Orfix Cv

Uses

Cefixime is used for the following infectious diseases -

Respiratory Tract Infections:

Pneumonia

Sinusitis

Pharyngitis and Tonsillitis

Acute Bronchitis and Acute Exacerbations of Chronic

Bronchitis (AECB)

Otitis Media

Typhoid Fever

Urinary Tract Infections

Uncomplicated gonorrhea (cervical/urethral)

Clavulanic acid is a beta lactamase inhibitor used to enhance the effectiveness of beta lactam antibiotics.

Clavulanic acid combined with other antibiotics is indicated to prevent the development of drug-resistant strains of bacteria and promotes their therapeutic antibacterial effects.

The following conditions, when they produced beta-lactamases, have been treated with a combination of amoxicillin and clavulanic acid or ticarcillin and clavulanic acid:

Acute otitis media caused by H. influenzae and M. catarrhalis

Sinusitis due to H. influenzae and M. catarrhalis

Lower respiratory tract infections due to Haemophilus influenzae, S.aureus, Klebsiella species, and Moraxella catarrhalis

Skin and skin structure infections caused by Staphylococcus aureus, Escherichia coli, and Klebsiella species

Urinary Tract Infections due to E. coli, Klebsiella species of bacteria, and Enterobacter species of bacteria, S.marcescens, or S.aureus

Gynecologic infections due to a variety of bacteria, including P.melaninogenicus, Enterobacter species, E.Coli species, Klebsiella species, S. aureus, S.epidermidis

Septicemia due to a variety of bacteria, including Klebsiella species, E.Coli species, S.aureus, or Pseudomonas species

Bone and joint infections due to S.aureus

Intraabdominal infections due to E.Coli, K.pnemoniae, or B.fragilis group

A note on susceptibility

It should be noted that it is only to be administered in infections that are confirmed or highly likely to be caused by susceptible bacteria. Culture and susceptibility tests should be performed if possible and used in selecting whether this antibiotic is prescribed. When beta-lactamase enzyme production is not detected during microbiological testing, clavulanic acid should not be used. When these tests are not available patterns of local infection and susceptibility may be used to determine the appropriateness of using clavulanic acid. Ticarcillin with clavulanate has shown particular efficacy in mixed infections in addition to empiric therapy before determining the susceptibility of causative organisms. The ticarcillin-clavulanic acid combination may prove to be an effective single-agent antibiotic therapy to treat infections where a regimen of several drugs may normally be used.

Orfix Cv is also used to associated treatment for these conditions: Acute Exacerbation of Chronic Bronchitis caused by Streptococcus Pneumoniae, Acute Exacerbations of Chronic Bronchitis caused by Haemophilus Influenzae, Bacterial Sinusitis, Community Acquired Pneumonia (CAP), Gonorrhea of anus, Lyme Disease, Salmonella Infections, Salmonella Typhi Infection, Shigella Infection, Streptococcal Pharyngitis, Streptococcal tonsillitis, Uncomplicated Urinary Tract Infections, Bacterial otitis media, Bacterial rhinosinusitis, Uncomplicated GonorrheaAcute Cystitis, Acute Uncomplicated Pyelonephritis, Bacterial Infections, Bacterial Pneumonia, Bacterial infection due to streptococcus, group A, Bloodstream Infections, Bone and Joint Infections, Bronchitis, Cysto-Urethritis, Gonorrhoea, Gynaecological infection, Haemophilus Influenzae, Infection Due to Escherichia Coli, Intraabdominal Infections, Lower Respiratory Infection, Lower Respiratory Tract Infection (LRTI), Moraxella catarrhalis, Otitis Media (OM), Pharyngitis, Proteus mirabilis, Sinusitis, Skin and skin structure infections, Streptococcus Pneumoniae, Tonsillitis, Upper Respiratory Tract Infection, Urinary Tract Infection, Skin and skin-structure infections, Susceptible Bacterial Infections

How Orfix Cv works

Like all beta-lactam antibiotics, cefixime binds to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, causing the inhibition of the third and last stage of bacterial cell wall synthesis. Cell lysis is then mediated by bacterial cell wall autolytic enzymes such as autolysins; it is possible that cefixime interferes with an autolysin inhibitor.

Clavulanic acid contains a beta-lactam ring in its structure that binds in an irreversible fashion to beta-lactamases, preventing them from inactivating certain beta-lactam antibiotics, with efficacy in treating susceptible gram-positive and gram-negative infections.

Dosage

Orfix Cv dosage

The usual treatment of Cefixime is 7 days. This may be continued for up to 14 days according to the severity of infection.

Cefixime Capsule

Adult and child over 12 years: 200 or 400 mg daily as a single dose or in two divided doses.

Cefixime Suspension

Child over 6 months: 8 mg/kg daily as a single dose or in 2 divided doses

Direction for Reconstitution of Suspension

• To prepare 50 ml suspension, 25 ml boiled and cooled water is required.

• To prepare 40 ml suspension, 20 ml boiled and cooled water is required.

• To prepare 30 ml suspension, 15 ml boiled and cooled water is required.

• To prepare 50 ml DS suspension, 25 ml boiled and cooled water is required.

Tap the bottle several times to loosen powder contents prior to reconstitution. Add approximately half of the total amount of water and shake well. Add remainder of water, and then shake again.

Note: Shake the suspension well before each use. Keep the bottle tightly closed. The reconstituted suspension should be stored in a cool and dry place, preferably in refrigerator and unused portion should be discarded after 14 days.

