Dermosav Plus

Dermosav Plus Uses, Dosage, Side Effects, Food Interaction and all others data.

Ciprofloxacin is a synthetic 4-quinolone derivative with bactericidal activity against a wide range of gram-positive and gram-negative organism. It is active against most gram-negative aerobic bacteria including Enterobacteriaceae and Pseudomonas aeruginosa. Ciprofloxacin is also active against gram-positive aerobic bacteria including penicillinase producing, non-penicillinase producing and methicillin resistant Staphylococci. However many strains of Streptococci are relatively resistant to the drug. The bactericidal activity of Ciprofloxacin results from interference with the enzyme DNA gyrase needed for the synthesis of bacterial DNA. The mode of action of Ciprofloxacin is different from other antibiotics like penicillins, cephalosporins, aminoglycosides, tetracyclines and for this reason it is observed that organisms resistant to these antibiotics are susceptible to Ciprofloxacin. Ciprofloxacin is well absorbed from the GIT after oral administration and it is widely distributed into the body tissues and fluid. The half-life of Ciprofloxacin is 3.5 - 4.5 hours. About 30-50% of an oral dose of Ciprofloxacin is excreted in the urine within 24 hours as unchanged drug and active metabolites.

Ciprofloxacin (Eye/Ear) drops (Ciprofloxacin Hydrochloride ophthalmic solution) is a synthetic, sterile, multiple dose, antimicrobial for topical use. Ciprofloxacin is a fluoroquinolone antibacterial active against a broad spectrum of gram positive and gram-negative ocular pathogens. It is available as the monohydrochloride monohydrate salt of 1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)- 3-quinoline-carboxylic acid. It is a faint to light yellow crystalline powder with a molecular weight of 385.8. Its empirical formula is C17H18FN3O3.HCl.H2O.

Ciprofloxacin is a second generation fluoroquinolone that is active against many Gram negative and Gram positive bacteria. It produces its action through inhibition of bacterial DNA gyrase and topoisomerase IV. Ciprofloxacin binds to bacterial DNA gyrase with 100 times the affinity of mammalian DNA gyrase. There is no cross resistance between fluoroquinolones and other classes of antibiotics, so it may be of clinical value when other antibiotics are no longer effective. Ciprofloxain and its derivatives are also being investigated for its action against malaria, cancers, and AIDS.

Clobetasol Propionate Cream is a multiple combination cream which exhibits anti-bacterial, anti-protozoal, anti-fungal and steroid properties to control inflammation. Ofloxacin is a broad-spectrum antibiotic that acts against many gram-positive and gram-negative bacteria. Ornidazole belongs

to the nitroimidazole group of antibiotics and is used to treat amoeba and trichomonas infections. Terbinafine is a topical antifungal and antiparasitic drug. Clobetasol is a potent corticosteroid which exhibits anti-inflammatory, anti-pruritic and vasoconstrictive properties.

Corticosteroids bind to the glucocorticoid receptor, inhibiting pro-inflammatory signals, and promoting anti-inflammatory signals. Clobetasol propionate is generally applied twice daily so the duration of action is long. Corticosteroids have a wide therapeutic window as patients may require doses that are multiples of what the body naturally produces. Patients taking corticosteroids should be counselled regarding the risk of hypothalamic-pituitary-adrenal axis suppression and increased susceptibility to infections.

Metronidazole, a nitroimidazole has an extremely broad spectrum antiprotozoal and antimicrobial activities, with high activity against anaerobic bacteria and protozoa. Metronidazole is usually completely and rapidly absorbed after oral administration. The half-life in plasma is about 8 hours. About 10% of the drug is bound to plasma proteins. Metronidazole penetrates well into body tissues and fluids. The liver is the main site of metabolism. Both unchanged Metronidazole and metabolites are excreted in various proportions in the urine after oral administration.

Metronidazole treats amebiasis, trichomoniasis, and giardiasis, exerting both antibacterial and antiprotozoal activities. Metronidazole is an effective treatment for some anaerobic bacterial infections. Metronidazole has shown antibacterial activity against the majority of obligate anaerobes, however, during in vitro studies, it does not demonstrate significant action against facultative anaerobes or obligate aerobes. The nitro group reduction of metronidazole by anaerobic organisms is likely responsible for the drug's antimicrobial cytotoxic effects, causing DNA strand damage to microbes.

A note on convulsions and neuropathy and carcinogenesis

It is important to be aware of the risk of peripheral neuropathy and convulsions associated with metronidazole, especially at higher doses. If convulsions or numbness of an extremity occur, discontinue the drug immediately. Metronidazole has been found to be carcinogenic in mice and rats. The relevance to this effect in humans is unknown. It is advisable to only administer metronidazole when clinically necessary and only for its approved indications.

