Rifampicin

Indications: Tuberculosis
MIMS CLASS: Anti-TB Agents
Dosage: Adult : PO 8-12 mg/kg/day. <50 kg: 450 mg/day; ≥50 kg: 600 mg/day. IV 10 mg/kg once daily,
via infusion. Max: 600 mg/day.Dosage Details:

Dosage Details:
Intravenous
Tuberculosis
Adult: 10 mg/kg once daily, via infusion. Max: 600 mg daily.
Child: Same as adult dose.
Oral
Tuberculosis
Adult: 8-12 mg/kg once daily. <50 kg: 450 mg daily; ≥50 kg: 600 mg daily.
Child: 10-20 mg/kg daily. Max: 600 mg/day.

Administration: Should be taken on an empty stomach. Best taken on an empty stomach 1 hr before or
2 hr after meals.

Reconstitution: Add 10 mL of sterile water for inj to the vial labelled as containing 600 mg to provide a
60 mg/mL soln. Further dilute in appropriate vol of a compatible soln (e.g. 100 mL of dextrose 5%)
immediately before admin.

Contraindications: Hypersensitivity to rifampicin or other rifamycins. Patient w/ jaundice. Concurrent

use w/ saquinavir/ritonavir therapy.

Special Precautions: Patient w/ history of alcoholism. Hepatic and renal impairment. Elderly,
malnourished patients, childn <2 yr. Pregnancy and lactation.

Adverse Drug Reaction: Facial flushing and itching, w/ or w/o a rash, flu-like syndrome characterised by
episodes of fever, chills, headache, dizziness, bone pain, shortness of breath, and malaise; GI adverse
effects (e.g. nausea, vomiting, anorexia, diarrhoea, epigastric distress), pseudomembranous colitis,
eosinophilia, leucopenia, haemolytic anaemia; alterations in kidney function and renal failure, menstrual
disturbances, oedema, myopathy, muscular weakness; orange-red discolouration of the urine, faeces,
sweat, saliva, sputum, tears, and other body fluids; thrombophlebitis, local irritation and inflammation
after prolonged IV infusion. Rarely, eye irritation and visual disturbances, anaphylaxis or shock.
Potentially Fatal: Hepatotoxicity, hypotension, sinus tachycardia, ventricular arrhythmias, seizures and
cardiac arrest, thrombocytopenia and purpura.

