Product Index

Composition

NOVAMOX CV 1.2 g Injection
Each vial contains:
Amoxycillin Sodium, IP,
equivalent to Amoxycillin ...... 1000 mg
Potassium Clavulanate,IP equivalent to
Clavulanic Acid ....... ...................200 mg

NOVAMOX CV 375 mg Tablets
Each film-coated tablet contains:
Amoxycillin Trihydrate, IP
equivalent to Amoxycillin . . . . . ....................250 mg
Potassium Clavulanate diluted IP equivalent to
Clavulanic Acid ................................125 mg

NOVAMOX CV 625 mg Tablets
Each film-coated tablet contains:
Amoxycillin Trihydrate, IP equivalent to
Amoxycillin . . . . . ................................500 mg
Potassium Clavulanate diluted IP
Equivalent to Clavulanic Acid .........125 mg

NOVAMOX CV 457 mg DT
Each uncoated dispersible tablet contains:
Amoxycillin Trihydrate IP equivalent to
Amoxycillin ...........................400 mg
Potassium Clavulanate diluted IP equivalent to
Clavulanic Acid .................... 57 mg
In a flavoured base

NOVAMOX CV 228.5 mg DT
Each uncoated dispersible tablet contains:
Amoxycillin Trihydrate, IP
equivalent to Amoxycillin ...... 200 mg
Potassium Clavulanate diluted IP equivalent to
Clavulanic Acid........................28.5 mg

NOVAMOX CV Forte Syrup
Each 5 mL (on reconstitution) contains:
Amoxycillin Trihydrate, IP
equivalent to Amoxycillin ..........400 mg
Potassium Clavulanate diluted IP equivalent to
Clavulanic Acid..............................57 mg

NOVAMOX CV 228.5 mg Syrup
Each 5 mL (on reconstitution) contains:
Amoxycillin Trihydrate IP equivalent to
Amoxycillin ............................200 mg
Potassium Clavulanate diluted IP equivalent to
Clavulanic Acid....................28.5 mg

NOVAMOX CV 91.4 mg Drops
Each mL (on reconstitution) contains:
Amoxycillin Trihydrate, IP
equivalent to Amoxycillin ..... 80 mg
Potassium Clavulanate diluted IP equivalent to
Clavulanic Acid.........................11.4 mg

Dosage Form/s

Powder for reconstitution for I.V. injection or infusion, tablet and dispersible tablet, syrup, and drops

Pharmacology

Pharmacodynamics

Amoxycillin is a semisynthetic antibiotic with in vitro bactericidal activity against Gram-positive and gram-negative bacteria. Amoxycillin is, however, susceptible to degradation by beta-lactamases and, therefore, the spectrum of activity does not include organisms that produce these enzymes. Clavulanic acid is a beta-lactam structurally related to the penicillins, which possesses the ability to inactivate some beta-lactamase enzymes commonly found in microorganisms resistant to penicillins and cephalosporins. In particular, it has good activity against the clinically important plasmid-mediated beta-lactamases frequently responsible for transferred drug resistance.

The formulation of amoxicyllin and clavulanic acid in NOVAMOX CV protects amoxicyllin from degradation by some beta-lactamase enzymes and extends the antibiotic spectrum of amoxycillin to include many bacteria normally resistant to amoxycillin.

Amoxycillin/clavulanic acid has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections:

Gram-positive Bacteria
Staphylococcus aureus

Gram-negative Bacteria
Enterobacter species
Escherichia coli
Haemophilus influenzae
Klebsiella species
Moraxella catarrhalis

The following in vitro data are available, but their clinical significance is unknown. At least 90% of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for amoxycillin/clavulanic acid. However, the efficacy of amoxycillin/clavulanic acid in treating clinical infections due to these bacteria has not been established in adequate and well-controlled clinical trials:

