Sullivan

Tab 625 mg: Each film-coated tablet contains: Amoxicillin (as trihydrate) 500 mg, Clavulanic Acid (as Clavulanate Potassium) 125 mg.
Tab 1 g: Each film-coated tablet contains: Amoxicillin (as Trihydrate), USP 875 mg, Clavulanic Acid (as Clavulanate potassium) 125 mg.
Powd for oral susp 125 mg/31.25 mg: Each 5 mL contains (1 teaspoonful) of reconstituted product contains: Amoxicillin (as trihydrate) 125 mg, Clavulanic Acid (as Clavulanate Potassium) 31.25 mg.
Powd for oral susp 250 mg/62.5 mg: Amoxicillin (as trihydrate) 250 mg, Clavulanic Acid as Clavulanate Potassium) 62.5 mg.
Powd for oral susp 400 mg/57 mg: Amoxicillin (as trihydrate) 400 mg, Clavulanic Acid as Clavulanate Potassium) 57 mg.

Pharmacology: Mechanism of Action: Amoxicillin acts through inhibition of biosynthesis of the bacterial cell wall mucopeptide. It is a bactericidal against susceptible organisms during the stage of active multiplication. Amoxicillin is active against many Gram-positive and Gram-negative pathogens. However, it is susceptible to degradation by beta-lactamase and therefore its spectrum does not include organisms which produce these enzymes. Clavulanic acid is a beta-lactam structurally related to the penicillins, found in microorganisms resistant to penicillins.
The formulation of amoxicillin with clavulanic acid protects amoxicillin from degradation by beta-lactamase enzymes and effectively extends the antibiotic spectrum of amoxicillin to include many bacteria normally resistant to amoxicillin and other beta-lactam antibiotics.
Pharmacodynamics: Tab 1 g: Amoxicillin is an orally active member of the penicillin family. In amoxicillin, the benzyl ring in site change extends the range of antimicrobial activity, the gram-negative bacteria. It is bactericidal for both gram-positive and negative bacteria.
Clavulanate is a β-lactam antibiotic and interacts with β-lactamase, this interaction may lead to enzyme induction, inactivation of the enzyme and bacteriolysis of the β-lactam ring is used clinically only in combination with amoxicillin. Amoxicillin kills bacteria by interfering with the synthesis of the bacterial cell wall. As the lactamase enzyme secreted by the bacteria destroys amoxicillin, the drug is ineffective in the most staphylococcal infections. Increasing percentage of Salmonella spp., E. coli, Proteus mirabilis, Shigella spp. are not sensitive to amoxicillin. The spectrum of activity of Amoxicillin may be extended by the concomitant use of β-lactamase inhibitors such as clavulanic acid. Clavulanic acid has been reported to enhance activity of amoxicillin, against several species not generally considered sensitive. Clavulanate by itself has little antibacterial activity. However, in association with amoxicillin, it produces an antibiotic agent of broad-spectrum.
Pharmacokinetics: Tab 625 mg/Powd for oral susp 125 mg/31.25 mg/Powd for oral susp 250 mg/62.5 mg/Powd for oral susp 400 mg/57 mg: Amoxicillin and clavulanate potassium are both well absorbed after oral administration and are stable in the presence of gastric acid. Food does not affect the absorption and this combination product may be given without regard to meals. The oral bioavailability of amoxicillin and clavulanic acid are approximately 90% and 75% respectively.
Clavulanic acid has about the same plasma elimination half-life (1 hr) as that of amoxicillin (1.5 hrs).
Amoxicillin and clavulanic acid are widely distributed to most tissues and body fluids including peritoneal fluid, blister fluid, pleural fluid, middle ear fluid, intestinal mucosa, bone, gallbladder, lungs, female reproductive tissues and bile. The secretions is low. Amoxicillin and clavulanic acid readily cross the placenta and are distributed into breast milk into low concentrations. Amoxicillin is bound to serum proteins to an extent of 17-20% while clavulanic acid is 20-30% bound to serum proteins.
Approximately 10% of the dose of amoxicillin and less than 50% of the dose of clavulanic acid are metabolized. Amoxicillin and clavulanic acid are eliminated primarily unchanged through the renal route (glomerular filtration and tubular secretion). Approximately 50-70% of amoxicillin and 25-40% of clavulanic acid are excreted unchanged in urine within the first 6 hours after administration.
Tab 1 g: Amoxicillin and clavulanate potassium are both well absorbed after oral administration and are stable in the presence of gastric acid. Food does not affect the absorption and this combination product may be given without regard to meals. The oral bioavailability of amoxicillin and clavulanic acid is approximately 90% and 75% respectively.
Clavulanic acid has about the same plasma elimination half-life (1 hour) as that of amoxicillin (1.3 hours).
Amoxicillin and clavulanic acid are both widely distributed to most tissues and body fluids including peritoneal fluid, blister fluid, pleural fluid, middle fluid, intestinal mucosa, bone, gallbladder, lungs, female reproductive tissues, and the bile. The penetration into CSF through non-inflamed meninges and into purulent bronchial secretions is low. Amoxicillin and clavulanic acid readily cross the placenta and are distributed into breast milk in low concentrations. Amoxicillin is bound to serum proteins to an extent of 17-20% while clavulanic acid is 20-30% bound to serum proteins.
Approximately 10% of the dose of amoxicillin and less than 50% of dose of clavulanic acid are metabolized.
Amoxicillin and clavulanic acid are eliminated primarily unchanged through the renal route (glomerular filtration and tubular secretion).
Approximately 50-78% of amoxicillin and 25-40% of clavulanic acid are excreted unchanged in urine within the first 6 hours after administration.

