Ciprofloxacin And Hydrocortisone

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.

Hydrocortisone is used for the use in the following conditions: Primary or secondary adrenocortical insufficiency, Acute adrenocortical insufficiency, Shock unresponsive to conventional therapy, Congenital adrenal hyperplasia, Hypercalcemia associated with cancer, Nonsuppurative thyroiditis, Rheumatic Disorders, Dermatologic Diseases (Allergic States, Severe seborrheic dermatitis, Severe psoriasis, Pemphigus, Severe erythema multiforme), Control of severe or incapacitating allergic conditions (Bronchial asthma, Contact dermatitis, Atopic dermatitis, Serum sickness, Seasonal or perennial allergic rhinitis, Drug hypersensitivity reactions, Urticarial transfusion reactions, Acute noninfectious laryngeal edema), Ophthalmic Diseases (Herpes zoster ophthalmicus, Iritis, iridocyclitis, Chorioretinitis, Diffuse posterior uveitis and choroiditis, Optic neuritis), Gastrointestinal Diseases, Fulminating or disseminated pulmonary tuberculosis when used concurrently with appropriate antituberculous chemotherapy, Loeffler's syndrome, Aspiration pneumonitis, Hematologic Disorders (Acquired, autoimmune hemolytic anemia, Idiopathic thrombocytopenic purpura in adults, Secondary thrombocytopenia, Erythroblastopenia), Neoplastic Diseases (Leukemias and lymphomas in adults, Acute leukemia of childhood), Edematous States, Acute exacerbations of multiple sclerosis