Gram-positive Bacteria
Enterococcus faecalis
Staphylococcus epidermidis
Staphylococcus saprophyticus
Streptococcus pneumoniae
Streptococcus pyogenes
Viridans group Streptococcus

Gram-negative Bacteria
Eikenella corrodens
Proteus mirabilis

Anaerobic Bacteria
Bacteroides species, including Bacteroides fragilis
Fusobacterium species
Peptostreptococcus species

Pharmacokinetics

Amoxycillin and clavulanic acid, are fully dissociated in an aqueous solution at physiological pH. Both components are rapidly and well absorbed by the oral route of administration. Absorption of amoxycillin/clavulanic acid is optimized when taken at the start of a meal. 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 (T_max) in each case is approximately 1 hour.

The pharmacokinetic results for a study, in which amoxycillin/clavulanic acid (500 mg/125 mg tablets three times daily) was administered in the fasting state to groups of healthy volunteers are presented below.

Mean (± SD) Pharmacokinetic Parameters
Active Substance(s) Administered	Dose	Cmax	Tmax*	AUC(0-24h)	T 1/2
	(mg)	(μg/mL)	(h)	(μg.h/mL)	(h)
Amoxycillin
AMX/CA 500/125mg	500	7.19 ± 2.26	1.5 (1.0-2.5)	53.5 ± 8.87	1.15 ± 0.20
Clavulanic acid
AMX/CA 500/125mg	125	2.40 ± 0.83	1.5 (1.0-2.0)	15.72 ± 3.86	0.98 ± 0.12
AMX=Amoxycillin, CA=clavulanic acid * Median (range)

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.

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 I.V. 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.

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

The major route of elimination for amoxycillin is via the kidneys, whereas for clavulanic acid, it is by both renal and non-renal mechanisms.

Amoxycillin/clavulanic acid has a mean elimination half-life of approximately 1hour and a mean total clearance of approximately 25 l/h in healthy subjects. Approximately 60-70% of the amoxycillin and approximately 40-65% of the clavulanic acid are excreted unchanged in urine during the first 6hours after administration of single amoxycillin/clavulanic acid 250mg/125mg or 500 mg/125 mg tablets. Various studies have found the urinary excretion to be 50-85% for amoxycillin and between 27 and 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.

Age

The elimination half-life of amoxycillin 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.

As 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 amoxycillin/clavulanic acid to healthy males and female subjects, gender has no significant impact on the pharmacokinetics of either amoxycillin or clavulanic acid.

Renal Impairment

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

Hepatic Impairment

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

Indications

To reduce the development of drug resistant bacteria and maintain the effectiveness of amoxycillin/clavulanate potassium and other antibacterial drugs, amoxycillin/clavulanic acid should be used only to treat 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
NOVAMOX CV is a combination penicillin-class antibacterial and beta-lactamase inhibitor indicated in the treatment of infections due to susceptible isolates of the designated bacteria in the conditions listed below*

Dosage and Administration

NOVAMOX CV I.V.

NOVAMOX CV I.V. may be administered either by I.V. injection or intermittent infusion. It is not suitable for intramuscular administration.

Children Aged 0 to 3 Months	Children Aged 3 Months to 12 years	Adults and Children Aged Over 12 Years
30 mg/kg* NOVAMOX CV I.V.every 12-hourly in premature infants and in full-term infants during the perinatal period, increasing to 8 hours thereafter.	Usually 30mg/kg* NOVAMOX CV I.V.8- hourly. In more serious infections; increase frequency to 6-hourly.	Usually 1.2 g thrice daily. In more serious infections, increase frequency to 6- hourly intervals. Maximum adult daily dose should not exceed 7.2g by IV route. Maximum single dose is 1.2g
*Each 30 mg of NOVAMOX CV I.V. provides 5 mg clavulanic acid and 25 mg amoxycillin. Therapy can be started parenterally and continued with the oral preparation.
Treatment with NOVAMOX CV I.V. should not extend beyond 14 days without review.

