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Anti-infective Agents 277
11.1.3 Miconazole
Brand Names: Candistat cream, Daktarin gel, Decanazole cream, Dermizole cream, Fungitop
gel
Miconazole is an imidazole derivative having antifungal activity. It is a broad-spectrum azole
antifungal with some activity against Gram-positive bacteria as well. It is widely used to treat
mucosal yeast infections, including both oral and vaginal infections. It primarily acts through the
inhibition of fungal CYP450 14α-lanosterol demethylase activity. The structural formula of
miconazole is:
Nomenclature: 1-[2-(2, 4-dichlorophenyl)–2-[(2,4-dichlorophenyl) methoxy] ethyl] imidazole
Properties: It occurs as white to pale cream, crystalline or microcrystalline, odorless or almost
odorless powder with melting point 170.5°C. It is practically insoluble in water; freely soluble in
acetone; and soluble in alcohol, chloroform, ether, isopropyl alcohol, methyl alcohol, and
propylene glycol.
Pharmacological Uses: Miconazole is generally used to treat mucosal yeast infections, involving
both oral and vaginal infections. Externally, it is used for the treatment of ringworm including
jock itch and athlete’s foot. Internally, it is used for oral or vaginal thrush (yeast infection). The
oral gel may also be used for the lip disorder, angular cheilitis and other associated systems.
It may be given by mouth for the treatment of oral and intestinal candidiasis.
Topical miconazole is used to treat:
➢ Tinea corporis (ringworm; fungal skin infection that causes a red scaly rash on different
parts of the body).
➢ Tinea cruris (jock itch; fungal infection of the skin in the groin or buttocks)
➢ Tinea pedis (athlete’s foot; fungal infection of the skin on the feet and between the toes).
Different Types of Formulations: Topical miconazole comes as a spray, spray powder, cream,
powder, and tincture to apply to the skin, although intravenous miconazole is no longer available.
Different types of formulations of the myconazole are available as follows:
➢ Oral treatment (brand names – Daktarin and Fungimin Oral Gel):
• Oral gel 24 mg/mL (20 mg/g)
• Oravig 50 mg once daily buccal tablet
278 Text Book of Pharmaceutical Chemistry
➢ External skin treatment (brand name – Daktarin):
• Dusting powder: 2% powder with chlorhexidine hydrochloride (myco dust)
• Topical cream: 2-5%
➢ Vaginal treatment (brand names – Miconazex, Monistat, Femizol or Gyno-daktarin):
• Vaginal cream: 2% (7-day treatment), 4% (3-day treatment)
• Topical cream: 2-5%
• Dusting powder: 2% powder with chlorhexidine hydrochloride (myco dust)
• Pessaries: 200 or 100 mg
Storage: It should be stored at room temperature between 20°C to 25°C. Protect the tablets from
moisture. Miconazole vaginal suppositories should be store at 15°C to 30°C.
Marketed Preparations: Miconazole, Neomycin and Fluocinolone Cream – Trio Lifescience
Pvt. Ltd.
11.1.4 Ketoconazole
Brand Names: Nizoral, Extina, Ketodan, Ketoderm
Ketoconazole is an imidazole derivative used to treat seborrheic dermatitis and fungal skin
infections. It is a racemic mixture of two enantiomers, i.e., levo ketoconazole and dextro
ketoconazole. The structural formula of ketoconazole is given below:
Chemical Structure: Ketoconazole is cis-1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2-(1H-imidazol-
1-ylmethyl)-1,3-dioxolan-4-yl]methoxyl] phenyl] piperazine
Properties: Ketoconazole is a white to slightly beige, odorless crystalline powder with melting
point 146.0°C. It is practically insoluble in water and soluble in acids, with a molecular weight of
531.44.
Pharmacological Uses:
➢ Ketoconazole has a very broad spectrum of activity against various fungal species that is
used for the treatment of superficial and systemic fungal infections.
➢ It is applied to the skin for infections such as athlete’s foot, jock itch, ringworm, and
certain kinds of dandruff.
Anti-infective Agents 279
➢ This drug is also used for the treatment of pityriasis (tinea versicolor), seborrheic
dermatitis and cutaneous candidiasis.
➢ It is used in the treatment and prevention of fungal infections including blastomycosis,
candidiasis, coccidioidomycosis, histoplasmosis, chromomycosis and para
coccidioidomycosis.
