AMOXICLAV-DENK Tablet

In the treatment of acute and chronic infections that are receptive to oral therapy. Gram-positive and gran-negative microorganisms are possible pathogens whose resistance to beta-lactam antibiotics is caused by beta-lactams, which are however sensitive to the combination of amoxicillin and clavulanic acid.

If there is a reasonable suspicion that the afore-mentioned pathogens could be the cause of a certain infection, treatment with AmoiClav-Denk 500/62.5 can be commenced even before receiving the result of the susceptibility test (antibiogram)

This medicine is suitable for treatment of the following indications:

- infections of the upper and lower respiratory tract including: middle ear infection (otitis media), acute infection of the paranasal sinuses (acute sinusitis), acute exacerbations of chronic bronchitis, lung infection (pneumonia)

- kidney and lower urinary tract infections

- genital infections

Please note: Treatment of pneumonia should be started parenterally, particularly for severe forms of pneumonia acquired as an outpatient.

Consideration should be given to official national and international guidelines on the appropriate use of antimicrobial agents.

Dosage

The dosage depends on the age, weight and renal function of the individual patient, on the severity and site of infection and on the suspected or verified pathogens.

As a rule it is the patient’s body weight that is the deciding factor for determining dosage even if this is not in accordance with the given age in individual cases.

- Adults weighing in excess of 40kg

2 tablets 2-3 times a day. at regular intervals throughout the day if possible, at 12 hours intervals if taken twice a day.

- Elderly patients

2 tablets 2-3 times a day as long as there is no evidence of renal or hepatic impairment.

(See the package insert about the details below.)

- Patients with impaired liver function

- Patients with impaired renal function and dialysis patients

Mode of administration

Take the tables at regular intervals throughout the day with sufficient fluids (e.g. a glass of water).

Do not chew.

These tablets are best take at the start of a meal, after patients have taken first bite. Taken in this way, this tablet is most effective and tolerated best. However, these tablets are also effective when taken before or after meals.

Duration of treatment

As a rule this tablet should be taken for 7-10 days and for at least a further 2 days after regression of the symptoms.

The duration of treatment should be determined by the doctor for each individual patient and should not be extended beyond 14 days without review. the kidney, liver and blood parameters should be monitored regularly during long-term treatment.

The duration of treatment for acute bacterial maxillary sinusitis is 14 days.

As a precaution, patients should take this tablet for at least 10 days if being treatment for an infection with beta-haemolytic streptococci in order to guard against late complications (e.g. rheumatic fever, glomerulonephritis).

- Allergic (hypersensitive) to the active ingredients amoxicillin and/or clavulanic acid or any of the other ingredients of this tablet

- If there is a history of allergic reactions after using certain beta-lactam antibiotics (e.g. penicillins, cephalosporins), as in such cases there is a danger of allergic (anaphylactic) shock.

- In the past experienced liver problems or jaundice after using these tablets.

Infections

Common: Increased colonization of the skin and mucosae with yeast fungus (candidiasis). Prolonged and repeated use of amoxicillin/clavulanic acid can result in an infection or colonization with resistant bacteria or yeasts.

Blood and lymphatic system disorders

Rare: Changes in blood count such as reduction in the number of white blood cells (leukopenia including neutropenia), reduction in number of platelets (thrombocytopenia).

Very rare: Changes in blood count manifested by a reduction in the number of certain white blood cells (granulocytopenia, agranulocytosis), reduction in number of all blood cells (pancytopenia), haemolytic anaemia, suppression of blood cell production by the bone marrow (myelosuppression) and prolongation of the bleeding and prothrombin time. These manifestations are reversible upon discontinuation of therapy.

Immune system disorders

Very rare: Severe allergic reactions resulting from sensitisation to 6-amino penicillic acid group, e.g. in the form of drug fever, increase in special blood cells (eosinophilia), painful swelling of the skin and mucosa (Quincke’s edema), hypersensitivity reactions of every severity, sometimes resulting in allergic shock (anaphylaxis), serum sickness, allergic vessel and renal complaints (vasculitis and/or nephritis) and internal swelling of the larynx with airway restriction and labored breathing (laryngeal oedema).

Hypersensitivity reactions of every severity, sometimes resulting in anaphylactic shock, have been observed in association with the administration of penicillins. Severe anaphylactoid reactions may require appropriate emergency measures.

Nervous system disorders

Uncommon: Headache, dizziness

Very rare: Reversible hyperactivity, anxiety, insomnia, confusion, aggression and convulsions. As with other penicillins, cerebral convulsions may occur in patients with impaired renal function or in patients receiving high doses of amoxicillin/clavulanic acid. Care must therefore be taken to ensure an appropriate dosage, especially in patients with compromised renal function.

Gastrointestinal disorders

Very common: Diarrhoea

Common: Nausea (increases with higher dose), vomiting, stomach ache, flatulence and soft stool. These are generally of a mild nature and recede upon discontinuation of therapy. This tablet is tolerated better when taken with meals.

Uncommon: Upper abdominal complaints (dyspepsia)

Rare: Increased colonisation of the intestine with yeast fungus (intestinal candidiasis).

Very rare: Intestinal infection caused by antibiotics (antibiotic-associated enterocolitis including pseudomembranous enterocolitis and haemorrhagic enterocolitis) which may be life-threatening. In the event of severe persistent diarrhoea occurring during or in the first few weeks after treatment, the diagnosis of pseudomembranous enterocolitis should be considered (in most cases caused by the pathogen Clostridium difficile). Black tongue.