Dosage for Surgical Prophylaxis

The usual dose is 1.2 g NOVAMOX CV I.V. given at the induction of anaesthesia. Operations where there is a high risk of infection, e.g. colorectal surgery, may require three, and up to four, doses of 1.2 g NOVAMOX CV I.V.in a 24-hour period. These doses are usually given at 0, 8, 16 (and 24) hours. This regimen can be continued for several days if the procedure has a significantly increased risk of infection.

Clear clinical signs of infection at operation will require a normal course of I.V. or oral NOVAMOX CV therapy post-operatively.

Renal Impairment

Adults and Children Aged Over 12 Years

Renal Impairment	Recommended Dosage for Patients with Renal Impairment
Mild impairment (creatinine clearance >30 mL/min	No change in dosage
Moderate impairment (creatinine clearance 10-30 mL/min)	1.2 g I.V. stat. followed by 600 mg I.V. q12-hourly
Severe impairment (creatinine clearance	1.2 g I.V. stat. followed by 600 mg I.V. q24-hourly. Dialysis decreases serum concentrations of NOVAMOX CV I.V. and an additional 600 mg I.V. dose may need to be given during dialysis and at the end of dialysis.
*Each 30 mg of NOVAMOX CV I.V. provides 5 mg clavulanic acid and 25 mg amoxycillin. Therapy can be started parenterally and continued with the oral preparation.

Children

Similar reductions in dosage should be made for children.

Hepatic Impairment

Dose with caution; monitor hepatic function at regular intervals.

Preparation

1.2 g Vial: To reconstitute, dissolve contents in 20 mL of Water for Injection, IP (final volume, 20.9 mL).

A transient pink colouration may appear during reconstitution. Reconstituted solutions are normally a pale straw colour.

I.V.Injection

The stability of NOVAMOX CV I.V. solution is concentration-dependent; thus, NOVAMOX CV I.V. should be used immediately upon reconstitution and given by slow I.V. injection over a period of 3 4 minutes. NOVAMOX CV I.V. solutions should be used within 20 minutes of reconstitution. NOVAMOX CV I.V. may be injected directly into a vein or via a drip tube.

I.V.Infusion

NOVAMOX CV I.V. may be infused in Water for Injection, IP, or Sodium Chloride I.V.Injection, IP (0.9% w/v). Add without delay*, 1.2 g reconstituted solution to 100 mL infusion fluid. Infuse over 30 40 minutes and complete within 4 hours of reconstitution.

*Solutions should be made up to full infusion volume immediately after reconstitution. Any residual antibiotic solutions should be discarded.
Stability and Compatibility

Stability and Compatibility

I.V. infusions of NOVAMOX CV I.V. may be given in a range of different I.V. fluids. Satisfactory antibiotic concentrations are retained at 5 C and at room temperature (25 C) in the recommended volumes of the following infusions fluids. If reconstituted and maintained at room temperature, infusions should be completed within the times stated.

I.V.Infusion Fluids	Stability Period 25ºC
Water for Injections, IP	4 hours
Sodium Chloride I.V. Infusion, IP (0.9% w/v)	4 hours
Sodium Lactate I.V. Infusion, IP (one sixth molar)	4 hours
Compound Sodium Chloride I.V. Infusion, IP (Ringer's solution)	3 hours
Compound Sodium Lactate I.V. Infusion, I.P. (Ringer's-Lactate Solution; Hartmann's Solution)	3 hours
Potassium Chloride and Sodium Chloride I.V. Infusion, BP	3 hours

Reconstituted solutions should not be frozen.

NOVAMOX CV I.V.is less stable in infusions containing glucose, dextran or bicarbonate. Reconstituted solutions of NOVAMOX CV I.V.should, therefore, not be added to such infusions but may be injected into the drip tubing over a period of 3-4 minutes.

For storage at 5^ºC, the reconstituted solution should be added to pre-refrigerated infusion bags, which can be stored for up to 8 hours. Thereafter, the infusion should be administered immediately after reaching room temperatures.