Dosages of Ketoconazole: Ketoconazole Cream 2%:
➢ 15 gram NDC 0168-0099-15
➢ 30 gram NDC 0168-0099-30
➢ 60 gram NDC 0168-0099-60
Storage: It should be stored at a temperature between 20°C and 25°C. Protect this drug from
light. It should not be stored in moist or damp areas, such as bathrooms. Its topical cream should
be stored at a temperature less than 25°C and should not be frozen. Ketoconazole 2% shampoo
should be stored at temperatures not exceeding 25°C and should be protected from light.
11.1.5 Itraconazole
Brand Names: Sporanox, Tolsura
It is a member of triazoles, a dioxolane, an N-arylpiperazine, a dichlorobenzene, a cyclic
ketal, a conazole antifungal drug, a triazole antifungal drug and aromatic ether. Itraconazole
molecule has three chiral carbons. The two chiral centers in the dioxolane ring are fixed in
relation to one another, and the triazolo methylene and aryloxy methylene dioxolane-ring
substituents are always cis to each other.
Chemical Structure: 2-butan-2-yl-4-[4-[4-[4-[[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-
1-ylmethyl)-1,3-dioxolan-4-yl] methoxy]phenyl]piperazin-1-yl] phenyl]-1,2,4-triazol-3-one
Properties: It occurs as crystalline solid. It is practically insoluble in water and dilutes acidic
solutions. Melting point is 166.2°C. Itraconazole is extensively metabolized by the liver into a
large number of metabolite like hydroxyitraconazole.
Uses:
➢ Itraconazole is used for the treatment of various fungal infections in immune
compromised and non-immunocompromised patients.
➢ It is used in pulmonary and extra pulmonary blastomycosis, histoplasmosis, and
onychomycosis.
280 Text Book of Pharmaceutical Chemistry
➢ Oral Solution of itraconazole is only used to treat oropharyngeal or esophageal
candidiasis (thrush and oral thrush).
➢ Itraconazole capsule is used to treat fungal infections, such as aspergillosis (fungal
infection in the lungs), blastomycosis (Gilchrist’s disease), histoplasmosis (Darling’s
disease) or onychomycosis (fungal infection in the fingernails or toenails).
Storage: Itraconazole should be stored in a cool, dry and dark place. It should be protected from
direct sunlight. Capsules should be stored at room temperature 15°C to 25°C. The capsules should
be stored away from light and moisture. Itraconazole oral solution and injection should be stored
at 25°C or lower, and should not be frozen. The injection should be protected from light during
storage, but may be exposed to normal room light during administration.
Dosage Forms and Strengths:
➢ Capsule: 65 mg (Tolsura); 100 mg (Sporanox, generic)
➢ Oral solution: 10 mg/mL (Sporanox, generic)
➢ Tablet: 200 mg (Onmel)
Marketed Preparations:
Drug
Brand Name
Company
Itraconazole
Fungibond-200 Capsules
S.S. Pharma
Itraconazole Capsules 100 mg
Itrazax-100
Zoydec Pharmaceuticals Pvt. Ltd.
Itraconazole cap
Conitro 200
Highsky Medicare Pvt. Ltd.
11.1.6 Fluconazole
Brand Names: Azithral-XP, Diflucan
Fluconazole is a synthetic triazole with antifungal activity. It can chemically be represented
as 2,4-difluoro-α,α1-bis(1H-1,2,4-triazol-1-ylmethyl) benzyl alcohol with an empirical formula of
C
13
H
12
F
2
N
6
O and molecular weight of 306.3. The structural formula is:
IUPAC Name: 2-(2,4-difluorophenyl)-1,3-bis(1,2,4-triazol-1-yl)propan-2-ol
Properties: Fluconazole occurs as a white crystalline solid with boiling point 579.8 and melting
point 138°C to 140°C. It is poorly soluble in water but can be dissolved in organic solvents such
as chloroform, propylene glycol, and poly ethoxylated castor oil.
Anti-infective Agents 281
Uses:
➢ Fluconazole is used in the treatment of systemic and superficial fungal infections.
➢ It is used to treat vaginal yeast infections due to Candida.
➢ It is sometimes used to treat serious fungal infections that begin in the lungs and can
spread through the body and fungal infections of the eye, skin and nails.
➢ It is used to prevent fungal infections in people who are likely to become infected
because they have human immunodeficiency virus (HIV) or cancer or have had a
transplant operation (surgery to remove an organ and replace it with a donor or artificial
organ).
