NOVAMOX-LB Capsule (Amoxycillin + Lactic acid bacillus)

Table of Content

Composition

Novamox- LB 250 Capsules
Each capsule contains
Amoxycillin Trihydrate IP equivalent to Amoxycillin .........250 mg
Lactic acid Bacillus ...........................................................60x106 cells

Novamox-LB 500 Capsules
Each capsule contains
Amoxycillin Trihydrate IP equivalent to Amoxycillin.........500 mg
Lactic acid Bacillus ..........................................................60x106 cells

Dosage Form/s

Capsules

Pharmacology

NOVAMOX LB is a combination of amoxycillin trihydrate and lactobacillus. Amoxycillin is a semi-synthetic penicillin which exerts its bactericidal action by inhibition of cell wall synthesis. It acts against a broad spectrum of gram-positive and gram-negative microorganisms. 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. The inhibitory process known as 'competitive exclusion' can be expanded by the competition for the adherence sites of the intestinal mucosa between pathogens and lactobacilli and by the inhibitory substance.

Microbiology

Amoxycillin is similar to ampicillin in its bactericidal action against susceptible organisms during the stage of active multiplication. It acts through the inhibition of biosynthesis of cell wall mucopeptide. Amoxycillin has been shown to be active against most strains of the following microorganisms, both in vitro and in clinical infections:

Aerobic Gram-positive Microorganisms

Enterococcus faecalis
Staphylococcus spp.* (beta-lactamase-negative strains only)
Streptococcus pneumoniae
Streptococcus spp. (alpha- and beta-haemolytic strains only)
* Staphylococci that are susceptible to amoxycillin but resistant to methicillin/oxacillin should be considered as resistant to amoxycillin.

Aerobic Gram-negative Microorganisms

Escherichia coli (beta-lactamase-negative strains only)
Haemophilus influenzae (beta-lactamase-negative strains only)
Neisseria gonorrhoeae (beta-lactamase-negative strains only)
Proteus mirabilis (beta-lactamase-negative strains only)

Helicobacter

Helicobacter pylori

Pharmacokinetics

Amoxycillin is stable in the presence of gastric acid and is rapidly absorbed after oral administration. The effect of food on the absorption of amoxycillin from amoxycillin tablets and amoxycillin suspension has been partially investigated. The 400 mg and 875 mg formulations have been studied only when administered at the start of a light meal. However, food effect studies have not been performed with the 200 mg and 500 mg formulations. Amoxycillin diffuses readily into most body tissues and fluids, with the exception of brain and spinal fluid, except when meninges are inflamed. The half-life of amoxycillin is 61.3 minutes. Most of the amoxycillin is excreted unchanged in the urine; its excretion can be delayed by concurrent administration of probenecid. In blood serum, amoxycillin is approximately 20% protein-bound.

Orally administered doses of 250 mg and 500 mg amoxycillin capsules result in average peak blood levels 1 to 2 hours after administration in the range of 3.5 mcg/mL to 5 mcg/mL and 5.5 mcg/mL to 7.5 mcg/mL, respectively.

Mean amoxycillin pharmacokinetic parameters from an open, two-part, single-dose crossover bioequivalence study in 27 adults comparing 875 mg of amoxycillin with 875 mg of amoxycillin/clavulanate potassium showed that the 875 g tablet of amoxycillin produces an AUC0-infinity of 35.4 ±8.1 mcg hr/mL and a Cmax of 13.8 ±4.1 mcg/mL. Dosing was at the start of a light meal following an overnight fast.

Orally administered doses of amoxycillin suspension, 125 mg/5 mL and 250 mg/5 mL, result in average peak blood levels 1 to 2 hours after administration in the range of 1.5 mcg/mL to 3 mcg/mL and 3.5 mcg/mL to 5 mcg/mL, respectively.

