Antimicrobial Dosage Forms

and Its Application

Adisti Dwijayanti, Desak Gede BK

Department of Medical Pharmacy
Infection Immunology Module TA 3013/2014
Faculty of Medicine Universitas Indonesia KURFAK 2005

OUTLINE

Introduction
Dosage forms
Route of administration
Dosing

Steps in Prescribing
Pathophysiology/Pathogenesis

Drug of Choice (Efficacy, Safety, Suitability, Cost)

Mechanism of action, Indication, Contraindication,
side effect, interaction

Route of administration
Dosage form

Dose, frequency, length of therapy,

time of administration

Drug Dosage Form

The

way of identifying the drug in its

physical form
Classification
Physical
Chemical

liquid

solid

semisol
id

Gas

Prescribing errors involving

medication dosage forms
Incident

= 10%
Outcome = fatal 0,7%, serious 12,2%
E.g. order to give IV dose PO

Vancomycin 1 g PO every 12 h

Background

Inadequate drug therapy knowledge

Inadequate consideration of patient
characteristics
Inadequate dose calculations

Lesar TS.J Gen Intern Med. 1002;17:579

solid

semisol
id

liquid

tablet

cream

solution

capsule

ointment

suspensi
on

Powder/
pulveres

gel

injection

supposito
ry

paste

syrup

ovule

drops

gas
aerosol

Dosage
form

Systemic or
Local
effects

Route of
Administrati
on

Routes of Administration
Oral

Parenter
al

Subling
ual

Rectal

Vaginal

Ocular

Nasal

Inhalati
on

Topical

Advantage & Disadvantage

Oral

Injections

Efficacy

Uncertain absorption
First pass
metabolism
Gradual effect

Accurate dosage
possible
No first pass
metabolism
Fast effect

Safety

Low peak values

Gastric irritation

Overdose possible
Sterility may be a
problem

Convenience

Handling
(children, elderly)

Painful
Need trained staff
More costly

WHO. Guide to good prescribing.1995

Routes of Administration,
Bioavailability, and General
Characteristics
Route

Bioavailabilit
y (%)

Characteristics

Intravenous (IV) 100

Most rapid onset

Intramuscular
(IM)

75 to 100

Large volumes often feasible, may be

painful

Subcutaneous
(SC)

75 to 100

Smaller volumes than IM, may be

painful

Oral (PO)

5 to < 100

Most convenient, first-pass effect may

be significant

Rectal (PR)

30 to < 100

Less first-pass effect than oral

Inhalation

5 to < 100

Often very rapid onset

Transdermal

80 to 100

Usually very slow absorption; used for

lack of first-pass effect; prolonged
duration of action

Intravenous route

For critically ill patients

For patients with
bacterial meningitis or
endocarditis
For patients with nausea,
vomiting, gastrectomy,
or diseases that may
impair oral absorption
Antimicrobials that are
poorly absorbed
following oral
administration
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Antimicrobial Dosage
Forms
Antibacterial, Antifungal, Antiviral, Antiparasitic

ANTIBACTERIAL
Inhibition of Cell
Wall Synthesis
Penicillins
Cephalosporin
Bacitracin
Vancomycin

Inhibitors of
Tetrahydrofolate
Synthesis
Sulfonamides
(bacteriostatic)
Trimethoprim
(bacteriostatic)
Co-trimoxazole (bactericidal)
Sulfasalazine

Inhibitors of Protein
Synthesis
Tetracycline
Aminoglycosides
Chloramphenicol
Erythromycin
Clindamycin

Inhibitors of DNA
function
Gyrase inhibitors
Nalidixic acid
Norfloxacin
Ofloxacin
Ciprofloxacin
Lefofloxacin
Nitroimidazole
Metronidazole
Timidazole
Rifampin

Drugs for Treating

Mycobacterial Infections
Isoniazid
Ethambutol
Pyrazinamide
Dapsone

Penicillins
Penicillin G
(Benzyl
penicillin)

Penicillin V
(Phenoxyl
penicillin)

