Combace

Uses

Moxifloxacin is used for the treatment of adults (>18 years of age) with infections caused by susceptible strains of the designated microorganisms in the conditions listed below-

• Acute Bacterial Sinusitis caused by Streptococcus pneumoniae, Haemophilus infuenzae or Moraxella catarrhalis.
• Acute Bacterial Exacerbation of Chronic Bronchitis caused by Streptococcus pneumoniae, Haemophilus infuenzae, Haemophilus parainfuenzae, Klebsiella pneumoniae, methicillin-susceptible Staphylococcus aureus or Moraxella catarrhalis
• Community Acquired Pneumonia caused by Streptococcus pneumoniae (including multi-drug resistant strains), Haemophilus infuenzae, Moraxella catarrhalis, methicillin-susceptible Staphylococcus aureus, Klebsiella pneumoniae, Mycoplasma pneumoniae or Chlamydophilia pneumoniae.
• Uncomplicated Skin and Skin Structure Infections caused by methicillin-susceptible Staphylococcus aureus or Streptococcus pyogen.
• Complicated Skin and Skin Structure Infections caused by methicillin-susceptible Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae or Enterobacter cloacae.
• Complicated Intra-Abdominal Infections including polymicrobial infections such as abscess caused by Escherichia coli, Bacteroides fragilis, Streptococcus anginosus, Streptococcus constellatus, Enterococcus faecalis, Proteus mirabilis, Clostridium perfringens, Bacteroides thetaiotaomicron or Peptostreptococcus species.

Prednisolone is a glucocorticoid used to treat adrenocortical insufficiency, inflammatory conditions, and some cancers.

Prednisolone is indicated to treat endocrine, rheumatic, and hematologic disorders; collagen, dermatologic, ophthalmic, respiratory, and gastrointestinal diseases; allergic and edematous states; and other conditions like tuberculous meningitis.

Combace is also used to associated treatment for these conditions: Acute Exacerbation of Chronic Bronchitis (AECB), Bacterial Conjunctivitis, Community Acquired Pneumonia (CAP), Plague, Postoperative Inflammatory Response, Sinusitis, Skin Infections, Ocular bacterial infections, Post-operative infectionAcne Rosacea, Acute Gouty Arthritis, Allergic Bronchopulmonary Aspergillosis, Allergic Contact Dermatitis, Allergic corneal marginal ulcers, Alveolitis, Extrinsic Allergic, Anal Fissures, Ankylosing Spondylitis (AS), Aspiration Pneumonitis, Atopic Dermatitis (AD), Bell's Palsy, Berylliosis, Bullous dermatitis herpetiformis, Burns, Chorioretinitis, Choroiditis, Chronic Obstructive Airways Disease Exacerbated, Congenital Adrenal Hyperplasia (CAH), Congenital Hypoplastic Anemia, Conjunctivitis, Corneal Inflammation, Corneal injuries, Corneal ulceration, Crohn's Disease (CD), Cyclitis, Dermatitis exfoliative generalised, Dermatitis, Contact, Dermatomyositis, Dermatosis of the Ear Canal, Drug hypersensitivity reaction, Edema of the cerebrum, Epicondylitis, Erythroblastopenia, Exacerbation of asthma, Eye inflammation caused by Cataract Surgery, Eye inflammation caused by Infection, Herpes Zoster Keratitis, Hot Water Burns (Scalds), Hypercalcemia of Malignancy, Idiopathic Pulmonary Fibrosis (IPF), Idiopathic Thrombocytopenic Purpura, Inflamed External Hemorrhoid, Inflamed Hemorrhoids, Internal, Inflammatory Reaction caused by susceptible Bacterial Infections, Iridocyclitis, Iritis, Itching caused by susceptible Bacterial Infections, Leukemia, Acute, Loeffler's syndrome, Malignant Lymphomas, Multiple sclerosis exacerbation, Mycosis Fungoides (MF), Ocular Inflammation, Ophthalmia, Sympathetic, Optic Neuritis, Otic Eczema, Pemphigus, Perennial Allergic Rhinitis (PAR), Pericarditis, Pneumocystis Jirovecii Pneumonia, Pneumonia, Aspiration, Polymyalgia Rheumatica, Post-traumatic Osteoarthritis, Proctitis, Proteinuria, Pruritus, Pruritus Ani, Psoriatic Arthritis, Pulmonary Tuberculosis (TB), Pure Red Cell Aplasia, Rash, Rejection, Transplant, Relapsing Polychondritis, Rheumatoid Arthritis, Rheumatoid Arthritis, Juvenile, Seasonal Allergic Conjunctivitis, Seasonal Allergic Rhinitis, Secondary Adrenal Insufficiency, Secondary thrombocytopenia, Serum Sickness, Severe Asthma, Sjögren's Syndrome, Skin Infections, Bacterial, Stevens-Johnson Syndrome, Superficial punctate keratitis, Synovitis, Systemic Lupus Erythematosus (SLE), Trichinosis, Tuberculosis (TB), Tuberculous Meningitis, Ulcerative Colitis, Uveitis, Vasculitis, Acquired immune hemolytic anemia, Acute Bursitis, Acute Rheumatic heart disease, unspecified, Acute Tenosynovitis, Allergic skin manifestations, Anal eczema, Exfoliative erythroderma, Idiopathic Bronchiolitis obliterans with organizing pneumonia, Idiopathic eosinophilic pneumonias, Non-suppurative Thyroiditis, Primary adrenocoritical insufficiency, Severe Psoriasis, Severe Seborrhoeic dermatitis, Severe alcoholic liver disease, Steroid-responsive inflammation of the eye, Subacute Bursitis, Susceptible Bacterial Infections, Symptomatic Sarcoidosis, Varicella-zoster virus acute retinal necrosis

How Combace works

The bactericidal action of moxifloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV. DNA gyrase is an essential enzyme that is involved in the replication, transcription and repair of bacterial DNA. Topoisomerase IV is an enzyme known to play a key role in the partitioning of the chromosomal DNA during bacterial cell division.

