Augpen Lb Tab

Amoxycillin, Potassium Clavulanate and Lactic Acid Bacillus Tablets

Augpen LB 375

Each film coated tablet contains :

Amoxycillin Trihydrate IP equivalent to Amoxycillin 250 mg

Potassium Clavulanate Diluted IP

equivalent to Clavulanic Acid 125 mg

Lactic Acid Bacillus 30 million spores

Excipients q.s

Colours : Iron Oxide Yellow & Titanium Dioxide IP

(Appropriate overages of Lactic Acid Bacillus spores added.)

Augpen LB 625

Each film coated tablet contains :

Amoxycillin Trihydrate IP equivalent to Amoxycillin 500 mg

Potassium Clavulanate Diluted IP

equivalent to Clavulanic Acid 125 mg

Lactic Acid Bacillus 60 million spores

Excipients q.s.

Colours : Iron Oxide Yellow & Titanium Dioxide IP

(Appropriate overages of Lactic Acid Bacillus spores added.)

Augpen LB 1g BID

Each film coated tablet contains :

Amoxycillin Trihydrate IP equivalent to Amoxycillin 875 mg

Potassium Clavulanate Diluted IP

equivalent to Clavulanic Acid 125 mg

Lactic Acid Bacillus 60 million spores

Excipients q.s

Colours : Iron Oxide Yellow & Titanium Dioxide IP

(Appropriate overages of Lactic Acid Bacillus spores added.)

Film coated tablet, 375 mg / 625 mg / 1 g

4.1 Therapeutic indication

Augpen LB 375

“For the treatment of bacterial infections such as sinusitis, otitis media, tonsillitis, acute and chronic bronchitis, skin and post-operative pain in adults, prone to antibiotic associated diarrhoea”.

Augpen LB 625

“For the treatment of bacterial infections such as sinusitis otitis media, tonsillitis, acute and chronic bronchitis, skin and soft tissue infections, pelvic infections, ocsteromylitis, post-operative pain in adults, prone to antibiotic associated diarrhoea”.

Augpen LB 1g BID

“For the treatment of mild to moderate bacterial lower respiratory tract infections in adults, prone to antibiotic associated diarrhoea”.

4.2 Posology and method of administration

Dosage depends on the age and renal function of the patient and the severity of the infection. To minimise potential gastrointestinal intolerance, administer at the start of ameal. The absorption ofAugpen LBis optimised when taken at the start of ameal. Treatment should not be extended beyond 14 dayswithoutreview. Therapy can be started parenterally and continued with an oral preparation. Tablets should be swallowed whole without chewing.Ifrequired,tabletsmay be broken in half and swallowedwithout chewing

Augpen LB tablets are not recommended in children of 12 years and under

Adults and children over 12 years

The usual recommended daily dosage is :

Renal impairment

No adjustment in dose is required in patients with creatinine clearance (CrCl) greater than 30 mL/min. The Augpen LB 1g BID tablet should only be used in patients with a creatinine clearance (CrCl) rate of more than 30 mL/min.

Hepatic impairment

Dose with caution; monitor hepatic function at regular intervals.

4.3 Contraindications

Patients with a history of hypersensitivity to beta-lactams, e.g. penicillins and cephalosporins.

Patients with a previous history of Augpen LB-associated jaundice/hepatic dysfunction.

4.4 Special warnings and precautions for use

Before initiating therapy with Augpen LB, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other allergens. Serious and occasionally fatal hypersensitivity reactions (including anaphylactoid and severe cutaneous adverse reactions) have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity (see Contraindications). If an allergic reaction occurs, Augpen LB therapy must be discontinued and appropriate alternative therapy instituted. Serious anaphylactic reactions require immediate emergency treatment with adrenaline. Oxygen, intravenous (I.V.) steroids and airway management (including intubation) may also be required. Augpen LB should be avoided if infectious mononucleosis is suspected since the occurrence of a morbilliform rash has been associated with this condition following the use of Amoxycillin. Prolonged use may also occasionally result in overgrowth of non-susceptible organisms. Pseudomembranous colitis has been reported with the use of antibiotics and may range in severity from mild to life-threatening. Therefore, it is important to consider its diagnosis in patients who develop diarrhoea during or after antibiotic use. If prolonged or significant diarrhoea occurs or the patient experiences abdominal cramps, treatment should be discontinued immediately and the patient investigated further. Abnormal prolongation of prothrombin time (increased INR) has been reported rarely in patients receiving Augpen LB and oral anticoagulants. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation. Changes in liver function tests have been observed in some patients receiving Augpen LB. The clinical significance of these changes is uncertain but Augpen LB should be used with caution in patients with evidence of hepatic dysfunction.

