TREATMENT OF T.B.

1. DRUG NAME: RIFAMPIN
STATUS OF DRUG:
1)(WHO) ESSENTIAL DRUG LIST: ( Exist)
2)NATIONAL ESSENTIAL DRUG LIST: (Exist)
PRODUCTDESCRIPTIONS:
SR
N
O
BRANDS MANUFACTURER
S
DOSAGEFORM &
DESIGN
PACK SIZE PRICE/UNIT
IN RUPEES
1 Rifinah(300)mg
1)INH=75mg
2)RMP=150mg
Pacific
pharmaceutica
l
Tablets(300)Mg (3×10)=30 Rs:257
2 Myrin(600)mg
1)EMB=300 mg
2)INH=75mg
3)RMP=150mg
Wyeth
pharmaceutical
Pak(ltd).
Tablets(600)mg (8×10)=80 Rs:629
3 Rimactal Novartis
pharma(pak)ltd
1)Capsule(300m
g)
2)Tablet(450mg)
3)Syrup( 20mg/ml)
(4×10)=40
(10×3)=30
60 ml
Rs:243
Rs:282
Rs:70
4 Rifatol
1)RMP=150mg
2)INH=75mg
3)EMB=300mg
SChazoo zaka
Pharmaceutical
Pvt).
Tablet
(600)mg
10×10) Rs:786
5 MYRIN-P( FORT)
1)EMB=275mg
2)RMP=150mg
3)INH=75mg
4)PZA=400mg
Wyeth
pharmac eutical
Pak(ltd).
Tablet (10×8)=80 Rs:875
STORAGE: 1) store at temperature not exceeding 25°c in an
atmosphere of nitrogen in air tight container. 2) Protect from light.

2. CHEMISTRY OF THE PRODUCT
CHEMICAL CLASS CHEMICAL STRUCTURE PHYSICAL PROPERTIES
4-methyl-1-
piperazinaminylgroup,
1)Rifampicinis a reddish
brown crystalline powder
2)slightly solubleinwater
,alcohol and in acetone and
soluble inmethyl alcohol.
CHEMICAL PROPERTIES
1)Melting point:(183–188) °C
2)1%SUSPENSION PH=4.5-6.5
3) Molecular mass: 822.94 g/mol
Formula: C43H58N4O12
PHARMACOKINETICS :
A)ABSORPTION:
Orally administeredrifampicinresults inpeak plasmaconcentrations inabout (
2 -4) hours.Rifampicinis easily absorbedfromthe gastrointestinal tract;its ester
functional group is quickly hydrolyzed in the bile, and it is catalyzedby a high
pH and substrate-specific enzymes calledesterases. After about six hours,
almost all of the drug is deacetylated. Eveninthis deacetylatedform, rifampinis
still apotent antibiotic;however, it canno longer be reabsorbedby the
intestines andit is subsequently eliminatedfromthe body. . Whenrifampicinis
takenwith a meal, peak blood concentrationfalls by 36%.

3. B)DISTRIBUTION:
Distributionof the drug is high throughout the body, and reaches effective
concentrations inmany organs and body fluids, including the CSF . Since the
substance itself is red, this highdistributionis the reasonfor the orange-red
color of the saliva, tears, sweat, urine, andfeces.
C)ELIMINATION:
Only about( 4-20)% of the administereddrug will be excretedunchanged
throughthe urine, though urinary eliminationaccounts for only about 20% of
the drug excretion.Rifampin is excretedmainly throughliver intobile,then
undergoes enterohepatic recirculationwiththe bulk excretedas adeacylated
metabolite infeces About 60% to85%.
BIOAVAILABILITY %PROTEIN
BINDING
PLACENTAL
BARRIER
BBB SECRETION
IN MILK
VOLUME OF
DISTRIBUTION
TIME
OF
ONSET
OF
ACTION
THERAPEUTIC
SERUM LEVEL
90 – 95)%
80 -90)%
rifampin
has been
reportedto
cross the
placental
barrier and
appear in
cord blood,
The
combination
of isoniazid
and
rifampicin
for 1 year,
with
appropriate
management
increasesthe
intracranial
pressure.
RIFAMPIN
excreted
during
lactation,
relatively
safe in the
minimal
quantities
,nursing
infants
ingest
through
breast milk.
Rifampin
may harm a
nursing
baby.
The apparent
volume of
distribution
is1.6 L/Kg in
adults and
1.1L/Kg in
children.
(2-3)h
Rifampicin
therapeutic
levels( 7-10)
Microgram/ml
are attained
after 2-3
hours.

