Aelxim L

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)

Vancomycin-Resistant Enterococcus faecium infections including cases with concurrent bacteremia.

Nosocomial pneumonia caused by Staphylococcus aureus (methicillin-susceptible and -resistant strains) or Streptococcus pneumoniae (including multi-drug resistant strains). Combination therapy may be clinically used if the documented or presumptive pathogens include Gram-negative organism.

Complicated skin and skin structure infections, including diabetic foot infections (without concomitant osteomyelitis) caused by Staphylococcus aureus (methicillin-susceptible and ¬resistant strains), Streptococcus pyogenes, or Streptococcus agalactiae.

Uncomplicated skin and skin structure infections caused by Staphylococcus aureus (methicillin-susceptible only) or Streptococcus pyogenes.

Community-acquired pneumonia caused by Streptococcus pneumoniae (including multi-drug resistant strains) including cases with concurrent bacteremia, or Staphylococcus aureus (methicillin-susceptible strains only)

Aelxim L 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 GonorrheaCommunity Acquired Pneumonia (CAP) caused by Staphylococcus Aureus Infections, Community acquired pneumonia caused by Susceptible strains of Streptococcus pneumoniae, Complicated Skin and Skin Structure Infection caused by Staphylococcus Aureus Infections, Complicated Skin and Skin Structure Infection caused by Streptococcus Agalactiae Infection, Complicated Skin and Skin Structure Infection caused by Streptococcus Pyogenes Infection, Nosocomial Pneumonia caused by Staphylococcus Aureus Infections, Nosocomial Pneumonia caused by Streptococcus Pneumoniae Infections, Uncomplicated Skin and Skin Structure Infections caused by Staphylococcus Aureus Infections, Uncomplicated Skin and Skin Structure Infections caused by Streptococcus Pyogenes Infection, Vancomycin-resistant Enterococcus faecium infection

How Aelxim L 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.

Linezolid exerts its antibacterial effects by interfering with bacterial protein translation. It binds to a site on the bacterial 23S ribosomal RNA of the 50S subunit and prevents the formation of a functional 70S initiation complex, which is essential for bacterial reproduction, thereby preventing bacteria from dividing.

Point mutations in the bacterial 23S rRNA can lead to linezolid resistance, and the development of linezolid-resistant Enterococcus faecium and Staphylococcus aureus have been documented during its clinical use. As antimicrobial susceptibility patterns are geographically distinct, local antibiograms should be consulted to ensure adequate coverage of relevant pathogens prior to use.

Dosage

Aelxim L 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

Patients who commence treatment on the parenteral formulation may be switched to either oral presentation when clinically indicated. In such circumstances, no dose adjustment is required as Linezolid has an oral bioavailability of approximately 100%. The injection should be administered over a period of 30 to 120 minutes. The film coated tablets or oral suspension may be taken with or without food.Adults and Adolescents (12 Years and Older):

• Complicated skin and skin structure infections & Community-acquired pneumonia, including concurrent bacteremia: 600 mg IV or oral b.i.d. for 10 to 14 days.
• Vancomycin-resistant Enterococcus faecium infections, including concurrent bacteremia: 600 mg IV or oral b.i.d. for 14-28

For Pediatric Patients (Birth through 11 Years of Age):

• Complicated skin and skin structure infections & Community-acquired pneumonia, including concurrent bacteremia: 600 mg IV or oral b.i.d. for 10 to 14 days.
• Vancomycin-resistant Enterococcus faecium infections, including concurrent bacteremia: 600 mg IV or oral b.i.d.for 14-28.

Neonates <7 days: Most pre-term neonates <7 days of age (gestational age <34 weeks) have lower systemic linezolid clearance values and larger AUC values than many full-term neonates and older infants. These neonates should be initiated with a dosing regimen of 10 mg/kg every 12 hours. Consideration may be given to the use of 10 mg/kg in every eight hours regimen in neonates with a sub-optimal clinical response. All neonatal patients should receive 10 mg/kg t.i.d. by 7 days of life.

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.

Intravenous Administration: Linezolid IV Injection is supplied in single-use, ready-to-use infusion bags. Parenteral drug products should be inspected visually for particulate matter prior to administration. Minute leaks should be checked by firmly squeezing the bag. If leaks are detected, the solution should be discarded, as sterility may be impaired. Linezolid IV Injection should be administered by intravenous infusion over a period of 30 to 120 minutes. The intravenous infusion bag should not be used in series connections. Additives should not be introduced into this solution. The infusion bag should be stored at room temperature and protected from freezing. Linezolid IV Injection may exhibit a yellow color that can intensify over time without adversely affecting potency.

Patients who commence treatment on the parenteral formulation may be switched to either oral presentation when clinically indicated. In such circumstances, no dose adjustment is required as Linezolid has an oral bioavailability of approximately 100%.

The injection should be administered over a period of 30 to 120 minutes. The film coated tablets or oral suspension may be taken with or without food.

Reconstitution of Oral Suspension: Shake the bottle to loosen powder. Add 75 ml (with the help of given cup) of boiled & 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. Shake the suspension well before use. Keep the bottle tightly closed. The reconstituted suspension should be stored in a cool & dry place. Use within 21 days after reconstitution.