A single study in women with premature rupture of the amnion reported that prophylactic treatment with this medicine can be associated with a severe form of intestinal infection (necrotising enterocolitis) in neonates.

Hepatobiliary disorders

Uncommon: Moderate, asymptomatic rise in liver enzyme values (AST, ALT, alkaline phosphatase). However, this is not necessarily a sign of liver damage associated with this tablet.

Very rare: Transitory liver infection and jaundice caused by bile obstruction (cholestatic jaundice). These reactions have also been observed in association with other penicillins or cephalosporins.

Symptoms of liver impairment (unusually severe itching, yellowing of the skin and whites of the eyes, darker urine and paler stools than usual) may occur during and shortly after treatment with this tablet. In some cases, however, they do not become apparent until several weeks after treatment cessation.

Liver impairment may be severe and occurs predominately in males and elderly patients (aged 60 and over) or with treatment courses exceeding 14 days. It is usually temporary. However, in extremely rare cases a fatal outcome has been reported. These have mostly occurred in patients with a serious underlying illness or in patients taking other medicines at the same time.

Liver impairment also has been observed in children in very rare cases.

Skin and subcutaneous tissue disorders

Uncommon: Hives (urticaria), itching (pruritus), skin rash (exanthema).

The typical measles-like skin rash occurs 5-11 days after the commencement of treatment.

Patients with infectious mononucleosis (Pfeiffer’s disease) and patients with a certain type of leukaemia (lymphatic leukaemia) have a higher risk of developing exanthema. An immediate skin reaction in the form of a nettle rash usually points to a real penicillin allergy and treatment must be discontinued.

Furthermore, mucositis, particularly oral mucositis, may occur. Dry mouth and taste alteration may occur.

Rare: Life-threatening extensive peeling of the skin (erythema exsudativum multiforme).

Very rare: Life-threatening genera reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis, acute generalised pustular exanthema), life-threatening illnesses manifested by blisters of the skin (Bullous and exfoliative dermatitis).

If skin reactions occur, the patient should discontinue treatment with this medicine and inform doctor.

Hypersensitivity reactions cannot be ruled out in patients who have or have had a yeast infection even when given penicillin for the first time (antigen community between yeasts and penicillin).

Renal and urinary disorders

Very rare: Kidney infection (acute interstitial nephritis), crystallization of the active ingredient amoxicillin in urine (crystalluria).

General disorders and administration site conditions:

Very rare: As seen with other antibiotics teeth discolouration has been observed. This discolouration remained in about half of those affected (usually children under the age of 10) despite intensive oral hygiene.

See the package insert about the details below:

- Other antibiotics and/or chemotherapeutic agents

- Probenecid

- Allopurinol

- Water pills (diuretics)

- Digoxin

- disulfiram

- Anticoagulants

- Hormonal contraceptives (pill)

(See the package insert about the details.)

Pregnancy

Temporary reduced levels of estradiol and its chemically related compounds were detected in pregnant women who had received treatment with ampicillin. This effect may also occur with amoxicillin/clavulanic acid.

This tablet should only be used during pregnancy if in the judgment of the doctor the potential benefits outweigh the possible risks.

Lactation

This tablet is permitted after appropriate consideration of the benefits and risks.

See the package insert about the details below:

- In patients with pre-existing impaired liver function/liver damage.

- In patients with severe allergies or asthma

- In patients with severe gastrointestinal disturbances with vomiting and diarrhoea

- In patients with renal dysfunction

- In persons on a potassium-restricted diet

- In patients with reduced renal output (restricted diuresis)

- In patients with a bladder catheter

- In the presence of viral infections, particularly infectious mononucleosis (Pfeiffer’s disease), and a certain type of leukaemia (Lymphatic leukaemia).

- Teeth discolouration can be prevented by carrying out intensive oral hygiene during treatment.

- The presence of this medicine may cause a non-specific binding of IgG and albumin to the red blood cells leading to a false positive Coombs test.

Acute life-threatening adverse drug reactions may occur during treatment with this drug and treatment may therefore have to be discontinued prematurely, e.g.

- intestinal infection (pseudomembranous enterocolitis),

- severe, acute life-threatening hypersensitivity reactions,

- occurrence of (epilepsy-like) convulsions.

Long-term use

Children and adolescents

The elderly

Amoxicillin is semi-synthetic amino penicillin that is not beta-lactamase-resistant. Clavulanic acid is a beta-lactamase-resistant. Clavulanic acid is a beta-lactamase inhibitor that is similar in structure to amoxicillin and other penicillins.

Amoxicillin acts by inhibiting the synthesis of bacterial cell walls (in the growth phase) by blocking the penicillin binding proteins (PBPs) such as the transpeptidases. This causes a bactericidal effect.

In combination with clavulanic acid amoxicillin is protected from inactivation by certain beta-lactamases. Clavulanic acid protects amoxicillin from degradation by most beta-lactamases of staphylococci as well as some plasmid-mediated beta-lactamases and certain chromosomally mediated beta-lactamases of gram-negative bacteria. These beta-lactamases are found for example in Escherichia coli, Klebsiella spp., Proteus mirabilis and Haemophilus influenzae. The antibacterial therapeutic spectrum of amoxicillin is extended to include those bacteria whose beta-lactamases can be inhibited by clavulanic acid.