Oral administration of single doses of 400 mg amoxycillin chewable tablets and 400 mg/5 mL suspension to 24 adult volunteers yielded comparable pharmacokinetic data:

Dose
AUC0-infinity(mcg hr/mL)
Cmax(mcg/mL)
Amoxycillin
Amoxycillin (± S.D.)
Amoxycillin (± S.D.)
400 mg (5 mL of suspension)
17.1 (3.1)
5.92 (1.62)
400 mg (1 chewable tablet)
17.9 (2.4)
5.18 (1.64)

Detectable serum levels are observed up to 8 hours after an orally administered dose of amoxycillin. Following a 1-gram dose and utilizing a special skin window technique to determine levels of the antibiotic, it was noted that therapeutic levels were found in the interstitial fluid. Approximately 60% of an orally administered dose of amoxycillin is excreted in the urine within 6 to 8 hours.

Indications

Amoxycillin is indicated in the treatment of infections due to susceptible (ONLY beta-lactamase-negative) strains of the designated microorganisms in the conditions listed below:

Infections of the Ear, Nose and Throat due to Streptococcus spp. (alpha- and beta-haemolytic strains only), S. Pneumoniae, Staphylococcus spp., or H. influenzae.

Infections of the Genitourinary Tract due to E. coli, P. mirabilis, or E. faecalis.

Infections of the Skin and Skin Structure due to Streptococcus spp. (alpha- and beta-haemolytic strains only), Staphylococcusspp., or E. coli.

Infections of the Lower Respiratory Tract due to Streptococcus spp. (alpha- and beta-haemolytic strains only), S. pneumoniae, Staphylococcus spp., or H. influenzae.

Gonorrhoea, Acute, Uncomplicated (Ano-Genital and Urethral Infections)
due to N. gonorrhoeae (males and females).

H. pylori  Eradication to Reduce the Risk of Duodenal Ulcer Recurrence.

Triple Therapy: Amoxycillin/Clarithromycin/Lansoprazole
Amoxycillin, in combination with clarithromycin plus lansoprazole as triple therapy, is indicated for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or 1-year history of a duodenal ulcer) to eradicate H. pylori. Eradication of H. pylori has been shown to reduce the risk of duodenal ulcer recurrence.

Dual Therapy: Amoxycillin/Lansoprazole

Amoxycillin, in combination with lansoprazole delayed-release capsules as dual therapy, is indicated for the treatment of patients with H. pylori infection and duodenal ulcer disease (active or 1-year history of a duodenal ulcer) who are either allergic or intolerant to clarithromycin or in whom resistance to clarithromycin is known or suspected. Eradication of H. pylorihas been shown to reduce the risk of duodenal ulcer recurrence.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of amoxycillin capsules, amoxycillin tablets, amoxycillin tablets (chewable) and amoxycillin for oral suspension and other antibacterial drugs, amoxycillin capsules, amoxycillin tablets, amoxycillin tablets (chewable) and amoxycillin for oral suspension should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available, they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.

Indicated surgical procedures should be performed.

Dosage and Administration

Amoxycillin capsules, tablets and oral suspension may be given without regard to meals. The 400 mg suspension, 400 mg tablet and the 875 mg tablet have been studied only when administered at the start of a light meal. However, food effect studies have not been performed with the 200 mg and 500 mg formulations.

Amoxycillin chewable tablets should be chewed before swallowing.

Neonates and Infants Aged ≤12 Weeks (≤3 Months) 

Due to incompletely developed renal function affecting the elimination of amoxycillin in this age group, the recommended upper dose of amoxycillin is 30 mg/kg/day divided q12h.

Adults and Paediatric Patients Aged >3 months
Infection
Severity
Usual
Adult
Dose
Usual Dose for Children
Aged >3 months§
Ear/Nose/Throat
Mild/Moderate
500 mg
every12
hours or
250 mg
every 8
hours
25 mg/kg/day in divided
doses every 12 hours
or 20 mg/kg/day
in divided doses
every 8 hours
 
Severe
875 mg every
12 hours or
500 mg every
8 hours
45 mg/kg/day in divided
doses every 12 hours
or 40 mg/kg/day in
divided doses
every 8 hours
Lower Respiratory
Tract
Mild/Moderate
or Severe
875 mg every
12 hours or 500
mg every
8 hours
45 mg/kg/day in divided
doses every 12 hours
or 40 mg/kg/day
in divided doses
every 8 hours
Skin/Skin Structure
Mild/Moderate
500 mg
every12 hours
or 250 mg
every 8 hours
25 mg/kg/day in divided
doses every 12 hours
or 20 mg/kg/day in
divided doses
every 8 hours
 
