Amoxy Co 1000/200 And 500/100 Gdc Tablets

AMOXY CO GDC is indicated when oral formulations cannot be used for the treatment of infections, caused by amoxicillin resistant organisms producing beta-lactamase sensitive to clavulanic acid:

• Upper respiratory tract infections such as sinusitis, recurrent otitis media, tonsillitis.
• Lower respiratory tract infections, such as bronchitis and bronchopneumonia
• Genito-urinary tract infections, such as cystitis, urethritis, pyelonephritis
• Skin and soft tissue infections.

AMOXY CO GDC will also be effective in the treatment of infections caused by amoxicillin sensitive organisms, at appropriate amoxicillin dosages, since in this situation the clavulanic acid component does not contribute to the therapeutic effect.

Posology

General information

For infections caused by amoxicillin sensitive organisms the dosage is that approved for amoxicillin, as the clavulanic acid component does not contribute to the therapeutic effect.

Adults

For severe infections of the respiratory tract, urinary tract and skin and soft tissue requiring parenteral therapy initially one AMOXY CO 1000/200 GDC vial containing the equivalent of 1000 mg amoxicillin and 200 mg clavulanic acid, can be administered intravenously 6 to 8 hourly by intravenous injection (2 minutes) or intravenous infusion (30 minutes) until the condition settles followed by oral therapy at the recommended dose. If no response is obtained within 48 hours therapy must be reviewed. Intravenous treatment with AMOXY CO GDC should not be extended beyond 10 days without review and the total daily administration of clavulanic acid should not exceed 800 mg. Treatment can be continued orally where appropriate after a satisfactory therapeutic response has been obtained.

Dosage guide

AMOXICILLIN SENSITIVE ORGANISMS

Product

Upper Respiratory Tract Infections

Lower Respiratory tract Infections

Urinary Tract Infections

Skin & Soft Tissue Infections

Adults

AMOXY CO 1000/200 GDC

1 vial (a) 6 - 8 hourly

1 vial (a) 6 - 8 hourly

1 vial (a) 6 - 8 hourly

1 vial (a) 6 - 8 hourly

AMOXY CO 500/100 GDC

-

-

2 vials (a) 6 - 8 hourly

2 vials (a) 6 - 8 hourly

(a) Intravenous therapy should not be continued for longer than 10 days.

Renal impairment

Each AMOXY CO 500/100 GDC vial contains 0,5 mmol of potassium and 1,37 mmol of sodium. Each AMOXY CO 1000/200 GDC vial contains 1,0 mmol of potassium and 2,74 mmol of sodium. As the kidneys excrete both the amoxicillin and clavulanic acid components of AMOXY CO GDC, accumulation of both may occur in patients with renal insufficiency. In these cases, monitoring of the serum levels and a reduction in the number of administrations of the suggested dosage may be required. Experience in a limited number of patients with varying degrees in renal insufficiency suggest that the following schedule of dosage based on the creatinine clearance of the patient may be used as a guideline:

Creatinine clearance Dosage

> 30 mL/min No dosage adjustment

10 u2013 30 mL/min 1,2 g AMOXY CO GDC initially and then 600 mg 12 hourly

< 10 mL/min 1,2 g AMOXY CO GDC initially and then 600 mg daily

Hepatic impairment

Dose with caution and monitor hepatic function at regular intervals (see sections 4.3 and 4.4).

Paediatric population

Insufficient evidence exists at present to recommend an intravenous dosage in children.

Method of administration

AMOXY CO GDC is for intravenous use and is not suitable for intramuscular or subcutaneous administration. The reconstituted vial can be administered intravenously by injection (2 minutes) or slow intravenous infusion (30 minutes). Infusion should be completed within the period of stability of AMOXY CO GDC infusions after reconstitution and dilution, as reflected in the table under the section u201cCompatibility of AMOXY CO GDC with IV fluids and stability of reconstituted solutionu201d presented in section 6.6. The contents of the vial must be used within 20 minutes and thereafter any unused material should be discarded. Please refer to section 6.6 below for u201cPreparation of solutions for intravenous injection and intravenous infusionu201d.

