Amoxicillin-clavulanate-vista
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT AMOXICILLIN-CLAVULANATE-VISTA (AMOXICILLIN-CLAVULANATE-VISTA)
Composition:
Active substances: sterile amoxicillin (in the form of sterile sodium amoxicillin), sterile clavulanic acid (in the form of sterile potassium clavulanate);
One vial contains sterile sodium amoxicillin equivalent to 1000 mg of sterile amoxicillin, and sterile potassium clavulanate equivalent to 200 mg of sterile clavulanic acid.
Pharmaceutical form. Powder for solution for injection or infusion.
Main physicochemical properties: white or almost white powder.
Pharmacotherapeutic group. Antibacterials for systemic use. Beta-lactam antibiotics, penicillins. Combinations of penicillins with beta-lactamase inhibitors. ATC code J01CR02.
Pharmacological properties.
Pharmacodynamics.
Mechanism of action.
Amoxicillin is a semisynthetic penicillin (beta-lactam antibiotic) that inhibits one or more enzymes (often referred to as penicillin-binding proteins, PBPs) involved in the biosynthetic metabolism of bacterial peptidoglycan, an essential structural component of the bacterial cell wall. Inhibition of peptidoglycan synthesis leads to weakening of the cell wall, resulting in cell lysis and death. Amoxicillin is susceptible to degradation by beta-lactamases produced by resistant bacteria. Therefore, the antimicrobial spectrum of amoxicillin as monotherapy does not include organisms producing these enzymes. Clavulanic acid is a beta-lactam compound structurally related to penicillins. It inactivates certain beta-lactamase enzymes, thereby preventing the inactivation of amoxicillin. Clavulanic acid alone has no clinically useful antibacterial activity.
Pharmacokinetic/pharmacodynamic (PK/PD) relationship.
Time above the minimum inhibitory concentration (T > MIC) is considered the primary factor determining the efficacy of amoxicillin.
Resistance mechanisms.
There are two main mechanisms of resistance to amoxicillin/clavulanic acid:
- Inactivation by bacterial beta-lactamases that are not themselves inhibited by clavulanic acid, including Class B, C, and D enzymes;
- Modification of PBPs, leading to reduced affinity of the antibacterial agent to its target; bacterial impermeability or efflux pump mechanisms may also contribute to resistance, particularly in Gram-negative bacteria.
Breakpoints.
Breakpoint values for MIC of amoxicillin/clavulanic acid established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST)
| Microorganisms |
Breakpoint susceptibility values (μg/ml) |
||
| Susceptible |
Intermediate |
Resistant |
|
| Haemophilus influenzae 1 |
≤ 1 |
- |
> 1 |
| Moraxella catarrhalis 1 |
≤ 1 |
- |
> 1 |
| Staphylococcus aureus 2 |
≤ 2 |
- |
> 2 |
| Coagulase-negative staphylococci 2 |
≤ 0.25 |
> 0.25 |
|
| Enterococcus 1 |
≤ 4 |
8 |
> 8 |
| Streptococcus A, B, C, G 5 |
≤ 0.25 |
- |
> 0.25 |
| Streptococcus pneumoniae 3 |
≤ 0.5 |
1–2 |
> 2 |
| Enterobacteriaceae 1,4 |
- |
- |
> 8 |
| Gram-negative anaerobic bacteria 1 |
≤ 4 |
8 |
> 8 |
| Gram-positive anaerobic bacteria 1 |
≤ 4 |
8 |
> 8 |
| Breakpoint values not specific to individual species 1 |
≤ 2 |
4–8 |
> 8 |
| 1 The reported values refer to amoxicillin concentrations. For susceptibility testing, the concentration of clavulanic acid is set at 2 mg/L. 2 The reported values refer to oxacillin concentrations. 3 The breakpoint values listed in the table are based on ampicillin breakpoints. 4 The resistance breakpoint R > 8 mg/L indicates that all strains with resistance mechanisms are classified as resistant. 5 The breakpoint values listed in the table are based on benzylpenicillin breakpoints. |
|||
The prevalence of resistance can vary geographically and over time for individual species; therefore, local information on susceptibility should be sought, especially when treating severe infections. Expert advice may be necessary if local resistance prevalence is such that the benefit of the medicinal product, at least for certain types of infections, is questionable.