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.

Dosage

Combace dosage

The dose of Moxifloxacin is 400 mg once every 24 hours. The duration of therapy depends on the type of infection as described bellow-

• In Acute Bacterial Sinusitis: Moxifloxacin 400 mg is given once daily for 10 days.
• In Acute Bacterial Exacerbation of Chronic Bronchitis: Moxifloxacin 400 mg is given once daily for 5 days.
• In Community Acquired Pneumonia: Moxifloxacin 400 mg is given once daily for 7-14 days.
• In Uncomplicated Skin & Skin Structure infections: Moxifloxacin 400 mg is given once daily for 7 days.
• In Complicated Skin & Skin Structure infections: Moxifloxacin 400 mg is given once daily for 7-21 days.
• In Complicated Intra-Abdominal infections: Moxifloxacin 400 mg is given once daily for 5-14 days.

Moxifloxacin 400 mg IV infusion can be administered intravenously for the entire treatment duration. Alternatively, therapy may be initial intravenous administration, followed by oral administration when clinically indicated. The recommended duration of treatment for the indication being treated should not be exceeded. The solution for infusion should be infused intravenously over 60 minutes.

Side Effects

The following one or more side effects may be observed: tendinopathy and tendon rupture, QT prolongation, hypersensitivity reactions, Clostridium difficile-associated diarrhea, peripheral neuropathy, photosensitivity, phototoxicity etc.

Toxicity

Symptoms of overdose include CNS and gastrointestinal effects such as decreased activity, somnolence, tremor, convulsions, vomiting, and diarrhea. The minimal lethal intravenous dose in mice and rats is 100 mg/kg.

The intraperitoneal LD₅₀ in rats is 2g/kg and 65mg/kg in mice. The subcutaneous LD₅₀ in rats is 147mg/kg and >3500mg/kg in mice. The oral LD₅₀ in mice is 1680mg/kg. In humans, the oral TDLO in men is 9mg/kg/2W and in women is 14mg/kg/13D.

Patients experiencing an overdose of prednisolone may present with gastrointestinal disturbances, insomnia, and restlessness. Overdose of oral prednisolone may be treated by gastric lavage or inducing vomiting if the overdose was recent, as well as supportive and symptomatic therapy. Chronic overdosage may be treated by dose reduction or treating patients on alternate days. An overdose by the ophthalmic route is not expected to cause problems.

Precaution

Moxifloxacin should be discontinued at the first appearance of a skin rash or any other sign of hypersensitivity. Moxifloxacin should be discontinued if the patient experiences pain, swelling, inflammation or rupture of a tendon.

Interaction

No quinolone should be co-administered with any solution containing multivalent cations (e.g. magnesium) through the same intravenous line. Antacids, iron and adsorbents reduce absorption of Moxifloxacin. NSAID may increase the risk of CNS stimulation. Warfarin may increase the risk of bleeding.

Volume of Distribution

• 1.7 to 2.7 L/kg

A 0.15mg/kg dose of prednisolone has a volume of distribution of 29.3L, while a 0.30mg/kg dose has a volume of distribution of 44.2L.

Elimination Route

Well absorbed from the gastrointestinal tract. Absolute oral bioavailability is approximately 90%. Food has little effect on absorption.

Oral prednisolone reaches a C_max of 113-1343ng/mL with a T_max of 1.0-2.6 hours. Oral prednisolone is approximately 70% bioavailable.

Half Life

11.5-15.6 hours (single dose, oral)

Prednisolone has a plasma half life of 2.1-3.5 hours. This half life is shorter in children and longer in those with liver disease.

Clearance

• 12 +/- 2 L/hr

A 0.15mg/kg dose of prednisolone has a clearance of 0.09L/kg/h, while a 0.30mg/kg dose has a clearance of 0.12L/kg/h.

Elimination Route

Approximately 45% of an oral or intravenous dose of moxifloxacin is excreted as unchanged drug (~20% in urine and ~25% in feces).

Prednisolone is over 98% eliminated in urine.

Pregnancy & Breastfeeding use

Pregnancy Category C. Moxifloxacin is not recommended during pregnancy & lactation.

Contraindication

Moxifloxacin is contraindicated in persons with a history of hypersensitivity to Moxifloxacin or any member of the quinolone class of antimicrobial agents and any component of this formulation.

Special Warning

Elderly: No adjustment of dosage is required in the elderly.

Children: Efficacy and safety of Moxifloxacin IV infusion in children and adolescent have not been established.

Acute Overdose

In the events of an acute overdose, the stomach should be emptied. The patient should be kept under observation and appropriate hydration should be maintained.

Storage Condition

Store between 15 to 30° C. Protect from light and moisture. Keep away from reach of children.

Innovators Monograph

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