Amoxiclav® 2s: detailed information

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT AMOKSIKLAV® 2S (AMOKSIKLAV® 2S)

Composition:

Active substances: amoxicillin, clavulanic acid;

5 ml of suspension contains 400 mg of amoxicillin (as amoxicillin trihydrate) and 57 mg of clavulanic acid (as potassium clavulanate);

Excipients: colloidal anhydrous silicon dioxide, xanthan gum, strawberry flavor, crospovidone, aspartame (E 951), sodium carmellose, anhydrous silicon dioxide.

Pharmaceutical form. Powder for oral suspension.

Main physicochemical properties: powder from white to slightly yellowish color.

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 has no clinically useful antibacterial activity when used as monotherapy.

PK/PD relationship

Time above the minimum inhibitory concentration (T>MIC) is considered the primary pharmacodynamic determinant of efficacy for 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;
Alteration of PBPs, leading to reduced affinity of the antimicrobial agent for its target.

Reduced bacterial permeability or efflux pump mechanisms may contribute to or cause bacterial resistance, particularly in Gram-negative bacteria.

Breakpoints

MIC breakpoints for amoxicillin/clavulanic acid established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST)

Microorganisms	Breakpoints for susceptibility (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
Breakpoints not specific to individual species 1	≤2	4–8	> 8
1 The reported values are for amoxicillin concentrations. For susceptibility testing, the concentration of clavulanic acid is set at 2 mg/L. 2 The reported values are for oxacillin concentrations. 3 The breakpoints listed in the table are derived from ampicillin breakpoints. 4 The resistance breakpoint R>8 mg/L means that all strains with resistance mechanisms are classified as resistant. 5 The breakpoints listed in the table are derived from benzylpenicillin breakpoints.

The prevalence of resistance may vary geographically and over time for individual species, so local information on susceptibility is desirable, especially when treating severe infections. Expert advice should be sought if local resistance prevalence is such that the benefit of the drug, at least for certain types of infections, is questionable.

Typically susceptible species

Gram-positive aerobes: Enterococcus faecalis, Gardnerella vaginalis, Staphylococcus aureus

(methicillin-susceptible)£, Coagulase-negative staphylococci (methicillin-susceptible), Streptococcus agalactiae, Streptococcus pneumoniae1, Streptococcus pyogenes and other beta-haemolytic streptococci, Streptococcus viridans group.

Gram-negative aerobes: Capnocytophaga spp., Eikenella corrodens, Haemophilus influenzae2, Moraxella catarrhalis, 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 sp., Citrobacter freundii, Enterobacter sp., Legionella pneumophila, Morganella morganii, Providencia spp., Pseudomonas sp., Serratia sp., 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.

1 Streptococcus pneumoniae resistant to penicillin should not be treated with this medicinal formulation of amoxicillin/clavulanic acid (see sections "Posology and method of administration" and "Special warnings and precautions for use").

2 Strains with reduced susceptibility have been reported in some EU countries with a frequency greater than 10%.

Pharmacokinetics.

Absorption. Amoxicillin and clavulanic acid are completely dissociated in aqueous solutions at physiological pH levels. Both components are rapidly and well absorbed following oral administration. The bioavailability of amoxicillin and clavulanic acid is approximately 70% following oral administration. The plasma profiles of both components are identical, and the time to reach maximum plasma concentration (Tmax) for each component is approximately 1 hour.

Serum concentrations of amoxicillin and clavulanic acid achieved after administration of amoxicillin/clavulanic acid are identical to those achieved after oral administration of equivalent doses of amoxicillin or clavulanic acid given separately.

Distribution. Approximately 25% of total clavulanic acid in plasma 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.

Following intravenous administration, amoxicillin and clavulanic acid have been detected in the gallbladder, abdominal tissue, skin, adipose tissue, muscle tissue, synovial and peritoneal fluids, bile, and pus. Amoxicillin does not distribute adequately into cerebrospinal fluid.

Animal studies have not revealed any evidence of significant retention of substances derived from either component of the drug 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").

Metabolism. 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 elimination for amoxicillin is renal, whereas clavulanic acid is eliminated via both renal and non-renal mechanisms.

In healthy volunteers, the mean elimination half-life of amoxicillin/clavulanic acid is approximately 1 hour, and the mean total clearance is approximately 25 L/h. 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 majority of the substance is excreted within the first 2 hours after administration.