Terbinafine is an allylamine with a range of antifungal activity. It is fungicidal against dermatophytes, moulds and certain dimorphic fungi. Terbinafine is either fungicidal or fungistatic against yeasts, depending on the species. Terbinafine interferes with fungal ergosterol biosynthesis by inhibiting squalene epoxidase in the fungal cell membrane at an early stage. This leads to a deficiency in ergosterol and to intracellular accumulation of squalene, resulting in fungal cell death. Terbinafine is highly effective in fungal infections of the skin, hair and nails caused by Trichophyton spp., Microsporum spp. and Epidermophyton floccosum. It is also effective against yeast infections of the skin, principally those caused by the genus candida. Topical terbinafine appears to be effective in pityriasis versicolor due to Pityrosporum arbiculare.

Terbinafine is an allylamine antifungal that inhibits squalene epoxidase (also known as squalene monooxygenase) to prevent the formation of ergosterol and cause an accumulation of squalene, weakening the cell wall of fungal cells. Terbinafine distributes into tissues and has a long terminal elimination half life, so the duration of action is long. Overdose with terbinafine is rare, even above the therapeutic dose, so the therapeutic index is wide. Patients taking oral terbinafine should have liver function tests performed prior to treatment to reduce the risk of liver injury.

Dermosav Plus
Uses
Dosage
Side Effect
Precautions
Interactions
Uses during Pregnancy
Uses during Breastfeeding
Accute Overdose
Food Interaction
Half Life
Volume of Distribution
Clearance
Interaction With other Medicine
Contradiction
Storage

Trade Name	Dermosav Plus
Generic	Ciprofloxacin + Clobetasol Propionate + Metronidazole + Terbinafine
Weight	1%w/w
Type	Cream
Therapeutic Class
Manufacturer	Bennet Mypher Pharmaceuticals Llp
Available Country	India
Last Updated:	September 19, 2023 at 7:00 am

Uses

Ciprofloxacin is used for the treatment of the following infections caused by sensitive bacteria:

Severe systemic infections: e.g; septicemia, bacteremia, peritonitis, infections in immunosuppressed patients with haematological or solid tumors and in patients in intensive care unit with specific problems such as infected burns.

Respiratory tract infections: Lobar and broncho pneumonia, acute and chronic bronchitis and empyema.

Urinary tract infections: Uncomplicated and complicated urethritis, cystitis, pyelonephritis, prostatitis and epididymitis.

Skin and soft tissue infections: Infected ulcers, wound infections, abscesses, cellulitis, otitis externa, erysipelas and infected burns.

Gastrointestinal infections: Enteric fever, infective diarrhea.

Infections of the biliary tract: Cholangitis, cholecystitis, empyema of the gall bladder.

Intra-abdominal infections: Peritonitis, intra abdominal abscesses.

Bone and joint infections: Osteomyelitis, septic arthritis.

Pelvic infections: Salpingitis, endometritis, pelvic inflammatory diseases.

Eye, ear, nose and throat infections: Otitis media, sinusitis, mastoiditis, tonsillitis.

Gonorrhoea: Urethral, rectal and pharyngeal gonorrhoea caused by beta-lactamase producing organism or organisms moderately sensitive to penicillin.

Ciprofloxacin (Eye/Ear) Solution is used for the treatment of infections caused by susceptible strains of the designated microorganisms in the conditions listed below:

Eye

Corneal Ulcers:

• Pseudomonas aeruginosa

• Serratia marcescens

• Staphylococcus aureus

• Staphylococcus epidermidis

• Streptococcus pneumonia

• Streptococcus (Viridans Group)

Conjunctivitis:

• Haemophilus influenza

• Staphylococcus aureus

• Staphylococcus epidermidis

• Streptococcus pneumoniae

Ear

Otitis externa, acute otitis media, cronic suppurative otitis media. Prophylaxis in otic surgeries such as mastoid surgery.

Clobetasol Propionate is used for:

Initial control of all forms of hyperacute eczema in all age groups
Chronic hyperkeratotic eczema of the hands and feet and patches of chronic lichen simplex
Chronic hyperkeratotic psoriasis of any area of the body
Severe acute photosensitivity
Hypertrophic lichen planus
Localized bullous disorders
Keloid scarring
Pretibial myxoedema
Vitiligo
Suppression of reaction after cryotherapy
Scalp Solution is used for the topical therapy of recalcitrant corticosteroid-responsive dermatoses of the scalp, including recalcitrant cases of psoriasis and seborrheic dermatitis.

Metronidazole is used for:

All forms of amoebiasis (intestinal and extra-intestinal disease including liver abscess and that of symptomless cyst passers)
Trichomoniasis
Giardiasis
Bacterial vaginosis
Acute ulcerative gingivitis
Anaerobic infections including septicaemia, bacteraemia, peritonitis, brain abscess, necrotising pneumonia, osteomyelitis, puerperal sepsis, pelvic abscess, pelvic cellulitis etc.
Anaerobically-infected leg ulcers and pressure sores
Acute dental infections (e.g. acute pericoronitis and acute apical infections)
Surgical prophylaxis (prevention of postoperative infections due to anaerobic bacteria, particularly species of bacteroides and anaerobic streptococci
Chronic symptomatic peptic ulcer disease (as an agent of triple therapy to eradicate H. pylori-the most important aetiological factor of peptic ulcer)

Terbinafine cream is used for the treatment of the following dermatological infections: interdigital tinea pedis (Athlete’s foot), tinea cruris (jock itch) or tinea corporis (ring worm) due to susceptible organisms and planter tinea pedis (mocasin type) due to Trichophyton spp.