• Hypersensitivity to the active substances or any excipients listed in section 6.1.
• Patients with a history of hypersensitivity (e.g. anaphylaxis) to beta-lactam antibiotics such as penicillins, cephalosporins, carbapenems or to monobactams. Cross-sensitivity between penicillins and cephalosporins is well documented.
• Patients that have a previous history of amoxicillin/clavulanic-associated jaundice/hepatic dysfunction.
• Safety and efficacy in children have not been established with AMOXY CO GDC.

Hypersensitivity

Before initiating therapy with AMOXY CO GDC, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam medicines (see sections 4.3 and 4.8). Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral penicillins. Serious and occasional fatal hypersensitivity reactions (including anaphylactoid and severe cutaneous adverse reactions such as Stevens-Johnson syndrome (SJS), Toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS)) have been reported in patients on penicillin therapy. Hypersensitivity reactions can also progress to Kounis syndrome, a serious allergic reaction that can result in myocardial infarction (see section 4.8). These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and in atopic individuals. There have been reports of individuals with a history of penicillin hypersensitivity, who have experienced severe reactions when treated with cephalosporins.

Drug-induced enterocolitis syndrome (DIES) has been reported mainly in children receiving amoxicillin/clavulanate as in AMOXY CO GDC (see section 4.8). DIES is an allergic reaction with the leading symptom of protracted vomiting (1 - 4 hours after drug administration) in the absence of allergic skin or respiratory symptoms. Further symptoms could comprise abdominal pain, diarrhoea, hypotension or leucocytosis with neutrophilia. There have been severe cases including progression to shock. If an allergic reaction occurs, AMOXY CO GDC should be discontinued and the appropriate therapy instituted which may include epinephrine (adrenaline), intravenous corticosteroids and antihistamines. Oxygen and airway management, including intubation may also be required.

Convulsions

Convulsions may occur in patients with impaired renal function or in those receiving high doses (see section 4.8).

Infectious mononucleosis

Since AMOXY CO GDC contains amoxicillin, an aminopenicillin, it is not the treatment of choice in patients presenting with sore throat or pharyngitis because of the possibility that the underlying cause is infectious mononucleosis, in the presence of which there is a high incidence of morbilliform rash if amoxicillin is used. AMOXY CO GDC should be avoided if infectious mononucleosis is suspected.

Prolonged use, overgrowth and antibiotic associated colitis

Periodic assessment of organ system functions, including renal, hepatic and haematopoietic function is advisable during prolonged therapy. Prolonged use may result in overgrowth of non-susceptible organisms. The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If superinfections occur (usually involving Aerobacter, Pseudomonas or Candida), AMOXY CO GDC should be discontinued and/or appropriate therapy instituted.

Antibiotic-associated colitis, such as Pseudomembranous enterocolitis and haemorrhagic colitis, has been reported with nearly all antibacterial medicines including amoxicillin and may range in severity from mild to life threatening (see section 4.8). Therefore, AMOXY CO GDC should be used with caution in patients with a history of gastrointestinal disease, especially antibiotic associated colitis. It is important to consider this diagnosis in patients who present with diarrhoea during or subsequent to the administration of any antibiotics. Should antibiotic-associated colitis occur, AMOXY CO GDC should immediately be discontinued, a doctor be consulted, and an appropriate therapy initiated. Antiperistaltic medicines are contraindicated in this situation.

Acute generalised exanthemous pustulosis (AGEP)

The occurrence at the treatment initiation of a feverish generalised erythema associated with pustula may be a symptom of acute generalised exanthemous pustulosis (AGEP) (see section 4.8). This reaction requires AMOXY CO GDC discontinuation and contraindicates any subsequent administration of amoxicillin.

