, myalgias, arthralgias, headache
• Interstitial nephritis (rare):
-Kidney failure due to hypersensitivity reaction to rifampin
-May be accompanied by rash, fever, eosinophilia in blood

Pyrazinamide—Side Effects
• GI symptoms
• Arthralgias (joint pain)
• Rash
• Hyperuricemia (elevated uric acid)
-usually asymptomatic
-may precipitate gout, kidney stones
-TB medications do not usually require discontinuation

Ethambutol— Side Effects

• Optic neuritis:
-blurred vision
-”spots” in patient’s field of vision
-red/green color blindness
• Dose-related
• Uncommon with intermittent tx
• Drug should be discontinued
• Usually reversible if stopped right away
• Risk increased when used in renal failure

Moxifloxacin side effect

• Nausea/GI side effects

• CNS: headache, insomnia, confusion

• Tendonitis:
-stop exercise, consider NSAIDS
• Tendon rupture
-stop drug
• Not used in children due to concern for joint pain, damage to cartilage
INSTRUCTIONS

1.Avoid spending long periods of time in enclosed spaces with individuals who have active tuberculosis or who
have just begun treatment. Someone who has been undergoing treatment for several weeks should no longer
be contagious.

2.Seek employment that does not put you into direct contact with those who may be suffering from
tuberculosis. Health care settings, jails and homeless shelters are some locations that you would want to avoid
working in.

3.Use face masks, especially if you work with tuberculosis sufferers or come into contact with one regularly.

4.Live, work and visit locations with good ventilation. The NAIAD states that one of the best ways to prevent TB
is adequate ventilation.

5.Vaccinate children in high TB areas. The BCG vaccine is used in some countries to help protect individuals
against active tuberculosis.

6.Have active tuberculosis sufferers follow the appropriate treatment as prescribed by their doctor. Without
treatment, the bacteria can be passed on to those around the ill person.

7.Get tested yourself to find out whether you have contracted tuberculosis, and seek appropriate treatment if
you do or if you've come into contact with someone with active TB.

SUMMARY

Tuerculosis is a bacterial infection that can be fatal.The bodys immune system can usually fight the
infection and confine it successfully.

When the immune system is weak, confined TB bacteria can become active and spread to other parts
of the body.This is active TB.
Thanks to advances in medicine, treatment is available to teat active TB. It is very important for the patient to
follow the prescribed treatment.

TB can be prevented through good hygiene,including good ventilation and covering the mouth when coughing.

A vaccine is available for some infants and recommended for those who live in parts of the world with high
occurance of tuberculosis.

References

1. Global Tuberculosis Control 2011 [http://www.who.int/tb/publications/ global_report/en/index.html]

2. The World Health Report 2004 [http://www.who.int/whr/2004/annex/ topic/en/annex_2_en.pdf]
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