➢ It is also effective for the treatment of Candida urinary tract infections, peritonitis, and
systemic Candida infections including candidemia, disseminated candidiasis, and
pneumonia.
➢ It is also indicated to decrease the incidence of candidiasis in patients undergoing bone
marrow transplantation who receive cytotoxic chemotherapy and/or radiation therapy.
Dosage Forms:
➢ Intravenous solution (200 mg/100 ml-0.9%; 400 mg/200 ml-0.9%)
➢ Oral powder for reconstitution (10 mg/mL; 40 mg/mL)
➢ Oral table (100 mg; 150 mg; 200 mg; 50 mg)
Storage: Fluconazole tablets and powder for oral suspension should be stored in tight containers
at a temperature less than 30°C. Store reconstituted suspension between 86°F (30°C) and 41°F
(5°C) and discard unused portion after 2 weeks. Protect from freezing.
Marketed Preparations
Drug
Brand Name
Company
Fluconazole 150 Mg Tablet,
Avezole-150
Jasco Labs Pvt. Ltd.
Fluconazole 400 mg Tablets
F-Bert-400
Hilbert Healthcare
Fluconazole Gel 0.5% w/w
Flukin
MDC Pharmaceuticals Limited
11.1.7 Naftifine Hydrochloride
Brand Name: Naftin
Naftifine is a tertiary amine in which the nitrogen is substituted by methyl, alpha-naphthyl
methyl, and (1E)-cinnamyl groups. It is used as its hydrochloride salt for the treatment of fungal
skin infections. Naftifine hydrochloride can be fungicidal as well as fungistatic to yeasts
depending on the concentration and the organisms involved. The structural formula of Naftifine
hydrochloride is:
282 Text Book of Pharmaceutical Chemistry
IUPAC Name: (E)-N-methyl-N-(naphthalen-1-ylmethyl)-3-phenylprop-2-en-1-amine
Properties: It occurs as a clear to yellow gel for topical use only. It is soluble in ethanol. Its
melting point is 172°C to 175°C.
Uses:
➢ Naftifine is used as antibiotic drugs, antifungal agents with broad spectrum and strong
effect.
➢ It is used for the treatment of dermatophyte infection, superficial moniliasis,
onychomycosis and skin, and its accessories (hair finger, fingernail and toe) by achorion,
microspore and Epidermis Trichophyton.
➢ It is indicated for erasing mycosis of the lower breast as well as erasing mycosis between
finger (toes), the buttocks, and the groin.
➢ Naftin gel, 1%, is used for the topical treatment of tinea pedis, tinea cruris, and tinea
corporis caused by the organisms Trichophyton rubrum, Trichophyton mentagrophytes,
Trichophyton tonsurans1, Epidermophyton floccosum.
Dosage Forms and Strengths: Gel, 2%. Each gram contains 20 mg of naftifine hydrochloride in
a colorless to yellow gel.
Storage: Naftifine cream store at 25°C; excursions permitted to 15°C to 30°C. Keep in dark
place, inert atmosphere, 2°C to 8°C.
Marketed Preparations:
Drug
Brand Name
Company
Naftifine hydrochloride gel 2%
Naftin
Amneal Pharmaceuticals
Naftifine Cream
Naftin
Merz Pharmaceuticals Limited
11.2 URINARY TRACT ANTI-INFECTIVE AGENTS
A urinary tract infection (UTI) is an infection in any part of urinary system and involves
kidneys, urethra, ureters and bladder. Most infections involve the lower urinary tract – the bladder
and the urethra. Most of the UTIs are caused by bacteria. However, several are caused by fungi
and in atypical cases by viruses. UTIs are among the most common infections in humans.
Anti-infective Agents 283
Symptoms of UTIs:
The symptoms of a lower UTI involves burning feeling with urination, frequent urination
without passing much urine, bloody urine, Feeling tired, urine has a strong odors, fever or chills,
pain or pressure in your back or lower abdomen.
Types of UTIs:
An infection can occur in different parts of urinary tract. There are different types of UTI
based on where it is:
➢ Urethritis (urethra): Infection of the urethra
➢ Cystitis (bladder): Infection of the bladder
➢ Pyelonephritis (kidneys): Infection of the kidneys
➢ Vaginitis: Infection of the vagina.