Hepatic impairment

AMOXY CO GDC acid should be used with caution in patients with evidence of hepatic impairment (see sections 4.2, 4.3 and 4.8). Changes in liver function tests, transient hepatitis and cholestatic jaundice have been reported.

Hepatic events have been reported predominantly in males and elderly patients and may be associated with prolonged treatment. These events have been less frequently reported in children. In all populations, signs and symptoms usually occur during or shortly after treatment but in some cases may not become apparent until several weeks after treatment has ceased. These are usually reversible. Hepatic events may be severe, and in extremely rare circumstances deaths have been reported. These have almost always occurred in patients with serious underlying disease or taking concomitant medicines known to have the potential for hepatic effects (see section 4.8).

Renal impairment

In patients with moderate or severe renal impairment, the dose should be adjusted according to the degree of impairment (see section 4.2). In patients with reduced urine output, crystalluria (including acute renal injury) has been observed less frequently, predominantly with parenteral therapy. During the administration of high doses of amoxicillin, it is advisable to maintain adequate fluid intake and urinary output in order to reduce the possibility of amoxicillin crystalluria. In patients with bladder catheters, a regular check of patency should be maintained (see sections 4.8 and 4.9).

Concomitant use with anticoagulants

Prolongation of prothrombin time has been reported less frequently in patients receiving amoxicillin/clavulanic acid as in AMOXY CO GDC. Appropriate monitoring should be undertaken when anticoagulants are prescribed concomitantly. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation (see sections 4.5 and 4.8).

Patients with syphilis

Caution is needed when administering amoxicillin to patients with syphilis, as the Jarisch- Herxheimer reaction may occur in these patients.

Patients with lymphatic leukaemia

AMOXY CO GDC should be given with caution to patients with lymphatic leukaemia, since they are especially susceptible to amoxicillin-induced skin rashes.

Resistance

The use of AMOXY CO GDC may lead to the selection of resistant strains of organisms and sensitivity testing should, therefore, be carried out whenever possible, to demonstrate the appropriateness of therapy.

Laboratory tests

Glucose test

During treatment with amoxicillin, enzymatic glucose oxidase methods should be used whenever testing for the presence of glucose in urine because false positive results may occur with non-enzymatic methods (e.g., chemical methods).

Coombs test

The presence of clavulanic acid in AMOXY CO GDC may cause a non-specific binding of lgG and albumin by red cell membranes leading to a false positive Coombs test.

Aspergillus test

There have been reports of positive test results using the Bio-Rad Laboratories Platelia Aspergillus EIA test in patients receiving amoxicillin/clavulanic acid as in AMOXY CO GDC who were subsequently found to be free of Aspergillus infection. Cross-reactions with non-Aspergillus polysaccharides and polyfuranoses with Bio-Rad Laboratories Platelia Aspergillus EIA test have been reported. Therefore, positive test results in patients receiving AMOXY CO GDC should be interpreted cautiously and confirmed by other diagnostic methods.

Sodium and potassium

AMOXY CO 500/100 GDC contains 31,45 mg sodium per vial, equivalent to 1,57 % of the WHO recommended maximum daily intake of 2 g sodium for an adult. AMOXY CO 500/100 GDC contains potassium, less than 1 mmol (39 mg) per vial, i.e. essentially u2018potassium-freeu2019. AMOXY CO 1000/200 GDC contains 62,90 mg sodium, equivalent to 3,15 % of the WHO recommended maximum daily intake of 2 g sodium for an adult. AMOXY CO 1000/200 GDC contains 1 mmol (or 39,25 mg) potassium per vial. To be taken into consideration by patients with reduced kidney function or patients on a controlled potassium diet.

Probenecid

Concomitant use of probenecid is not recommended. Concurrent use of probenecid with AMOXY CO GDC may result in increased and prolonged blood levels of amoxicillin, but not of clavulanic acid.

