HIGHLIGHT
Zisuva 625/Zisuva 1G

Zisuva 625/Zisuva 1G

amoxicillin + clavulanic acid

Manufacturer:

Zifam Pinnacle

Distributor:

Pinnacle House
Full Prescribing Info
Contents
Amoxicillin trihydrate, potassium clavulanate.
Description
Each 625-mg film coated tablet contains: Amoxicillin Trihydrate BP Equivalent to Amoxicillin 500 mg, Potassium Clavulanate BP (as Diluted Potassium Clavulanate BP) Equivalent to Clavulanic Acid 125 mg.
Each  1-g film coated tablet contains: Amoxicillin Trihydrate BP Equivalent to Amoxicillin 875 mg, Potassium Clavulanate BP (as Diluted Potassium Clavulanate BP) Equivalent to Clavulanic Acid 125 mg.
Excipients/Inactive Ingredients: q.s.
Action
Pharmacology: Amoxicillin and Potassium Clavulanate is an oral antibacterial combination consisting of the semisynthetic antibiotic amoxicillin and the β-lactamase inhibitor, Potassium Clavulanate (the potassium salt of clavulanic acid).
Clavulanic acid binds and inhibits beta-lactamases that inactivate amoxicillin resulting in amoxicillin having an expanded spectrum of activity. Amoxicillin inhibits bacterial cell wall synthesis by binding to one or more of the penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls, thus inhibiting cell wall biosynthesis. Bacteria eventually lyse due to ongoing activity of cell wall autolytic enzymes (autolysins and murein hydrolases) while cell wall assembly is arrested.
Pharmacokinetics: Amoxicillin and Potassium Clavulanate are well absorbed from the gastrointestinal tract after oral administration of amoxicillin and potassium clavulanate. Dosing in the fasted or fed state has minimal effect on the pharmacokinetics of amoxicillin. While amoxicillin and potassium clavulanate can be given without regard to meals, absorption of potassium clavulanate when taken with food is greater relative to the fasted state. In 1 study, the relative bioavailability of clavulanate was reduced when amoxicillin 1 potassium clavulanate was dosed at 30 and 150 minutes after the start of a high - fat breakfast. The safety and efficacy of amoxicillin and potassium clavulanate was taken without regard to meals.
Amoxicillin serum concentration achieved with amoxicillin and potassium clavulanate are similar to those produced by the oral administration of equivalent doses of amoxicillin alone. The half-life of amoxicillin after the oral administration of amoxicillin and potassium clavulanate is 1.3 hours and that of clavulanic acid is 1.0 hour. Approximately 50% to 70% of the amoxicillin and approximately 25% to 40% of the clavulanic acid are excreted unchanged in urine during the first 6 hours after administration of a single 250 mg or 500 mg tablet of amoxicillin and potassium clavulanate.
Concurrent administration of Probenecid delays amoxicillin excretion but does not delay renal excretion of clavulanic acid.
Neither component in amoxicillin and potassium clavulanate is highly protein - bound: clavulanic acid has been found to be approximately 25% bound to human serum and amoxicillin approximately 18% bound.
Amoxicillin diffuses readily into most body tissues and fluids with the exception of the brain and spinal fluid. The results of experiments involving the administration of clavulanic acid to animals suggest that this compound, like amoxicillin, is well distributed in body tissues.
Indications/Uses
Treatment of otitis media, sinusitis, and infections caused by susceptible organisms involving the lower respiratory tract, skin and skin structure, and urinary tract: spectrum same as amoxicillin with additional coverage of beta-lactamase producing B. catarrhalis, H. influenzae, N. gonorrhoeae, and S. aureus (not MRSA). The expanded coverage of this combination makes it a useful alternative when amoxicillin resistance is present and patients cannot tolerate alternative treatments.
Dosage/Direction for Use
(Direction for use): ZISUVA 625 mg and 1 g: Usual dosages for the treatment of infection: Adults and children over 12 years: Mild - Moderate infections: One ZISUVA 625 mg tablet twice daily.
Severe infections: One ZISUVA 1g tablet twice daily or One ZISUVA 625 mg tablet 3 times a day.
Therapy can be started parenterally and continued with an oral preparation.
ZISUVA 625mg / 1g tablets are not recommended in children of 12 years and under.
Dosage in renal impairment: Adults: ZISUVA 1g tablet should only be used in patients with a glomerular filtration rate of >30 ml/min. (See table.)