Aminopenicillin

Inactivated by gastric acid (cleaves the beta

lactam ring) parenteral administration
Inj IM 1.200.000 IU/mL; inj IM 2.400.000 IU/mL
Acid resistant
Tab 125 mg; tab 250 mg; tab 500 mg, dry syrup
250 mg/mL
Ampicillin
Acid sensitive
Inj powder IM/IV 250
mg/vial & 500 mg/vial;
Inj powder IV 1 g/vial

Amoxicillin
Acid resistant, Better absorbed than
ampicillin
Drops 125 mg/1,25 mL (Amoxyl ) (10
mL), pipette calibration 125 mg; 62,5
mg
tab 500 mg; tab 250 mg; inj 1g; dry
syrup 125 mg/5 mL

Carboxypenicilli
ns

E.g. Carbenicillin, ticarcillin

Acid sensitive

Acylaminopenici
llins

E.g. Mexclocillin, azlocillin,

piperacillin
Acid sensitive

Cephalosporins

Acid stable but poorly absorbed parenteral

administration
Soluble in water

1st generation

Cefadroxil, cefazolin

2nd generation

Cefuroxime

3rd generation

Cefixime, cefoperazone,
cefotaxime, ceftriaxon

4th generation

Cefepime

 Cephalosporin Dosage Forms

example

Oral

Parenteral

Cefazolin

Inj 500 mg &

1g

Cefadroxil

Tab 500 mg; Caps 500 mg; Dry Syr

125 mg/5 mL & 250 mg/5 mL

Ceftriaxone

Inj 1 g

Cefotaxime

Inj 0,5 g; inj 1

g

Cefixime

Caps 100 mg; Caps 200 mg; Dry syr

100 mg/5 mL

Cefepime
Ceftriaxone

Inj 1 g

Ceftriaxone sodium injection 1 g

For intravenous use, maximum concentration 100 mg/mL
For intramuscular use, maximum concentration 250 mg/mL

Bacitracin

Vancomycin

Only for topical therapy

Not absorbed via GI tract

Oral treatment of bowel inflammations occuring as a
complication of antibiotic therapy (pseudomembranous
enterocolitis caused by Clostridium difficile)

Sulfonamides

Most are well absorbed via the enteral route

Some are poorly absorbed from the gut suitable for the
treatment of bacterial bowel infections

Metronidazole

Well absorbed via enteral route

Also given IV or topically (vaginal insert)

Dosage forms

Tablet :
Syrup :
Ovula :
Infusion:

250, 500 mg
125 mg/5ml
500 mg
500 mg/100 ml

Antituberculosis

Isoniazid (INH) : Tab 100 mg; Tab 300 mg

Rifampicin
: Tab scored 300 mg; Tab 450 mg
Pirazinamide
: Tab 500 mg
Ethambutol
: Tab 250, Tab 500 mg
Combination : FDC

Adult

R/H/Z/E: 150 mg/75 mg/400 mg/275 mg

R/H: 150 mg/150 mg

Pediatric

R/H/Z: 75 mg/50 mg/150 mg

R/H: 75 mg/50 mg

KOMBIPAK

Adult
R/H/Z/E: 450 mg/300 mg/500 mg/ 250 mg &
500 mg
Pediatric
R/H/Z: 75 mg/100 mg/200 mg
R/H: 75 mg/100 mg

Ciprofloxacin

Tab scored 500 mg

Infus 2%

Levofloxacin

Tabl 250 mg; 500 mg

Infusion 500 mg/100 mL; 750 mg/150 mL

Tetracycline

Low solubility
More soluble in hydrochloride
Absorption nearly complete for doxycycline and minocycline
Form insoluble complexes with plurivalent cations (e.g. Ca2+, Mg2+,
Al3+, Fe2+/3+) >< concurrent ingestion of antacids and dairy products
Dosage forms

Tetracyclin: Caps 250 mg; caps 500 mg

Doxycyclin: Caps 100 mg
Oxytetracyclin: Inj IM 50 mg/mL (HCl); inj IM 250 mg/3 mL (HCL)

Chloramphenicol

Completely absorbed after oral ingestion

Good penetration through barriers
Soluble in alcohol, poorly soluble in water
Chloramphenicol succinate, highly water soluble,
used for parenteral administration