Oral contraceptives

Following administration of ampicillin to pregnant woman a transient decrease in plasma concentration of total conjugate estriol, estriol-glucuronide, conjugated estrone and estradiol has been noted. This effect may also occur with AMOXY CO GDC leading to lower estrogen re-absorption and reduced efficacy of combined oral contraceptives. Patients should be warned accordingly.

Allopurinol

The concomitant administration of allopurinol and amoxicillin substantially increases the incidence of skin rashes in patients receiving both agents as compared to patients receiving AMOXY CO GDC alone. It is not known whether this potentiation of AMOXY CO GDC rashes is due to allopurinol or the hyperuricaemia present in these patients.

Tetracyclines and other bacteriostatics

Tetracyclines and other bacteriostatic drugs may interfere with the bactericidal effects of AMOXY CO GDC.

Methotrexate

Penicillins may reduce the excretion of methotrexate causing a potential increase in toxicity.

Mycophenolate mofetil

In patients receiving mycophenolate mofetil, reduction in pre-dose concentration of the active metabolite mycophenolic acid (MPA) 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. Therefore, a change in the dose of mycophenolate mofetil should not normally be necessary in the absence of clinical evidence of graft dysfunction. However, close clinical monitoring should be performed during the combination and shortly after antibiotic treatment.

Oral anticoagulants

Oral anticoagulants and penicillin antibiotics have been widely used in practice without reports of interaction. However, in the literature there are cases of increased international normalised ratio (INR) in patients maintained on acenocoumarol or warfarin and prescribed a course of amoxicillin as in AMOXY CO GDC. If co-administration is necessary, the prothrombin time or international normalised ratio should be carefully monitored with the addition or withdrawal of AMOXY CO GDC. Moreover, adjustments in the dose of oral anticoagulants may be necessary (see section 4.4 and 4.8).

Alcohol

No information is available about the concurrent use of AMOXY CO GDC and alcohol. However, the ingestion of alcohol whilst being treated with some other beta-lactam antibiotics has precipitated a disulfiram-like reaction in some patients. Therefore, the ingestion of alcohol should be avoided during and for several days after treatment with AMOXY CO GDC.

Pregnancy

The safety of AMOXY CO GDC in pregnancy has not been established. In women with pre-term, premature rupture of the foetal membrane (pPROM), it was reported that prophylactic treatment with amoxicillin-clavulanate may be associated with an increased risk of necrotising enterocolitis in neonates. Use of AMOXY CO GDC should be avoided during pregnancy.

Breastfeeding

Both amoxicillin and clavulanic acid are distributed into breast milk (nothing is known of the effects of clavulanic acid on the breast-fed infant). The use of AMOXY CO GDC by nursing mothers may lead to sensitisation, diarrhoea, candidiasis and skin rashes in the infant. Mothers on treatment with AMOXY CO GDC should not breastfeed their infants.

No studies on the effects on the ability to drive and use machines have been performed. Since adverse reactions such as allergic reactions, dizziness, convulsions have been reported in patients receiving co-amoxiclav as in AMOXY CO GDC, patients should not drive, use machinery or perform any tasks that require concentration, until they are certain AMOXY CO GDC does not adversely affect their ability to do so (see sections 4.4 and 4.8).

a. Summary of the safety profile

The most frequently reported adverse drug reactions are mucocutaneous candidiasis, diarrhoea, nausea and vomiting. Life-threatening skin adverse reactions such as the Stevens-Johnson and Lyell's syndromes (the latter is also known as toxic epidermal necrolysis (TEN)) and severe and sometimes fatal hepatic events have been reported with an unknown frequency (see section 4.4).

b. Tabulated list of adverse reactions

System Organ Class Frequency Adverse reactions

Infections and infestations Frequent mucocutaneous candidiasis (including vaginitis, stomatitis, glossitis) Frequency unknown overgrowth of non-susceptible organisms

Blood and lymphatic system disorders Less frequent reversible leukopenia (including neutropenia), thrombocytopenia Frequency unknown reversible agranulocytosis, haemolytic anaemia, prolongation of bleeding time and prothrombin time* (see section 4.4)