Click on icon to see table/diagram/image

Dosage in hepatic impairment: Dose with caution; monitor hepatic function at regular intervals.
Method of Administration: Tablet to be consumed in whole, not to be broken.
To minimise potential gastrointestinal intolerance, administer at the start of a meal.
The absorption of ZISUVA is optimised when taken at the start of a meal.
Treatment should not be extended beyond 14 days without review.
Overdosage
Following overdosage, patients have experienced primarily gastrointestinal symptoms including stomach and abdominal pain, vomiting, and diarrhea. Rash, hyperactivity, or drowsiness have also been observed in a small number of patients. In the case of overdosage, discontinue amoxicillin and potassium clavulanate, treat symptomatically, and institute supportive measures as required. If the overdosage is very recent and there is no contraindication, an attempt at emesis or other means of removal of drug from the stomach may be performed. A prospective study of 51 pediatric patients at a poison 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.
Warnings
Concerns related to adverse effects: Anaphylactoid/hypersensitivity reactions: Serious and occasionally severe or fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy, especially with a history of beta-lactam hypersensitivity, history of sensitivity to multiple allergens, or previous lgE-mediated reactions (eg, anaphylaxis, angioedema, urticaria). Use with caution in asthmatic patients. Low incidence of cross-allergy with cephalosporins exists.
Diarrhea: Incidence of diarrhea is higher than with amoxicillin alone.
Hepatic effects: Although rare, hepatic dysfunction is more common in elderly and/or males, and occurs more frequently with prolonged treatment, and may occur after therapy is complete.
Superinfection: Prolonged use may result in fungal or bacterial superinfection, including C. difficile - associated diarrhea (CDAD) and pseudomembranous colitis; CDAD has been observed >2 months postantibiotic treatment.
Disease-related concerns: Hepatic impairment: Use with caution in patients with hepatic impairment.
Infectious mononucleosis: A high percentage of patients with infectious mononucleosis have developed rash during therapy; ampicillin-class antibiotics not recommended in these patients.
Renal impairment: Use with caution in patients with renal impairment; dosage adjustment recommended.
Dosage form specific issues: Due to differing content of clavulanic acid, not all formulations are interchangeable.
Concerns related to Pregnancy and lactation: Pregnancy: Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. Limited data on the use of amoxicillin and clavulanic acid during pregnancy in humans do not indicate an increased risk of congenital malformations. In a single study in women with preterm, premature rupture of the foetal membrane it was reported that prophylactic treatment with amoxicillin and clavulanic acid may be associated with an increased risk of necrotising enterocolitis in neonates. Use should be avoided during pregnancy, unless considered essential by the physician.
Lactation: Both substances are excreted into breast milk (nothing is known of the effects of clavulanic acid on the breast-fed infant). Consequently, diarrhoea and fungus infection of the mucous membranes are possible in the breast-fed infant, so that breast-feeding might have to be discontinued. Amoxicillin and clavulanic acid should only be used during breast-feeding after benefits - risk assessment by the physician in charge.
Use In Pregnancy & Lactation
Pregnancy: Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development. Limited data on the use of amoxicillin and clavulanic acid during pregnancy in humans do not indicate an increased risk of congenital malformations. In a single study in women with preterm, premature rupture of the foetal membrane it was reported that prophylactic treatment with amoxicillin and clavulanic acid may be associated with an increased risk of necrotising enterocolitis in neonates. Use should be avoided during pregnancy, unless considered essential by the physician.
Lactation: Both substances are excreted into breast milk (nothing is known of the effects of clavulanic acid on the breast-fed infant). Consequently, diarrhoea and fungus infection of the mucous membranes are possible in the breast-fed infant, so that breast-feeding might have to be discontinued. Amoxicillin and clavulanic acid should only be used during breast-feeding after benefits - risk assessment by the physician in charge.
Side Effects
Amoxicillin and Potassium Clavulanate is generally well tolerated. The majority of side effects observed in clinical trials were of a mild and transient nature and less than 3% of patients discontinued therapy because of drug-related side effects. The most frequently reported adverse effects were diarrhea/loose stools (9%), nausea (3%), skin rashes and urticaria (3%), vomiting (1%) and vaginitis (1%). The overall incidence of side effects, and in particular diarrhea, increased with the higher recommended dose. Other less frequently reported reactions include: Abdominal discomfort, flatulence, and headache.
Gastrointestinal: Diarrhea, nausea, vomiting, indigestion, gastritis, stomatitis, glossitis, black "hairy" tongue, mucocutaneous candidiasis, enterocolitis, and hemorrhagic/pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment.
Drug Interactions
Allopurinol: May enhance the potential for allergic or hypersensitivity reactions to Amoxicillin. Risk C: Monitor therapy.
Fusidic Acid: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification.
Methotrexate: Penicillins may decrease the excretion of Methotrexate. Risk C: Monitor therapy.
Mycophenolate: Penicillins may decrease serum concentrations of the active metabolite(s) of Mycophenolate. This effect appears to be the result of impaired enterohepatic recirculation. Risk C: Monitor therapy.
Tetracycline Derivatives: May diminish the therapeutic effect of Penicillins. Risk D: Consider therapy modification.
Typhoid Vaccine: Antibiotics may diminish the therapeutic effect of Typhoid Vaccine. Only the live attenuated Ty21a strain is affected. Risk D: Consider therapy modification.
Uricosuric Agents: May decrease the excretion of Penicillins. Risk C: Monitor therapy.
Storage
Store below 30°C. Protect from light and moisture.
MIMS Class
ATC Classification
J01CR02 - amoxicillin and beta-lactamase inhibitor ; Belongs to the class of penicillin combinations, including beta-lactamase inhibitors. Used in the systemic treatment of infections.
Presentation/Packing
Zisuva 625: FC tab 2 x 7's.
Zisuva 1G: FC tab 1 x 10's.
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