I.V.Infusion Fluids	Stability Period 5ºC
Water for Injections, IP	8 hours
Sodium Chloride I.V. Infusion, IP (0.9% w/v)	8 hours

Oral Administration

To minimize potential gastrointestinal intolerance, administer at the start of a meal. The absorption of NOVAMOX CV I.V. is optimized when taken at the start of a meal. Treatment should not be extended beyond 14 days without review. Therapy can be started parenterally and continued with an oral preparation.

NOVAMOX CV Tablets

Adults and Children Aged Over 12 Years

Mild to Moderate Infections	One 625 mg tablet twice a day or one 375mg table thrice a day
Severe Infections	One 625 mg tablet thrice a day

Renal Impairment

Adults
Patients with impaired renal function do not generally require a reduction in dose unless the impairment is severe. Severely impaired patients with a glomerular filtration rate of <30 mL/min. should not receive the 1g tablet.

Mild impairment (creatinine clearance >30 mL/min)	No change in dosage.
Moderate impairment (creatinine clearance 10-30 mL/min)	One 625 mg tablet twice a day.
Severe impairment (creatinine clearance <10 mL/min)	Not more than one 625 mg tablet every 24 hours.

Hepatic Impairment

Dose with caution; monitor hepatic function at regular intervals.

NOVAMOX CV Tablets 625mg is not recommended in children aged 12 years and below.

Tablets should be swallowed whole without chewing. If required, tablets may be broken in half and swallowed without chewing.

NOVAMOX CV DT

Patients Aged 2 Years and Older

Mild to Moderate Infections(upper respiratory tract infections, e.g. recurrent tonsillitis, lower respiratory tract infections and skin and soft tissue infections)	25/3.6 mg/kg/day	b.i.d
Severe Infections (upper respiratory tract infections, e.g.otitis media, sinusitis; lower respiratory tract infections, e.g. bronchopneumonia and urinary tract infections)	45/6.4 mg/kg/day	b.i.d

There is insufficient experience with NOVAMOX CV 457mg/ 228.5 mg DT to make dosage recommendations for children aged below 2 months.

Infants with Immature Kidney Function

For infants with immature renal function, NOVAMOX CV 457mg/ 228.5 mg DT is not recommended.

Renal Impairment

For children with a GFR of >30 mL/min no adjustment in dosage is required. For children with a GFR of <30 mL/min, NOVAMOX CV 457 mg/ 228.5 mg DT is not recommended.

Hepatic Impairment

Dose with caution; monitor hepatic function at regular intervals. There is, as yet, insufficient evidence on which to base a dosage administration.

Dispersible tablets should be dissolved in 30-60 mL of water before administration.

Mild to Moderate Infections(upper respiratory tract infections, e.g. recurrent tonsillitis, lower respiratory tract infections and skin and soft tissue infections)	25/3.6 mg/kg/day
Severe Infections (upper respiratory tract infections, e.g.otitis media, sinusitis; lower respiratory tract infections, e.g. bronchopneumonia and urinary tract infections)	45/6.4 mg/kg/day

Children Aged Over 2 Years

25/3.6 mg/kg/day	2 to 6 years (13-21 kg)	2.5 mL NOVAMOX CV Forte Syrup b.i.d	5.0 mL NOVAMOX CV 228.5 mg Syrup b.i.d
	7 to12 years (22-40 kg)	5.0 mL NOVAMOX CV Forte Syrups b.i.d	10.0 mL NOVAMOX CV 228.5 mg Syrup b.i.d
45/6.4 mg/kg/day	2 to6 years (13-21 kg)	5.0 mL NOVAMOX CV Forte Syrup b.i.d	10.0 mL NOVAMOX CV 228.5 mg Syrup b.i.d
	7 to12 years (22-40 kg)	10.0 mL NOVAMOX CV Forte Syrup b.i.d	20.0 mL NOVAMOX CV 228.5 mg Syrup b.i.d