4.5 Drugs interactions

Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular secretion of Amoxycillin. Concomitant use with Augpen LB may result in increased and prolonged blood levels of Amoxycillin but not of Clavulanic Acid. Concomitant use of Allopurinol during treatment with Amoxycillin can increase the likelihood of allergic skin reactions. There are no data on the concomitant use of Augpen LB and Allopurinol. In common with other antibiotics, Augpen LB may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral contraceptives. In the literature there are rare cases of increased international normalised ratio in patients maintained on Acenocoumarol or Warfarin and prescribed a course of Amoxycillin. If co-administration is necessary, the prothrombin time or international normalised ratio should be carefully monitored with the addition or withdrawal of Augpen LB. In patients receiving Mycophenolate Mofetil, reduction in pre-dose concentration of the active metabolite Mycophenolic acid of approximately 50% has been reported following commencement of oral Amoxycillin plus Clavulanic Acid. The change in pre-dose level may not accurately represent changes in overall MPA exposure

4.6 Use in special populations

Pregnancy and lactation

Reproduction studies in animals (mice and rats) with orally and parenterally administered Augpen LB have shown no teratogenic effects. In a single study in women with preterm, premature rupture of the foetal membrane (pPROM), it was reported that prophylactic treatment with Augpen LB may be associated with an increased risk of necrotising enterocolitis in neonates. As with all medicines, use should be avoided in pregnancy, especially during the first trimester, unless considered essential by the Physician. Augpen LB may be administered during the period of lactation. With the exception of the risk of sensitisation, associated with the excretion of trace quantities in breast milk, there are no detrimental effects for the infant.

4.7 Effects on ability to drive and use machines

Adverse effects on the ability to drive or operate machinery have not been observed.

4.8 Undesirable effects

Data from large clinical trials were used to determine the frequency of very common to rare undesirable effects. The frequencies assigned to all other undesirable effects (i.e., those occurring at <1/10,000) were mainly determined using post-marketing data and refer to a reporting rate rather than a true frequency.

Infections and infestations

Common : Mucocutaneous candidiasis

Blood and lymphatic system disorders

Rare : Reversible leucopenia (including neutropenia) and thrombocytopenia.

Very rare : Reversible agranulocytosis and haemolytic anaemia. Prolongation of bleeding time and prothrombin time.

Immune system disorders

Very rare : Angioneurotic oedema, Anaphylaxis, Serum sickness-like syndrome, Hypersensitivity vasculitis.

Nervous system disorders

Uncommon : Dizziness, Headache

Very rare : Reversible hyperactivity, Aseptic meningitis, Convulsions. Convulsions may occur in patients with impaired renal function or in those receiving high doses.

Gastrointestinal disorders

Adults

Very common : Diarrhoea

Common : Nausea, Vomiting

Children

Common : Diarrhoea, Nausea, Vomiting

All populations

Nausea is more often associated with higher oral dosages. If gastrointestinal reactions are evident, they may be reduced by taking Augpen LB at the start of a meal.

Uncommon : Indigestion

Very rare : Antibiotic-associated colitis (including pseudomembranous colitis and haemorrhagic colitis), black hairy tongue, superficial tooth discolouration has been reported very rarely in children. Good oral hygiene may help to prevent tooth discolouration as it can usually be removed by brushing.

Hepatobiliary disorders

Uncommon : A moderate rise in AST and/or ALT has been noted in patients treated with beta-lactam class antibiotics, but the significance of these findings is unknown.

Very rare : Hepatitis and cholestatic jaundice. These events have been noted with other penicillins and cephalosporins.

Hepatic events have been reported predominantly in males and elderly patients and may be associated with prolonged treatment. These events have been very rarely reported in children. 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 medications known to have the potential for hepatic effects.

Skin and subcutaneous tissue disorders

Uncommon : Skin rash, Pruritus, Urticaria

Rare : Erythema multiforme

Very rare : Stevens-Johnson syndrome, Toxic epidermal necrolysis, Bullous exfoliative-dermatitis, Acute generalised exanthematous pustulosis (AGEP), and drug reaction with eosinophilia and systemic symptoms (DRESS).

If any hypersensitivity dermatitis reaction occurs, treatment should be discontinued.

Renal and urinary disorders

Very rare : Interstitial nephritis, Crystalluria

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via email to : medico@zuventus.com. By reporting side effects, you can help provide more information on the safety of this medicine.

4.9 Overdose

Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident. Gastrointestinal symptoms may be treated symptomatically with attention to the water-electrolyte balance. Amoxycillin crystalluria, in some cases leading to renal failure, has been observed. Augpen LB can be removed from the circulation by haemodialysis

5.1 Mechanism of action

Amoxycillin is a semisynthetic penicillin (beta-lactam antibiotic) that inhibits one or more enzymes (often referred to as penicillin-binding proteins, PBPs) in the biosynthetic pathway of bacterial peptidoglycan, which is an integral structural component of the bacterial cell wall. Inhibition of peptidoglycan synthesis leads to weakening of the cell wall, which is usually followed by cell lysis and death. Amoxycillin is susceptible to degradation by beta-lactamases produced by resistant bacteria and therefore the spectrum of activity of Amoxycillin alone does not include organisms which produce these enzymes. Clavulanic acid is a beta-lactam structurally related to penicillins. It inactivates some beta-lactamase enzymes thereby preventing inactivation of Amoxycillin. Clavulanic acid alone does not exert a clinically useful antibacterial effect. Lactobacillus is an aerobic gram-positive, ubiquitous inhabitant of the human oral cavity, vagina and gastrointestinal tract. It inhibits the colonization of pathogenic bacteria upon the intestinal epithelium

5.2 Pharmacodynamic properties

The prevalence of resistance may vary geographically and with time for selected species, and local information on resistance is desirable, particularly when treating severe infections. As necessary, expert advice should be sought when the local prevalence of resistance is such that the utility of the agent in at least some types of infections is questionable.

