Megamox ES-600 Powder for Oral Suspension is indicated for the treatment of pediatric patients with recurrent or persistent acute otitis media due to S. pneumoniae (penicillin MICs    ≤   2  mcg/mL), H. influenzae (including β-lactamase– producing,strains),or M.catarrhalis (includingβ-lactamase–producingstrains) characterized by the following risk factors:

• an antibiotic exposure for acute otitis media within the preceding 3 months, and either of the following:
• age ≤ 2 years
• daycare attendance

NOTE: Acute otitis media due to S. pneumoniae alone can be treated with amoxicillin. MEGAMOX ES-600 Powder for Oral Suspension is not indicated for the treatment of acute otitis media due to S. pneumoniae with penicillin MIC ≥ 4 mcg/mL.

Therapy may be instituted prior to obtaining the results from bacteriological studies when there is reason to believe the infection may involve both S. pneumoniae (penicillin MIC ≤ 2 mcg/mL) and the β-lactamase–producing organisms listed above.

To reduce the development of drug-resistant bacteria and maintain the effectiveness of MEGAMOX ES-600 Powder for Oral Suspension and other an bacterial drugs, MEGAMOX ES-600 Powder 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.

 

MEGAMOX ES 600 Powder for Oral Suspension, does not contain the same amount of clavulanic acid (as the potassium salt) as any of the other suspensions of MEGAMOX ES. MEGAMOX ES 600 Powder for Oral Suspension contains 42.9 mg of clavulanic acid per 5 mL, whereas the 200 mg/5 mL suspension of MEGAMOX ES contains 28.5 mg of clavulanic acid per 5 mL and the 400 mg/5 mL suspension contains 57 mg of clavulanic acid per 5 mL. Therefore, the 200 mg/28.5 mg/5 mL and 400 mg/57 mg/5 mL suspensions of MEGAMOX ES should not be substituted for MEGAMOX ES 600 Powder for Oral Suspension as they are not interchangeable.

Dosage:

Pediatric pa ents 3 months and older: Based on the amoxicillin component (600 mg/5 mL,) the recommended dose of MEGAMOX ES 600 Powder for Oral Suspension is 90 mg/kg/day divided every 12 hours, administered for 10 days (see chart below).

Body Weight (kg)	Volume of MEGAMOX ES 600 Powder for Oral Suspension providing 90 mg/kg/day
8	3.0 mL twice daily
12	4.5 mL twice daily
16	6.0 mL twice daily
20	7.5 mL twice daily
24	9.0 mL twice daily
28	10.5 mL twice daily
32	12.0 mL twice daily
36	13.5 mL twice daily

Pediatric pa ents weighing 40 kg and more: Experience with MEGAMOX ES 600 Powder for Oral Suspension in this group is not available.

Adults : Experience with MEGAMOX ES 600 Powder for Oral Suspension in adults is not available and adults who have difficulty swallowing should not be given MEGAMOX ES 600 Powder for Oral Suspension in place of the 500-mg or 875-mg tablet of MEGAMOX ES.

Elderly: No dose adjustment is considered necessary.

Renal impairment: No adjustment in dose is required in patients with creatinine clearance (CrCl) greater than 30 ml/min.

In patients with creatinine clearance less than 30 ml/min, the use of Megamox ES 400/57mg/5ml Powder for Oral Suspensionpresenta ons with an amoxicillin to clavulanic acid ra o of 7:1 is not recommended, as no recommenda ons for dose adjustments are available.

Hepatic impairment: AUGMENTIN ES-600 Powder for Oral Suspension should be used with caution in patients with evidence of hepatic dysfunction. Hepatic toxicity associated with the use of amoxicillin/clavulanate potassium is usually reversible. On rare occasions, deaths have been reported (less than 1 death reported per es mated 4 million prescriptions worldwide). These have generally been cases associated with serious underlying diseases or concomitant medications. (see sec on 4.3 and sec on 4.8).

Method of administration

Megamox ES 600/42.9mg/5ml Powder for Oral Suspension is for oral use.

Shake to loosen powder, add water as directed, invert and shake.

Shake the bo le before each dose (see sec on 6.6).

Hypersensitivity to the active substances, to any of the penicillins or to any of the excipients. History of a severe immediate hypersensitivity reaction (e.g. anaphylaxis) to another beta-lactam agent (e.g. a cephalosporin, carbapenem or monobactam). History of jaundice/hepatic impairment due to amoxicillin/clavulanic acid (see section 4.8).

