Apoxyclav Tablet, Powder For Suspension
- 375 mg tablet: Each film coated tablet contains Amoxycillin 250 mg with Clavulanic acid 125 mg.
- 625 mg Tablet: Each film coated tablet contains Amoxycillin 500 mg with Clavulanic acid 125 mg.
- 1 gm Tablet: Each film coated tablet contains Amoxycillin 875 mg with Clavulanic acid 125 mg.
- Suspension: Each 5 ml reconstituted suspension contains Amoxycillin 125 mg and Clavulanic acid 31.25 mg.
- Forte/bid/DS Suspension: Each 5 ml reconstituted suspension contains Amoxycillin 400 mg and Clavulanic acid 57.50 mg
- 0.6 gm injection: Sterile powder in vials providing Amoxycillin 500 mg and Clavulanic Acid 100 mg.
- 1.2 gm injection: Sterile powder in vials providing Amoxycillin 1000 mg and Clavulanic Acid 200 mg.
Amoxycillin & Clavulanic Acidis an antibacterial combination consisting of the antibiotic Amoxicillin and the beta-lactamase inhibitor Clavulanic Acid.
Amoxicillin has a broad spectrum of bactericidal activity against many Gram-positive & Gram-negative microorganisms but it is susceptible to degradation by beta-lactamases and therefore the spectrum of activity does not include microorganisms, which produce these enzymes.
Clavulanic acid possesses the ability to inactivate a wide range of beta-lactamase enzymes commonly found in microorganisms resistant to penicillins and cephalosporins. Thus Clavulanic acid in combination of Amoxicillin and Clavulanic acid protects Amoxicillin from degradation by beta-lactamase enzymes and effectively extends the antibiotic spectrum to embrace a wide range of microorganisms.
Amoxycillin & Clavulanic Acid is used for short-term treatment of bacterial infections at the following sites:
- Upper respiratory tract infections (including ENT); e.g., tonsillitis, sinusitis, otitis media.
- Lower respiratory tract infections; e.g., acute and chronic bronchitis, lobar and bronchopneumonia.
- Genito-urinary tract infections; e.g., cystitis, urethritis, pyelonephritis.
- Skin and soft tissue infections.
- Bone and joint infections; e.g., osteomyelitis.
- Other infections; e.g., septic abortion, puerperal sepsis, intra-abdominal sepsis, etc.
Apoxyclav is also used to associated treatment for these conditions: Acute Bacterial Sinusitis (ABS), Acute Otitis Media, Acute Otitis Media (AOM), Bacterial Infections, Community Acquired Pneumonia (CAP), Duodenal ulcer caused by helicobacter pylori, Genitourinary infections, Helicobacter Pylori Infection, Lower Respiratory Tract Infection (LRTI), Peptic Ulcer With H. Pylori Infection, Sinusitis, Skin and Subcutaneous Tissue Bacterial Infections, Urinary Tract Infection, Acute, uncomplicated Gonorrhea, Ear, nose, and throat 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 Apoxyclav works
Amoxicillin competitively inhibits penicillin-binding protein 1 and other high molecular weight penicillin binding proteins. Penicillin bind proteins are responsible for glycosyltransferase and transpeptidase reactions that lead to cross-linking of D-alanine and D-aspartic acid in bacterial cell walls. Without the action of penicillin binding proteins, bacteria upregulate autolytic enzymes and are unable to build and repair the cell wall, leading to bacteriocidal action.
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.
- Adults and children over 12 years: One 375 mg tablet 3 times a day. In severe infection one 625 mg tablet 3 times a day or one 1 gm tablet two times a day.
- Children of 6-12 years: 2 teaspoonful Powder for Suspension every 8 hours.
- Children of 1 -6 years: 1 teaspoonful Powder for Suspension every 8 hours.
- Children below 1 year: 25 mg/kg/day in divided doses every 8 hours.
- Adults and children over 12 years: 1.2 g every 6-8 hours
- Children up to 3 months: 30 mg/kg every 8 hours (every 12 hours in the perinatal period and in premature infants)
- Child 3 months to 12 years: 30 mg/kg every 6-8 hours.
Suspension: Shake the bottle well before adding water. Then add 12 tea spoonful (60 ml) of boiled and cooled water to the bottle and shake well to make 100 ml suspension.