Mechanism of Action:
Description: Rifampicin suppresses initiation of chain formation for RNA synthesis in susceptible bacteria
by binding to the β subunit of DNA-dependent RNA polymerase, thus blocking RNA transcription.
Duration: ≤24 hr.
Pharmacokinetics:
Absorption: Readily absorbed from the GI tract. May be reduced or delayed by food. Time to peak
plasma concentration: 2-4 hr (oral).
Distribution: Widely distributed in body tissues and fluids including CSF. Crosses the placenta and enters
breast milk. Plasma protein binding: Approx 80%.
Metabolism: Undergoes hepatic metabolism to active 25-O-desacetylrifampicin via deacetylation.
Excretion: Via faeces (approx 60%) and urine (up to 30% of a dose, approx half of it as unchanged drug).
Plasma half-life: 2-5 hr.
 Isoniazid
Indications: Tuberculosis
MIMS Class: Anti-TB Agents
Dosage: Adult : PO/IM 5 mg/kg up to 300 mg/day as a single dose or 15 mg/kg up to 900
mg/day, 2 or 3 times wkly. Dosage Details: Intramuscular Tuberculosis Adult: 5 mg/kg up to 300
mg daily as a single dose or 15 mg/kg up to 900 mg/day, 2 or 3 times wkly. Child: 10-15 mg/kg
up to 300 mg daily as a single dose or 20-40 mg/kg up to 900 mg/day, 2 or 3 times wkly.
Renal Impairment: Severe: Dose reduction may be needed. Administration: Should be taken on
an empty stomach. Best taken on an empty stomach 1 hr before or 2 hr after meals. May be
taken w/ meals to reduce GI discomfort.
Contraindications: Hypersensitivity. Patient w/ acute liver disease or a history of isoniazid-
associated hepatic injury.
Special Precautions: Patient w/ convulsive disorders, history of psychosis. Patient at risk of
neuropathy (e.g. diabetics, alcoholics, malnourished, uraemic, infected w/ HIV) or pyridoxine
deficiency. Hepatic and severe renal impairment. Pregnancy and lactation. Oral Tuberculosis
Adult: 5 mg/kg up to 300 mg daily as a single dose or 15 mg/kg up to 900 mg/day, 2 or 3 times
wkly. Child: 10-15 mg/kg up to 300 mg daily as a single dose or 20-40 mg/kg up to 900 mg/day,
2 or 3 times wkly.
Adverse Drug Reaction: Peripheral neuritis, psychotic reactions, convulsions, optic neuritis,
transient increases in liver enzymes; haematological effects (e.g. anaemias, agranulocytosis,
thrombocytopenia, eosinophilia); hypersensitivity reactions include skin eruptions (including
erythema multiforme), fever, vasculitis; nausea, vomiting, dry mouth, constipation, pellagra,
purpura, hyperglycaemia, lupus-like syndrome, vertigo, hyperreflexia, urinary retention,
gynaecomastia. Potentially Fatal: Hepatitis.
Mechanism of Action: Description: Isoniazid inhibits the synthesis of mycoloic acids in
susceptible bacteria which results in loss of acid-fastness and disruption of bacterial cell wall. At
therapeutic levels, it is bacteriocidal against actively growing intracellular and extracellular
Mycobacterium tuberculosis organisms.
Pharmacokinetics:
Absorption: Readily absorbed from the GI tract and after IM inj. Rate and extent of absorption
is reduced by food. Time to peak plasma concentration: After 1-2 hr (oral).
Distribution: Distributed into all body tissues and fluids including CSF. Crosses the placenta and
enters breast milk.
Metabolism: Undergoes acetylation of isoniazid to acetylisoniazid by N-acetyltransferase found
in the liver and small intestine, which is then hydrolysed to isonicotinic acid and
monoacetylhydrazine; isonicotinic acid is conjugated w/ glycine to isonicotinyl glycine
(isonicotinuric acid) and monoacetylhydrazine is further acetylated to diacetylhydrazine.
Excretion: Via urine (>75%, mainly as metabolites) and faeces (small amounts). Plasma half-life:
Approx 1-6 hr.
 Ethambutol
Indications: Tuberculosis
MIMS Class: Anti-TB Agents
Dosage: Adult : PO In combination with other antituberculars: For prophylaxis and primary
treatment: 15 mg/kg/day. For re-treatment: 25 mg/kg/day for 60 days; then, 15 mg/kg/day. For
more information, consult product literature.

Dosage Details:

Oral
Tuberculosis
Adult: In combination with other antituberculars (e.g. isoniazid, pyrazinamide, rifampicin): For
prophylaxis and primary treatment: 15 mg/kg once daily. For re-treatment: 25 mg/kg once daily
for 60 days; then, 15 mg/kg once daily. Recommended Max dose: 1.6 g daily (regardless of
weight). For more information (e.g. alternative regimens), consult product literature.
Child: In combination with other antituberculars (e.g. isoniazid, pyrazinamide, rifampicin): For
prophylaxis: 15 mg/kg once daily. For primary treatment and re-treatment: 25 mg/kg once daily
for 60 days; then, 15 mg/kg once daily. For more information (e.g. alternative regimens),
consult product literature.

Renal Impairment: Reduce dose based on serum-ethambutol levels. Alternatively, for patients
with CrCl <30 mL/min, 15 mg/kg 3 times weekly or 15-25 mg/kg (depending on serum-
ethambutol levels), to a Max of 2.5 g 3 times weekly.

Administration: Should be taken before food

Contraindications: Hypersensitivity. Optic and retrobulbar neuritis. Inability to report visual
disturbances (e.g. unconscious).

Special Precautions: Patient with ocular disease (e.g. ocular inflammatory conditions, cataracts,
diabetic retinopathy). Renal impairment. Children. Pregnancy and lactation.

Adverse Drug Reaction:

Significant: Optic neuritis, visual disturbances (e.g. colour blindness and irreversible blindness).
Blood and lymphatic system disorders: Thrombocytopenia, eosinophilia, leucopenia,
neutropenia.
Gastrointestinal disorders: Nausea, vomiting, abdominal pain, gastrointestinal upset.
General disorders and administration site conditions: Malaise, fever.
Hepatobiliary disorders: Jaundice.
Immune system disorders: Hypersensitivity reactions, erythema multiforme.
Investigations: Hyperuricaemia.
Metabolism and nutrition disorders: Anorexia.
Musculoskeletal and connective tissue disorders: Acute gout.
Nervous system disorders: Headache, dizziness, peripheral neuropathy.
Psychiatric disorders: Confusion, disorientation, hallucinations.
Respiratory, thoracic and mediastinal disorders: Pulmonary infiltrates.
Skin and subcutaneous tissue disorders: Dermatitis, erythema multiforme, pruritus.
Potentially Fatal: Hepatotoxicity.