4. Eliminationhalf
life
Site of metabolism Active metabolites Route of excretion
Elimination half
life increases with
increasing doses
and amounts to
2.5h,3.5h,and
about 5h after
single doses of
300mg,600mg
and900mg
respectively.
Rifampin is
metabolized in the
liver.
principal active
metabolite is
deacetylrifampicin
Rifampicin
metabolite
deacetylrifampicin is
excreted in the bile
and also in the urine.
Approximately 50% of
the rifampicin dose is
eliminated within 24
hours and (6 to 30)%
of the drug is
excreted unchanged
in the urine, while
15% is excreted as
active metabolite.
Approximately( 43-
60)% of oral dose is
excreted in the
faeces.
CLINICAL PHARMACOLOGY
1)THERAPEUTICCLASS: Antituberculosis
2)PHARMACOLOGICALCLASS: rifampinis a bactericidal
antibioticdrug of the rifamycin group. It is a semisynthetic
compound derived from Amycolatopsis mediterranei and
Streptomyces mediterranei).
3)MECHANISM OF ACTION: RifampininhibitsDNA-
dependentRNA polymerase activity in susceptible
Mycobacterium tuberculosis organisms. Specifically,it interacts
with bacterialRNA polymerase but does not inhibitthe
mammalianenzyme.

5. 4)SPECTRUM: ( broad spectrum bactericidal)
the most susceptible bacteria are:
1) Aerobic Gram-Negative Microorganisms
Neisseria meningitidis
Mycobacterium tuberculosis
2)Aerobic Gram-Positive Microorganisms
Staphylococcus aureus (including Methicillin-Resistant S. aureus/MRSA)
Staphylococcus epidermidis
3)Aerobic Gram-Negative Microorganisms
Haemophilus influenzae
4)“Other” Microorganisms
Mycobacterium leprae
5)INDICATIONS:
Rifampicin is typically used to treat Mycobacterium infections,
including tuberculosis and Hansen's disease (Leprosy). Rifampicin is
used in the treatment of methicillin-resistant Staphylococcus aureus
(MRSA) in combination with fusidic acid , including in difficult to treat
infections such as osteomyelitis and prosthetic joint infections.It is

6. also used in prophylactic therapy against Neisseria meningitidis
(meningococcal) infection.
It is also used to treat infection by Listeria species, Neisseria
gonorrhoeae, Haemophilus influenzae and Legionella pneumophila
6A)CONTRAINDICATION :
Rifampinis contraindicated in patients who are also receiving
ritonavir-boosted saquinavir due to an increased risk of severe
hepatocellular toxicity.
Rifampinis contraindicated in patients who are also receiving
atazanavir, darunavir, fosamprenavir,saquinavir, or tipranavir
due to the potential of rifampin to substantially decrease
plasma concentrations of these antiviral drugs, which may
result in loss of antiviral efficacy and/or development of viral
resistance.
6B)PRECAUTIONS:
Rifampin is not recommended for intermittent therapy; the
patient should be cautioned against intentional or accidental
interruption of the daily dosage regimen since rare renal
hypersensitivity reactions have been reported when therapy
was resumed in such cases.
Rifampinhas enzyme induction properties that can enhance
the metabolism of endogenous substrates including adrenal
hormones, thyroid hormones, and vitamin D.

7. 7)POSSIBLE SIDE EFFECTS:
Headache,drowsiness,dizziness,numbness,thrombocytopenia,
Eosinophilia,leukopenia,hemolyticanemia,epigastric distress,
Nausea,vomiting,anorexia,skin allergy.
8) ADVERSE REACTIONS:
A)Hepatic
Transient abnormalities inliver functiontests (e.g., elevations inserum
bilirubin, BSP, alkaline phosphatase, serumtransaminases) have beenobserved.
B)Hematologic
 Rare reports of disseminatedintravascular coagulationhave been
observed.
C)Central Nervous System :Psychoses have beenrarely reported.
D)Endocrine Rare reports of adrenal insufficiency inpatients with
compromisedadrenal functionhave beenobserved.
E)Renal Acute tubular necrosis
F)Hypersensitivity Reactions; Erythemamultiforme including Stevens-
Johnson Syndrome, toxic epidermal necrolysis,vasculitis. Anaphylaxis has been
reportedrarely.
G)Gastrointestinal : Pancreatitis
H)Hypersensitivity Reactions:( Stevens-Johnson syndrome)