Typically susceptible species.
Gram-positive aerobes: Enterococcus faecalis, Gardnerella vaginalis, Staphylococcus aureus (methicillin-sensitive)£, Coagulase-negative staphylococci (methicillin-sensitive), Streptococcus agalactiae, Streptococcus pneumoniae1, Streptococcus pyogenes, and other beta-haemolytic streptococci, Streptococcus viridans group.
Gram-negative aerobes: Actinobacillus actinomycetemcomitans, Capnocytophaga spp., Eikenella corrodens, Haemophilus influenzae2, Moraxella catarrhalis, Neisseria gonorrhoeae§, Pasteurella multocida.
Anaerobes: Bacteroides fragilis, Fusobacterium nucleatum, Prevotella spp.
Species for which acquired resistance may be a problem.
Gram-positive aerobes: Enterococcus faecium$.
Gram-negative aerobes: Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris.
Naturally resistant microorganisms.
Gram-negative aerobes: Acinetobacter spp., Citrobacter freundii, Enterobacter spp., Legionella pneumophila, Morganella morganii, Providencia spp., Pseudomonas spp., Serratia spp., Stenotrophomonas maltophilia.
Other microorganisms: Chlamydophila pneumoniae, Chlamydophila psittaci, Coxiella burnetii, Mycoplasma pneumoniae.
$ Naturally moderate susceptibility in the absence of acquired resistance mechanisms.
£ All methicillin-resistant staphylococci are resistant to amoxicillin/clavulanic acid.
§ All strains resistant to amoxicillin not mediated by beta-lactamases are resistant to amoxicillin/clavulanic acid.
1 This dosage form of amoxicillin/clavulanic acid may be inappropriate for treatment of Streptococcus pneumoniae resistant to penicillin (see sections "Special warnings and precautions for use" and "Posology and method of administration").
2 Strains with reduced susceptibility have been reported in some European Union countries with a frequency greater than 10%.
Pharmacokinetics.
Absorption.
Pharmacokinetic data obtained from studies in groups of healthy volunteers administered amoxicillin/clavulanic acid 1000/200 mg (1.2 g) as an intravenous bolus injection are given below.
Mean pharmacokinetic parameters
| Amoxicillin |
|||||
| Dose administered |
Dose |
Mean peak plasma concentration, mcg/ml |
Elimination half-life (T½), hours |
Area under the concentration-time curve (AUC), h·mg/L |
Urinary excretion within 0–6 hours, % |
| Amoxicillin/clavulanic acid 1000/200 mg |
1 g |
105.4 |
0.9 |
76.3 |
77.4 |
Clavulanic acid
| Amoxicillin/clavulanic acid 1000/200 mg |
200 mg |
28.5 |
0.9 |
27.9 |
63.8 |
Distribution. Approximately 25% of the total plasma volume of clavulanic acid and 18% of total amoxicillin in plasma are protein-bound. The apparent volume of distribution is approximately 0.3–0.4 L/kg for amoxicillin and approximately 0.2 L/kg for clavulanic acid.
After intravenous administration, amoxicillin and clavulanic acid have been detected in the gallbladder, abdominal tissue, skin, adipose tissue, muscle tissue, synovial and peritoneal fluid, bile, and pus. Amoxicillin does not achieve adequate distribution into cerebrospinal fluid.
Animal studies have not revealed any evidence of significant retention of substances derived from any component of the medicinal product in body tissues. Amoxicillin, like most penicillins, may be detected in breast milk. A small amount of clavulanic acid may also be detected in breast milk (see section "Use during pregnancy or breastfeeding").
It has been demonstrated that both amoxicillin and clavulanic acid cross the placental barrier (see section "Use during pregnancy or breastfeeding").
Biological transformation. Amoxicillin is partially excreted in urine as inactive penicilloic acid in amounts equivalent to 10–25% of the initial dose. Clavulanic acid is extensively metabolized in the human body and excreted in urine and feces, as well as in the form of carbon dioxide in expired air.