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.

Most of the adverse events reported with Linezolid were mild to moderate in intensity. The most common adverse events in patients treated with Linezolid were diarrhea, headache and nausea. Other adverse included oral moniliasis, vaginal moniliasis, hypertension, dyspepsia, localized abdominal pain, pruritus, and tongue discoloration.

Toxicity

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

Clinical signs of overdosage observed in rats were decreased activity and ataxia (2000 mg/kg/day) and in dogs were vomiting and tremors (3000 mg/kg/day). Treatment of overdose should involve symptomatic and supportive measures and may include hemodialysis if clinically necessary.

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)

Patients who develop recurrent nausea or vomiting, unexplained acidosis, or low bicarbonate level while receiving Linezolid should receive immediate medical evaluation. Where administration of Linezolid and concomitant serotonergic agents is clinically appropriate, patients should be closely observed for signs and symptoms of serotonin syndrome such as cognitive dysfunction, hyperpyrexia, hyper reflexia and incoordination. If signs or symptoms occur physicians should consider discontinuation of either one or both agents. If the concomitant serotonergic agent is withdrawn, discontinuation symptoms can be observed. If patients experience symptoms of visual impairment, such as changes in visual acuity, changes in color vision, blurred vision, or visual field defect, prompt ophthalmic evaluation is recommended. Convulsions have been reported in patients when treated with Linezolid. In some of these cases, a history of seizures or risk factors for seizures was reported.

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.

Monoamine Oxidase Inhibition: Linezolid is a reversible, nonselective inhibitor of monoamine oxidase. Therefore, Linezolid has the potential for interaction with adrenergic and serotonergic agents.

Adrenergic Agents: Some individuals receiving Linezolid may experience a reversible enhancement of the pressor response to indirect-acting sympathomimetic agents, vasopressor or dopaminergic agents. Initial doses of adrenergic agents, such as dopamine or epinephrine, should be reduced and titrated to achieve the desired response.

Serotonergic Agents: Physicians should be alert to the possible signs and symptoms of serotonergic syndrome in patients receiving concomitant Linezolid and serotonergic agents.

Volume of Distribution

At steady-state, the volume of distribution of linezolid in healthy adults is approximately 40-50 liters.

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.

Linezolid is extensively absorbed following oral administration and has an absolute bioavailability of approximately 100%. Maximum plasma concentrations are reached within approximately 1 to 2 hours after dosing (T_max) and range from 8.1-12.9 mcg/mL after single doses and 11.0-21.2 mcg/mL after multiple dosing.

The absorption of orally administered linezolid is not significantly affected by co-administration with food and it may therefore be given without regard to the timing of meals.

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 elimination half-life is estimated to be between 5 and 7 hours.

Clearance

Total clearance of linezolid is estimated to be 100-200 mL/min, the majority of which appears to be non-renal. Mean renal clearance is approximately 40 mL/min, which suggests net tubular reabsorption, while non-renal clearance is estimated to account for roughly 65% of total clearance, or 70-150 mL/min on average. Variability in linezolid clearance is high, particularly for non-renal clearance.

Elimination Route

Urinary excretion is the primary means by which linezolid and its metabolic products are excreted. Following the administration of a radiolabeled dose of linezolid under steady-state conditions, approximately 84% of radioactivity was recovered in the urine, of which approximately 30% is unchanged parent drug, 40% is the hydroxyethyl glycine metabolite, and 10% is the aminoethoxyacetic acid metabolite. Fecal elimination is comparatively minor, with no parent drug observed in feces and only 6% and 3% of an administered dose found in the feces as the hydroxyethyl glycine metabolite and the aminoethoxyacetic acid metabolite, respectively.

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

Pregnancy Category C. There are no adequate and well-controlled studies in pregnant women. Linezolid should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Lactation: It is not known whether Linezolid is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Linezolid is administered to a nursing woman.

Contraindication

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

Linezolid formulations are contraindicated for use in patients who have known hypersensitivity to Linezolid or any of the other product components. Linezolid should not be used in patients taking any medicinal product which inhibits monoamine oxidases A or B (e.g. phenelzine, isocarboxazid) or within two weeks of taking any such medicinal product. Linezolid should not be administered to patients with uncontrolled hypertension, pheochromocytoma, thyrotoxicosis, carcinoid syndrome and/or patients taking directly and indirectly acting sympathomimetic agents (e.g. pseudoephedrine), vasopressive agents (e.g. epinephrine, norepinephrine), dopaminergic agents (e.g. dopamine, dobutamine), serotonin re-uptake inhibitors, tricyclic antidepressants, serotonin 5-HT1 receptor agonists (triptans), meperidine or buspirone.

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.

No cases of overdose have been reported. Symptomatic and supportive care is advised together with maintenance of glomerular filtration. Approximately 30% of a Linezolid dose is removed during 3 hours of haemodialysis. No data are available for the removal of Linezolid by peritoneal dialysis or haemoperfusion.

Storage Condition

Store in a cool and dry place below 30ºC

Should be stored at room temperature 25° C, away from light and moisture.

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