Before initiating therapy with amoxicillin/clavulanic acid, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other beta-lactam agents.

Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and in atopic individuals. If an allergic reaction occurs, amoxicillin/clavulanic acid therapy must be discontinued and appropriate alternative therapy instituted.

In the case that an infection is proven to be due to an amoxicillin-susceptible organisms(s) then consideration should be given to switching from amoxicillin/clavulanic acid to amoxicillin in accordance with official guidance.

This presentation of Megamox ES is not suitable for use when there is a high risk that the presumptive pathogens have reduced susceptibility or resistance to beta-lactam agents that is not mediated by beta-lactamases susceptible to inhibition by clavulanic acid (e.g. penicillin-insusceptible S. pneumoniae).

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

Amoxicillin/clavulanic acid 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 amoxicillin.

Concomitant use of allopurinol during treatment with amoxicillin can increase the likelihood of allergic skin reactions.

Prolonged use may occasionally result in overgrowth of non-susceptible organisms.

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 Sec on 4.8). This reac   on requires Megamox ES discontinuation and contra- indicates any subsequent administration of amoxicillin.

Amoxicillin/clavulanic acid should be used with caution in patients with evidence of hepaticc impairment (see sec ons 4.2, 4.3 and 4.8).

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. 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 medica ons known to have the poten al for hepa c effects (see sec on 4.8).

Antibiotic-associated colitis has been reported with nearly all antibacterial agents and may range in severity from mild to life threatening (see sec on 4.8). Therefore, 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, amoxicillin/clavulanic acid should immediately be discontinued, a physician be consulted and an appropriate therapy initiated. Anti-peristaltic medicinal products are contra-indicated in this situation.

Periodic assessment of organ system functions, including renal, hepatic and haematopoietic function is advisable during prolonged therapy.

Prolongation of prothrombin time has been reported rarely in patients receiving amoxicillin/clavulanic acid. 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 sec on 4.5 and 4.8).

In patients with renal impairment, the dose should be adjusted according to the degree of impairment (see sec on 4.2).

In patients with reduced urine output, crystalluria has been observed very rarely, 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 sec on 4.9).

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.

The presence of clavulanic acid in Megamox ES may cause a non-specific binding of IgG and albumin by red cell membranes leading to a false positive Coombs test.

There have been reports of positive test results using the Bio-Rad Laboratories Platelia Aspergillus EIA test in patients receiving amoxicillin/clavulanic acid 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 amoxicillin/clavulanic acid should be interpreted cautiously and confirmed by other diagnostic methods.

Megamox ES 600 mg/42.9 mg/5 ml powder for oral suspension contains 2.5 mg of aspartame per ml, a source of phenylalanine. This medicine should be used with caution in patients with phenylketonuria.

Patients with rare heriditary problems of fructose intolerance or glucose-galactose malabsorption should not take this medicine.

 

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 in patients maintained on acenocoumarol or warfarin and prescribed a course of amoxicillin. If co-administration is necessary, the prothrombin time or international normalised ratio should be carefully monitored with the addition or withdrawal of amoxicillin. Moreover, adjustments in the dose of oral an coagulants may be necessary (see sec on 4.4 and 4.8).

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

Probenecid: Concomitant use of probenecid is not recommended. Probenecid decreases the renal tubular secretion of amoxicillin. Concomitant use of probenecid may result in increased and prolonged blood levels of amoxicillin but not of clavulanic acid.

The concurrent administration of allopurinol and ampicillin increases substantially the incidence of rashes in patients receiving both drugs as compared to patients receiving ampicillin alone. It is not known whether this potentiation of ampicillin rashes is due to allopurinol or the hyperuricemia present in these patients. There are no data with AUGMENTIN ES-600 Powder for Oral Suspension and allopurinol administered concurrently.

Oral contraceptive: In common with other broad-spectrum antibiotics, amoxicillin/clavulanate may reduce the efficacy of oral contraceptives

 

Pregnancy:   Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/foetal development, parturition or postnatal development (see sec   on 5.3). Limited data on the use of amoxicillin/clavulanic acid during pregnancy in humans do not indicate an increased risk of congenital malformations. In a single study in women with preterm, premature rupture of the foetal membrane it was reported that prophylactic treatment with amoxicillin/clavulanic acid may be associated with an increased risk of necrotising enterocolitis in neonates. Use should be avoided during pregnancy, unless considered essential by the physician.