Ciprofloxacin And Hydrocortisone is also used to associated treatment for these conditions: Acute Otitis Externa, Acute Otitis Externa caused by Pseudomonas Aeruginosa, Acute Otitis Media, Acute Sinusitis, Acute Uncomplicated Pyelonephritis, Acute exacerbation of chronic bronchitis caused by Moraxella catarrhalis, Bone and Joint Infections, Chronic Otitis Media, Complicated Intra-Abdominal Infections, Complicated Urinary Tract Infection, Conjunctivitis caused by Haemophilus influenzae, Conjunctivitis caused by Staphylococcus epidermidis, Corneal Ulcers caused by Serratia marcescens, Corneal Ulcers caused by Staphylococcus aureus, Corneal Ulcers caused by Staphylococcus epidermidis, Corneal Ulcers caused by Streptococcus Pneumoniae, Corneal Ulcers caused by Streptococcus Viridans Group, Corneal Ulcers caused by pseudomonas aeruginosa, Escherichia urinary tract infection, External ear infection NOS, Febrile Neutropenia, Infection of the outer ear caused by susceptible bacteria, Infectious diarrhea, Lower respiratory tract infection caused by Enterobacter cloacae, Lower respiratory tract infection caused by Escherichia coli, Lower respiratory tract infection caused by Haemophilus influenzae, Lower respiratory tract infection caused by Haemophilus parainfluenzae, Lower respiratory tract infection caused by Klebsiella pneumoniae, Lower respiratory tract infection caused by Proteus mirabilis, Lower respiratory tract infection caused by penicillin-susceptible Streptococcus pneumoniae, Nosocomial Pneumonia, Otitis Media (OM), Otitis Media, Purulent, Plague caused by Yersinia pestis, Skin Infections, Typhoid fever caused by Salmonella typhi, UTI caused by Citrobacter diversus, UTI caused by Citrobacter frendii, UTI caused by Entercococcus faecalis, UTI caused by Enterobacter cloacae, UTI caused by Klebsiella pneumoniae, UTI caused by Morganella morganii, UTI caused by Proteus mirabilis, UTI caused by Providencia rettgeri, UTI caused by Pseudomonas aeruginosa, UTI caused by Serratia marcescens, UTI caused by methicillin-susceptible Staphylococcus epidermidis, Uncomplicated Urinary Tract Infections, Acute otitis externa caused by Staphylococcus aureus, Acute, uncomplicated Cystitis caused by Escherichia coli, Acute, uncomplicated Cystitis caused by Staphylococcus saprophyticus, Chronic Prostatitis caused by Escherichia coli, Chronic Prostatitis caused by Proteus mirabilis, Complicated Pyelonephritis caused by Escherichia coli, Complicated Urinary Tract Infection caused by Escherichia Coli, Inhaled anthrax caused by Bacillus anthracis, Uncomplicated Gonorrhea caused by Neisseria gonorrhoeaeAcute Gouty Arthritis, Acute Otitis Externa, Adrenal Insufficiency, Allergic Rhinitis (AR), Allergic corneal marginal ulcers, Anal Fissures, Ankylosing Spondylitis (AS), Anterior Segment Inflammation, Aspiration Pneumonitis, Asthma, Atopic Dermatitis (AD), Berylliosis, Bullous dermatitis herpetiformis, Chorioretinitis, Choroiditis, Congenital Adrenal Hyperplasia (CAH), Congenital Hypoplastic Anemia, Corneal Inflammation, Crohn's Disease (CD), Dermatitis, Dermatitis exfoliative generalised, Dermatitis, Contact, Dermatomyositis, Dermatosis, Drug hypersensitivity reaction, Epicondylitis, Erythroblastopenia, Hemorrhoids, Herpes Labialis, Hypercalcemia of Malignancy, Idiopathic Thrombocytopenic Purpura, Infection of the Fenestration Cavity, Infection of the Mastoidectomy Cavity, Iridocyclitis, Iritis, Itching caused by Hemorrhoids, Itching of the Anus, Leukemia, Acute, Leukemias, Loeffler's syndrome, Lymphomas NEC, Malignant Lymphomas, Mycosis Fungoides (MF), Ophthalmia, Sympathetic, Optic Neuritis, Pain caused by Hemorrhoids, Pemphigus, Post-traumatic Osteoarthritis, Primary adrenocortical insufficiency, Proctitis, Proteinuria, Psoriatic Arthritis, Rectal inflammations NEC, Rheumatic heart disease, unspecified, Rheumatoid Arthritis, Rheumatoid Arthritis, Juvenile, Seasonal Allergic Conjunctivitis, Secondary adrenocortical insufficiency, Secondary thrombocytopenia, Serum Sickness, Severe Seborrheic Dermatitis, Skin Diseases, Stevens-Johnson Syndrome, Synovitis, Systemic Lupus Erythematosus (SLE), Trichinosis, Tuberculous Meningitis, Ulcerative Colitis, Acquired immune hemolytic anemia, Acute Bursitis, Acute Tenosynovitis, Acute rheumatic carditis, Cryptitis, Disseminated Pulmonary Tuberculosis, Fulminating Pulmonary Tuberculosis, Itching skin, Non-suppurative Thyroiditis, Severe Erythema multiforme, Severe Psoriasis, Subacute Bursitis, Superficial infection of the external auditory canal with inflammation, Symptomatic Sarcoidosis, Systemic Dermatomyositis, Varicella-zoster virus acute retinal necrosis, Palliative

How Ciprofloxacin And Hydrocortisone 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.[A187463] Corticosteroids binding to the glucocorticoid receptor mediates changes in gene expression that lead to multiple downstream effects over hours to days.[A187463]

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.[A187463]

Lower doses of corticosteroids provide an anti-inflammatory effect, while higher doses are immunosuppressive.[A187463] High doses of glucocorticoids for an extended period bind to the mineralocorticoid receptor, raising sodium levels and decreasing potassium levels.[A187463]

Dosage

Ciprofloxacin And Hydrocortisone 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.

Tablet: The initial dosage of Hydrocortisone Tablets may vary from 20 mg to 240 mg of hydrocortisone per day depending on the specific disease entity being treated. In situations of less severity, lower doses will generally suffice, while in selected patients higher initial doses may be required. The initial dosage should be maintained or adjusted until a satisfactory response is noted. If after a reasonable period of time there is a lack of satisfactory clinical response, Hydrocortisone Tablets should be discontinued and the patient transferred to other appropriate therapy.