Elimination. The primary route of amoxicillin elimination is renal, whereas clavulanic acid is eliminated both renally and via extrarenal mechanisms.
In healthy volunteers, the mean elimination half-life of amoxicillin/clavulanic acid is approximately one hour, and the mean total clearance is approximately 25 L/hour. Various studies have shown urinary excretion of 50–85% for amoxicillin and 27–60% for clavulanic acid over a 24-hour period. In the case of clavulanic acid, the greatest amount of the substance is excreted within the first 2 hours after administration.
Concomitant administration of probenecid slows the elimination of amoxicillin but does not delay renal excretion of clavulanic acid (see section "Interaction with other medicinal products and other forms of interaction").
Age. The elimination half-life of amoxicillin is identical in children aged 3 months to 2 years, older children, and adults. For infants (including premature newborns) during the first week of life, the dosing frequency should not exceed twice daily due to immaturity of the renal elimination pathway. Since elderly patients are more likely to have decreased renal function, dosage should be selected with caution; monitoring of renal function is also recommended.
Renal impairment. Total serum clearance of amoxicillin/clavulanic acid decreases proportionally with decreasing renal function. The reduction in clearance of the medicinal product is more pronounced for amoxicillin than for clavulanic acid, as a larger fraction of amoxicillin is eliminated by the kidneys. In renal impairment, dosage should prevent excessive accumulation of amoxicillin while maintaining adequate levels of clavulanic acid (see section "Method of administration and dosage").
Hepatic impairment. The medicinal product should be used with caution in patients with hepatic insufficiency, and liver function should be monitored regularly.
Clinical characteristics.
Indications.
Treatment in adults and children of bacterial infections caused by microorganisms sensitive to amoxiclav:
- severe infections of the throat, nose, and ears (mastoiditis, peritonsillar infections, epiglottitis, and sinusitis with accompanying severe systemic signs and symptoms);
- acute exacerbations of chronic bronchitis (after diagnosis has been confirmed);
- community-acquired pneumonia;
- cystitis;
- pyelonephritis;
- skin and soft tissue infections, including bacterial cellulitis, animal bites, severe dentoalveolar abscesses with extensive cellulitis;
- bone and joint infections, including osteomyelitis;
- intra-abdominal infections;
- genital tract infections in women.
Prophylaxis of bacterial infections during major surgical procedures in the following areas:
- gastrointestinal tract;
- pelvic organs;
- head and neck;
- biliary tract.
When prescribing antibacterial agents, the principles of appropriate use should be followed.
Contraindications.
- Hypersensitivity to any component of the medicinal product or to any penicillin-class antibacterial agents.
- History of severe hypersensitivity reactions (including anaphylaxis) associated with the use of other beta-lactam agents (including cephalosporins, carbapenems, or monobactams).
- History of jaundice or liver dysfunction associated with the use of amoxicillin/clavulanic acid.
Interaction with other medicinal products and other forms of interaction.
Oral anticoagulants. Oral anticoagulants and penicillin-class antibiotics are commonly used together in clinical practice without reports of interaction. However, cases of increased international normalized ratio (INR) have been reported in patients receiving acenocoumarol or warfarin who were prescribed a course of amoxicillin treatment. If concomitant use of these medicinal products is necessary, prothrombin time or INR should be closely monitored when starting or stopping treatment with AMOXICILLIN-CLAVULANATE-VISTA. Dose adjustment of oral anticoagulants may also be required (see sections "Special precautions for use" and "Adverse reactions").
Methotrexate. Penicillins may reduce the renal clearance of methotrexate, potentially increasing its toxicity.
Probenecid. Concomitant use of probenecid is not recommended. Probenecid reduces renal tubular secretion of amoxicillin. Concomitant administration may lead to increased and prolonged blood levels of amoxicillin.
Mycophenolate mofetil. In patients receiving mycophenolate mofetil, initiation of oral amoxicillin with clavulanic acid may reduce the pre-dose concentration of the active metabolite mycophenolic acid by approximately 50%. This change in pre-dose levels may not fully reflect changes in total exposure to mycophenolic acid. Therefore, dosage adjustment of mycophenolate mofetil is usually not required unless there is clinical evidence of transplant dysfunction. However, close monitoring is necessary during concomitant use and for some time after antibiotic therapy.