Terbinafine tablet is used for the treatment of onychomycosis of the toe nail or finger nail due to dermatophytes and also by non-dermatophyte fungi.

How Dermosav Plus works

Ciprofloxacin acts on bacterial topoisomerase II (DNA gyrase) and topoisomerase IV. Ciprofloxacin's targeting of the alpha subunits of DNA gyrase prevents it from supercoiling the bacterial DNA which prevents DNA replication.

The short term effects of corticosteroids are decreased vasodilation and permeability of capillaries, as well as decreased leukocyte migration to sites of inflammation. Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.

Glucocorticoids inhibit neutrophil apoptosis and demargination; they inhibit phospholipase A2, which decreases the formation of arachidonic acid derivatives; they inhibit NF-Kappa B and other inflammatory transcription factors; they promote anti-inflammatory genes like interleukin-10.

Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive. High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.

The exact mechanism of action of metronidazole has not been fully established, however, it is possible that an intermediate in the reduction of metronidazole which is only made by anaerobic bacteria and protozoa, binds deoxyribonucleic acid and electron-transport proteins of organisms, blocking nucleic acid synthesis. After administration, metronidazole enters cells by passive diffusion. Following this, ferredoxin or flavodoxin reduce its nitro group to nitro radicals. The redox potential of the electron transport portions of anaerobic or microaerophilic microorganisms renders metronidazole selective to these organisms, which cause nitro group reduction, leading to the production of toxic metabolites. These include N-(2-hydroxyethyl) oxamic acid and acetamide, which may damage DNA of replicating organisms.

Terbinafine inhibits the enzyme squalene monooxygenase (also called squalene epoxidase), preventing the conversion of squalene to 2,3-oxydosqualene, a step in the synthesis of ergosterol. This inhibition leads to decreased ergosterol, which would normally be incorporated into the cell wall, and accumulation of squalene.

Generation of a large number of squalene containing vesicles in the cytoplasm may leach other lipids away from, and further weaken, the cell wall.

Dosage

Dermosav Plus dosage

Adult Dose:

For oral dosage &suspension:

Urinary Tract infection: Acute uncomplicated: 250 mg twice daily for 3 days; Mild/Moderate: 250 mg twice daily for 7 to 14 days; Severe/Complicated: 500 mg twice daily for 7 to 14 days; Chronic Bacterial Prostitis : 500 mg twice daily for 28 days; Lower Respiratory Tract infection: Mild/Moderate: 500 mg twice daily for 7 to 14 days, Severe/Complicated : 750 mg twice daily for 7 to 14 days; Acute Sinusitis : 500 mg twice daily for 10 days; Skin and Skin Structure infection: Mild/Moderate : 500 mg twice daily for 7 to 14 days, Severe/Complicated : 750 mg twice daily for 7 to 14 days, Bone and joint infection: Mild/Moderate 500 mg twice daily for 4 to 6 weeks, Severe/Complicated : 750 mg twice daily for 4 to 6 weeks, Intra Abdominal Infection: 500 mg twice daily for 7 to 14 days, Infectious Diarrhea: Mild/Moderate/Severe: 500 mg twice daily for 5 to 7 days, Typhoid Fever : 500 mg twice daily for 10 days, Urethral & Cervical Gonococcal Infections: Uncomplicated: 250 mg Single dose.

For IV infusion :

Urinary Tract Infection: Mild to Moderate: 200 mg 12 hourly for 7-14 days;Severe or Complicated: 400 mg 12 hourly for 7-14 days; Lower Respiratory Tract infection: Mild to Moderate: 400 mg 12 hourly for 7-14 days; Severe or Complicated: 400 mg 8 hourly for 7-14 days; Nosocomial Pneumonia: Mild/Moderate/Severe: 400 mg 8 hourly for 10-14 days; Skin and Skin Structure: Mild to Moderate: 400 mg 12 hourly for 7-14 days; Severe or Complicated: 400 mg 8 hourly for 7-14 days; Bone and Joint Infection: Mild to Moderate: 400 mg 12 hourly for more than 4-6 weeks; Severe/Comlicated: 400 mg 8 hourly for more than 4-6weeks; Intra abdominal (Acute abdomen): Complicated: 400 mg 12 hourly for 7-14 days; Acute Sinusitis: Mild/Moderate: 400 mg 12 hourly for10 days: Chronic Bacterial Prostatitis: Mild/Moderate: 400 mg 12 hourly for 28 Days.

