Cefuroxime Dextrose

Uses

- Pharyngitis/tonsillitis caused by Streptococcus pyogenes

- Acute bacterial otitis media caused by Streptococcus pneumoniae, Haemophilus influenzae (including beta lactamase-producing strains), Moraxella Catarrhalis (including beta-lactamase-producing strains) or Streptococcus pyogenes.

- Acute bacterial maxillary sinusitis caused by Streptococcus pneumoniae, or Haemophilus influenzae (nonbeta-lactamase-producing strains only)

- Lower respiratory tract infections including pneumoniae, caused by Streptococcus pneumoniae, Haemophilus influenzae (including beta lactamase-producing strains), Klebsiella spp., Staphylococcus aureus (penicillinase- and non-penicillinase-producing strains), Streptococcus pyogenes, Escherichia coli.

- Acute bacterial exacerbations of chronic bronchitis and secondary bacterial infections of acute bronchitis caused by Streptococcus penumoniae, Haemophilus influenzae (beta-lactamase negative strains), or Haemophilus parainfluenzae (beta-lactamase negative strains).

- Skin and Skin-Structure Infections caused by Staphylococcus aureus (penicillinase- and non-penicillinase-producing strains), Streptococcus pyogenes, Escherichia coli, Klebsiella spp., and Enterobacter spp.

- Urinary tract infections caused by Escherichia coli or Klebsiella pneumoniae.

- Bone and Joint Infections caused by Staphylococcus aureus (penicillinase- and non-penicillinase-producing strains).

- Gonorrhea : Uncomplicated and disseminated gonococcal infections due to Neiseria gonorrhoeae (penicillinase- and non-penicillinase-producing strains) in both males and females.

- Early Lyme disease (erythema migrans) caused by Borrelia burgdorferi.

- Septicemia caused by Staphylococcus aureus (penicillinase- and non-penicillinase-producing strains), Streptococcus pneumoniae, Escherichia coli, Haemophilus influenzae (including ampicillin-resistant strains), and Klebsiella spp.

- Meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae (including ampicillin-resistant strains), Neisseira menintitidis, and Staphylococcus aureus (penicillinase- and non-penicillinase-producing strains).

- Surgical Prophylaxis: Prophylaxis against infections in abdominal, pelvic, orthopedic, cardiac, pulmonary, esophageal and vascular surgery where there is increased risk for infection.

Dextrose is administered as a parenteral nutrition solution in the treatment of carbohydrate depletion and hypoglycaemic coma. Because of its high dextrose content it is used in the treatment of cerebral edema, shock, circulatory collapse, unconsciousness and to correct hyperkalaemia with or without insulin.

Cefuroxime Dextrose is also used to associated treatment for these conditions: Acute Bacterial Exacerbation of Chronic Bronchitis (ABECB), Animal bite, Bacterial Infections, Bloodstream Infections, Bone and Joint Infections, Gonorrhea, Impetigo, Lower Respiratory Tract Infection (LRTI), Lyme Disease, Maxillary Sinusitis, Meningitis, Skin and Subcutaneous Tissue Bacterial Infections, Urinary Tract Infection, Bacterial otitis media, Mild Streptococcal pharyngitis, Mild Streptococcal tonsillitis, Moderate Streptococcal pharyngitis, Moderate Streptococcal tonsillitisArrhythmia, Caloric Deficit, Edema of the cerebrum, Metabolic Alkalosis, Hypoglycemic reaction, Blood Specimen Collection, Electrolyte replacement, Nutritional supplementation, Parenteral Nutrition, Parenteral rehydration therapy, Plasmapheresis, Positive cardiac inotropic effect, Total parenteral nutrition therapy, Urine alkalinization therapy, Fluid and electrolyte maintenance therapy

How Cefuroxime Dextrose works

Cefuroxime, like the penicillins, is a beta-lactam antibiotic. By binding to specific penicillin-binding proteins (PBPs) located inside the bacterial cell wall, it inhibits 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 cefuroxime interferes with an autolysin inhibitor.