Mechanism of Action:
Description: Ethambutol, an antimycobacterial, is bacteriostatic against susceptible bacteria. It
appears to inhibit synthesis of bacterial metabolites thereby, inhibiting cellular metabolism and
multiplication.
Pharmacokinetics:
Absorption: Absorbed from the gastrointestinal tract. Time to peak plasma concentration:
Within 4 hours.
Distribution: Distributed to most tissues, including kidneys, lungs, and erythrocytes. Crosses the
placenta and enters breastmilk. Plasma protein binding: 20-30%.
Metabolism: Partially metabolised in the liver into inactive aldehyde and dicarboxylic acid
derivatives.
Excretion: Mainly via urine (approx 50% as unchanged drug and 8-15% as metabolites); faeces
(approx 20% as unchanged drug). Elimination half-life: Approx 2.5-3.6 hours.
 Pyrazinamide
Indications: Tuberculosis
MIMS Class: Anti-TB Agents
Adult : PO As part of a mulitdrug regimen: <50 kg: 1.5 g daily or 2 g 3 times wkly; ≥50
kg: 2 g daily or 2.5 g 3 times wkly.
Dosage Details:
Oral
Tuberculosis
Adult: As part of a mulitdrug regimen: For standard unsupervised 2-mth treatment: <50 kg: 1.5
g daily; ≥50 kg: 2 g daily. For intermittent supervised 2-mth treatment: <50 kg: 2 g 3 times wkly;
≥50 kg: 2.5 g 3 times wkly.
Child: As part of a mulitdrug regimen: For standard unsupervised 2-mth treatment: 35 mg/kg
daily. For intermittent supervised 2-mth treatment: 50 mg/kg 3 times wkly.

Administration: Should be taken with food.

Contraindications: Hypersensitivity. Hyperuricaemia and/or gouty arthritis, acute porphyria.

Severe hepatic impairment.

Special Precautions: Patient w/ DM, history of gout. Mild to moderate hepatic and renal
impairment. Pregnancy and lactation.

Adverse Drug Reaction: Hyperuricaemia, leading to acute gout; anorexia, nausea, vomiting,
aggravation of peptic ulcer, arthralgia, malaise, fever, sideroblastic anaemia,
thrombocytopenia, dysuria. Rarely, photosensitivity, pellagra, rash.
Potentially Fatal: Hepatotoxicity.

Mechanism of Action:
Description: Pyrazinamide may be bacteriostatic or bactericidal in action, depending on the
concentration of the drug attained at the site of the infection and the susceptibility of the
infecting organism. Its activity appears to partly depend on conversion of the drug to pyrazinoic
acid (POA), which lowers the pH of the environment below that which is necessary for growth
of Mycobacterium tuberculosis. Susceptible strains of M. tuberculosis produce pyrazinamidase,
an enzyme that deaminates pyrazinamide to POA, and the in vitro susceptibility of a given strain
of the organism appears to correspond to its pyrazinamidase activity.
Pharmacokinetics:
Absorption: Readily absorbed from the GI tract. Time to peak plasma concentration: Approx 2
hr.
Distribution: Widely distributed in body fluids and tissues, diffuses in the CSF and enters breast
milk. Plasma protein binding: 50%.
Metabolism: Undergoes hepatic metabolism via hydrolysis to pyrazinoic acid (major active
metabolite) and subsequently hydroxylated to 5-hydroxypyrazinoic acid (major excretory
product).
Excretion: Via urine by glomerular filtration (approx 70% mainly as metabolites, approx 4% as
unchanged drug). Half-life: Approx 9-10 hr.
 Generic Name: PHENYTOIN
Brand Name: DILANTIN

Indications

- Parenteral DILANTIN is indicated for the treatment of generalized tonic-clonic status

epilepticus, and prevention and treatment of seizures occurring during neurosurgery.
Intravenous DILANTIN can also be substituted, as short-term use, for oral phenytoin.
Parenteral DILANTIN should be used only when oral DILANTIN administration is not
possible
- All forms of epilepsy except absence seizures.
- Trigeminal neuralgia if carbamazepine inappropriate.