5.3 Pharmacokinetic properties

Absorption

Amoxycillin and Clavulanic acid, are fully dissociated in aqueous solution at physiological pH. Both components are rapidly and well absorbed by the oral route of administration. Following oral administration, Amoxycillin and Clavulanic acid are approximately 70% bioavailable. The plasma profiles of both components are similar and the time to peak plasma concentration (Tmax) in each case is approximately one hour. The pharmacokinetic results for a study, in which Amoxycillin/Clavulanic acid (250 mg/125 mg tablets three times daily) was administered in the fasting state to groups of healthy volunteers are presented below.

Amoxycillin and Clavulanic acid serum concentrations achieved with Amoxycillin/Clavulanic acid are similar to those produced by the oral administration of equivalent doses of Amoxycillin or Clavulanic acid alone.

Distribution

About 25% of total plasma Clavulanic acid and 18% of total plasma Amoxycillin is bound to protein. The apparent volume of distribution is around 0.3 - 0.4 l/kg for Amoxycillin and around 0.2 l/kg for Clavulanic acid. Following intravenous administration, both Amoxycillin and Clavulanic acid have been found in gall bladder, abdominal tissue, skin, fat, muscle tissues, synovial and peritoneal fluids, bile and pus. Amoxycillin does not adequately distribute into the cerebrospinal fluid. From animal studies there is no evidence for significant tissue retention of drug-derived material for either component. Amoxycillin, like most penicillins, can be detected in breast milk. Trace quantities of Clavulanic acid can also be detected in breast milk. Both Amoxycillin and Clavulanic acid have been shown to cross the placental barrier.

Biotransformation

Amoxycillin is partly excreted in the urine as the inactive penicilloic acid in quantities equivalent to up to 10 to 25% of the initial dose. Clavulanic acid is extensively metabolized in man and eliminated in urine and faeces, and as Carbon Dioxide in expired air.

Elimination

The major route of elimination for Amoxycillin is via the kidney, whereas for Clavulanic acid it is by both renal and non-renal mechanisms. Amoxycillin/Clavulanic acid has a mean elimination half-life of approximately one hour and a mean total clearance of approximately 25 l/h in healthy subjects. Approximately 60 to 70% of the Amoxycillin and approximately 40 to 65% of the Clavulanic acid are excreted unchanged in urine during the first 6 h after administration of single Augpen LB 250 mg/125 mg or 500 mg/125 mg tablets. Various studies have found the urinary excretion to be 50 - 85% for Amoxycillin and between 27 - 60% for Clavulanic acid over a 24 hour period. In the case of Clavulanic acid, the largest amount of drug is excreted during the first 2 hours after administration. Concomitant use of probenecid delays Amoxycillin excretion but does not delay renal excretion of Clavulanic acid

6.1 Animal toxicology or pharmacology No known animal toxicology data.

Augpen LB is a fixed dose combination of Amoxycillin, a broad spectrum antibiotic, Clavulanic acid, a potent beta lactamase enzyme inhibitor and Lactic Acid Bacillus (Lactobacillus sporogenes species) a probiotic for treatment of infection caused by susceptible bacteria.

8.1 Incompatibilities

Not applicable

8.2 Shelf-life

Refer on the pack.

8.3 Packaging information

Alu-Alu blister strip of 10 tablets.

8.4 Storage and handing instructions

Store below 25°C. Protect from light & moisture.

Keep out of reach of children.

Patients should be informed that Augpen LB may be taken every 8 hours or every 12 hours, depending on the dose prescribed. Each dose should be taken with a meal or snack to reduce the possibility of gastrointestinal upset. Patients should be counselled that antibacterial drugs, including Augpen LB, should only be used to treat bacterial infections. They do not treat viral infections (e.g., the common cold). When Augpen LB is prescribed to treat a bacterial infection, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full course of therapy may : (1) decrease the effectiveness of the immediate treatment, and (2) increase the likelihood that bacteria will develop resistance and will not be treatable by Augpen LB or other antibacterial drugs in the future. Counsel patients that diarrhea is a common problem caused by antibacterials, and it usually ends when the antibacterial is discontinued. Sometimes after starting treatment with antibacterials, patients can develop watery and bloody stools (with or without stomach cramps and fever) even as late as 2 or more months after having taken their last dose of the antibacterial. If diarrhea is severe or lasts more than 2 or 3 days, patients should contact their physician. Patients should be aware that Augpen LB contains a penicillin class drug product that can cause allergic reactions in some individuals.