Dosage forms

Caps 250 mg; Caps 500 mg; Susp 125 mg/5mL; Inj powder IV 100 mg; Inj
powder IV 1 g

Aminoglycosides

Contain numerous hydroxyl groups and amino groups

that can bind protons highly polar, poorly membrane
permeable, not absorbed enterally
Injection

E.g. Gentamicin, Tobramycin, Amikacin, Netilmicin,

streptomycin

Inhalation e.g. Tobramycin

Dosage forms:

Gentamycin: Inj 10 mg/mL; Inj 40 mg/mL; Inj 80 mg/mL

Streptomycin: Inj powder 1 g/vial

Erythromycin

Poorly soluble in water, usually dispensed as a various esters and salts

as a salt (Erythromycin stearate)
as an ester (Erythromycin succinate)
Erythromycin base is destroyed by stomach acid, must be administered with
enteric coating
Food interferes with absorption
Stearates and esters are fairly acid-resistant better absorbed
Erythromycin estolate best absorbed oral preparation
Dosage forms

Drops (Erythrocine) 100 mg/2,5 mL (30 mL); Dry syrup 200 mg/5mL; Film coated tablet 250 mg, tablet 500 mg,
chewable tablet 200 mg; Caps 250 mg; Caps 500 mg

Derivatives: Azithromycin, clarithromycin better acid stability, better

bioavailability

Clindamycin

Orally, better absorbed than lincomycin

Anti Viral
Acyclovir

Enteral absorption incomplete (15-30%)

Tablet 200 mg; 400 mg
Cream 5% 5g; 10g
Injection 250 mg vial,

Gancyclovir

Injection 500 mg vial

Valacyclovir

Absortion rate >2x acyclovir

oral

Anti Viral

Anti HIV regimens

HAART: 3 antiHIV combination,

at least 2 different
mechanism
Zidovudine
Tab

300 mg

Lamivudine
Tab

150 mg

Nevirapine

Efavirenz

Tab 200 mg
Tab 600 mg

Zidovudine &
Lamivudine
combination

ANTIFUNGAL
Imidazol
e
derivativ
es
Polyene

Poorly absorbed, poorly tolerated systemically

Most for topical uses clotrimazole, isoconazole,
miconazole (Cream 2%)
Ketoconazole is well absorbed (tablet 200 mg, cream,
shampoo)
Trizaole derivates : fluconazole (Caps 50 mg; Caps 150 mg;
Inj 2 mg/mL), itraconazole (Capsule 100 mgl
Poor absorbance infusion
Amphotericin B (Inj IV 50 mg/10 mL)
Nystatin: only for topical therapy (Drops 100.000
IU/mL (12 mL); Susp 100.000 IU/mL (15 mL); vaginal
tablet)

Flucytosin
e

Given orally, rapidly absorbed

Griseofulvi
n

griseofulvin 125 mg; 500 mg,

griseofulvin ultramicronized (330 mg)
micronized (500 mg),

Antiparasitic
Anthelmintics

Praziquantel
tab

Mebendazole
tab

100 mg; tab 500 mg; syrup 100 mg/5mL

Albendazole
tab

scored 300 mg; tab scored 600 mg

200 mg; tab 400 mg

Pyrantel pamoate
tab

scored 125 mg;

tab scored 250 mg; susp 125 mg/5mL
Lindane
Permethrin

ANTIMALARIALS

Quinine-HCl

Chloroquine

Tablet 50 mg
Injection 60 mg/mL ampul 1 mL

Artemether

Syrup 80 mg/5 ml (50 ml)

Artesunate

Injection 250 mg/mL ampul 2 ml

Tab 200 mg; Tab 222 mg; Tab 250 mg

Injection 40 mg/mL; 80 mg/mL ampul 1 mL

Amodiaquine

Tablet 153 (amodiakuin base)