Children and adolescents:

RTI & GI infections: Neonate-15mg/kg twice daily, Child (1 month -18 years)-20mg/kg (max 750 mg) twice daily; UTI: Neonate-10 mg/kg twice daily, Child (1 month -18 years)-10mg/kg (max 750 mg) twice daily; Pseudomonal lower respiratory tract infection in cystic fibrosis: Child (1 month -18 years) - 20mg/kg (max 750 mg) twice daily; Anthrax (treatment & post exposure prophylaxis): Child (1 month -18 years) - 20mg/kg (max 750 mg) twice daily.

Use in Pregnancy and Lactation

Reproduction studies performed in rats and rabbits using parenteral and oral administration did not reveal any evidence of teratogenicity, impairment of fertility or impairment of pre or postnatal development. However, as with other quinolones, Ciprofloxacin has been shown to cause arthropathy in immature animals and therefore, its use during pregnancy is not recommended. Studies in rats have indicated that Ciprofloxacin is secreted in milk, administration to nursing mothers is thus not recommended.

Eye

Corneal Ulcers: The recommended dosage regimen for the treatment of corneal ulcers is 2 drops into the affected eye every 15 minutes for the first 6 hours and then 2 drops into the affected eye every 30 minutes for the remainder of the first day. On the second day, instill 2 drops in the affected eye hourly. On the third through the fourteenth day, place 2 drops in the affected eye every four hours. Treatment may be continued after 14 days if corneal re-epithelialization has not occurred.

Conjunctivitis: The recommended dosage regimen for the treatment of bacterial conjunctivitis is 1 or 2 drops instilled into the conjunctival sac(s) every 2 hours while awake for 2 days and one or 2 drops every 4 hours while awake for the next 5 days.

Ear

For all infections, 2-3 drops every 2-3 hours initially, reducing the frequency of the instillation with control of infection. Treatment should be continued at least 7 days.

Nyclobate Cream & Ointment

Adults and children over 1 year:

• Apply sparingly to cover the affected area, and gently rub into the skin. Frequency of application is 2 to 3 times daily according to the severity of the condition. The total dose applied should not exceed 50 g weekly.

• Treatment should not be continued for more than 7 days without medical supervision. If a longer course is necessary, it is recommended that treatment should not be continued for more than 4 weeks without the patient\\\'s condition being reviewed.

• Repeated short courses of Clobetasol may be used to control exacerbations

Children below 1 year: Under 1 year this preparation is not recommended

Nyclobate Scalp Application

• It should be applied to the affected scalp areas twice daily, once in morning and once at night.

• Total dosage should not exceed 50 ml per week.

• As with other highly active topical steroid preparations, therapy should be discontinued when control is achieved

Children: Under 1 year this preparation is not recommended.

Nyclobate Shampoo

• It should be applied to the dry (not wet) scalp once a day to the affected areas only.

• It should be massaged gently into the lesions and left in place for 15 minutes before lathering and rinsing.

• Treatment should be limited to 4 consecutive weeks.

• Total dosage of shampoo should not exceed 50 g per week.

• Under 18 years this preparation is not recommended.

Tablet and Suspension:

Amoebic dysentery: Duration 5-10 Days;

For Tablet: Adults- 750 mg t.i.d. Children- (7-10 years) 500 mg t.i.d. (3-7 years) 250 mg q.i.d. (1-3 years) 250 mg t.i.d.
For Suspension: Adults- 800 mg t.i.d. Children- (7-10 years) 500 mg t.i.d. (3-7 years) 200 mg q.i.d. (1-3 years) 200 mg t.i.d.

Asymptomatic amoebiasis: Duration 5-10 Days;

For Tablet: Adults- 500-750 mg t.i.d. Children- (7-10 years) 250-500 mg t.i.d. (3-7 years) 250 mg q.i.d. (1-3 years) 250 mg t.i.d.
For Suspension: Adults- 500-800 mg t.i.d. Children- (7-10 years) 200-500 mg t.i.d.; (3-7 years) 200 mg q.i.d.; (1-3 years) 200 mg t.i.d.

Hepatic extraintestinal amoebiasis : Duration 5-10 Days (or 2days);

For Tablet: Adults- 500-750 mg t.i.d.; Children- (7-10 years) 250-500 mg t.i.d.; (3-7 years) 250 mg q.i.d.; (1-3 years) 250 mg t.i.d.
For Suspension: Adults- 500-800 mg t.i.d.; Children- (7-10 years) 200-500 mg t.i.d.; (3-7 years) 200 mg q.i.d.; (1-3 years) 200 mg t.i.d.

Giardiasis: Duration 3 Days;

For Tablet: Adults- 2 g once daily; Children-(7-10 years) 1g once daily; (3-7 years) 750 mg once daily; (1-3 years) 500 mg once daily.
For suspension: Adults- 2 g once daily; Children-(7-10 years) 1g once daily; (3-7 years) 800 mg once daily; (1-3 years) 500 mg once daily.

Trichomoniasis: Duration 7 Days;

For Tablet: Adults- 250 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.
For Suspension: Adults- 200 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.

