Xofex Xl

Uses

URTIs

-Pharyngitis

-Tonsillitis

LRTIs

-Acute exacerbations of chronic bronchitis

-Acute community acquired pneumonia

SSTIs

UTIs

-Cystitis

-Uncomplicated urinary tract infections

Enteric fever

General gonorrhea and rectal gonococcal infections.

Xofex Xl is also used to associated treatment for these conditions: Acute Bacterial Exacerbation of Chronic Bronchitis (ABECB), Acute Otitis Media, Acute Sinusitis, Acute Tracheobronchitis, Acute maxillary sinusitis, Bacterial Infections, Bacterial Pneumonia, Community Acquired Pneumonia (CAP), Gonorrhea, Lower Respiratory Tract Infection (LRTI), Otitis Media (OM), Pharyngitis, Skin and Soft Tissue Infections, Streptococcal Pharyngitis, Streptococcal tonsillitis, Superinfection bacterial, Tonsillitis, Uncomplicated Urinary Tract Infections, Upper Respiratory Tract Infection, Uncomplicated Lower Respiratory Tract Infection (LRTI), Uncomplicated Upper Respiratory Tract Infection, Uncomplicated Urethritis gonococcal, Uncomplicated skin and subcutaneous tissue bacterial infectionsAcute 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 Xofex Xl works

Cefpodoxime is active against a wide spectrum of Gram-positive and Gram-negative bacteria. Cefpodoxime is stable in the presence of beta-lactamase enzymes. As a result, many organisms resistant to penicillins and cephalosporins, due to their production of beta-lactamase, may be susceptible to cefpodoxime. Cefpodoxime is inactivated by certain extended spectrum beta-lactamases. The bactericidal activity of cefpodoxime results from its inhibition of cell wall synthesis. The active metabolite of cefpodoxime binds preferentially to penicillin binding protein 3, which inhibits production of peptidoglycan, the primary constituent of bacterial cell walls.

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

Xofex Xl dosage

Pharyngitis or tonsillitis:- (Duo-5 LS) 100 mg 12 hourly for 5 to 10 days

Uncomplicated urinary tract infections: (Duo-5 LS) 100 mg 12 hourly for 7 days

Complicated urinary tract infections: (Duo-5) 200 mg 12 hourly for7 days

Acute community acquired pneumonia: (Duo-5) 200 mg 12 hourly for 14 days

Acute bacterial exacerbations of chronic bronchitis: (Duo-5) 200 mg 12 hourly for 10 days

Uncomplicated gonorrhea and rectal gonococcal infections: (Duo-5) single dose

Skin and skin structure infections: (Duo-5) 200-400 mg 12 hourly for 7 to 14 days

Acute maxillary sinusitis: (Duo-5) 200 mg 12 hourly for 10 days

Enteric fever: (Duo-5) 200 mg 12 hourly for 7 to 14 days

Patients with renal dysfunction: For patients with severe renal impairment (< 30 ml/min creatinine clearance), the dosing intervals should be increased to 24 hourly. In patients maintained on hemodialysis, the dose frequency should be 3 times/week after hemodialysis.

Patients with cirrhosis: Cefpodoxime pharmacokinetics in cirrhotic patients (with or without ascites) is similar to those in healthy subjects. Dose adjustment is not necessary in this population.

Direction for Reconstitution of suspension:

For 100 ml suspension : Add 50 ml (10 measuring spoonful) of boiled and cooled water to the dry mixture in the bottle. For ease of preparation add water to the bottle in two portions. Shake well after each addition until all the powder is in suspension.

For 50 ml suspension : Add 25 ml (5 measuring spoonful) of boiled and cooled water to the dry mixture in the bottle. For ease of preparation add water to the bottle in two portions. Shake well after each addition until all the powder is in suspension.

For 50 ml DS suspension : Add 25 ml (5 measuring spoonful) of boiled and cooled water to the dry mixture in the bottle. For ease of preparation add water to the bottle in two portions. Shake well after each addition until all the powder is in suspension.

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 10 days.

Side Effects

It has very few side effects. The side effects include diarrhoea, nausea, skin and vaginal fungal infection, vulvo-vaginal infections, abdominal pain and headache.

Toxicity

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

Cross hypersensitivity in penicillin sensitive patients, leading to serious acute hypersensitivity reactions may need treatment with epinephrine along with other emergency measures such as intravenous fluids, oxygen, airway management and intravenous antihistamine, as clinically indicated.

Interaction

Probenecid: Renal excretion of Cefpodoxime proxetil was inhibited by Probenecid and resulted in an approximately 31% increase in AUC.

Nephrotoxic drugs: Close monitoring of renal function is advised when Cefpodoxime proxetil is administered concomitantly with compounds of known nephrotoxic potential.

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

Cefpodoxime proxetil is a prodrug that is absorbed from the gastrointestinal tract and de-esterified to its active metabolite, cefpodoxime. Following oral administration of 100 mg of cefpodoxime proxetil to fasting subjects, approximately 50% of the administered cefpodoxime dose was absorbed systemically.

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

2.09 to 2.84 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

Over the recommended dosing range (100 to 400 mg), approximately 29 to 33% of the administered cefpodoxime dose was excreted unchanged in the urine in 12 hours.

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

Cefpodoxime is pregnancy category B. And Clavulanic acid is pregnancy category B.

Contraindication

It is contraindicated in patients with a known allergy to cefpodoxime and clavulanic acid or to the cephalosporin group of antibiotics.

Special Warning

Patients with renal dysfunction: For patients with severe renal impairment (< 30 ml/min creatinine clearance), the dosing intervals should be increased to 24 hourly. In patients maintained on hemodialysis, the dose frequency should be 3 times/week after hemodialysis.

Patients with cirrhosis: Cefpodoxime pharmacokinetics in cirrhotic patients (with or without ascites) is similar to those in healthy subjects. Dose adjustment is not necessary in this population.

Acute Overdose

Symptoms: Nausea, vomiting, epigastric distress and diarrhoea.

Management: Haemodialysis or peritoneal dialysis may be useful in the event of a serious toxic reaction particularly if renal function is compromised.

Interaction with other Medicine

Probenecid: Renal excretion of Cefpodoxime proxetil was inhibited by Probenecid and resulted in an approximately 31% increase in AUC.

Nephrotoxic drugs: Close monitoring of renal function is advised when Cefpodoxime proxetil is administered concomitantly with compounds of known nephrotoxic potential.

Storage Condition

Store in cool and dry place. Keep away from children.

Innovators Monograph

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