8. Dosage and administration:
Sr
no
indications Route of
administration
Neonates/infants
mg/kg/day
frequency
Child
mg/kg/day
frequency
Adult
mg/kg/day
Duration
of
therapy
1 Rifampicin is
recommended
during the
initial initial
intensive
phaseof short
course
Treatment of
tuberculosis
which usually
lasts two
months on a
daily basis.
Rifampicin
and INH for
initial
intensive
phase.
Oralroute 5mg/kg daily in
two divided
doses.
60 ml syrup
(20mg/ml)
10mg/kg
Daily in
two
divided
doses.
600mg-
1200mg
daily in
two
divided
doses.
6-8
months
therapy
With
RMP+INH
+PZA
AND
EMB)
Administrationguidelines:
A)for oral route:
To ensure optimum absorption of oral rifampicinshould
preferably be taken on an empty stomach,at least ½ h before a
meal.syrup should be well shaken before use.
B)For I/V Route:

9. PREPARATIONof Solution for IV Infusion :
Reconstitute the lyophilizedpowder by transferring 10 mL of
sterile water for injection to a vialcontaining600 mg of
rifampin for injection.Swirl vial gently to completely dissolve
the antibiotic.The reconstituted solutioncontains60 mg
rifampin per mL and is stable at room temperature for 24
hours. Prior to administration,withdraw from the reconstituted
solutiona volume equivalentto the amount of rifampin
calculatedto be administered and add to 500 mL of infusion
medium. Mixwell and infuse at a rate allowingfor complete
infusion within 3 hours. Alternatively,the amount of rifampin
calculatedto be administered may be addedto 100 mL of
infusion medium and infused in 30 minutes.
STABILITY:
Dilutionsin dextrose 5% for injection(D5W) are stable at room
temperature for up to 4 hours and should be prepared and
used within this time. Precipitationof rifampin from the
infusion solutionmay occur beyond this time. Dilutionsin
normal saline are stable at room temperature for up to 24
hours and should be prepared and used within this time. Other
infusion solutionsare not recommended.

10. FOOD-DRUG INTERACTION: Food delays and
reduces the absorption of rifampicin from the gut:
Clinical evidence:The absorptionof a single 10-mg/kg dose of rifampicin
was reducedwhen it was givento 6 healthy subjects withastandard Indian
breakfast (125 g wheat, 10 g visible fat, 350 g vegetables). The AUC after 8 hours
was reducedby 26% and the peak plasma levels were prolonged(from
11.84 micrograms/mL at 2 hours to 8.35 micrograms/mL at 4 hours) and
reducedby about 30%.1 Inanother study, a high-fat breakfast reduced
the maximum serumlevel of rifampicin600 mg by 36% and delayedthe
absorption, but the AUC was not significantly altered.
Mechanism: Not understood.
Importance and management:Rifampicinshouldbe takenon an
empty stomach (at least 30 minutes before ameal, or 2 hours after a meal) to
ensure rapid and complete absorption.

11. DRUG-DRUG INTERACTIONS;
interactions Significance
level
outcome Mecha-
nism
Recomme-
ndation
ACE-inhibitors
(enalapril)
+Rifampin
Onset=rapid
Severity=moderate
Documentation=possi
ble
Phamacologi
cal effects of
enalapril
may
decrease.
unknow
n
Consider
monitoring of
B.P in patients
that are
receiving
combination
therapy.if B.P
increases
alternative
antihypertensiv
e therapy is
recommended.
Aminophylline+
rifampin
Onset=delay
Severity=moderate
Document=established
Phamacologica
l levels of
aminophylline
may decrease
with increase
exacerbation of
pulmonary
symptoms.
Increased
hepatic
metabolis
m via
enzyme
induction
of
rifampin.
Addition or
deletion of
rifampin
therapy.
Beta
blockers(propranolol)
+rifampin
Onset=delay
Severity=moderate
Document=probable
Beta blocker
effects may be
reduced via
rifampin.
Increased
hepatic
metabolis
m from
enzyme
induction
via
rifampin.
Consider
monitoring of
B.P in patients
that are
receiving
combination
therapy.if B.P
increases
alternative
antihypertensiv
e therapy is
recommended.
BARBITURATES(
phenobarbitol,pentobarbital,
Amobarbitol,Butabarbitol)+
rifampin
Onset=delay
Severity=minim
Document=possible
May result in
increase rate of
metabolism of
barbiturates and
reduce its
pharmacological
actions.
Rifampin
may
stimulate
microsomal
enzyme and
increase
degradatio
n of
barbiturate.
Barbiturate
plasma level is
monitored and
dosage mey
need to
increase.