Trichomoniasis: Duration 1 Day;

For Tablet: Adults- 2 g single dose;
For Suspension: Adults- 2 g single dose;

Vincent's infection (Ulceration of mucous membrane of respiratory tract & mouth): Duration 3 Days;

For Tablet: Adults- 250 mg t.i.d. or 500 mg b.i.d; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.
For Suspension: Adults- 200 mg t.i.d. or 500 mg b.i.d; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.

Periodontal infection: Duration 3 Days;

For Tablet: Adults- 250 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.
For Suspension: Adults- 200 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.

Severe dental infection: Duration 3 Days;

For Tablet: Adults- 500 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.
For Suspension: Adults- 500 mg t.i.d.; Children- (7-10 years) 100 mg t.i.d.; (3-7 years) 100 mg b.i.d.; (1-3 years) 50 mg t.i.d.

Anaerobic infection: Duration 7 Days;

For Tablet: Adults- 500 mg t.i.d.; Children- 7.5 mg/kg body weight t.i.d.
For Suspension: Adults- 500 mg t.i.d.; Children- 7.5 mg/kg body weight t.i.d.

Postoperative anaerobic infection (specially in operation abdominal or gynecological surgery): Duration 7 Days;

For Tablet: Adults- 500 mg t.i.d. before and after operation; Children- 7.5 mg/kg body weight t.i.d.
For Suspension: Adults- 500 mg t.i.d. before and after operation; Children- 7.5 mg/kg body weight t.i.d.

Bacterial vaginitis: Duration 7 Days;

For Tablet: Adults- 500 mg b.i.d.
For Suspension: Adults- 500 mg b.i.d.

Leg ulcers: Duration 1 Day;

For Tablet: Adults- 2 g as a single dose
For Suspension: Adults- 2 g as a single dose

Pressure sores: Duration 7 Days;

For Tablet: Adults- 500 mg t.i.d.
For Suspension: Adults- 500 mg t.i.d.

H. pylori infection: Duration 7 Days;

For Tablet: Adults- 500 mg b.i.d
For Suspension: Adults-500 mg b.i.d

Antibiotic Associated Pseudomembranus colitis: Duration 7 Days;

For Tablet: Adults- 500 mg b.i.d
For Suspension: Adults- 500 mg b.i.d

Vaginal Gel:

The recommended dose is one applicator full of Metronidazole GEL (approximately 5 grams containing approximately 37.5 mg of Metronidazole) intravaginally once or twice a day for 5 days. For once a day dosing, Metronidazole GEL should be administered at bedtime.

Suppository:

Anaerobic infections:

Adult: 1 g 8 hrly for 3 days, then 12 hrly thereafter until oral medication is possible.
Child: 5-10 yr 500 mg. All doses to be given 8 hrly for 3 days, then 12 hrly thereafter until oral medication is possible.

Prophylaxis of postoperative anaerobic bacterial infections:

Adult: 1 g 2 hr before surgery, repeated 8 hrly for 3 days, then 12 hrly thereafter until oral medication is possible.
Child: 5-10 yr 500 mg 2 hr before surgery, repeated 8 hrly for 3 days, then 12 hrly thereafter until oral medication is possible.

IV Infusion:

Metronidazole injection should be infused intravenously at an approximate rate of 5 ml/min. Oral medication should be substituted as soon as feasible. Treatment for 7 days should be satisfactory for most patients, but the physician might decide to prolong treatment.

For bacterial infections: Adults: 500 mg (100 ml) 8 hourly. Children: 7.5 mg/kg (1.5 ml/kg) 8 hourly.
For treatment before and during surgery: Adults: 500 mg (100 ml) shortly before operation, repeated 8 hourly. Children: 7.5 mg/kg (1.5 ml/kg) 8 hourly

Topical application:

Terbinafine cream to affected areas once or twice daily for 1-2 weeks may be adequate for fungal infections of the skin but certain infections may require oral Terbinafine tablet therapy.Usual duration of treatment of Terbinafine cream:

In Tinea corporis and Tinea cruris: 1-2 weeks.
In Tinea pedis: 2-4 weeks (One week of treatment will normally suffice if the cream is applied twice daily.).
In Cutaneous candidiasis: 1-2 weeks
In Pityriasis (tinea) versicolor: 2 weeks.

To prevent relapses in fungal infection, treatment should be continued for a adequate length of time. To apply Terbinafine cream clean and dry the affected areas thoroughly and apply the cream once or twice a day to the affected skin and surrounding area in a thin layer and rub in lightly. In the case of intertriginous infections the application may be covered with a gauze strip, especially at night.

Oral administration:

Terbinafine tablet is essential for hair or nail infections:

The usual oral dose: Terbinafine 250 mg daily for 2 to 12 weeks depending upon the infection.
Finger nail onychomycosis: Terbinafine 250 mg once daily for 6 weeks.
Toe nail onychomycosis: Terbinafine 250 mg once daily for 12 weeks.