Immune system disorders Frequency unknown angioedema, anaphylaxis, serum sickness-like syndrome, hypersensitivity vasculitis

Nervous system disorders Less frequent dizziness, headache Frequency unknown convulsions (see section 4.4)*, aseptic meningitis

Cardiac disorders Frequency unknown Kounis syndrome

Vascular disorders Less frequent thrombophlebitis at the site of injection

Gastrointestinal disorders Frequent diarrhoea* Less frequent nausea*, vomiting, indigestion, gastritis Frequency unknown antibiotic-associated colitis (including pseudomembranous colitis and haemorrhagic colitis) (see section 4.4), drug-induced enterocolitis syndrome (DIES), acute pancreatitis

Hepatobiliary disorders Less frequent increase in liver enzymes (AST and/or ALT) Frequency unknown hepatitis*, cholestatic jaundice* (see section 4.4)

Skin and subcutaneous tissue disorders* Less frequent skin rash, pruritus, urticaria, erythema multiforme Frequency unknown Stevens-Johnson syndrome (SJS), Toxic epidermal necrolysis (TEN), bullous exfoliative-dermatitis, acute generalised exanthemous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), linear IgA disease

Renal and urinary disorders Less frequent interstitial nephritis, crystalluria (including acute renal injury) (see section 4.9)

General disorders and administration site conditions Frequency unknown local irritation, induration and phlebitis at the injection site.

*See below section c for description of selected adverse reactions.

c. Description of selected adverse reactions

Life-threatening skin adverse reactions AMOXY CO GDC may cause life-threatening cutaneous reactions Steven-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) also known as Lyell's syndrome and drug reaction with eosinophilia and systemic symptoms (DRESS), If symptoms or signs of SJS, TEN and DRESS (e.g., progressive skin rash often with blisters or mucosal lesions) are present, AMOXY CO GDC treatment should be discontinued immediately because the danger of severe allergic reactions (see section 4.8).

Hepatic events Hepatic events may be severe and fatal. Signs and symptoms usually occur during or shortly after treatment but in some cases may not become apparent until several weeks after treatment has ceased. These events have been noted with other penicillins and cephalosporins (see also sections 4.2 and 4.4).

Convulsions Convulsions may occur in patients with impaired renal function or in those receiving high doses (see section 4.4).

Gastrointestinal side effects The incidence and severity of frequent and less frequent gastrointestinal adverse effects, particularly nausea and diarrhoea, increased with the higher recommended dose and can be minimised by administering AMOXY CO GDC at the start of a meal. In addition, as these symptoms are especially related to the potassium clavulanate component, where these gastrointestinal symptoms occur and a higher concentration of amoxicillin is required, consideration should be given to administering the additional amoxicillin separately.

Prolongation of bleeding time and prothrombin time (increased INR). Appropriate monitoring should be undertaken when anticoagulants are prescribed concomitantly with AMOXY CO GDC (see sections 4.4 and 4.5).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are requested to report any suspected adverse drug reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website. Alternately you can contact Gulf Drug Company (Pty) Ltd at +27 31 538 8700 or per [email protected].

Symptoms and signs

Gastrointestinal symptoms such as nausea, vomiting and diarrhoea and disturbance of the fluid and electrolyte balances may be evident. Amoxicillin crystalluria, in some cases leading to renal failure, has been observed (see sections 4.4 and 4.8). Convulsions may occur in patients with impaired renal function or in those receiving high doses (see section 4.4). Amoxicillin has been reported to precipitate in bladder catheters, predominantly after intravenous administration of large doses. A regular check of patency should be maintained (see section 4.4).

Treatment

Gastrointestinal symptoms may be treated symptomatically, with attention to the water/electrolyte balance. Adequate fluid intake and urinary output must be maintained to minimise the possibility of crystalluria. Amoxicillin and clavulanic acid may be removed from the circulation by haemodialysis.