11.2.1 Norfloxacin
Brand Names: Noroxin, Chibroxin
Norfloxacin is a synthetic, broad-spectrum antibacterial agent for oral administration. It is a
quinoline monocarboxylic acid, N-arylpiperazine, a quinolone antibiotic and a fluoroquinolone
antibiotic. Fluorine atom at position 6 increases potency against gram-negative organisms, and the
piperazine moiety at the position 7 are responsible for anti-pseudomonal activity. The structural
formula of Norfloxacin is:
IUPAC Name: 1-ethyl-6-fluoro-4-oxo-7-piperazin-1-ylquinoline-3-carboxylic acid
Properties: Norfloxacin occurs as a white to pale yellow crystalline powder with a melting point
of about 221°C. It is freely soluble in glacial acetic acid, and very slightly soluble in ethanol,
methanol and water.
Uses: Norfloxacin is used in the treatment of urinary tract infection, cystitis, urethral and cervical
gonorrhoea, syphilis, prostatitis due to Escherichia coli, traveler’s diarrhea, shigellosis,
salmonella gastroenteritis, salmonella enteric fever, prostatitis, bladder infection, campylobacter
gastroenteritis, epididymitis, non-specific, gonococcal infection, uncomplicated, kidney
infections. It has been shown to be active against most strains of the following microorganisms.
➢ Gram-positive aerobes: Enterococcus faecalis, Staphylococcus aureus, Staphylococcus
epidermidis, Staphylococcus saprophyticus, Streptococcus agalactiae.
➢ Gram-negative aerobes: Citrobacter freundii, Enterobacter aerogenes, Enterobacter
cloacae, Escherichia coli, Klebsiella pneumoniae, Neisseria gonorrhoeae, Proteus
mirabilis, Proteus vulgaris, Pseudomonas aeruginosa, Serratia marcescens.
284 Text Book of Pharmaceutical Chemistry
Mechanism of Action: Norfloxacin functions by inhibiting DNA gyrase, a type II topoisomerase,
and topoisomerase IV, which are required for bacterial DNA replication, transcription, repair, and
recombination. It is broad-spectrum antibiotic that is active against both Gram-positive and
Gram-negative bacteria.
Dosage Form: Noroxin is available in Oral Tablets, film-coated: 400 mg Noroxin. Each tablet
contains the following inactive ingredients: cellulose, croscarmellose sodium, hydroxypropyl
cellulose, hydroxypropyl methylcellulose, iron oxide, magnesium stearate, and titanium dioxide.
Storage: Norfloxacin tablets should be stored below 30°C, between temperature 15°C to 30°C, in
a tightly closed container.
11.2.2 Ciprofloxacin
Brand Names: Etraxal, Ciloxan, Cipro, Cipro HC, Ciprodex, Ciprofloxacin, Otiprio, Otixal,
Otovel, Proquin
Ciprofloxacin is a second generation broad-spectrum fluoroquinolone antibiotic, more active
against Gram-negative bacteria than Gram-positive bacteria. It is a quinolone that is quinolin-
4(1H)-one bearing cyclopropyl, carboxylic acid, fluoro and piperazin-1-yl substituents at
positions 1, 3, 6 and 7, respectively. The structural formula of Ciprofloxacin is:
IUPAC Name: 1-cyclopropyl-6-fluoro-4-oxo-7-piperazin-1-ylquinoline-3-carboxylic acid
Properties: It is faint to light yellow crystalline powder with melting point 255°C to 257°C. It is
soluble in water, soluble in hydrochloric acid and practically insoluble in ethanol.
Uses:
➢ It is used for the treatment and prevention of urinary tract infections, lower respiratory
tract infections, and skin infections.
➢ It is widely used in the therapy of mild-to-moderate urinary and respiratory tract
infections caused by susceptible organisms.
➢ It is used in adults for the treatment of bone and joint infections, including osteomyelitis.
Storage: Ciprofloxacin hydrochloride ophthalmic solution and ophthalmic ointment should be
stored in tight, light-resistant containers at 2-25°C. Its hydrochloride and hydrocortisone otic
suspension should be stored in light-resistant containers below 25°C. Freezing should be avoided.
Ciprofloxacin hydrochloride tablets should be stored in tight containers at a temperature <30°C.