Concomitant administration of probenecid slows the elimination of amoxicillin but does not affect the 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 similar in children aged 3 months to 2 years, older children, and adults. For neonates (including premature infants) 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 selection should be cautious, and monitoring of renal function is recommended.

Renal impairment. Total serum clearance of amoxicillin/clavulanic acid decreases proportionally with decreasing renal function. The reduction in clearance is more pronounced for amoxicillin than for clavulanic acid, as a larger fraction of amoxicillin is eliminated by the kidneys. In renal impairment, dosing should prevent excessive accumulation of amoxicillin while maintaining adequate levels of clavulanic acid (see section "Dosage and administration").

Hepatic impairment. Caution is recommended when administering the drug to patients with hepatic impairment, and regular monitoring of liver function is advised.

Clinical characteristics.

Indications.

Treatment in adults and children of bacterial infections caused by microorganisms susceptible to Amoxiclav®2S, such as:

acute bacterial sinusitis (confirmed);
acute otitis media;
confirmed exacerbation of chronic bronchitis;
community-acquired pneumonia;
cystitis;
pyelonephritis;
skin and soft tissue infections, including cellulitis, animal bites, severe dentoalveolar abscesses with spreading cellulitis;
bone and joint infections, including osteomyelitis.

When prescribing antibacterial agents, appropriate use guidelines should be followed.

Contraindications.

Hypersensitivity to any component of the drug, or to any antibacterial agents of the penicillin group.

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 hepatic dysfunction associated with the use of amoxicillin/clavulanic acid.

Interaction with other medicinal products and other types of interactions.

Oral anticoagulants

Oral anticoagulants and penicillin-class antibiotics are commonly used together in clinical practice, with no 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. If concomitant use is necessary, prothrombin time or INR should be closely monitored when starting or stopping amoxicillin. Additionally, dosage adjustment of oral anticoagulants may be required (see sections "Special precautions for use" and "Adverse reactions").

Methotrexate

Penicillins may reduce methotrexate excretion, potentially increasing its toxicity.

Probenecid

Concomitant use of probenecid is not recommended. Probenecid decreases 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 level 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 completion of antibiotic therapy.

Special precautions for use

Before initiating therapy with amoxicillin/clavulanic acid, a thorough history of previous hypersensitivity reactions to penicillins, cephalosporins, or other beta-lactam agents should be obtained (see sections "Contraindications" and "Side effects").

Severe hypersensitivity reactions, including anaphylactoid reactions and severe skin reactions, some with fatal outcomes, have been reported in patients receiving penicillin therapy. Hypersensitivity reactions may also progress to DRESS syndrome — a serious allergic reaction that may lead to myocardial infarction (see section "Side effects"). Such reactions are more likely in patients with a history of penicillin hypersensitivity or those with atopic diseases. If an allergic reaction occurs, amoxicillin should be discontinued and appropriate alternative therapy initiated.

If the infection is known to be caused by organism(s) susceptible to amoxicillin, consideration should be given to switching from amoxicillin/clavulanic acid to amoxicillin alone, in accordance with established guidelines.

This dosage form of Augmentin® is not suitable for use when there is a high risk of resistance of likely pathogens to beta-lactam agents that is not mediated by beta-lactamases susceptible to inhibition by clavulanic acid. This dosage form should not be used for the treatment of penicillin-resistant S. pneumoniae.

Seizures may occur in patients with impaired renal function or those receiving high doses of the drug (see "Side effects").

Amoxicillin/clavulanic acid should be avoided in suspected cases of infectious mononucleosis, as amoxicillin use has been associated with the development of a morbilliform rash in such patients.

Concomitant administration of allopurinol during amoxicillin therapy increases the likelihood of skin allergic reactions.

Prolonged use may occasionally lead to overgrowth of microorganisms not susceptible to the drug.

The onset of fever-associated generalized erythema with skin blistering at the beginning of treatment may be a symptom of acute generalized exanthematous pustulosis (AGEP) (see section "Side effects"). This reaction requires discontinuation of Augmentin® 2S, and future use of amoxicillin is contraindicated.

Amoxicillin/clavulanic acid should be used with caution in patients with signs of impaired liver function (see sections "Dosage and administration", "Contraindications", and "Side effects").