Side Effects

Cefixime is generally well tolerated. The majority of adverse reactions observed in clinical trials are mild and self limiting in nature.

Gastro-intestinal disturbance: Diarrhea (if severe diarrhea occurs, Cefixime should be discontinued), changes in the color of stool, nausea, abdominal pain, dyspepsia, vomiting, flatulence have been reported. CNS disturbances: Headache, dizziness.

Others: Hypersensitivity reactions which usually subsided upon discontinuation of therapy; infrequent and reversible hematological changes; elevation of serum amylase.

Toxicity

Symptoms of overdose include blood in the urine, diarrhea, nausea, upper abdominal pain, and vomiting.

LD50 information

Clavulanic acid has demonstrated low oral acute toxicity in adult rodents, having an LD50 of more than 2000 mg/kg. The toxicity of clavulanic acid on pre-weaning rats was also studied. Gastrointestinal disturbance and mortality occurred, even at lower clavulanic acid doses of 125 mg/kg.

Overdose information

Overdose information has been obtained for the combination of amoxicillin and clavulanic acid, as these drugs are frequently administered together in a single product. Changes in fluid and electrolyte balances and gastrointestinal symptoms may occur in the case of an overdose. Offer symptomatic treatment or gastrointestinal disturbances, while considering the importance of fluid and electrolyte balance. This drug may be removed by a session of hemodialysis. When coadministered with amoxicillin, crystalluria causing renal failure has been observed. Seizures may also occur in a case of overdose, or in a patient with renal failure.

Precaution

Cefixime should be prescribed with caution in individuals with a history of gastrointestinal diseases, particularly colitis. Dosage adjustment is only necessary in severe renal failure (creatinine clearance < 20 ml/min)

Interaction

Increased prothrombin time (with or withot bleeding) with anticoagulants (e.g. warfarin). Increased plasma carbamazepine concentrations with concomitant use. Increased bioavailability with nifedipine. Increased serum concentration with probenecid.

Volume of Distribution

A study in 4 healthy volunteers administered a radiolabeled dose of clavulanic acid determined a volume of distribution of 12L.Clavulanic acid is distributed to various tissues and interstitial fluid. Clinically significant concentrations have been measured in the gallbladder, abdomen, skin, fat, and muscle tissues. Bile, pus, synovial and peritoneal fluids are also found to have therapeutic concentrations of clavulanic acid. Studies of animals have demonstrated that clavulanic crosses the placenta.

Elimination Route

About 40%-50% absorbed orally whether administered with or without food, however, time to maximal absorption is increased approximately 0.8 hours when administered with food.

Clavulanic acid, when taken orally, is well absorbed in the gastrointestinal tract. After administration of radiolabeled clavulanic acid to four human subjects, a minimum of 73% absorption and the average absolute bioavailability was calculated at 64%. The mean Cmax in a group of 8 healthy research volunteers was 2.098 ± 0.441 micrograms/ml in a pharmacokinetic study. The same study reported a mean Tmax of 1.042 ± 0.80 hours. Tmax is reported to be 40-120 minutes according to another pharmacokinetic study.

Half Life

3-4 hours (may range up to 9 hours). In severe renal impairment (5 to 20 mL/min creatinine clearance), the half-life increased to an average of 11.5 hours.

The half-life of clavulanic acid is reported to be similar to amoxicillin, and last 45-90 minutes. A study of radiolabeled clavulanic acid administered to 4 healthy volunteers determined a half-life of 0.8 h.

Clearance

The clearance of clavulanic acid in a pharmacokinetic study of 4 healthy volunteers administered a radiolabeled dose of clavulanic acid was 0.21 l/min. Another resource indicates the average clearance of clavulanic acid is 12.20 liters/h/70 kg. Dose adjustments may be required in patients with renal failure.

Elimination Route

About 40 to 65% of the clavulanic acid is excreted as unchanged drug in urine during the first 6 hours following ingestion. The metabolites of clavulanic acid are found to be excreted in the urine and feces and as carbon dioxide in expired air. Clavulanate is cleared by both renal and non-renal processes. About 17% of radiolabeled dose of clavulanic acid was found to be exhaled in expired air and 8% of a dose was found to be excreted in the feces.

Pregnancy & Breastfeeding use

Pregnancy: Pregnancy category B. There are no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Lactation: It is not known whether Cefixime is excreted in human milk. Consideration should be given to discontinuing nursing temporarily during treatment with this drug.

Use in Elderly

No special precautions are necessary. No dosage adjustment is required for elderly

Contraindication

Patients with known hypersensitivity to cephalosporin antibiotics, children under 6 months.

Special Warning

Use in Children: Safety and effectiveness of cefixime in children aged less than 6 months have not been established. For children younger than 12 years or weighing less than 50 kg, the usual dose is 8 mg/kg/day.

Use in elderly: No special precautions are necessary. Old age is not an indication for dose adjustment.

Dosage in renal impairment:

• Creatinine clearance: 20 ml/min or greater: normal dose
• Creatinine clearance: <20 ml/min or chronic ambulatory peritoneal dialysis
• Haemodialysis: daily dose should not exceed 200 mg.

Acute Overdose

Gastric lavage may be indicated; otherwise, no specific antidote exists. Cefixime is not removed in significant quantities from the circulation by hemodialysis or peritoneal dialysis. Adverse reactions in small numbers of healthy adult volunteers receiving single doses up to 2 g of Cefixime did not differ from the profile seen in patients treated at the recommended doses.

Storage Condition

Store in a cool and dry place below 30ºC

Innovators Monograph

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