Information for patients: Should be swallowed whole with an adequate amount of liquid, it may be taken with or without meals. The preferred time of dosing is two hours after a meal and patients should not take antacid within two hours of dosing.

Directions for use of granules for suspension

Whole contents of the packet should be taken into a small glass containing 2-3 teaspoonful of water. Other liquids or foods should not be used. The mixer should be stirred well and drink immediately. The glass should be refilled with water and drink.

Direction for reconstitution of suspension (60 ml)

Shake the bottle well to loosen the granules. Add 50 ml (with the help of supplied measuring cup) of boiled cool water to the dry granules in the bottle. Shake the bottle vigorously until all the granules is in suspension.

Side Effects

Ciprofloxacin is generally well tolerated. Frequent adverse reactions are- Gastrointestinal disturbance: e.g. nausea diarrhea, vomiting, dyspepsia, abdominal pain. Disturbance of the CNS: e.g. dizziness, headache, tiredness, confusion, convulsions. Hypersensitivity reactions: e.g. skin rashes, pruritus, and possible systemic reactions. Other possible side effects are - joint pain, light sensitivity, transient increase in liver enzyme (especially in patients with history of liver damage), serum bilirubin, urea or serum creatinine. Arthralgia and myalgia may also occur.

The most frequently reported drug related adverse reaction is local burning or discomfort. In corneal ulcer studies with frequent administration of the drug, white crystalline precipitates were seen in approximately 17% of patients. Other reactions occurring in less than 10% of patients included lid margin crusting, crystals/scales, foreign body sensation, itching, conjunctival hyperemia and a bad taste following instillation. Additional events occurring in less than 1% of patients included corneal staining, keratopathy/keratitis, allergic reactions, lid edema, tearing, photophobia, corneal infiltrates, nausea and decreased vision.

Generally Clobetasol Propionate is well tolerated. However, few side effects after prolonged and intensive treatment may cause local atrophic changes in the skin such as Burning, itching, irritation, dry skin eczema.

Side effects of Metronidazole include gastrointestinal discomfort, nausea, coated tongue, dryness of mouth and unpleasant metallic or bitter taste, headache, pruritus and skin rashes and less frequently, vertigo, depression, insomnia, drowsiness, urethral discomfort, and darkening of the urine. Occasionally there may be temporary moderate leucopenia. Peripheral neuropathy has been reported in patients on prolonged therapy.

Terbinafine Tablet: Abdominal discomfort, anorexia, nausea, diarrhoea, headache, rash and urticaria occasionally with arthralgia or myalgia. Less frequently taste disturbance. Rarely liver toxicity, photosensitivity, serious skin reactions etc.

Terbinafine Cream: Redness, itching, or stinging; rarely allergic reactions.

Toxicity

Patients experiencing an overdose may present with nausea, vomiting, abdominal pain, crystalluria, nephrotoxicity, and oliguria. Ciprofloxacin overdose typically leads to acute renal failure. An overdose may progress over the next 6 days with rising serum creatinine and BUN, as well as anuria. Patients may require prednisone therapy, urgent hemodialysis, or supportive therapy. Depending on the degree of overdose, patients may recover normal kidney function or progress to chronic kidney failure.

The oral LD50 in rats is >2000mg/kg.

Ciprofloxacin for intratympanic injection or otic use has low systemic absorption and so it unlikely to be a risk in pregnancy or lactation. There is generally no harm to the fetus in animal studies, however high doses may lead to gastrointestinal disturbances in the mother which may increase the incidence of abortion. In human studies there was no increase in fetal malformations above background rates. The risk and benefit of ciprofloxacin should be weighed in pregnancy and breast feeding.

2/8 in vitro tests and 0/3 in vivo tests of mutagenicity of ciprofloxacin have yielded a positive result.

Oral doses of 200 and 300 times the maximum recommended clinical dose in rats and mice have shown no carcinogenicity or tumorigenicity.

Oral doses above the maximum recommended clinical dose have shown no effects on fertility in rats.

Data regarding acute overdoses of glucocorticoids are rare. Overdoses of clobetasol propionate can lead to reversible HPA axis suppression and glucocorticoid insufficiency. Chronic high doses of glucocorticoids can lead to the development of cataract, glaucoma, hypertension, water retention, hyperlipidemia, peptic ulcer, pancreatitis, myopathy, osteoporosis, mood changes, psychosis, dermal atrophy, allergy, acne, hypertrichosis, immune suppression, decreased resistance to infection, moon face, hyperglycemia, hypocalcemia, hypophosphatemia, metabolic acidosis, growth suppression, and secondary adrenal insufficiency.[A188405] Overdose may be treated by adjusting the dose or stopping the corticosteroid as well as initiating symptomatic and supportive treatment.[A188405]

LD50 information

The oral LD50 of metronidazole in rats is 5000 mg/kg

Overdose information

Adverse effects that may be exaggerated with an overdose include peripheral neuropathy, central nervous system toxicity, seizures, disulfiram-like effect (if combined with alcohol) dark urine, a metallic taste in the mouth, nausea, epigastric discomfort, and vertigo, in addition to neutropenia. There is no specific antidote for metronidazole overdose. Symptomatic and supportive treatment should be employed in addition to the administration of activated charcoal to remove the unabsorbed drug from the gastrointestinal tract. In addition to the above measures, contact the local poison control center for updated information on the management of a metronidazole overdose.