Hepatic complications have been reported, primarily in males and elderly patients, and may be associated with prolonged treatment. Such complications have been reported very rarely in children. In all patient groups, symptoms usually occur during or shortly after treatment, although in some cases they may manifest only several weeks after therapy has ended. These events are usually reversible. Hepatic complications may be severe and, in exceptionally rare cases, fatal. Such events have always been observed in patients with severe underlying disease or those receiving concomitant medications that may cause hepatic complications (see section "Side effects").

Antibiotic-associated colitis, with severity ranging from mild to life-threatening, has been reported with nearly all antibacterial agents, including amoxicillin (see section "Side effects"). Therefore, it is important to consider this diagnosis in patients presenting with diarrhea during or after antibiotic therapy. If antibiotic-associated colitis occurs, Augmentin® 2S should be discontinued immediately, medical advice sought, and appropriate treatment initiated. Antiperistaltic agents are contraindicated in such cases.

During prolonged therapy, periodic monitoring of organ system functions, including renal, hepatic, and hematopoietic function, is recommended.

Prolongation of the prothrombin time has been rarely observed in patients receiving amoxicillin/clavulanic acid. Appropriate monitoring is required when anticoagulants are co-administered. 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 "Side effects").

Dosage adjustment is required in patients with impaired renal function depending on the degree of impairment (see section "Dosage and administration").

Crystalluria (including acute renal injury) has been very rarely observed in patients with reduced urine output, primarily during parenteral therapy. Adequate fluid intake and diuresis should be maintained when high doses of amoxicillin are administered to reduce the risk of amoxicillin crystalluria. In patients with urinary catheters, catheter patency should be checked regularly (see sections "Side effects" and "Overdose").

During amoxicillin therapy, enzymatic methods for glucose oxidase testing should be used to detect glucose in urine, as non-enzymatic methods may yield false-positive results.

The presence of clavulanic acid in Augmentin® 2S may lead to non-specific binding of IgG and albumin to red blood cell membranes, potentially causing false-positive results in the Coombs test.

Positive results in the enzyme immunoassay using Platelia Aspergillus (Bio-Rad Laboratories) have been reported in patients receiving amoxicillin/clavulanic acid, despite subsequent confirmation of absence of Aspergillus infection. Cross-reactions with non-Aspergillus polysaccharides and polyfuranoses have been reported when using the Platelia Aspergillus assay (Bio-Rad Laboratories). Therefore, positive test results in patients receiving amoxicillin/clavulanic acid should be interpreted with caution and confirmed by other diagnostic methods.

Cases of drug-induced enterocolitis syndrome (DIES) have been reported, primarily in children receiving amoxicillin/clavulanic acid (see section "Side effects"). Drug-induced enterocolitis syndrome is an allergic reaction characterized primarily by persistent vomiting (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, including progression to shock, have been documented.

Use during pregnancy or breastfeeding

Pregnancy. Animal studies have not shown direct or indirect harmful effects on pregnancy, embryonic/fetal development, parturition, or postnatal development. Limited human data on the use of amoxicillin/clavulanic acid during pregnancy do not indicate an increased risk of congenital malformations. In a single study of women with premature rupture of membranes, prophylactic treatment with amoxicillin/clavulanic acid was associated with an increased risk of necrotizing enterocolitis in newborns. The drug should be avoided during pregnancy unless deemed necessary by the physician.

Breastfeeding period

Both components are excreted into breast milk (no data on the effect of clavulanic acid on breastfed infants). Diarrhea and fungal mucosal infections may therefore occur in the breastfed infant, and breastfeeding should be discontinued during treatment. The possibility of allergic reactions should also be considered. Use of amoxicillin/clavulanic acid during breastfeeding is possible only after a physician has evaluated the risk-benefit ratio.

Ability to affect the speed of reaction when driving vehicles or operating machinery

Studies on the ability of the drug to affect reaction speed during driving or operating machinery have not been conducted. However, adverse effects such as allergic reactions, dizziness, and seizures may occur, which could impair the ability to drive or operate machinery.

Method of Administration and Dosage

Dosage is expressed in terms of amoxicillin/clavulanic acid content, except when dosage is specified in terms of a single component.

When prescribing Amoxiclav® 2S for the treatment of a specific infection, the following should be considered:

likely pathogens and their probable susceptibility to antibacterial agents (see section "Special Warnings and Precautions for Use");
severity and site of infection;
patient's age, body weight, and renal function, as indicated below.