Tab 625 mg/Powd for oral susp 125 mg/31.25 mg/Powd for oral susp 250 mg/62.5 mg/Powd for oral susp 400 mg/57 mg: Amoxicillin and Clavulanic Acid is used for actinomycosis, anthrax, biliary tract infections, bronchitis, endocarditis (particularly prophylaxis), gastroenteritis (including salmonella enteritis), gonorrhea, Lyme disease mouth infections, otitis media, pneumonia, spleen disorders, pneumococcal infections prophylaxis, typhoid & paratyphoid fever and urinary tract infections.
Tab 1 g: Co-Amoxiclav is Indicated for the treatment of following infections caused by susceptible pathogens: Lower respiratory tract infections, acute otitis media, sinusitis, urinary tract infections, skin and soft tissue infections.
Co-Amoxiclav is also indicated for bacterial infections likely to be caused by amoxicillin-resistant beta-lactamase producing strains and that treatment should not usually exceed 14 days.
It is also considered for the following indications: Recurrent tonsilitis.
Acute exacerbations of chronic bronchitis, bronchopneumonia.
Urinary tract infection especially recurrent & complicated but not prostatitis.
Septic abortion, pelvic or puerperal sepsis & intra-abdominal sepsis.
Cellulitis, animal bites & severe dental abscess with spreading cellulitis.

Tab 625 mg/Powd for oral susp 125 mg/31.25 mg/Powd for oral susp 250 mg/62.5 mg/Powd for oral susp 400 mg/57 mg: Adult and children over 12 years old: Severe infections: One 625 mg tablet three times a day or as prescribed by the physician.
Children: 7-12 years old: 10 mL (1 tablespoonful) 156.25 mg suspension three times a day or 5 mL (1 teaspoonful) 312.5 mg suspension three times a day or as prescribed by the physician.
2-6 years old: 5 mL (1 teaspoonful ) 156.25 mg suspension three times a day or as prescribed by the physician.
2.5 mL (½ teaspoon) 312.5 mg suspension three times a day or as prescribed by the physician.
9 months-1 year old: 2.5 mL (½ teaspoon) 156.25 mg suspension three times a day or as prescribed by the physician.
7-12 years: 400 mg/57 mg every 12 hours or as prescribed by the physician.
2-6 years: 200 mg/28.5 mg every 12 hours or as prescribed by the physician.
9 months-1 year: 100 mg/14.25 mg every 12 hours or as prescribed by the physician.
Under 20 kg bodyweight dose of 20-40 mg per kg daily in divided dose every 12 hours.
Tab 1 g: Severe infections: One tablet containing 875 mg of Amoxicillin & 125 mg of Clavulanic acid every 12 hours or as prescribed by the physician.