Lactation: Both substances are excreted into breast milk (nothing is known of the effects of clavulanic acid on the breast-fed infant). Consequently, diarrhoea and fungus infection of the mucous membranes are possible in the breast-fed infant, so that breast- feeding might have to be discontinued. The possibility of sensitisation should be taken into account. Amoxicillin/clavulanic acid should only be used during breast-feeding after benefit/risk assessment by the physician in charge.

 

 

 

No studies on the effects on the ability to drive and use machines have been performed. However, undesirable effects may occur (e.g. allergic reactions, dizziness, convulsions), which may influence the ability to drive and use machines (see sec on 4.8).

 

The most commonly reported adverse drug reactions (ADRs) are diarrhoea, nausea and vomiting.

The ADRs derived from clinical studies and post-marketing surveillance with Amoxicillin/Clavulanic, sorted by MedDRA System Organ Class are listed in table 1 below.

The following terminologies have been used in order to classify the occurrence of undesirable effects.

Very common (≥1/10)

Common (≥1/100 to <1/10)

Uncommon (≥1/1,000 to <1/100)

Rare (≥1/10,000 to <1/1,000)

Very rare (<1/10,000)

Not known (cannot be estimated from the available data)

Table 1: Undesirable effacts

Infections and infestations
Mucocutaneous candidosis	Common
Overgrowth of non-susceptible organisms	Not known
Blood and lymphatic system disorders
Reversible leucopenia (including neutropenia)	Rare
Reversible agranulocytosis	Not known
Haemolytic anaemia	Not known

Haemolytic anaemia	Not known
Prolongation of bleeding time and prothrombin time1	Not known
Immune system disorders10
Angioneurotic oedema	Not known
Anaphylaxis	Not known
Serum sickness-like syndrome	Not known
Hypersensitivity vasculitis	Not known
Nervous system disorders
Dizziness	Uncommon
Headache	Uncommon
Reversible hyperactivity	Not known
Convulsions2	Not known
Gastrointestinal disorders
Diarrhoea	Very common
Nausea3	Common
Vomiting	Common
Indigestion	Uncommon
Antibiotic-associated colitis4	Not known
Black hairy tongue	Not known
Hepatobiliary disorders
Rises in AST and/or ALT5	Uncommon
Hepatitis6	Not known
Cholestatic jaundice6	Not known

Skin and subcutaneous tissue disorders 7
Skin rash	Uncommon
Pruritus	Uncommon
Urticaria	Uncommon
Erythema multiforme	Rare
Stevens-Johnson syndrome	Not known
Toxic epidermal necrolysis	Not known
Bullous exfoliative-dermatitis	Not known
Acute generalised exanthemous pustulosis (AGEP)9	Not known
Renal and urinary disorders
Interstitial nephritis	Not known
Crystalluria8	Not known
1 See sec on 4.4 2 See sec on 4.4. 3 Nausea is more often associated with higher oral doses. If gastrointestinal reactions are evident, they may be reduced by taking amoxicillin/clavulanic acid at the start of a meal. 4 Including pseudomembranous coli s and haemorrhagic coli s (see sec on 4.4) 5 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. 6 These events have been noted with other penicillins and cephalosporins (see section 4.4). 7 If any hypersensitivity dermatitis reaction occurs, treatment should be discontinued (see sec on 4.4). 8 See sec on 4.9 9 See sec on 4.4 10 See sec ons 4.3 and 4.4

Reporting of suspected adverse reactions

• Saudi Arabia:

− The National Pharmacovigilance and Drug Safety Centre (NPC)

Fax: +966-11-205-7662 Call NPC at +966-11-2038222, Exts: 2317-2356-2353-2354-2334-2340.

Toll free phone: 8002490000

E-mail: npc.drug@sfda.gov.sa

Website: www.sfda.gov.sa/npc

• Other GCC States: Please contact the relevant competent authority.

Symptoms and signs of overdose

Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident. Amoxicillin crystalluria, in some cases leading to renal failure, has been observed (see sec on 4.4).

Convulsions may occur in patients with impaired renal function or in those receiving high doses.

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 sec on 4.4)

Treatment of intoxication

Gastrointestinal symptoms may be treated symptomatically, with attention to the water/electrolyte balance.

Amoxicillin/clavulanic acid can be removed from the circulation by haemodialysis.

Pharmacotherapeutic group: Combinations of penicillins, incl. beta-lactamase inhibitors; ATC code: J01CA04.

Mode of action

Amoxicillin 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.