	NOVAMOX CV Forte Syrup		NOVAMOX CV 228.5 mg Syrup
Weight (kg)	25/3.6 mg/kg/day (mL/b.i.d)	45/6.4 mg/kg/day (mL/b.i.d)	25/3.6 mg/kg/day (mL/b.i.d)	45/6.4 mg/kg/day (mL/b.i.d)
2	0.3	0.6	0.5	1.0
3	0.5	0.8	0.8	1.5
4	0.6	1.1	1.1	2.0
5	0.8	1.4	1.4	2.5
6	0.9	1.7	1.6	3.0
7	1.1	2.0	1.9	3.4
8	1.3	2.3	2.2	3.9
9	1.4	2.5	2.5	4.4
10	1.6	2.8	2.7	4.9
11	1.7	3.1	3.0	5.4
12	1.9	3.4	3.3	5.9
13	2.0	3.7	3.6	6.4
14	2.2	3.9	3.8	6.9
15	2.3	4.2	4.1	7.4

There is insufficient experience with NOVAMOX CV Forte Syrup and 228.5 mg Syrup to make dosage recommendations for children aged below2 months.

Infants with Immature Kidney Function

For infants with immature renal function, NOVAMOX CV Forte Syrup and 228.5 mg Syrup is not recommended.

Renal Impairment

For children with GFR of >30 mL/min, no adjustment in dosage is required. For children with a GFR of <30 mL/min, NOVAMOX CV Forte Syrup and 228.5 mg Syrup is not recommended.

Hepatic Impairment

Dose with caution; monitor hepatic function at regular intervals. There is, as yet, insufficient evidence on which to base a dosage administration.

NOVAMOX CV Drops

Weight (kg)	25/3.6 mg/kg/day (mL/b.i.d)	45/6.4 mg/kg/day (mL/b.i.d)
5	0.8	1.4
6	0.9	1.7
7	1.1	2.0
8	1.3	2.3
9	1.4	2.5
10	1.6	2.8
11	1.7	3.1
12	1.9	3.4
13	2.0	3.7
14	2.2	3.9
15	2.3	4.2

Instructions for Use/Handling

At the time of dispensing, the dry powder should be reconstituted to form an oral suspension. First shake the bottle to loosen the powder. Add Sterile Water (given with the pack) to two-thirds of the fill mark on the bottle. Replace the cap, and shake the bottle until all of the powder is suspended. Add more water until the level of the fill line is attained, and shake again. When first reconstituted, allow to stand for 5 minutes to ensure full dispersion. After reconstitution, keep in there frigerator when not in use. Use the reconstituted syrup within 7 days (NOVAMOX CV Forte Syrup and NOVAMOX CV Drops) and 10 days (NOVAMOX CV 228.5 mg Syrup).

Contraindications

NOVAMOX CV is contraindicated in patients with a history of serious hypersensitivity reactions (e.g. anaphylaxis or Stevens-Johnson syndrome) to amoxycillin, clavulanate or to other betalactam antibacterial drugs (e.g.penicillins and cephalosporins).

NOVAMOX CV is contraindicated in patients with a previous history of cholestatic jaundice/hepatic dysfunction associated with NOVAMOX CV.

Warnings and Precautions

Hypersensitivity Reactions

Serious, and occasionally fatal, hypersensitivity (anaphylactic) reactions have been reported in patients receiving beta-lactam antibacterials, including co-amoxyclav. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and/or a history of sensitivity to multiple allergens. Before initiating therapy with co-amoxyclav, careful inquiry should be made regarding previous hypersensitivity reactions to penicillins, cephalosporins, or other allergens. If an allergic reaction occurs, co-amoxyclav should be discontinued and appropriate therapy instituted.