Tab 1 g: Sign and Symptoms: Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident. Amoxicillin crystalluria, in some cases leading to renal failure, has been observed.
Treatment: GI symptoms may be treated symptomatically, with attention to the water/electrolyte balance. Co-amoxiclav can be removed from the circulation by hemodialysis.
Children (additional statement): A prospective study of 51 pediatric patients at a poison control center suggested that overdosages of less than 250 mg/kg of amoxicillin are not associated with significant clinical symptoms and do not require gastric emptying.

Tab 625 mg/Powd for oral susp 125 mg/31.25 mg/Powd for oral susp 250 mg/62.5 mg/Powd for oral susp 400 mg/57 mg: A history of allergic reactions to beta-lactam antibiotics, penicillin hypersensitivity, history of Amoxicillin and Clavulanic Acid associated jaundice or hepatic dysfunction.
Tab 1 g: A history of allergic reactions to beta-lactam antibiotics.

Changes in the liver function test have been observed in some patients receiving Amoxicillin and Clavulanic Acid. Therefore, dosage should be reduced for patients with severe renal impairment. The clinical significance of the change is uncertain but Amoxicillin and Clavulanic Acid should be used with caution in patients with evidence of hepatic dysfunction. Cholestatic jaundice, which may be severe, but is usually reversible, has been reported rarely. Amoxicillin and Clavulanic Acid should be avoided if glandular fever is suspended. Prolonged use may also occasionally result in overgrowth on non-susceptible organisms.
Tab 1 g: Signs and symptoms may not become apparent for up to six weeks after treatment ceased. Erythematous rashes have been associated with glandular fever in patients receiving Amoxicillin.

Tab 1 g: Use in Pregnancy: Reproduction studies in animals (mice and rats at doses up to 10 times the human dose) with orally and parenterally administered co-amoxiclav have shown no teratogenic effects. In a single study in women with pre-term, premature rupture of the fetal membrane (pPROM), it is reported that prophylactic treatment with Co-amoxiclav may be associated with an increased risk of necrotizing enterocolitis in neonates. As with all medicines, use should be avoided in pregnancy, unless considered essential by the physician.
Use in Lactation: Co-amoxiclav may be administered during the period of lactation. With the exception of the risk of sensitization, associated with the excretion of trace quantities in breast milk, there are no known detrimental effects for the breast-fed infant.

Tab 625 mg/Powd for oral susp 125 mg/31.25 mg/Powd for oral susp 250 mg/62.5 mg/Powd for oral susp 400 mg/57 mg: Hepatitis and cholestatic jaundice have been reported with the combination amoxicillin with clavulanic acid, the clavulanic acid component has been implicated erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis, exfoliative dermatitis, nausea, vomiting, diarrhea, rashes and antibiotic associated colitis have been occasionally noted.
Tab 1 g: Significant: Diarrhea, fungal or bacterial superinfection, convulsions (at high doses or in patients with renal impairment), morbilliform rash (in) patients with mononucleosis). Rarely, crystalluria (IV), prothrombin time prolongation.
Blood and lymphatic system disorders: Hemolytic anemia, reversible agranulocytosis. Rarely, thrombocytopenia, reversible leucopenia or neutropenia.
Gastrointestinal disorders: Nausea, vomiting, indigestion, black hairy tongue.
Immune system disorders: Serum sickness-like syndrome, urticaria, hypersensitivity, vasculitis.
Infections and Infestations: Mucocutaneous candidiasis.
Investigations: Increased AST/ALT.
Nervous system disorders: Headache, dizziness, reversible hyperactivity.
Renal and urinary disorders: Interstitial nephritis.
Reproductive system and breast disorders: Vaginal mycosis.
Skin and subcutaneous tissue disorders: Rash, pruritus, Stevens-Johnson syndrome. Rarely, erythema multiforme.
Potentially Fatal: Severe hypersensitivity reactions, including anaphylactoid and severe cutaneous reactions (e.g., acute generalized exanthematous pustulosis); Clostridium difficile-associated diarrhea or pseudomembranous colitis. Rarely, hepatic dysfunction (e.g., cholestatic jaundice, hepatitis).