Glucose supplies most of the energy to all tissues by generating energy molecules ATP and NADH during a series of metabolism reactions called glycolysis. Glycolysis can be divided into 2 main phases where the preparatory phase is initiated by the phosphorylation of glucose by a hexokinase to form glucose 6-phosphate. The addition of the high-energy phosphate group activates glucose for subsequent breakdown in later steps of glycolysis and is the rate-limiting step. Products end up as substrates for following reactions, to ultimately convert C6 glucose molecule into two C3 sugar molecules. These products enter the energy-releasing phase where total of 4ATP and 2NADH molecules are generated per one glucose molecule. The total aerobic metabolism of glucose can produce up to 36 ATP molecules. This energy-producing reactions of glucose is limited to D-glucose as L-glucose cannot be phosphorlyated by hexokinase. Glucose can act as precursors to generate other biomolecules such as vitamin C. It plays a role as a signaling molecule to control glucose and energy homeostasis. Glucose can regulate gene transcription, enzyme activity, hormone secretion, and the activity of glucoregulatory neurons. The types, number and kinetics of glucose transporters expressed depends on the tissues and fine-tunes glucose uptake, metabolism, and signal generation in order to preserve cellular and whole body metabolic integrity .

Dosage

Cefuroxime Dextrose dosage

Oral :

INFECTIONS DOSAGE DURATION

Tablet

(May be administered without regard to meals)

Adolescents & adults(13 years & above)

Pharyngitis or Tonsillitis 250 mg twice daily 5-10 days

Acute bacterial maxillary sinusitis 250 mg twice daily 10 days

Acute bacterial exacerbation of chronic bronchitis 250-500 mg twice daily 10 days

Secondary bacterial infections of acute bronchitis 250-500 mg twice daily 5-10 days

Uncomplicated skin & skin-structure infections 250-500 mg twice daily 10 days

Uncomplicated urinary tract infection 125-250 mg twice daily 7-10 days

Uncomplicated gonorrhea 1000 mg single dose - - -

Lyme disease 500 mg twice daily 20 days

Paediatric patients (Upto12 years)

(Who can swallow tablets whole)

Pharyngitis or Tonsillitis 125 mg twice daily 5-10 days Acute otitis media 250 mg twice daily 10 days

Acute bacterial maxillary sinusitis 250 mg twice daily 10 days

Suspension

(Must be administered with food. Shake the bottle

well before each use)

Paediatric patients (3 months to 12 years)

Pharyngitis or Tonsillitis 20 mg/kg/day in two divided doses 5-10 days Acute otitis media 30 mg/kg/day in two divided doses 10 days

Acute bacterial maxillary sinusitis 30 mg/kg/day in two divided doses 10 days

Injection :

Adult: 750 mg three times daily by IM or IV injection. In severe infections, dose can be increased upto 1.5 gm three times daily by IV injection. The frequency may be increased to four times daily, if necessary, giving total daily doses of 3 to 6 gms.

Children (above 3 months of age): 30 - 100 mg/kg/day given in 3 or 4 equally divided doses. A dose of 60mg/kg/day is appropriate for most infections.

Neonate: 30 - 100 mg/kg/day given in 2 or 3 equally divided doses.

Surgical prophylaxis: 1.5 gm by IV injection at induction of anaesthesia; up to 3 further doses of 750 mg may be given by IV/IM injection every 8 hours for high risk procedures.

Sequential therapy in adults

Pneumonia: 1.5 gm IV injection twice daily for 2-3 days, followed by 500 mg twice daily (oral) for 7-10 days.

Acute exacerbations of chronic bronchitis: 750 mg twice daily (IM or IV injection) for 2-3 days, followed by 500 mg twice daily (oral) for 5-10 days. (Duration of both parenteral and oral therapy is determined by the severity of the infection and the clinical status of the patient.)

Other recommendations

In Gonorrhoea: Adult: 1.5g as a single dose (as 2 x 750mg injections intramuscularly with different sites, e.g. each buttock).

In Meningitis: Adults: 3gm IV injection three times daily. Children (above 3 months of age): 200-240 mg/kg/day by IV injection in 3 or 4 divided doses reduced to 100 mg/kg/day after 3 days or on clinical improvement. Neonate: 100 mg/kg/day by IV injection reduced to 50 mg /kg/day.

In bone and joint infections: Adult: 1.5 gm IV injection four times daily. Children (above 3 months of age): 150 mg/kg/day (not to exceed the maximum adult dose) in equally divided doses every 8 hours.