Amoxicillin is susceptible to degradation by beta-lactamases produced by resistant bacteria and therefore the spectrum of activity of amoxicillin 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 amoxicillin. Clavulanic acid alone does not exert a clinically useful antibacterial effect.

PK/PD relationship

The time above the minimum inhibitory concentration (T>MIC) is considered to be the major determinant of efficacy for amoxicillin.

Mechanisms of resistance

The two main mechanisms of resistance to amoxicillin/clavulanic acid are:

• Inactivation by those bacterial beta-lactamases that are not themselves inhibited by clavulanic acid, including class B, C and D.
• Alteration of PBPs, which reduce the affinity of the antibacterial agent for the target.

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

Breakpoints

MIC breakpoints for amoxicillin/clavulanic acid are those of the European Committee on Antimicrobial Susceptibility Testing (EUCAST).

Organism	Susceptibility Breakpoints (μg/ml)
	Susceptible	Intermediate	Resistant
Haemophilus influenzae1	≤ 1	-	> 1
Moraxella catarrhalis1	≤ 1	-	> 1

Staphylococcus aureus 2	≤ 2	-	> 2
Coagulase-negative staphylococci2	≤ 0.25		> 0.25
Enterococcus1	≤ 4	8	> 8
Streptococcus A, B, C, G5	≤ 0.25	-	> 0.25
Streptococcus pneumoniae3	≤ 0.5	1-2	> 2
Enterobacteriaceae1,4	-	-	> 8
Gram-negative Anaerobes1	≤ 4	8	> 8
Gram-positive Anaerobes1	≤ 4	8	> 8
Non-species related breakpoints1	≤ 2	4-8	> 8
1 The reported values are for Amoxicillin concentrations. For susceptibility testing purposes, the concentration of Clavulanic acid is fixed at 2 mg/l. 2 The reported values are Oxacillin concentrations. 3 Breakpoint values in the table are based on Ampicillin breakpoints. 4 The resistant breakpoint of R>8 mg/l ensures that all isolates with resistance mechanisms are reported resistant. 5 Breakpoint values in the table are based on Benzylpenicillin breakpoints.

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.

Commonly susceptible species

Aerobic Gram-positive micro-organisms

Enterococcus faecalis Staphylococcus aureus ( methicillin-susceptible)£ Streptococcus agalactiae Streptococcus pneumoniae1 Streptococcus pyogenes and other beta-hemolytic streptococci Streptococcus viridans group Aerobic Gram-negative micro-organisms Capnocytophaga spp. Eikenella corrodens Haemophilus influenzae2 Moraxella catarrhalis Pasteurella multocida Anaerobic micro-organisms Bacteroides fragilis Fusobacterium nucleatum Prevotella spp.

Species for which acquired resistance may be a problem

Aerobic Gram-positive micro-organisms Enterococcus faecium $ Aerobic Gram-negative micro-organisms Escherichia coli Klebsiella oxytoca Klebsiella pneumoniae Proteus mirabilis Proteus vulgaris

Inherently resistant organisms

Aerobic Gram-negative micro-organisms Acinetobacter sp. Citrobacter freundii Enterobacter sp. Morganella morganii Providencia spp. Pseudomonas sp. Serratia sp. Stenotrophomonas maltophilia

$ Natural intermediate susceptibility in the absence of acquired mechanism of resistance. £All methicillin-resistant staphylococci are resistant to amoxicillin/clavulanic acid 1Streptococcus pneumoniae that is fully susceptible to penicillin may be treated with this presentation of amoxicillin/clavulanic acid. Organisms that show any degree of reduced suscep bility to penicillin should not be treated with this presenta on (see sec ons 4.2 and 4.4). 2 Strains with decreased susceptibility have been reported in some countries in the EU with a frequency higher than 10%.

Absorption

The pharmacokine cs of amoxicillin and clavulanate were determined in a study of 19 pediatric pa ents, 8 months to 11 years, given amoxicillin at dose of 45 mg/kg q12h with a snack or meal. The mean plasma amoxicillin and clavulanate pharmacokinetic parameter values are listed in the following table.