Anti-infective Agents 285
11.2.3 Ofloxacin
Brand Names: Floxin, Floxin IV
Ofloxacin is synthetic fluoroquinolone antibacterial agent, used to treat bacterial infections of
the skin, lungs, prostate, or urinary tract (bladder and kidneys). It is an oxazinoquinolone carrying
carboxy, fluoro, methyl and 4-methylpiperazino substituents. The structural formula of Ofloxacin:
IUPAC Name: (±)-9-fluoro-2, 3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido
[1,2,3-de]-1,4-benzoxazine-6-carboxylic acid
Properties: Ofloxacin occurs as off-white to pale yellow crystalline powder; colorless needles
from ethanol. It is sparingly to slightly soluble in aqueous solutions with pH 7 (solubility falls to 4
mg/mL) and freely soluble in aqueous solutions with pH above 9.
Uses:
➢ Ofloxacin is used to treat infections like pneumonia, infections of the skin, bladder,
reproductive organs, and prostate (a male reproductive gland).
➢ It is also used to treat other types of infections, bronchitis, including legionnaires’ disease
(type of lung infection).
➢ It is used in certain sexually transmitted diseases, and infections of the bones and joints
and of the stomach and intestines.
➢ It is used in the treatment of acute pelvic inflammatory disease (PID).
➢ It is used in adults for the treatment of non-gonococcal urethritis and cervicitis caused by
Chlamydia trachomatis.
➢ It is used in adults for the treatment of uncomplicated urinary tract infections (UTIs)
(cystitis).
Dosage Forms: Oral tablet (200 mg, 300 mg and 400 mg)
Storage: It should be stored in tight, light-resistant container as defined in the USP-NF. Its
ophthalmic solution and otic solution should be stored at 15-30°C.
11.2.4 Moxifloxacin
Brand Names: Avalox, Avelon, Avelox, Bacterol, Izilox, Megaxin, Moxif, Vigamox.
Moxifloxacin is a broad-spectrum fluoroquinolone antibiotic that consists of 4-oxo-1,4-
dihydroquinoline-3-carboxylic acid bearing a cyclopropyl substituent at position 1, a fluoro
substituent at position 6, a-octahydro-6H-pyrrolo, pyridin-6-yl group at position 7 and a methoxy
substituent at position 8.
286 Text Book of Pharmaceutical Chemistry
IUPAC Name: 7-[(4aS,7aS)-1,2,3,4,4a,5,7,7a-octahydropyrrolo[3,4-b]pyridin-6-yl]-1-cyclopropyl-
6-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid; hydrochloride
Properties: Moxifloxacin is almost white to yellowish crystalline powder. It is soluble in water
(2.4 g/100 ml), methanol and DMSO. Its melting point is 324°C to 325°C.
Mechanism of Action: Moxifloxacin is active against both Gram-positive and Gram-negative
bacteria. It functions by inhibiting DNA gyrase, a type II topoisomerase, and topoisomerase IV,
enzymes necessary to separate bacterial DNA, resulting in inhibition of DNA replication, and
repair and cell death in sensitive bacterial species.
Uses:
➢ Moxifloxacin is used for the treatment of number of infections, including respiratory tract
infection, cellulites, anthrax, intra-abdominal infections, endocarditis, meningitis and
tuberculosis.
➢ It is used for the treatment of acute bacterial sinusitis caused by susceptible Streptococcus
pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis.
➢ It is used for the treatment of uncomplicated skin and skin structure infections caused by
susceptible S. aureus or Streptococcus pyogenes.
➢ It is used for the treatment of complicated skin and skin structure infections caused by
susceptible S. aureus, E. coli and K. pneumonia.
Dosage Forms:
➢ Intravenous solution (400 mg/250 ml);
➢ Oral tablet (400 mg)
Storage: It should be stored at 25°C in tight, light-resistant container as defined in the USP-NF.
This material should be handled and stored per label instructions to ensure product integrity.
11.3 ANTI-TUBERCULAR AGENTS
Tuberculosis (TB) is an infectious disease that usually affects the lungs. It can also spread to
other parts of the body. The bacteria called Mycobacterium tuberculosis and M. bovis are the main
causative agents of tuberculosis. The bacteria primarily attack the lungs, but they can also damage
other parts of the body such as the kidney, spine, and brain. Tuberculosis is mainly an airborne
infection, which spreads from one person to other through the air. When someone with
tuberculosis coughs, spit, speak, or sneeze, tiny droplets containing the bacteria are released and
infect the healthy person.