The subcutaneous LD₅₀ in rats and mice is >2g/kg. The TDLO for women is 210mg/kg/6W.

Overdose data with terbinafine is rare, however symptoms are expected to be nausea, vomiting, abdominal pain, dizziness, rash, frequent urination, and headache. Treat overdose with activated charcoal as well as symptomatic and supportive therapy.

Precaution

Ciprofloxacin should be used with caution in patients with a history of convulsive disorders. Crystalluria related to the use of Ciprofloxacin has been observed only rarely. Patients receiving Ciprofloxacin should be well hydrated to avoid excessive alkalinity of the urine.

Beuflox Injection should only be administered by slow intravenous infusion over a period of 60 minutes. Local IV site reactions have been reported with the intravenous administration of Ciprofloxacin. These reactions are more frequent if infusion time is 30 minutes or less or if small vein of the hand are used.

Do not swallow. For external use only.

Metronidazole should not be used in patients with blood dyscrasia. It is suggested that it should not be given in the first three months of pregnancy. When given in conjunction with alcohol, Metronidazole may provoke a disulphiram like effect.

Terbifine cream is for external use only. Contact with eyes should be avoided.Good general hygiene is necessary in conjunction with the use of Terbinafine in order to prevent reinfection (eg. from underwear, socks,shoes etc).

Terbinafine tablet is not recommended for patients with chronic or active liver disease. Before prescribing terbinafine, pre-existing liver disease should be assessed. Hepatotoxicity may occur in patients with and without pre-existing liver disease. Pretreatment serum transaminase (ALT and AST) tests are advised for all patients before taking terbinafine tablets.

Interaction

Increased plasma levels of theophylline have been observed following concurrent administration with Ciprofloxacin. Ciprofloxacin suspension should not be administered within 4 hours of medications containing magnesium, aluminium, calcium or iron salts as interference with absorption may occur.

No hazardous interactions have been reported with use of Clobetasol Propionate.

Metronidazole interacts with warfarin, nicoumalone, phenytoin, phenobarbitone, fluorouracil, disulfiram, lithium, cimetidine etc.

In vivo studies have shown that terbinafine is an inhibitor of the CYP450 2D6 isozyme. Drugs predominantly metabolized by the CYP450 2D6 isozyme include the following drug classes: tricyclic antidepressants, selective serotonin reuptake inhibitors, beta-blockers, antiarrhythmics class 1C (e.g., flecainide and propafenone) and monoamine oxidase inhibitors Type B. Co-administration of terbinafine should be done with careful monitoring and may require a reduction in dose of the 2D6-metabolized drug.

Volume of Distribution

Cirpofloxacin follws a 3 compartment distribution model with a central compartment volume of 0.161L/kg and a total volume of distribution of 2.00-3.04L/kg.

Data regarding the volume of distribution of clobetasole propionate are not readily available.

Metronidazole is widely distributed throughout the body and various body fluids. They include the bile, saliva, breastmilk, cerebrospinal fluid, and the placenta. Steady-state volume distribution of metronidazole in adults ranges from 0.51 to 1.1 L/kg. It attains 60 to 100% of plasma concentrations in various tissues, such as the central nervous system, however, is not measured in high concentrations in the placental tissue.

A single 250mg oral dose of terbinafine has a volume of distribution at steady state of 947.5L or 16.6L/kg.

Elimination Route

A 250mg oral dose of ciprofloxacin reaches an average maximum concentration of 0.94mg/L in 0.81 hours with an average area under the curve of 1.013L/h*kg. The FDA reports an oral bioavailability of 70-80% while other studies report it to be approximately 60%. An early review of ciprofloxacin reported an oral bioavailability of 64-85% but recommends 70% for all practical uses.

Twice daily application of clobetasol foam leads to a C_max of 59±36pg/mL with a T_max of 5 hours. Clobetasol cream showed an increase in clobetasol concentrations from 50.7±96.0pg/mL to 56.3±104.7pg/mL.

After the intravenous infusion of a 1.5g dose, peak concentration was reached within 1 hour and was peak level of 30-40 mg/L. When a multiple-dose regimen of 500mg three times a day administered intravenously, steady-state concentrations were achieved within about 3 days and peak concentration was measured at 26 mg/L. When administered orally in the tablet form, metronidazole is absorbed entirely absorbed, showing a bioavailability of greater than 90%. One resource indicates that Cmax after a single oral dose of 500mg metronidazole ranges from 8 to 13 mg/L, with a Tmax of 25 minutes to 4 hours. The AUC following a single 500mg oral dose of metronidazole was 122 ± 10.3 mg/L • h.