Special precautions for use.
Before initiating treatment with the medicinal product AMOXICILLIN-CLAVULANATE-VISTA, it is necessary to carefully assess the patient's history for hypersensitivity reactions to penicillins, cephalosporins, or other beta-lactam medicinal products (see sections "Contraindications" and "Adverse reactions").
Severe, and sometimes even fatal, cases of hypersensitivity (including anaphylactoid and anaphylactic reactions and severe skin adverse reactions) have been observed in patients during penicillin therapy. Hypersensitivity reactions may also progress to Kounis syndrome—a serious allergic reaction that may lead to myocardial infarction (see section "Adverse reactions"). These reactions are most likely to occur in individuals with a history of similar reactions to penicillin. In the event of allergic reactions, administration of AMOXICILLIN-CLAVULANATE-VISTA should be discontinued and appropriate alternative therapy initiated. If it is established that the infection is caused by microorganisms sensitive to amoxicillin, consideration should be given to switching from the combination amoxicillin/clavulanic acid to amoxicillin alone in accordance with official recommendations.
Cases of drug-induced enterocolitis syndrome have been reported, primarily in children receiving amoxicillin (see section "Adverse reactions"). Drug-induced enterocolitis syndrome is an allergic reaction characterized mainly by persistent vomiting (occurring 1–4 hours after drug administration) in the absence of allergic skin or respiratory symptoms. Additional symptoms may include abdominal pain, diarrhea, hypotension, or leukocytosis with neutrophilia. Severe cases have been reported, including progression to shock. This medicinal product (AMOXICILLIN-CLAVULANATE-VISTA) is not suitable for use when there is a high risk that the likely pathogens are resistant to beta-lactam agents via mechanisms not inhibited by clavulanic acid. Since specific data on T > MIC are lacking and data on oral formulations are limited, this medicinal product (without additional amoxicillin) may be unsuitable for the treatment of penicillin-resistant S. pneumoniae.
Seizures may occur in patients with impaired renal function or when high doses of the medicinal product are administered.
The medicinal product AMOXICILLIN-CLAVULANATE-VISTA should be discontinued if infectious mononucleosis is suspected, as the development of a measles-like rash associated with this disease may be linked to amoxicillin use.
Concomitant use of allopurinol during amoxicillin treatment may increase the risk of skin allergic reactions.
Prolonged use of the medicinal product may occasionally lead to overgrowth of non-susceptible microorganisms.
Development of erythema multiforme associated with pustules at the beginning of treatment may be a symptom of acute generalized exanthematous pustulosis (see section "Adverse reactions"). In such cases, treatment must be discontinued, and subsequent administration of amoxicillin is contraindicated.
AMOXICILLIN-CLAVULANATE-VISTA should be used with caution in patients with impaired liver function. Hepatitis occurs primarily in men and elderly patients and may be associated with prolonged use of the medicinal product. Very rarely, such adverse reactions may occur in children. Signs and symptoms may appear during or immediately after treatment, but in some cases may develop several weeks after treatment has ended. These events are usually reversible. Fatal outcomes have been reported extremely rarely and have always occurred in patients with severe underlying diseases or in those receiving concomitant medications with hepatotoxic potential (see section "Adverse reactions"). Antibiotic-associated colitis, ranging from mild to life-threatening severity, has been reported with nearly all antibacterial agents (see section "Adverse reactions"). Therefore, it is important to consider this possibility in patients who develop diarrhea during or after antibiotic use. In case of antibiotic-associated colitis, treatment should be immediately discontinued, medical advice sought, and appropriate therapy initiated.
During prolonged therapy, monitoring of organ and system functions, including kidneys, liver, and hematopoietic system, is recommended.
Occasionally, patients receiving AMOXICILLIN-CLAVULANATE-VISTA and oral anticoagulants may exhibit excessive prolongation of prothrombin time (elevated international normalized ratio (INR)). Appropriate monitoring is required when anticoagulants are used concomitantly. Dose adjustment of oral anticoagulants may be necessary to maintain the desired level of anticoagulation (see sections "Interaction with other medicinal products and other forms of interaction" and "Adverse reactions"). In patients with renal impairment, the dose should be adjusted according to the degree of renal function impairment.