If necessary, consider the possibility of using alternative formulations of Amoxiclav® (i.e., those containing higher doses of amoxicillin and/or different ratios of amoxicillin to clavulanic acid) (see sections "Special Warnings and Precautions for Use" and "Pharmacodynamics").

The medicine is intended for use in children with body weight < 40 kg.

For children with body weight < 40 kg, Amoxiclav® 2S provides a maximum daily dose of 1000–2800 mg amoxicillin/143–400 mg clavulanic acid, when following the dosage recommendations below. If a higher daily dose of amoxicillin is required, to avoid administering excessively high daily doses of clavulanic acid, an alternative formulation of Amoxiclav® should be selected (see sections "Special Warnings and Precautions for Use" and "Pharmacodynamics").

Duration of treatment should be determined individually for each patient. Some infections (e.g., osteomyelitis) require longer treatment. Treatment should not exceed 14 days without re-evaluation (see section "Special Warnings and Precautions for Use").

Children with body weight < 40 kg

Recommended doses:

from 25 mg/3.6 mg/kg/day to 45 mg/6.4 mg/kg/day, divided into two doses;
for treatment of certain infections (such as otitis media, sinusitis, and lower respiratory tract infections), children aged 2 years and older may receive up to 70 mg/10 mg/kg/day divided into two doses.

There are no clinical data on 7:1 formulations of Amoxiclav® for doses higher than 45 mg/6.4 mg/kg/day in patients under 2 years of age.

There are no clinical data on 7:1 formulations of Amoxiclav® in patients under 2 months of age. Therefore, dosage recommendations for this patient group are not available.

Elderly Patients

Dose adjustment is not required.

Renal Impairment

For patients with creatinine clearance (CrCl) > 30 mL/min, dose adjustment is not required.

For patients with CrCl < 30 mL/min, use of Amoxiclav® formulations with a 7:1 ratio of amoxicillin to clavulanic acid is not recommended, as there are no dosage adjustment recommendations.

Hepatic Impairment

Caution is recommended, with regular monitoring of liver function (see sections "Contraindications" and "Special Warnings and Precautions for Use").

Method of Administration

Amoxiclav® 2S is intended for oral administration.

The medicine should be administered before meals to minimize potential gastrointestinal intolerance and to optimize absorption of amoxicillin/clavulanic acid.

Treatment may be initiated parenterally using an appropriate formulation and continued with Amoxiclav® 2S for oral administration.

Instructions for Reconstituting the Suspension

Before reconstituting the suspension, open the screw cap and ensure that the cap seal is intact and tightly adhered to the rim of the bottle. Do not use the medicine if the seal is damaged.

Do not use the medicine if clumps of powder are visible in the bottle before adding water. After reconstitution, the suspension should be white to slightly yellowish in color.

Do not use the reconstituted suspension if its color differs from that described above.

Reconstitution of 35 mL or 70 mL of Suspension

Shake the bottle well to loosen the powder from the walls and bottom. Add 34 mL or 66 mL of drinking water to obtain 35 mL or 70 mL of suspension, respectively. For ease of reconstitution, add drinking water in two portions (first up to 2/3 of the bottle, then up to the mark specially indicated on the bottle label), shaking the bottle each time. After adding water, invert the bottle and shake again. SHAKE WELL BEFORE EACH DOSE.

A 5 mL measuring syringe with adapter, graduated in 0.1 mL increments, or a measuring spoon with markings at 1.25 / 2.5 / 5 mL is provided for measuring the suspension. The measuring syringe is calibrated to ensure accurate and repeatable dosing.

To measure the suspension using the syringe:

shake the suspension;
open the bottle cap and insert the adapter (stopper with opening) into the bottle neck;
firmly insert the syringe tip into the adapter; push the plunger fully down;
carefully invert the bottle upside down;
slowly draw the required amount of suspension into the syringe. If air bubbles are present in the drawn suspension, expel the suspension back into the bottle using the plunger and draw again;
return the bottle to upright position, remove the syringe, and close the bottle with the cap;
rinse the syringe with clean water after use.

Children. For use in children aged 2 months and older. For children with body weight exceeding 40 kg, another formulation of the medicine should be prescribed.

Overdose.

Symptoms

Gastrointestinal disturbances and fluid and electrolyte imbalances may occur.

Amoxicillin crystalluria has been observed, which in some cases led to renal failure (see section "Special Warnings and Precautions for Use").