In impaired renal function: A reduced dose must be employed when renal function is impaired. Dosage in adults should be determined by the degree of renal impairment and the susceptibility of the causative organism according to the table below -

Creatinine clearance (ml/min) Dose Frequency

> 20 750 mg - 1.5 gm q8h

10-20 750 mg q12h

< 10 750 mg q24h*

* Since Cefuroxime is dialyzable, patients on hemodialysis should be given a further dose at the end of the dialysis.

In paediatric patients with renal insufficiency, the frequency of dosing should be modified consistent with the recommendations for adults.

The volume and rate of infusion of dextrose solution will depend upon the requirements of the individual patient and the judgement of the physician.

The maximum rate at which dextrose can be infused without producing glycosuria is 0.5 gm/kg/hr.

The usual recommended flow rate for adult is 10-35 drops per minute infused intravenously.

Intravenous-

Hyperkalaemia:

• Adult: 25-50 g combined with 10 units of regular insulin, administered over 30-60 minutes; may repeat if necessary. Alternatively, 25 g combined with 5-10 units of regular insulin infused over 5 minutes; may repeat if necessary.
• Child and infants: 0.5-1 g/kg (using 25% or 50% solution) combined with regular insulin (1 unit for every 4-5 g dextrose given); infuse over 2 hr, may repeat if necessary.

Intravenous-

Hypoglycaemia:

• Adult: 10-25 g (40-100 ml of 25% solution or 20-50 ml of 50% solution). Doses may be repeated in severe cases.
• Child: ≤6 mth: 0.25-0.5 g/kg/dose; >6 mth: 0.5-1 g/kg/dose. Doses may be repeated in severe cases. Max: 25 g/dose.

Oral-

Hypoglycaemia:

• Adult: 10-20 g as single dose; may repeat in 10 min if needed.
• Child: >2 yr: 10-20 g as single dose; may repeat in 10 min if needed.

Directions for reconstitution:

Shake the bottle well to loosen the powder. Add required amount (with the help of supplied measuring cup) of boiled and cooled water to the dry mixture in the bottle. Shake the bottle vigorously until all the powder is in suspension.

Note: Shake the bottle vigorously before each use. Keep the bottle tightly closed. The reconstituted suspension should be stored in a cool and dry place, preferably in a refrigerator and used within 10 days after reconstitution.

Kilbac 250 IM/IV Injection :

Intramuscular injection : Add 1 ml of supplied water for injection BP to the vial and shake.

Intravenous injection: Add 2 ml of supplied water for injection BP to the vial and shake. The solution should be slowly injected directly into a vein over a 3 to 5 minute period.

Kilbac 750 IM/IV Injection :

Intramuscular injection : Add 3 ml of supplied water for injection BP to the vial and shake.

Intravenous injection: Add 8 ml of supplied water for injection BP to the vial and shake. The solution should be slowly injected directly into a vein over a 3 to 5 minute period.

Kilbac 1.5 IV Injection :

Intravenous injection: Add 16 ml of supplied water for injection BP to the vial and shake. The solution should be slowly injected directly into a vein over a 3 to 5 minute period.

Pharmaceutical precaution

Cefuroxime tablet, powder for suspension and vial (for injection) should be kept in a cool (15° - 30°C) and dry place and protected from light.

It should not be administered by SC or IM route. Dextrose should be infused through the largest available peripheral vein.

Side Effects

Generally Cefuroxime is well tolerated. However, a few side effects like nausea, vomiting, diarrhea, abdominal discomfort or pain may occur. As with other broad-spectrum antibiotics, prolonged administration of Cefuroxime may result in overgrowth of nonsusceptible microorganisms. Rarely (<0.2%) renal dysfunction, anaphylaxis, angioedema, pruritis, rash and serum sickness like urticaria may appear.

Venous thrombosis, phlebitis, hypovolemia, hypervolemia, dehydration, oedema, fever, mental confusion, unconsciousness, hyperosmolar syndrome, hyperglycaemia, hypokalaemia, acidosis, hypophosphataemia, hypomagnesemia, polyuria, glycosuria, ketonuria, nausea, diarrhoea, polydipsia, vein irritation, tissue necrosis, pulmonary oedema, tachypnoea.