Crystalluria (including acute kidney injury) may occur very rarely in patients with reduced urine output, primarily following parenteral administration of the medicinal product. Therefore, adequate fluid intake and monitoring of urine output are recommended when high doses of amoxicillin are administered to minimize the risk of amoxicillin crystalluria (see section "Overdose"). In patients with urinary catheters, catheter patency should be checked regularly (see sections "Adverse reactions" and "Overdose").
When monitoring urinary glucose levels during amoxicillin therapy, enzymatic glucose oxidase methods should be used, as other methods may yield false-positive results.
False-positive results in Aspergillus antigen tests have been reported in patients receiving amoxicillin/clavulanic acid (using the Bio-Rad Laboratories Platelia Aspergillus EIA test). Therefore, positive results in patients treated with amoxicillin/clavulanic acid should be interpreted with caution and confirmed by other diagnostic methods.
The presence of clavulanic acid in AMOXICILLIN-CLAVULANATE-VISTA may cause nonspecific binding of IgG and albumin to erythrocyte membranes, potentially resulting in a false-positive Coombs test.
Important information on excipients.
This medicinal product contains 62.9 mg (2.7 mmol) of sodium per vial. Caution is advised when administering to patients on a sodium-restricted diet.
This medicinal product contains 39.1 mg (1 mmol) of potassium per vial. Caution is advised when administering to patients with impaired renal function or those on a potassium-restricted diet.
Use during pregnancy or breastfeeding.
Pregnancy.
Animal studies do not provide sufficient data to conclude on direct or indirect adverse effects on pregnancy, embryonic/fetal development, parturition, or postnatal development. Limited data on the use of amoxicillin/clavulanic acid in pregnant women do not indicate an increased risk of congenital malformations. In one study involving pregnant women with premature rupture of membranes, prophylactic use of amoxicillin/clavulanic acid was associated with an increased risk of neonatal necrotizing enterocolitis. Use of this medicinal product during pregnancy should be avoided unless, in the opinion of the physician, such use is necessary.
Breastfeeding period.
Both components of the medicinal product are excreted in breast milk (no information is available on the effect of clavulanic acid on the breastfed infant). As a result, diarrhea and fungal mucosal infections may occur in the breastfed infant; therefore, breastfeeding should be discontinued. The medicinal product may be used during breastfeeding only if, in the physician’s opinion, the benefit outweighs the risk.
Ability to influence reaction rate while driving or operating machinery.
No studies have been conducted on the ability to influence reaction speed while driving or operating machinery. However, adverse reactions such as allergic reactions, dizziness, and seizures may impair the ability to drive or operate machinery (see section "Adverse reactions").
Method of administration and dosing.
Doses are expressed as the content of amoxicillin/clavulanic acid, unless the dose of an individual component is specified.
When selecting the dose of amoxicillin-clavulanate for treating a specific infection, the following factors should be considered:
- expected pathogens and their anticipated susceptibility to antibacterial agents (see section "Special instructions");
- severity and site of infection;
- patient's age, body weight, and renal function status, as described below.
If necessary, alternative formulations of amoxicillin-clavulanate may be used (e.g., those with higher doses of amoxicillin and/or different ratios of amoxicillin to clavulanic acid).
These amoxicillin-clavulanate formulations can be administered at a daily dose of up to 3000 mg of amoxicillin and 600 mg of clavulanic acid. If a higher dose of amoxicillin is required, another formulation of amoxicillin-clavulanate should be prescribed to avoid excessively high daily doses of clavulanic acid.
The duration of treatment should be determined individually. Some infections (e.g., osteomyelitis) require prolonged treatment. Treatment duration should not exceed 14 days without reassessment of treatment efficacy and clinical status (see section "Special instructions").
Dosing for adults and children weighing ≥ 40 kg.
Standard dose: 1000/200 mg every 8 hours.
Prevention of complications during surgical procedures.