Tab 1 g: Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular secretion of amoxicillin. Concomitant use with amoxicillin-clavulanate may result in increased and prolonged blood levels of amoxicillin, but not of clavulanic acid.
Concomitant use of allopurinol during treatment with amoxicillin can increase the likelihood of allergic skin reactions. There are no data on the concomitant use of co-amoxiclav and allopurinol. In common with other antibiotics, co-amoxiclav may affect the gut flora, leading to lower estrogen reabsorption and reduced efficacy of combined oral contraceptives.
In the literature, there are rare cases of increased international normalized ratio in patients maintained on acenocoumarol or warfarin and prescribed a course of amoxicillin. If co-administration is necessary, the prothrombin time or international normalized ratio should be carefully monitored with the addition or withdrawal of amoxicillin.
In patients receiving mycophenolate mofetil, reduction in pre-dose concentration of the active metabolite mycophenolic acid of approximately 50% has been reported following commencement of oral amoxicillin plus clavulanic acid. The change in pre-dose level may not accurately represent changes in overall MPA exposure.

Direction For Reconstitution: Co-Amoxiclav 125 mg/31.25 mg per 5 mL powder for suspension: To make 60 mL reconstituted suspension, mix thoroughly the contents with 50 mL cooled water and shake well until the powder are evenly suspended. After reconstitution, suspension is stable for 7 days under refrigeration (2-8°C).
To make 30 mL reconstituted suspension, mix thoroughly the contents with 25 mL cooled water and shake well until the powder are evenly suspended. After reconstitution, suspension is stable for 7 days under refrigeration (2-8°C).
Co-Amoxiclav 250 mg/62.5 mg per 5 mL powder for suspension: To make 60 mL reconstituted suspension, mix thoroughly the contents with 50 mL cooled water and shake well until the powder are evenly suspended. After reconstitution, suspension is stable for 7 days under refrigeration (2-8°C).
To make 30 mL reconstituted suspension, mix thoroughly the contents with 25 mL cooled water and shake well until the powder are evenly suspended. After reconstitution, suspension is stable for 7 days under refrigeration (2-8°C).
Co-Amoxiclav 400 mg/57 mg per 5 mL powder for suspension: To make 70 mL reconstituted suspension first shake bottle to loosen powder. Add 58 mL cooled water and shake well until the powder is evenly suspended or add water to 2/3 of fill line level on the label of the bottle. After reconstitution, suspension is stable for 7 days under refrigeration (2-8°C).

Tab: Store at temperatures not exceeding 25°C.
Powd for oral susp 125 mg/31.25 mg/Powd for oral susp 250 mg/62.5 mg: Unreconstituted product should be stored at temperatures below 25°C.
Shake well before using.
Powder for susp 400 mg/57 mg: Store at temperatures not exceeding 30°C.
Shake well before use.

Penicillins

J01CR02 - amoxicillin and beta-lactamase inhibitor ; Belongs to the class of penicillin combinations, including beta-lactamase inhibitors. Used in the systemic treatment of infections.

Rx