Toxicity

Allergic reactions might be expected, including rash, nasal congestion, cough, dry throat, eye irritation, or anaphylactic shock. Overdosage of cephalosporins can cause cerebral irritation leading to convulsions.

Oral LD50 value in rats is 25800mg/kg. The administration of glucose infusions can cause fluid and/or solute overloading resulting in dilution of the serum electrolyte concentrations, over-hydration, congested states, or pulmonary oedema. Hypersensitivity reactions may also occur including anaphylactic/anaphylactoid reactions from oral tablets and intravenous infusions.

Precaution

Cefuroxime should be given with care to patients receiving concurrent treatment with potent diuretics & who have history of colitis.

Concentrated dextrose solution should not be infused rapidly or for a long period. It may be hazardous in patients with impaired hepatic or renal function and severe sepsis.

Care should be taken to avoid circulatory overload, particularly in patients with cardiac insufficiency. Caution must be exercised in the administration of these injections to patients receiving corticosteroids or corticotropin. These injections should be used with caution in patients with overt or subclinical diabetes mellitus.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. Do not administer unless solution is clear and seal is intact.

Interaction

No potentially hazardous interactions have been reported.

There is no drug drug interaction and none well documented.

Volume of Distribution

The mean volume of distribution after intravenous infusion is 10.6L.

Elimination Route

Absorbed from the gastrointestinal tract. Absorption is greater when taken after food (absolute bioavailability increases from 37% to 52%).

Polysaccharides can be broken down into smaller units by pancreatic and intestinal glycosidases or intestinal flora. Sodium-dependent glucose transporter SGLT1 and GLUT2 (SLC2A2) play predominant roles in intestinal transport of glucose into the circulation. SGLT1 is located in the apical membrane of the intestinal wall while GLUT2 is located in the basolateral membrane, but it was proposed that GLUT2 can be recruited into the apical membrane after a high luminal glucose bolus allowing bulk absorption of glucose by facilitated diffusion . Oral preparation of glucose reaches the peak concentration within 40 minutes and the intravenous infusions display 100% bioavailability.

Half Life

Approximately 80 minutes following intramuscular or intravenous injection.

The approximate half-life is 14.3 minutes following intravenous infusion. Gut glucose half-life was markedly higher in females (79 ± 2 min) than in males (65 ± 3 min, P < 0.0001) and negatively related to body height (r = -0.481; P < 0.0001).

Clearance

The mean metabolic clearance rate of glucose (MCR) for the 10 subjects studied at the higher insulin level was 2.27 ± 0.37 ml/kg/min at euglycemia and fell to 1.51±0.21 ml/kg/ at hyperglycemia. The mean MCR for the six subjects studied at the lower insulin level was 1.91 ± 0.31 ml/kg/min at euglyglycemia.

Elimination Route

Glucose can be renally excreted.

Pregnancy & Breastfeeding use

Pregnancy: While all antibiotics should be avoided in the first trimester if possible. However, Cefuroxime has been safely used in later pregnancy to treat urinary and other infections.

Nursing mothers: Cefuroxime is excreted into the breast milk in small quantities. However, the possibility of sensitizing the infant should be kept in mind

Pregnancy Category C. Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Contraindication

Cefuroxime is contraindicated in patients with known allergy to Cephalosporins.

Concentrated dextrose solution is contraindicated in patients with Glucose-Galactose Malabsorption Syndrome and severe hydration. The infusion of hypertonic dextrose injections is contraindicated in patients having intracranial or intraspinal hemorrhage, in patients who are severely dehydrated, in patients who are anuric, and in patients in hepatic coma. Solutions containing dextrose may be contraindicated in patients with known allergy to corn or corn products.

Acute Overdose

Excessively large doses of all Cephalosporins can cause cerebral irritation and may cause convulsions. This complication is unlikely to occur in routine practice unless the patient is in renal failure. Hemodialysis or peritoneal dialysis can remove Cefuroxime.

Reevaluate patient's condition and institute appropriate symptomatic treatment.

Storage Condition

Tablet: Store below 30° C, protected from light and moisture.

Suspension: Store below 25° C, protected from light and moisture.

Injection: Store below 25° C, protected from light and moisture. Use reconstituted solution immediately. The reconstituted solution is stable for 2 hours at room temperature and for 12 hours when refrigerated at 2° - 8° C.

Store at 25°C.

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