12. interaction Significant level outcome mechanism recomendation
Contraceptives+
rifampin
Onset= delay
Severity=moderate
Document=established
May decrease
oral
contraceptive
efficacy and
also may
increase
incidences’ of
menstrual
abnormalities.
Rifampin
induces
hepatic
microsomal
enzymes that
may result in
more rapid
elimination of
estrogenic and
progestational
components of
oral
contraceptives.
Advise patient to
use an additional
form of
contraceptive in
rifampin
therapy.
Quinine
derivatives+rifampin
Onset=delay
Severity=moderate
Document=establish
May increase
metabolism of
quinine
derivatives
that may be
associated in
reduction in
therapeutic
effects.
Rifampin is
potent inducer
of hepatic
microsomal
enzymes that
may increase
the hepatic
clearance of
quinine
derivatives.
Advise patient
to increase
dosage of
quinine
derivaties to
maintain
therapeutic
effects.
Drug/Laboratory Interactions
1)Cross-reactivity and false-positive urine screening tests for
opiateshave been reported in patientsreceiving rifampin when
using the KIMS (Kinetic Interaction of Microparticlesin
Solution)method (e.g., Abuscreen On Line opiates assay; Roche
Diagnostic Systems). Confirmatory tests, such as gas
chromatography/ mass spectrometry, will distinguish rifampin
from opiates.
2)Therapeutic levelsof rifampin have been shown to inhibit
standard microbiologicalassays for serum folate and vitamin
B12. Thus, alternate assay methods shouldbe considered.

13. Transient abnormalitiesin liver function tests (e.g., elevationin
serum bilirubin,alkalinephosphatase,and serum
transaminases) and reduced biliaryexcretion of contrast media
used for visualization ofthe gallbladderhave also been
observed. Therefore, these tests should be performed before
the morning dose of rifampin.
Rifampin in pregnancy:
FDA pregnancy category C. This medication may be harmful to
an unborn baby. Rifampinhas beenshown to be teratogenic inrodents
givenoral doses of rifampin 15 to 25 times the human dose. Althoughrifampin
has beenreportedtocross the placental barrier andappear in cord blood, the
effect of rifampin, alone or in combinationwithother antituberculosis drugs on
the human fetus is not known. Neonates of rifampin-treatedmothersshouldbe
carefully observedfor any evidence of adverse effects. Isolatedcases of fetal
malformations have been reported;however, there are noadequate and well-
controlledstudiesinpregnant women. Rifampinshould be usedduring
pregnancy only if the potential benefit justifies the potential risk tothe fetus.
Pregnancy-Non-Teratogenic Effects:
When administeredduring the last fewweeks of pregnancy, rifampincan cause
post-natal hemorrhages inthe mother and infant for which treatment with
vitaminK may be indicated.
Nursing Mothers: Because of the potential for tumorigenicity shown
for rifampinin animal studies, adecisionshouldbe made whether to
discontinue nursing or discontinue the drug, taking intoaccount the importance
of the drug to the mother.

14. Toxicology: (OVERDOSAGE)
Signs and Symptoms: Nausea, vomiting, abdominal pain,
pruritus, headache and increasing lethargy will probably occur within
a short time after ingestion; unconsciousness may occur when there is
severe hepatic disease. Transient increases in liver enzymes and/or
bilirubin may occur. Brownish-red or orange discoloration of the skin,
urine, sweat, saliva, tears and feces will occur, and its intensity is
proportional to the amount ingested.Liver enlargement, possibly with
tenderness, can develop within a few hours after severe overdosage;
bilirubin levels may increase and jaundice may develop rapidly. A
direct effect upon the hematopoietic system, electrolyte levels, or
acid-base balance is unlikely. Hypotension, sinus tachycardia,
ventricular arrhythmias, seizures and cardiac arrest were reported in
some fatal cases.
Acute Toxicity: The LD50 of rifampin is approximately 885 mg/kg in the
mouse, and 2120 mg/kg in the rabbit.The minimum acute lethal or toxic dose is
not well established. However, nonfatal acute overdoses inadults have been
reportedwithdoses ranging from9 to 12 gm rifampin. Fatal acute overdoses in
adults have beenreportedwithdoses ranging from14- 16gm.
Treatment:The airway should be secured and adequate respiratory
exchange established. Since nausea and vomiting are likely to be
present, gastric lavage within the first 2 to 3 hours after ingestion is
probably preferable to induction of emesis. Following evacuation of the
gastric contents, the instillation of activated charcoal slurry into the
stomach may help absorb any remaining drug from the gastrointestinal
tract. Antiemetic medication may be required to control severe nausea
and vomiting.

15. REFRENCES:
1)Basic and clinical pharmacology by katzung(11th
edition)
2) http:/www.medincell.com
2) drugs interactions facts via Davis.Tatro(4th
edition)
3) http:/www.medincell.com
4) Pharmacology (Lippincott's Illustrated Reviews
Series)[Richard A. Harvey PhD,
Michelle A Clark PhD, Richard Finkel PharmD.
5) www.fda.gov/Food/default.htm .
6) www.pharmaguideindia.com/.