For surgeries lasting less than 1 hour, the recommended dose is 1000/200 mg to 2000/200 mg administered at induction of anesthesia (the 2000/200 mg dose may be achieved using another intravenous formulation of amoxicillin/clavulanic acid).
For surgeries lasting more than 1 hour, the recommended dose is 1000/200 mg to 2000/200 mg administered at induction of anesthesia, with the 1000/200 mg dose repeatable every 8 hours for up to 24 hours. If clinical signs of infection are present during surgery, a full course of treatment with intravenous or oral administration of the drug should be initiated in the postoperative period.
Dosing for children weighing < 40 kg.
Children aged 3 months and older: 25/5 mg/kg body weight every 8 hours.
Children under 3 months of age or weighing less than 4 kg: 25/5 mg/kg body weight every 12 hours. Elderly patients. Dose adjustment is not required.
Renal impairment. Dose adjustment is based on maximum recommended doses of amoxicillin. Creatinine clearance > 30 mL/min – no dose adjustment required.
Adults and children weighing ≥ 40 kg.
| Creatinine clearance 10–30 mL/min |
Initial dose – 1000/200 mg, then 500/100 mg twice daily |
| Creatinine clearance < 10 mL/min |
Initial dose – 1000/200 mg, then 500/100 mg every 24 hours |
| Hemodialysis |
Initial dose – 1000/200 mg, then 500/100 mg every 24 hours + 500/100 mg after dialysis |
Adults and children with body weight < 40 kg.
| Creatinine clearance 10–30 mL/min |
25/5 mg/kg every 12 hours |
| Creatinine clearance < 10 mL/min |
25/5 mg/kg every 24 hours |
| Hemodialysis |
25/5 mg/kg every 24 hours + 12.5/2.5 mg after dialysis |
Hepatic impairment. Caution is required in dosing, with regular monitoring of liver function at regular intervals.
Route of administration:
The medicinal product AMOXICILLIN-CLAVULANATE-VISTA is administered by intravenous injection (bolus) or by intermittent infusion (intravenous drip). This medicinal product must not be administered intramuscularly. In children under 3 months of age, the medicinal product AMOXICILLIN-CLAVULANATE-VISTA should be administered only as intravenous infusion. Treatment may be initiated with intravenous administration and continued with oral formulations of amoxicillin-clavulanate.
Preparation of solution for intravenous injection. 1000/200 mg: dissolve the contents of the vial in 20 ml of water for injections (final volume 20.9 ml). The medicinal product AMOXICILLIN-CLAVULANATE-VISTA should be administered by slow intravenous injection over 3–5 minutes, but no later than 20 minutes after reconstitution. It may be administered directly into the vein or via an infusion line.
Preparation of solution for intravenous infusion. The reconstituted solution (1000/200 mg) as described above should be immediately added without delay to 100 ml of infusion fluid (preferably using a mini-container or burette). The infusion should be administered over 30–40 minutes. AMOXICILLIN-CLAVULANATE-VISTA must be administered within 4 hours after reconstitution when using water for injections, or within 3 hours when using 0.9% sodium chloride solution for intravenous injection or lactated Ringer’s solution.
From a microbiological standpoint, the prepared solution should be administered immediately.
AMOXICILLIN-CLAVULANATE-VISTA is less stable in glucose, dextran, and bicarbonate solutions; therefore, solutions based on these must be used within 3–4 minutes after reconstitution. Any unused solution should be disposed of according to current regulations.
Children.
This medicinal product is indicated for use in children from the first days of life.
Overdose.
Symptoms. Gastrointestinal disturbances and fluid and electrolyte imbalance may occur. Crystalluria associated with amoxicillin administration has been observed, which in some cases led to renal failure (see section "Special precautions for use").
Seizures may occur in patients with impaired renal function or in patients receiving high doses of the medicinal product.
Amoxicillin precipitation in urinary catheters has been reported, primarily after high-dose intravenous administration. The patency of catheters should be monitored regularly (see section "Special precautions for use").
Treatment. Gastrointestinal disturbances can be treated symptomatically, with attention to fluid and electrolyte balance.