Severe
875 mg
every12 hours
or 500 mg
every 8 hours
45 mg/kg/day in divided
doses every 12 hours
or 40 mg/kg/day in
divided doses
every 8 hours
Genitourinary Tract
Mild/Moderate
500 mg
every12 hours
or 250 mg
every 8 hours
25 mg/kg/day in divided
doses every 12 hours
or 20 mg/kg/day
in divided doses
every 8 hours
 
Severe
875 mg
every12 hours or
500 mg every
8 hours
45 mg/kg/day in divided
doses every 12 hours
or 40 mg/kg/day
in divided doses
every 8 hours
Gonorrhoea, acute,
uncomplicated ano-
genital and urethral
infections in males
and females
 
3 grams
as a
single
oral dose
Prepubertal children: 50
mg/kg amoxycillin, combined
with 25 mg/kg probenecid as
a single dose.

NOTE: SINCE
PROBENECID IS
CONTRAINDICATED IN
CHILDREN AGEDE
BELOW2 YEARS, DO NOT
USE THIS REGIMEN IN
THESE CASES.

Method of reconstitution of dry syrup : Add boiled and cooled water upto the mark on the bottle and shake well. Adjust the volume upto the mark by adding more water if necessary. The reconstituted suspension should be stored in a cool place and used within a week of preparation

Directions for use of dispersible tablet: Disperse the tablet in a teaspoonful (5ml) of boiled and cooled water immediately before administration

All patients with gonorrhoea should be evaluated for syphilis

Larger doses may be required for stubborn or severe infections.

General

It should be recognized that in the treatment of chronic urinary tract infections, frequent bacteriological and clinical appraisals are necessary. Smaller doses than those recommended above should not be used. Even higher doses may be needed at times. In stubborn infections, therapy may be required for several weeks. It may be necessary to continue clinical and/or bacteriological follow-up for several months after cessation of therapy. Except for gonorrhoea, treatment should be continued for a minimum of 48 to 72 hours beyond the time that the patient becomes asymptomatic or evidence of bacterial eradication has been obtained. It is recommended that there be at least 10 days treatment for any infection caused by S.pyogenes to prevent the occurrence of acute rheumatic fever.

H. pylori  Eradication to Reduce the Risk of Duodenal Ulcer Recurrence

Triple Therapy: Amoxycillin/Clarithromycin/Lansoprazole
The recommended adult oral dose is 1 gram amoxycillin, 500 mg clarithromycin, and 30 mg lansoprazole, all given twice daily (q12h) for 14 days (see INDICATIONS).

Dual Therapy: Amoxycillin /Lansoprazole
The recommended adult oral dose is 1 gram amoxycillin and 30 mg lansoprazole, each given three times daily (q8h) for 14 days.

Please refer to the clarithromycin and lansoprazole full prescribing information for CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS, and for information regarding dosing in elderly and renally impaired patients.

Dosing Recommendations for Adults with Impaired Renal Function

30 mL/minute should not receive the 875 mg tablet. Patients with a glomerular filtration rate of 10 to 30 mL/minute should receive 500 mg or 250 mg every 12 hours, depending on the severity of the infection. Patients with <10 mL/minute glomerular filtration rate should receive 500 mg or 250 mg every 24 hours, depending on the severity of the infection.

Hsemodialysis patients should receive 500 mg or 250 mg every 24 hours, depending on the severity of the infection. They should receive an additional dose both during and at the end of dialysis.

There are currently no dosing recommendations for paediatric patients with impaired renal function.

Contraindications

A history of allergic reaction to any of the penicillins is a contraindication.

Warnings and Precautions

Serious, and occasionally fatal, hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral penicillins. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. There have been reports of individuals with a history of penicillin hypersensitivity, who have experienced severe reactions when treated with cephalosporins. Before initiating therapy with amoxycillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, amoxycillin should be discontinued and appropriate therapy instituted. Serious anaphylactic reactions require immediate emergency treatment with epinephrine. Oxygen, intravenous steroids, and airway management, including intubation, should also be administered as indicated.