A note on the absorption of topical preparations

Insignificant percutaneous absorption of metronidazole occurs after the application of 1% metronidazole cream topically. Healthy volunteers applied one 100 mg dose of 14C-labelled metronidazole 2% cream to unbroken skin. After 12 hours, metronidazole was not detected in the plasma. Approximately 0.1% to 1% of the administered metronidazole was measured in the urine and feces.

Oral terbinafine is >70% absorbed but only 40% bioavailable after first pass metabolism, reaching a C_max of 1µg/mL with a T_max of 2 hours an an AUC of 4.56µg*h/mL. Over the course of a week, 1% topical terbinafine's C_max increases from 949-1049ng/cm²

Half Life

The average half life following a 250mg oral dose was 4.71 hours and 3.65 hours following a 100mg intravenous dose. Generally the half life is reported as 4 hours.

Data regarding the half life of clobetasol propionate are not readily available.

The elimination half-life of metronidazole is 7.3 ± 1.0 after a single 500mg IV dose in healthy subjects. Another resource indicates that the elimination half-life for metronidazole ranges from 6 to 10 hours.

Oral terbinafine has an effective half life of approximately 36 hours. However, the terminal half life ranges from 200-400 hours as it distributes into skin and adipose tissue. 1% topical terbinafine's half life increases over the first seven days from approximately 10-40 hours.

Clearance

The average renal clearance after a 250mg oral dose is 5.08mL/min*kg. Following a 100mg intravenous dose, the average total clearance is 9.62mL/min*kg, average renal clearance is 4.42mL/min*kg, and average non renal clearance is 5.21mL/min*kg.

Data regarding the clearance of clobetasol propionate are not readily available.

Dose adjustments may be required in patients with hepatic impairment, as clearance is impaired in these patients. The clearance of metronidazole in the kidneys is estimated at 10 mL/min/1.73 m2. The total clearance from serum is about 2.1 to 6.4 L/h/kg.

A single 250mg oral dose of terbinafine has a clearance of 76L/h or 1.11L/h/kg.

Elimination Route

27% of an oral dose was recovered unmetabolized in urine compared to 46% of an intravenous dose. Collection of radiolabelled ciprofloxacin resulted in 45% recovery in urine and 62% recovery in feces.

Corticosteroids are eliminated predominantly in the urine.

Metronidazole and metabolites are 60 to 80% eliminated in the urine, and 6-15% excreted in the feces.

Terbinafine is approximately 80% eliminated in urine, while the remainder is eliminated in feces. The unmetabolized parent drug is not present in urine.

Pregnancy & Breastfeeding use

The safe use of Clobetasol Propionate during pregnancy & lactation has not been established.

Not recommended during first & later trimesters. Breast feeding should be delayed until 48 hours after discontinuing metronidazole in the mother.

Terbinafine tablet: There are no adequate and well controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, and because treatment of onychomycosis can be postponed until after pregnancy is completed, it is recommended that terbinafine not be initiated during pregnancy. After oral administration, terbinafine is present in breast milk of nursing mothers. Treatment with terbinafine in not recommended in nursing mothers.

Terbinafine cream: Foetal toxicity and fertility studies in animals suggest no adverse effects. There is no clinical experience with terbinafine in pregnant women; therefore, unless the potential benefits outweigh any potential risk, terbinafine should not be administered. Terbinafine is excreted in breast milk and therefore mothers should not receive terbinafine treatment whilst breast-feeding.

Contraindication

Ciprofloxacin is contra-indicated in patients who have shown hypersensitivity to Ciprofloxacin or other quinolones.

Contraindicated in Cutaneous infections such as impetigo, tinea corporis and herpes simplex, Infestations such as scabies, Acne vulgaris, Hypersensitivity, Rosacea, Gravitational ulceration, Perioral dermatitis, Children under 1 year

Metronidazole is contraindicated in patients with prior history of hypersensitivity to Metronidazole or other Nitroimidazole derivatives.

Hypersensitivity to Terbinafine or any of the excipients in thepreparation

Special Warning

Use in Paediatrics: The drug may be used in paediatrics patients in appropriate dosage, but large quantities for prolonged period should be avoided. It is contraindicated in children less than one year.

Use in Children: Terbinafine cream appears to be an effective and well-tolerated treatmenr of tinea corposis and tinea cruris in children.

Use in Elderly: Terbinafine appears to be safe in the elderly. The dose should be reduced by half if significant hepatic or renal impairment is present.

Acute Overdose

In case of acute overdose, the patient should be carefully observed and given supporative treatment, including monitoring of renal function. Adequate hydration must be maintained.

Acute overdosage is very unlikely to occur. However, in the case of chronic overdose or misuse the features of hypercortisolism may appear.

Clinical experience regarding overdose with terbinafine tablets is limited. Doses up to 5 grams (20 times the therapeutic daily dose) have been taken without inducing serious adverse reactions. The symptoms of overdose included nausea, vomiting, abdominal pain, dizziness, rash, frequent urination, and headache.