Primaquin

Tab 15 mg

ANTIMALARIALS
Combination

Artemether-Lumefantrine
tablet

Artemeter 20 mg + lumefantrin 120

mg

Sulfadoxine-Pirimethamine
Tablet

sulfadoksin 500 mg + pirimetamin 25

mg

Artesunate- Amodiaquine
Tab

artesunate 50 mg + amodiaquin 200 mg

Prescribing
Pathophysiology/Pathogenesis
Diagnosis, Therapeutic objective
Drug of Choice
Mechanism of action, Indication,
Contraindication, side effect, interaction
Route of administration
Dosage form

Dose, frequency, length of therapy,

time of administration

Antimicrobial Dosing

Patient-specific factors

Age
Weight, particularly for agents
with a low therapeutic index
(e.g. aminoglycosides,
imipenem, flucytosine)
mg/kg/day basis
E.g. UTI uncomplicated low
antimicrobial doses,
pyelonephritis high
antimicrobial doses

Anatomic and Physiologic

Barriers

Penetration into the CNS

higher doses
Vitreous humor, prostate gland

Route of elimination

Site of Infection

Renal: most beta lactams,

aminoglycosides,
vancomycin, acyclovir
Renal & non renal:
ceftriaxone, cefoperazone
Liver: azithromycin,
clindamycin,
metronidazole

Fever

Fever blood flow to

mesenteric, hepatic, and
renal drug clearance

Antimicrobial Dosing
Example(s)

Chloramphenicol
Full-term infants max 50 mg/kgBW/d
Premature infants max 25 mg/kgBW/day
Ampicillin

CrCl > 50 mL/min 1-2 g q4-6h

CrCl 10-50 mL/min 1-1,5 g q6h
CrCl < 10 mL/min 1 g q8-12 h

Amoxicillin
Adult: 3 x 500 mg
Pediatric: 25-50 mg/kgBW/day q8h

Neonates: 10-25 mg/kgBW q8h

Antimicrobial Selection

Organism(s)
Sites of infection
Resistance patterns
Side effects
Cost
Pharmacokinetic properties

Antimicrobials in pregnancy

Definitions of pregnancy
category

Special Population

Antimicrobial Drug
Combinations

To provide broad-spectrum empirical therapy in

seriously ill patients.
To treat poly microbial infections (e.g. intraabdominal abscesses)

The antimicrobial combination chosen should cover the

most common known or suspected pathogens but need not
cover all possible pathogens.

To decrease the emergence of resistant strains. (e.g.

tuberculosis).
To decrease dose-related toxicity by using reduced
doses of one or more components of the drug
regimen.
To obtain enhanced inhibition or killing.

Antimicrobial Drug
Combinations
Example(s)

Antibacterial

Trimethophrim-sulfamethoxazol (Cotrimoxazol)
Tablet TMP 80 mg + SMZ 400 mg (adult)
Tablet TMP 20 mg + SMZ 100 mg
(pediatric)
Forte caplet TMP 160 mg + SMZ 400 mg
Susp TMP 40 mg + SMZ 200 mg per 5
mL
Amoxicillin-Clavulanic Acid

Tablet 250 mg/125 mg

Tablet 500 mg/125 mg
Dry Syrup 125 mg/5 mL (100
mL)
Inj 1 g/vial

Antifungal:

Ointment Benzoic acid

6% + Salicyclic acid 3%

Antifungal +
antibacterial

Nistatin + Metronidazole
Ex. Flagystatin (MTZ
500 mg + Nystatin
100.000 IU) ovula

Antimicrobial Synergism
Three major mechanisms :
1. Blockade of Sequential Steps in a Metabolic
Sequence

2.

Inhibition of Enzymatic Inactivation

3.

Trimethoprim-sulfamethoxazole
Inhibition of -lactamase by -lactamase inhibitor drugs (eg,
sulbactam)

Enhancement of Antimicrobial Agent Uptake

Penicillins and other cell wall-active agents can increase the

uptake of aminoglycosides by a number of bacteria, including
staphylococci, enterococci, streptococci, and P aeruginosa.
amphotericin B enhance the uptake of flucytosine by fungi

Antimicrobial Antagonism
Two major mechanisms
1. Inhibition of Cidal Activity by Static Agents

2.