Seizures may occur in patients with impaired renal function and in those receiving high doses of the medicine.

Amoxicillin has been reported to precipitate in urinary catheters, primarily after intravenous administration of high doses. Therefore, catheter patency should be monitored regularly (see section "Special Warnings and Precautions for Use").

Treatment

Gastrointestinal symptoms can be treated symptomatically, with attention to maintaining fluid and electrolyte balance.

Amoxicillin and clavulanic acid are removed by hemodialysis.

Adverse Reactions

The most commonly reported adverse reactions were diarrhea, nausea, and vomiting.

The adverse effects listed below were observed during clinical trials and in the post-marketing period, grouped according to the MedDRA (Medical Dictionary for Regulatory Activities) system organ classes.

The frequency of adverse reactions is classified as follows:

Very common: ≥ 1/10
Common: ≥ 1/100 to < 1/10
Uncommon: ≥ 1/1000 to < 1/100
Rare: ≥ 1/10000 to < 1/1000
Very rare: < 1/10000
Not known: (frequency cannot be estimated from available data)

Infections and infestations

Common: Cutaneous and mucocutaneous candidiasis
Not known: Overgrowth of microorganisms not sensitive to the drug

Blood and lymphatic system disorders

Rare: Reversible leukopenia (including neutropenia) and thrombocytopenia
Not known: Reversible agranulocytosis and hemolytic anemia; prolonged bleeding time and prothrombin index¹

Immune system disorders¹⁰

Not known: Angioedema, anaphylaxis, serum sickness-like syndrome, allergic vasculitis

Nervous system disorders

Uncommon: Dizziness, headache
Not known: Reversible hyperactivity and convulsions²
Not known: Aseptic meningitis

Cardiac disorders

Not known: Kouwenhoven syndrome

Gastrointestinal disorders

Common: Diarrhea, nausea³, vomiting
Uncommon: Gastric discomfort
Not known: Antibiotic-associated colitis⁴, "black hairy tongue", discoloration of tooth enamel¹¹, drug-induced enterocolitis syndrome (DIES), acute pancreatitis

Hepatobiliary disorders

Uncommon: Increased levels of AST and/or ALT⁵
Not known: Hepatitis⁶ and cholestatic jaundice⁶

Skin and subcutaneous tissue disorders⁷

Uncommon: Skin rashes, pruritus, urticaria
Rare: Multiform erythema
Not known: Stevens-Johnson syndrome, toxic epidermal necrolysis, exfoliative bullous dermatitis, acute generalized exanthematous pustulosis⁹, drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), linear IgA disease

Renal and urinary disorders

Very rare: Interstitial nephritis
Not known: Crystalluria⁸ (including acute kidney injury)

1 See section "Special precautions for use".
2 See section "Special precautions for use".
3 Nausea is more frequently associated with higher oral doses of the drug. The severity of gastrointestinal reactions may be reduced by taking Amoxiclav with food.
4 Includes pseudomembranous colitis and hemorrhagic colitis (see section "Special precautions for use").
5 Mild elevations in AST and/or ALT levels have been more frequently observed in patients receiving beta-lactam antibiotics, but the clinical significance of these findings is unknown.
6 These events have been reported with other penicillin and cephalosporin antibiotics (see section "Special precautions for use").
7 If hypersensitivity reactions (dermatitis) occur, the drug should be discontinued (see section "Special precautions for use").
8 See section "Overdose".
9 See section "Special precautions for use".
10 See section "Contraindications" and "Special precautions for use".
11 Tooth enamel discoloration has been very rarely reported in children. Careful oral hygiene may prevent this effect, as the discoloration is usually removable by tooth brushing.

Shelf life

3 years.

Shelf life after reconstitution/dilution.

7 days when stored in the original packaging at 2–8 °C.

Storage conditions

Store at temperatures not exceeding 30 °C.
Keep out of the reach of children.

Packaging

5.70 g or 11.0 g of powder in a vial for preparation of 35 ml or 70 ml of suspension, respectively;
1 vial with a measuring spoon or oral syringe in a cardboard box.

Prescription status

Prescription only.

Manufacturer

Sandoz GmbH – Production site Anti-Infectives GLZ and Chemical Operations Kundl (AIHO GLZ Kundl)

Manufacturer's address and place of business

Biochemistrasse 10, 6250 Kundl, Austria