It should be emphasized that dosage requirements are variable and must be individualized on the basis of the disease under treatment and the response of the patients.After a favorable response is noted, the proper maintenance dosage should be determined by decreasing the initial drug dosage in small decrements at appropriate time intervals until the lowest dosage which will maintain an adequate clinical response. It should be kept in mind that constant monitoring is needed in regard to drug dosage. If, after long-term therapy the drug is to be stopped, it is recommended that it be withdrawn gradually, rather than abruptly.

Injection:

• Adult: By IM injection or slow IV injection or infusion. The initial dose of Hydrocortisone sterile powder is 100 mg to 500 mg, depending on the severity of the condition. This dose may be repeated at intervals of 2, 4 or 6 hours as indicated by the patient's response and clinical condition.
• Children: By slow IV injection, up to 1 year 25 mg, 1-5 years 50 mg, 6-12 years 100 mg.

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.

Hydrocortisone is generally well tolerated except in prolonged high doses. It may cause cardiac arrhythmia, esophageal candidiasis, menstrual irregularity, decreased carbohydrate & glucose tolerance, fluid retention, increased appetite, weight gain, euphoria, mood swings, depression, insomnia, acne etc.

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. 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. Overdose may be treated by adjusting the dose or stopping the corticosteroid as well as initiating symptomatic and supportive treatment.

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.

Hydrocortisone should be used with caution in patients with a history of peptic ulceration as it increases the incidence of peptic ulceration. This drug should be used with caution in patients with congestive heart failure, hypertension, glaucoma, diabetic mellitus and epilepsy.

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.

Drug interaction of hydrocortisone has been reported with amphotericin B, potassium-depleting agents, macrolide antibiotics, warfarin, antidiabetics, isoniazid, digitalis glycosides, estrogens, barbiturates, phenytoin, carbamazepine, ketoconazole, aspirin etc.

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.

Total hydrocortisone has a volume of distribution of 39.82L, while the free fraction has a volume of distribution of 474.38L.

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.

Oral hydrocortisone at a dose of 0.2-0.3mg/kg/day reached a mean C_max of 32.69nmol/L with a mean AUC of 90.63h*nmol/L A 0.4-0.6mg/kg/day dose reached a mean C_max of 70.81nmol/L with a mean AUC of 199.11h*nmol/L. However, the pharmacokinetics of hydrocortisone can vary by 10 times from patient to patient.

Topical hydrocortisone cream is 4-19% bioavailable[8546995] with a T_max of 24h.

Hydrocortisone retention enemas are have a bioavailability of 0.810 for slow absorbers and 0.502 in rapid absorbers. Slow absorbers take up hydrocortisone at a rate of 0.361±0.255/h while fast absorbers take up hydrocortisone at a rate of 1.05±0.255/h.

A 20mg IV dose of hydrocortisone has an AUC of 1163±277ng*h/mL.

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.

Total hydrocortisone via the oral route has a half life of 2.15h while the free fraction has a half life of 1.39h. A 20mg IV dose of hydrocortisone has a terminal half life of 1.9±0.4h.

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.

Total hydrocortisone by the oral route has a mean clearance of 12.85L/h, while the free fraction has a mean clearance of 235.78L/h. A 20mg IV dose of hydrocortisone has a clearance of 18.2±4.2L/h.

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.[A187436] However, data regarding the exact proportion is not readily available.

Pregnancy & Breastfeeding use

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.

Pregnancy category C. Corticosteroids should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Use in nursing mother: Systemically administered corticosteroids appear in human milk and could suppress growth, interfere with endogenous corticosteroid production, or cause other untoward effects. Because of the potential for serious adverse reactions in nursing infants from corticosteroids, a decision should be made whether to continue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

Contraindication

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

Hydrocortisone is contraindicated in severe systemic fungal infections and patients with known hypersensitivity to any component of this product.

Special Warning

Use in elderly patients: Clinical studies were not done in patients’ aged 65 and above. In general dose selection for an elderly patients should be cautious, usually starting at the low end of the dosing range.

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.

Storage Condition

Store in a cool dry place protected from light. Keep out of reach of children.

Store at 15-30°C.

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