Bacteriostatic agents such as tetracyclines and

chloramphenicol can antagonize the action of bactericidal
cell wall-active agents because cell wall-active agents
require that the bacteria be actively growing and dividing.

Induction of Enzymatic Inactivation

Some gram-negative bacilli, including enterobacter species, P

aeruginosa, Serratia marcescens, and Citrobacter freundii,
possess inducible - lactamases. Beta-lactam antibiotics such
as imipenem, cefoxitin, and ampicillin are potent inducers of
-lactamase production.

If an inducing agent is combined with an intrinsically active but

hydrolyzable -lactam such as piperacillin, antagonism may result.

Dr. ABCD
SIP No. 123456/Yan-Kes/2000
Jl. Sehat Raya No. 6 Jakarta Timur
Jakarta, 1 Maret
2012

betamethasone
+
dexchlorphenira
mine maleate

Cefixime (Capsule 50; 100 mg,

film-coated tablet 200 mg,
dry syrup 100 mg/5mL)
Triamcinolo
ne

Pro : XYZ
Umur : 3 tahun 3 bulan ; 14 kg

Cefixime Dose:
20 mg/kgBW/day (2 times a
day)

Dr. ABCD
SIP No. 123456/Yan-Kes/2000
Jl. Sehat Raya No. 6 Jakarta Timur
Jakarta, 1 Maret
2012

R/ Cefixime dry syr fl No. I

S 2dd C Orig 1
R/ Ambroxol syr fl No.I
S 3dd C Orig I

Pro : XYZ
Umur : 3 tahun 3 bulan ; 14 kg

1. Tanggal penulisan resep

RESEP LENGKAP
2. Mengisi kolom riwayat alergi obat pada bagian kanan
atas lembar resep manual atau secara elektronik
dalam sistem informasi farmasi untuk memastikan ada
tidaknya riwayat alergi obat
1. Tanda R/ pada setiap sediaan
2. Untuk nama obat tunggal ditulis dengan nama generik.
Untuk obat kombinasi ditulis sesuai nama dalam
Formularium, dilengkapi dengan bentuk sediaan obat
(contoh: injeksi, tablet, kapsul, salep), serta
kekuatannya (contoh: 500 mg, 1 gram)
3. Jumlah sediaan
4. Bila obat berupa racikan dituliskan nama setiap
jenis/bahan obat dan jumlah bahan obat (untuk bahan
padat: mikrogram, miligram, gram) dan untuk cairan:
tetes, milliliter, liter.
5. Pencampuran beberapa obat jadi dalam satu sediaan
tidak dianjurkan, kecuali sediaan dalam bentuk
campuran tersebut telah terbukti aman dan efektif.
6. Aturan pakai (frekuensi, dosis, rute pemberian). Untuk
aturan pakai jika perlu atau prn atau pro re nata, harus
dituliskan
dosis maksimal
1.
Nama lengkap
pasiendalam sehari.
2. Nomor rekam medik
3. Tanggal lahir atau umur
pasien (jika tidak dapat
mengingat tanggal lahir)
4. Berat badan pasien (untuk
pasien anak)
5. Nama dokter

Novianti Y. Medication management and use. RSCM. 20

 References

Katzung. Basic and Clinical Pharmacology 10 th edition. 2006.

Lullmann. Color Atlas of Pharmacology. Thieme. 2000.
WHO. Guide to good prescribing. 2005
Guglielmo BJ (ed). Infectious disorders. In: Applied
Therapeutics: The Clinical Use of Drugs 9 th ed. Lippincott
Williams & Wilkins. USA. 2009
Departemen Kesehatan RI. Daftar Obat Esensial Nasional 2008.
Purwaningsih et al. Buku Panduan Praktikum Ilmu Farmasi
Kedokteran Edisi Revisi. UI-Press. 2008
Cleveland clinic. Guidelines for Antimicrobial Usage 20112012. Professional Communications, Inc. 2012
Kementerian Kesehatan RI. KepMenkes No.
89/MENKES/SK/II/2013 tentang Formularium program jaminan
kesehatan masyarakat. Jakarta: Kementerian Kesehatan RI.
2011.

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