Contraindications

DILANTIN is contraindicated in patients with:

- A history of hypersensitivity to phenytoin, its inactive ingredients, or other hydantoins
- Sinus bradycardia, sino-atrial block, second and third degree A-V block, and Adams-
Stokes syndrome because of the effect of parenteral phenytoin on ventricular
automaticity.
- A history of prior acute hepatotoxicity attributable to phenytoin
- Coadministration with delavirdine because of the potential for loss of virologic response
and possible resistance to delavirdine or to the class of non-nucleoside reverse
transcriptase inhibitors.

Nursing Responsibility

- On the basis of single dose tests there are no clinically relevant differences in
bioavailability between available phenytoin sodium tablets and capsules but there may
be a pharmacokinetic basis for maintaining the same brand of phenytoin in some
patients.
- Doses should be adjusted carefully, starting with low doses and increasing gradually
until seizures are controlled or there are overdose effects.
- Leukopenia that is severe, progressive or associated with clinical symptoms requires
withdrawal.
- Side-effects such as acne or hirsutism may be particularly undesirable in adolescent
patients.
- Monitoring plasma concentration greatly assists adjustment. A few missed doses or a
small change in absorption may result in a marked change in plasma concentration.
Small dosage increases in some patients may produce large rises in plasma
concentrations with acute toxic side-effects.
- Ataxia, slurred speech, nystagmus and blurred vision are signs of overdose.
- Avoid sudden withdrawal.
 Generic Name: CARBAMAZEPINE
Brand Name: TEGRETOL

Indication

Epilepsy
- Tegretol is indicated for use as an anticonvulsant drug. Evidence supporting efficacy of
Tegretol as an anticonvulsant was derived from active drug-controlled studies that
enrolled patients with the following seizure types:
- Partial seizures with complex symptomatology (psychomotor, temporal lobe). Patients
with these seizures appear to show greater improvement than those with other types.
- Generalized tonic-clonic seizures (grand mal).
- Mixed seizure patterns which include the above, or other partial or generalized seizures.
Absence seizures (petit mal) do not appear to be controlled by Tegretol (see
PRECAUTIONS, General).

Trigeminal Neuralgia
- Tegretol is indicated in the treatment of the pain associated with true trigeminal
neuralgia.
- Beneficial results have also been reported in glossopharyngeal neuralgia.
- This drug is not a simple analgesic and should not be used for the relief of trivial aches
or pains.

Contraindications

Tegretol should not be used in patients with a history of previous bone marrow depression,
hypersensitivity to the drug, or known sensitivity to any of the tricyclic compounds, such as
amitriptyline, desipramine, imipramine, protriptyline, nortriptyline, etc. Likewise, on theoretical
grounds its use with monoamine oxidase (MAO) inhibitors is not recommended. Before
administration of Tegretol, MAO inhibitors should be discontinued for a minimum of 14 days, or
longer if the clinical situation permits.

Coadministration of carbamazepine and nefazodone may result in insufficient plasma

concentrations of nefazodone and its active metabolite to achieve a therapeutic effect.
Coadministration of carbamazepine with nefazodone is contraindicated.

Nursing Responsibility

- Observe for confusion and agitation in older people.

- Observe for changes in mental state.
- Observe for allergic reactions such as rashes, purpura. - Leucopenia which is severe,
progressive or associated with clinical symptoms requires withdrawal.
 Generic Name: RIFAMPIN
Brand Name: RIFADIN

Indications

- Tuberculosis
- Staphylococcal infections
- Meningococcal Infection prophylaxis
- H influenza prophylaxis (off-label)
- Cholestasis - pruritus

Contraindications

RIFADIN is contraindicated in patients with a history of hypersensitivity to rifampin or any of the

components, or to any of the rifamycins.

Rifampin is contraindicated in patients who are also receiving ritonavir-boosted saquinavir due to an
increased risk of severe hepatocellular toxicity.

Rifampin is 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.

Rifampin is contraindicated in patients receiving praziquantel since therapeutically effective blood levels
of praziquantel may not be achieved. In patients receiving rifampin who need immediate treatment with
praziquantel alternative agents should be considered. However, if treatment with praziquantel is
necessary, rifampin should be discontinued 4 weeks before administration of praziquantel. Treatment
with rifampin can then be restarted one day after completion of praziquantel treatment.

- Hypersensitivity to rifampinobstructive biliary disease

- meningococcal disease
- intermittent rifampin therapy
- lactation.
- Safe use during pregnancy (category C) or in children <5 y is not established.

Nursing Responsibility

Assessment & Drug Effects

 Lab tests: Periodic liver function tests are advised. Closely monitor patients with hepatic
disease.
 Check prothrombin time daily or as necessary to establish and maintain required
anticoagulant activity when patient is also receiving an anticoagulant.