Hepatic Dysfunction

Hepatic dysfunction, including hepatitis and cholestatic jaundice, has been associated with the use of co-amoxyclav. Hepatic toxicity is usually reversible; however, deaths have been reported. Hepatic function should be monitored at regular intervals in patients with hepatic impairment.

Clostridium difficile Associated Diarrhoea (CDAD)

Clostridium difficile-associated diarrhoea (CDAD) has been reported with the use of nearly all antibacterial agents, including co-amoxyclav, 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 a colectomy. CDAD must be considered in all patients who present with diarrhoea following antibacterial 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 antibacterial use not directed against C. difficile may need to be discontinued. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C. difficile, and surgical evaluation should be instituted as clinically indicated.

Skin Rash in Patients with Mononucleosis

A high percentage of patients with mononucleosis who receive amoxycillin develop an erythematous skin rash. Thus, co-amoxyclav should not be administered to patients with mononucleosis.

Potential for Microbial Overgrowth

The possibility of superinfections with fungal or bacterial pathogens should be considered during therapy. If superinfection occurs, amoxycillin/clavulanate potassium should be discontinued and appropriate therapy instituted.

Development of Drug-Resistant Bacteria

Prescribing co-amoxyclav in the absence of a proven or strongly suspected bacterial infection is unlikely to provide benefit to the patient, and increases the risk of the development of drug resistant bacteria.

Drug Interactions

Probenecid
Probenecid decreases the renal tubular secretion of amoxycillin but does not delay renal excretion of clavulanic acid. Concurrent use with co-amoxyclav may result in increased and prolonged blood concentrations of amoxycillin. Co-administration of probenecid is not recommended.

Oral Anticoagulants
Abnormal prolongation of prothrombin time (increased international normalized ratio ) has been reported in patients receiving amoxycillin and oral anticoagulants. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently with co-amoxyclav. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation.

Allopurinol
The concurrent administration of allopurinol and amoxycillin increases the incidence of rashes in patients receiving both drugs as compared with patients receiving amoxycillin alone. It is not known whether this potentiation of amoxycillin rashes is due to allopurinol or the hyperuricaemia present in these patients.

Oral Contraceptives
Coamoxyclav may affect intestinal flora, leading to lower oestrogen reabsorption and reduced efficacy of combined oral oestrogen/progesterone contraceptives.

Effects on Laboratory Tests
High urine concentrations of amoxycillin 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 co-amoxyclav, it is recommended that glucose tests based on enzymatic glucose oxidase reactions be used.

Following administration of amoxycillin to pregnant women, a transient decrease in plasma concentration of total conjugated oestriol, oestriol-glucuronide, conjugated oestrone, and oestradiol has been noted.

Pregnancy

Pregnancy Category B
There are 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

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

Paediatric Use

The safety and effectiveness of co-amoxyclav powder for oral suspension has been established in paediatric patients. Use of co-amoxyclav in paediatric patients is supported by evidence from studies of co-amoxyclav tablets in adults with additional data from a study of co-amoxyclav powder for oral suspension in paediatric patients aged 2 months to 12 years with acute otitis media.

Because of incompletely developed renal function in neonates and young infants, the elimination of amoxycillin may be delayed; clavulanate elimination is unaltered in this age group. Dosing of co-amoxyclav should be modified in paediatric patients aged

Geriatric Use

Of the 3,119 patients in an analysis of clinical studies of co-amoxyclav, 32% were ≥65 years old, and 14% were ≥75 years old. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but the greater sensitivity of some older individuals cannot be ruled out.

This drug is known to be substantially excreted by the kidneys, and the risk of adverse 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.

Dosing in Renal Impairment

Amoxycillin is primarily eliminated by the kidneys and dosage adjustment is usually required in patients with severe renal impairment (GFR renal impairment.