Clostridium difficile-associated diarrhoea (CDAD) has been reported with the use of nearly all antibacterial agents, including amoxycillin, and may range in severity from mild diarrhoea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon, leading to overgrowth of C. difficile.

C. difficile produces toxins A and B, which contribute to the development of CDAD. Hypertoxin-producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhoea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over 2 months after the administration of antibacterial agents.

If CDAD is suspected or confirmed, ongoing antibiotic use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibiotic treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

General

The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If super infections occur, amoxycillin should be discontinued and appropriate therapy instituted.

A high percentage of patients with mononucleosis who receive ampicillin develop an erythematous skin rash. Thus, ampicillin-class antibiotics should not be administered to patients with mononucleosis.

Prescribing amoxycillin capsules, amoxycillin tablets, and amoxycillin for oral suspension in the absence of a proven or strongly suspected bacterial infection or a prophylactic indication is unlikely to provide benefit to the patient and increases the risk of the development of drug-resistant bacteria.

Laboratory Tests

As with any potent drug, periodic assessment of renal, hepatic and haematopoietic function should be made during prolonged therapy.

All patients with gonorrhoea should have a serologic test for syphilis at the time of diagnosis. Patients treated with amoxycillin should have a follow-up serologic test for syphilis after 3 months.

Information for Patients

Amoxycillin may be taken every 8 hours or every 12 hours, depending on the strength of the product prescribed.

Patients should be counselled that antibacterial drugs, including amoxycillin capsules, amoxycillin tablets, and amoxycillin for oral suspension should only be used to treat bacterial infections. They do not treat viral infections (e.g. the common cold). When amoxycillin capsules, amoxycillin tablets, and amoxycillin for oral suspension are 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 amoxycillin capsules, amoxycillin tablets, and amoxycillin for oral suspension or other antibacterial drugs in the future.

Diarrhoea is a common problem caused by antibiotics, which usually ends when the antibiotic is discontinued. Sometimes, after starting treatment with antibiotics, 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 the last dose of the antibiotic. If this occurs, patients should contact their physician as soon as possible.

Drug Interactions

Probenecid decreases the renal tubular secretion of amoxycillin. Concurrent use of amoxycillin and probenecid may result in increased and prolonged blood levels of amoxycillin.

Chloramphenicol, macrolides, sulphonamides and tetracyclines may interfere with the bactericidal effects of penicillin. This has been demonstrated in vitro; however, the clinical significance of this interaction is not well documented.

In common with other antibiotics, amoxycillin may affect the gut flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral oestrogen/progesterone contraceptives.

Drug/Laboratory Test Interactions

High urine concentrations of ampicillin may result in false-positive reactions when testing for the presence of glucose in urine using CLINITEST, Benedict's Solution, or Fehling's Solution. Since this effect may also occur with amoxycillin, it is recommended that glucose tests based on enzymatic glucose oxidase reactions (such as CLINISTIX) be used.

Following administration of ampicillin to pregnant women, a transient decrease in plasma concentration of total conjugated oestriol, oestriol-glucuronide, conjugated oestrone, and oestradiol has been noted. This effect may also occur with amoxycillin.

Pregnancy

Teratogenic Effects
Pregnancy Category B
Reproduction studies have been performed in mice and rats at doses up to 10 times the human dose and have revealed no evidence of impaired fertility or harm to the foetus due to amoxycillin. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Lactation

Penicillins have been shown to be excreted in human milk. Amoxycillin use by nursing mothers may lead to sensitization of the infants. Caution should be exercised when amoxycillin is administered to a nursing mother.

Paediatric Use

Because of incompletely developed renal function in neonates and young infants, the elimination of amoxycillin may be delayed. Dosing of amoxycillin should be modified in paediatric patients 12 weeks or younger (≤3 months).

Geriatric Use

An analysis of clinical studies of amoxycillin was conducted to determine whether subjects aged ≥65 years and over respond differently from younger subjects. Of the 1,811 subjects treated with capsules of amoxycillin, 85% were

This drug is known to be substantially excreted by the kidneys, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Undesirable Effects

As with other penicillins, it may be expected that untoward reactions will be essentially limited to sensitivity phenomena. They are more likely to occur in individuals who have previously demonstrated hypersensitivity to penicillins and in those with a history of allergy, asthma, hay fever, or urticaria. The following adverse reactions have been reported as associated with the use of penicillins:

Infections and Infestations: Mucocutaneous candidiasis.