Amoxicillin and clavulanic acid can be removed from the bloodstream by hemodialysis.
Side effects
The most commonly reported adverse reactions to the medicinal product are diarrhea, nausea, and vomiting. The list of adverse reactions known from clinical trials of amoxicillin/clavulanic acid and post-marketing surveillance, classified by MedDRA system organ class, is provided below.
The following frequency classification is applied: very common (≥ 1/10); common (≥ 1/100 to < 1/10); uncommon (≥ 1/1000 to < 1/100); rare (≥ 1/10,000 to < 1/1000); very rare (< 1/10,000); frequency not known (cannot be estimated from available data).
Infections and infestations: common – candidiasis of skin and mucous membranes; frequency not known – overgrowth of microorganisms not sensitive to the medicinal product.
Blood and lymphatic system disorders: rare – reversible leukopenia (including neutropenia) and thrombocytopenia; frequency not known – reversible agranulocytosis and hemolytic anemia. Prolongation of bleeding time and prothrombin time\1.
Immune system disorders\10: frequency not known – angioedema, anaphylaxis, serum sickness-like syndrome, allergic vasculitis.
Nervous system disorders: uncommon – dizziness, headache; frequency not known – seizures\2, aseptic meningitis.
Vascular disorders: rare – thrombophlebitis\3; frequency not known – Kounis syndrome.
Gastrointestinal disorders: common – diarrhea; uncommon – nausea, vomiting, gastrointestinal discomfort; frequency not known – antibiotic-associated colitis\4, including pseudomembranous colitis and hemorrhagic colitis (see section "Special precautions for use"), frequency not known – drug-induced enterocolitis syndrome (DIES).
Hepatobiliary disorders: uncommon – increased levels of AST and/or ALT; frequency not known – hepatitis\6\ and cholestatic jaundice\6.
Skin and subcutaneous tissue disorders\7: uncommon – skin rash, pruritus, urticaria; rare – erythema multiforme; frequency not known – Stevens-Johnson syndrome, toxic epidermal necrolysis, linear IgA disease, bullous exfoliative dermatitis, acute generalized exanthematous pustulosis\9, drug reaction with eosinophilia and systemic symptoms (DRESS).
Renal and urinary disorders: very rare – interstitial nephritis, crystalluria\8; frequency not known – crystalluria (including acute kidney injury).
1 See section "Special precautions for use".
2 See section "Special precautions for use".
3 At the injection site.
4 Including pseudomembranous colitis and hemorrhagic colitis (see section "Special precautions for use").
5 Mild elevations in AST and/or ALT levels have been observed more frequently in patients receiving beta-lactam antibiotics, but the clinical significance of these findings is unknown.
6 These events have been observed with other penicillin and cephalosporin antibiotics (see section "Special precautions for use").
7 If hypersensitivity reactions (dermatitis) occur, the medicinal product should be discontinued (see section "Special precautions for use").
8 See section "Overdose".
9 See section "Special precautions for use".
10 See sections "Contraindications" and "Special precautions for use".
Reporting suspected adverse reactions
Reporting of suspected adverse reactions after medicinal product authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, as well as patients or their legal representatives, are encouraged to report any suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua
Shelf life. 3 years.
Storage conditions. Store in the original packaging at a temperature not exceeding 25 °C. Keep out of reach of children.
Incompatibilities.
Amoxicillin-clavulanate should not be mixed with blood products, other protein-containing solutions (including protein hydrolysates), or fat emulsions intended for intravenous administration.
If AMOXICILLIN-CLAVULANATE-VISTA is administered concomitantly with an aminoglycoside, the antibiotics should not be mixed in the same syringe, intravenous container, or other vessels, as the aminoglycoside may lose its activity.
AMOXICILLIN-CLAVULANATE-VISTA should not be mixed with infusions containing glucose, dextran, or bicarbonate.
Packaging.
1000 mg / 200 mg per vial; 10 vials per cardboard box.
Prescription status. Prescription only.
Manufacturer.
LABORATORIO REIG JOFRE, S.A.
Manufacturer's address and location of operations.
Calle del Rio Jarama 111, Poligono Industrial, Toledo, 45007, Spain.