Table 2. Mean (± SD) Plasma Amoxicillin and Clavulanate Pharmacokinetic Parameter Values Following Administra on of 45 mg/kg of Amoxcillin/clavulanic ES-600 Powder for Oral Suspension Every 12 Hours to Pediatric Patients
Parameters* Active substance(s)	Cmax	Tmax *	AUC (0-24h)	T 1/2	CL/F
	(mcg/ml)	(hours)	(mcg.h/ml)	(houurs)	(L/hr/kg)
AMX/CA 600mg/42.9mg/5ml (14:1)   Dosed at 45mg/kg Amoxicillin 12- hourly	Amoxicillin
	15.7   ± 7.7	2.0   (1.0-4.0)	59.8   ± 20.0	1.4   ± 0.3	0.9 ± 0.4
	Clavulanic Acid
	1.7   ± 0.9	1.1   (1.0-4.0)	4.0   ± 1.9	1.1   ± 0.3	1.1   ± 1.1
AMX – amoxicillin, CA – clavulanic acid *Arithmetic mean ± standard deviation, except Tmax values which are medians (ranges).

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

Distribution

About 25% of total plasma clavulanic acid and 18% of total plasma amoxicillin is bound to protein. The apparent volume of distribu on is around 0.3-0.4 l/kg for amoxicillin and around 0.2 l/kg for clavulanic acid.

Following intravenous administration, both amoxicillin and clavulanic acid have been found in gall bladder, abdominal tissue, skin, fat, muscle tissues, synovial and peritoneal fluids, bile and pus. Amoxicillin 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. Amoxicillin, like most penicillins, can be detected in breast milk. Trace quantities of clavulanic acid can also be detected in breast milk (see sec on 4.6).

Both amoxicillin and clavulanic acid have been shown to cross the placental barrier (see sec on 4.6).

Biotransformation

Amoxicillin is partly excreted in the urine as the inactive penicilloic acid in quantities equivalent to up to 10 to 25% of the ini al 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 amoxicillin is via the kidney, whereas for clavulanic acid it is by both renal and non-renal mechanisms.

Amoxicillin/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 amoxicillin and approximately 40 to 65% of the clavulanic acid are excreted unchanged in urine during the first 6 h a er administra on of single Megamox ES 250 mg/125 mg or 500 mg/125 mg tablets. Various studies have found the urinary excre on to be 50-85% for amoxicillin 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 a er administraion.

Concomitant use of probenecid delays amoxicillin excretion but does not delay renal excretion of clavulanic acid (see sec on 4.5).

Age

The elimination half-life of amoxicillin is similar for children aged around 3 months to 2 years and older children and adults. For very young children (including preterm newborns) in the first week of life the interval of administration should not exceed twice daily administration due to immaturity of the renal pathway of elimination. 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.

Gender

Following oral administration of amoxicillin/clavulanic acid to healthy males and female subjects, gender has no significant impact on the pharmacokinetics of either amoxicillin or clavulanic acid.

Renal impairment

The total serum clearance of amoxicillin/clavulanic acid decreases proportionately with decreasing renal function. The reduction in drug clearance is more pronounced for amoxicillin than for clavulanic acid, as a higher proportion of amoxicillin is excreted via the renal route. Doses in renal impairment must therefore prevent undue accumulation of amoxicillin while maintaining adequate levels of clavulanic acid (see sec on 4.2).

Hepatic impairment

Hepatically impaired patients should be dosed with caution and hepatic function monitored at regular intervals.

Nonclinical data reveal no special hazard for humans based on studies of safety pharmacology, genotoxicity and toxicity to reproduction.

Repeat dose toxicity studies performed in dogs with amoxicillin/clavulanic acid demonstrate gastric irritancy and vomiting, and discoloured tongue.

Carcinogenicity studies have not been conducted with Megamox ES or its components.

-  Xanthan Gum

-  Succinic Acid micronized

-  Colloidal Silicon Dioxide

-  Predried nutra sweet-aspartam treated

-  Predried hydroxypropyl methyl cellulose

-  Orange Powder Flavor

-  Predried Silicon Dioxide

None.

Dry powder 2 years. The reconstituted suspension is stable for 10 days when stored at 2 – 8 °C.

Store below 30°C

The reconstituted suspension should be stored in a refrigerator (2 – 8 °C) and used within 10 days.

Keep in the original container. Keep the container tightly closed.

Glass bo le Amber 125 ml,28mm induc on plas c CRC Caps.

At time of dispensing, the dry powder should be reconstituted to form an oral suspension, as detailed below:

After opening the bottle remove the membrane carefully and completely and discard before reconstituting the product. Fill the bottle with water to just below the mark on the label and shake well at once. Then add water exactly to the mark and shake vigorously again.

Shake the bottle well before every withdrawal.

After reconstitution the ready-for-use suspension is off-white.