Gastrointestinal: Nausea, vomiting, diarrhoea, black hairy tongue, and haemorrhagic/pseudomembranous colitis.

Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment.

Hypersensitivity Reactions: Anaphylaxis

Serum sickness-like reactions, erythematous maculopapular rashes, erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis, toxic epidermal necrolysis, acute generalized exanthematous pustulosis, hypersensitivity vasculitis and urticaria have been reported.

Note: These hypersensitivity reactions may be controlled with antihistamines and, if necessary, systemic corticosteroids. Whenever such reactions occur, amoxycillin should be discontinued unless, in the opinion of the physician, the condition being treated is life-threatening and amenable only to amoxycillin therapy.

Liver: A moderate rise in AST (SGOT) and/or ALT (SGPT) has been noted, but the significance of this finding is unknown. Hepatic dysfunction, including cholestatic jaundice, hepatic cholestasis and acute cytolytic hepatitis,hasbeen reported.

Renal: Crystalluria has also been reported

Haemic and Lymphatic Systems: Anaemia, including haemolytic anaemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leucopenia, and agranulocytosis have been reported during therapy with penicillins. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena.

Central Nervous System:Reversible hyperactivity, agitation, anxiety, insomnia, confusion, convulsions, behavioural changes, and/or dizziness have been reported rarely.

Miscellaneous:Tooth discolouration (brown, yellow, or grey staining) has been rarely reported. Most reports occurred in paediatric patients. Discolouration was reduced or eliminated with brushing or dental cleaning in most cases.

Combination Therapy with Clarithromycin and Lansoprazole: In clinical trials using combination therapy with amoxycillin plus clarithromycin and lansoprazole, and amoxycillin plus lansoprazole, no adverse reactions peculiar to these drug combinations were observed. Adverse reactions that have occurred have been limited to those that had been previously reported with amoxycillin, clarithromycin, or lansoprazole.

Triple Therapy: Amoxycillin/Clarithromycin/Lansoprazole:The most frequently reported adverse events for patients who received triple therapy were diarrhoea (7%), headache (6%), and taste perversion (5%). No treatment-emergent adverse events were observed at significantly higher rates with triple therapy than with any dual therapy regimen.

Dual Therapy: Amoxycillin/Lansoprazole The most frequently reported adverse events for patients who received amoxycillin three times daily plus lansoprazole three times daily dual therapy were diarrhoea (8%) and headache (7%). No treatment-emergent adverse events were observed at significantly higher rates with amoxycillin three times daily plus lansoprazole three times daily dual therapy than with lansoprazole alone.

For more information on adverse reactions with clarithromycin or lansoprazole, refer to the ADVERSE REACTIONS section in their package inserts.

Overdosage

In case of overdosage, discontinue medication, treat symptomatically, and institute supportive measures as required. If the overdosage is very recent and there is no contraindication, an attempt at emesis or other means of removal of drug from the stomach may be performed. A prospective study of 51 paediatric patients at a poison-control centre suggested that overdosages of less than 250 mg/kg of amoxycillin are not associated with significant clinical symptoms and do not require gastric emptying.

Interstitial nephritis resulting in oliguric renal failure has been reported in a small number of patients after overdosage with amoxycillin.

Crystalluria, in some cases leading to renal failure, has also been reported after amoxycillin overdosage in adult and paediatric patients. In case of overdosage, adequate fluid intake and diuresis should be maintained to reduce the risk of amoxycillin crystalluria.

Renal impairment appears to be reversible with cessation of drug administration. High blood levels may occur more readily in patients with impaired renal function because of decreased renal clearance of amoxycillin. Amoxycillin may be removed from circulation by haemodialysis.

Storage and Handling Instructions

Store in a cool dry place

Packaging Information

NOVAMOX LB 250 : Strip of 10 capsules
NOVAMOX LB 500 : Strip of 6 capsules