Amoxycillin 500 mg Injection:
- Intramuscular : Add 2.5 ml water for injection to Amoxycillin 500 mg injection vial.
- Intravenous : Dissolve Amoxycillin 500 mg injection in 10 ml water for injection.
Side effects, as with Amoxicillin, are uncommon and mainly of a mild and transitory nature. Diarrhoea, pseudomembranous colitis, indigestion, nausea, vomiting and candidiasis have been reported. If gastrointestinal side effects occur with oral therapy, that may be reduced by taking Amoxycillin & Clavulanic Acid at the start of meals. Hepatitis and cholestatic jaundice have been reported rarely but are usually reversible. Urticarial and erythematous rashes sometimes occur.
Rarely erythema multiforme, Stevens-Johnson Syndrome and exfoliative dermatitis have been reported. In common with other beta-lactam antibiotics angioedema and anaphylaxis have been reported.
Patients experiencing an overdose may present with hematuria, oliguria, abdominal pain, acute renal failure, vomiting, diarrhea, rash, hyperactivity, and drowsiness. Treat overdose with symptomatic and supportive treatment, which may include emesis or hemodialysis.
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 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.
Amoxycillin & Clavulanic Acid should be used with care in patients on anti-coagulation therapy or with severe hepatic dysfunction. In patients with moderate or severe renal impairment, dosage should be adjusted. During the administration of high dose of Amoxycillin & Clavulanic Acid adequate fluid intake and urinary output should be maintained to minimize the possibility of crystalluria.
Prolongation of bleeding time and prothrombin time have been reported in some patients receiving Coamoxiclav. In common with other broad-spectrum antibiotics, Co-amoxiclav may reduce the efficacy of oral contraceptives and patient should be warned accordingly. Concomitant use of allopurinol during treatment with amoxycillin can increase the likelihood of allergic skin reactions. There are no data on the concomitant use of Co-amoxiclav and allopurinol.
Volume of Distribution
The central volume of distribution of amoxicillin is 27.7L.
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.
Amoxicillin is approximately 60% bioavailable. A 250mg dose of oral amoxicillin reaches a Cmax 3.93±1.13mg/L with a Tmax 1.31±0.33h and an AUC of 27.29±4.72mg*h/L. A 875mg dose of oral amoxicillin reaches a Cmax 11.21±3.42mg/L with a Tmax 1.52±0.40h and an AUC of 55.04±12.68mg*h/L.
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.
The half life of amoxicillin is 61.3 minutes.
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.
The mean clearance of amoxicillin is 21.3L/h.
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.
125mg to 1g doses of amoxicillin are 70-78% eliminated in the urine after 6 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
Amoxicillin and Clavulanic acid has been used orally in human pregnancy in a limited number of cases with no untoward effect; however use of Amoxycillin & Clavulanic Acid in pregnancy is not recommended unless considered essential by the physician. During lactation, trace quantities of Amoxicillin can be detected in breast milk.
History of Penicillin hypersensitivity. Attention should be paid to possible cross sensitivity with other beta-lactam antibiotics e.g., cephalosporins. Also contraindicated for patients with previous history of Amoxycillin & Clavulanic Acid or penicillin associated cholestatic jaundice.
Dosage in renal impairment: The dose should be adjusted in case of patients with renal impairment.Adults or Children:
- Mild impairment (CrCl > 30 ml/min): No change in dose.
- Moderate impairment (CrCl 10- 30 ml/min): 625 mg tablet 12 hourly.
- Severe impairment (CrCl < 10 ml/min): Not more than one tablet 12 hourly; 625 mg tablet is not recommended.
Dosage in hepatic impairment: Dose with caution; monitor hepatic function at regular intervals.This may be taken without regard to meals; however, absorption of Clavulanate potassium is enhanced when Amoxicillin/Clavulanic acid is administered at the start of a meal. To minimize the potential for gastrointestinal intolerance, Amoxicillin/Clavulanic acid should be taken at the start of the meal.
Problems of overdose with Co-amoxiclav are unlikely to occur, if encountered gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident. Co-amoxiclav may be removed from the circulation by haemodialysis.
Should be stored at a temperature not exceeding 25° C or below. Protect from light and moisture. Once reconstituted suspension should be kept in refrigerator (but not frozen) and should be used by 7 days.