Effects on the Ability to Drive and Use Machines

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,

Undesirable Effects

Clinical Trial Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The most frequently reported adverse reactions were diarrhoea/loose stools (9%), nausea (3%), skin rashes and urticaria (3%), vomiting (1%), and vaginitis (1%). Less than 3% of patients discontinued therapy because of drugrelated adverse reactions. The overall incidence of adverse reactions and, in particular, diarrhoea, increased with the higher recommended dose. Other less frequently reported adverse reactions (<1%) included abdominal discomfort, flatulence, and headache.

In paediatric patients (aged 2months to 12 years),one US/Canadian clinical trial was conducted, which compared 45/6.4 mg/kg/day (divided every 12 hours) of co-amoxyclav for 10 days versus 40/10 mg/kg/day (divided every 8 hours) of co-amoxyclav for 10 days in the treatment of acute otitis media. A total of 575 patients were enrolled, and only the suspension formulations were used in this trial. Overall, the adverse reactions seen were comparable to that noted above; however, there were differences in the rates of diarrhoea, skin rashes/urticaria, and diaper area rashes.

Postmarketing Experience

In addition to adverse reactions reported from clinical trials, the following have been identified during postmarketing use of co-amoxyclav. Because they are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. These events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to co-amoxyclav.

Gastrointestinal: Indigestion, gastritis, stomatitis, glossitis, black 'hairy' tongue, mucocutaneous candidiasis, enterocolitis, and haemorrhagic/pseudomembranous colitis. Onset of pseudomembranous colitis symptoms may occur during or after antibiotic treatment.

Hypersensitivity Reactions: Pruritus, angio-oedema, serum sickness-like reactions (urticaria or skin rash accompanied by arthritis, arthralgia, myalgia, and frequently fever), erythema multiforme, StevensJohnson syndrome, acute generalized exanthematous pustulosis, hypersensitivity vasculitis, and cases of exfoliative dermatitis (including toxic epidermal necrolysis) have been reported.

Liver: Hepatic dysfunction, including hepatitis and cholestatic jaundice, increases in serum transaminases (AST and/or ALT), serum bilirubin, and/or alkaline phosphatase, has been reported with co-amoxyclav. It has been reported more commonly in the elderly, in males, or in patients on prolonged treatment. The histologic findings on liver biopsy have consisted of predominantly cholestatic, hepatocellular, or mixed cholestatic hepatocellular changes. The onset of signs/symptoms of hepatic dysfunction may occur during or several weeks after therapy has been discontinued. The hepatic dysfunction, which may be severe, is usually reversible. Deaths have been reported.

Renal: Interstitial nephritis, haematuria, and crystalluria have been reported.

Haemic and Lymphatic Systems: Anaemia, including haemolytic anaemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leucopenia, and agranulocytosis have been reported. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena. Thrombocytosis was noted in less than 1% of the patients treated with co-amoxyclav. There have been reports of increased prothrombin time in patients receiving co-amoxyclav and anticoagulant therapy concomitantly.

Central Nervous System: Agitation, anxiety, behavioural changes, confusion, convulsions, dizziness, insomnia, and reversible hyperactivity have been reported.

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

Overdosage

In case of overdosage, discontinue medication, treat symptomatically, and institute supportive measures as required. 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.

Interstitial nephritis resulting in oliguric renal failure has been reported in patients after overdosage with amoxycillin/clavulanate potassium.

Crystalluria, in some cases leading to renal failure, has also been reported after amoxycillin/clavulanate potassium overdosage in adult and paediatric patients. In case of overdosage, adequate fluid intake and diuresis should be maintained to reduce the risk of amoxycillin/clavulanate potassium 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/clavulanate potassium. Amoxycillin/clavulanate potassium may be removed from circulation by haemodialysis.

Incompatibility

NOVAMOX CV I.V should not be mixed with blood products,other proteinaceous fluid such as protein hydrolysates or with intravenous lipid emulsions. If NOVAMOX CV I.V is prescribed concurrently with an aminoglycoside, the antibiotics should not be mixed in the syringe, intravenous fluid container or giving set because loss of activity of the Aminoglycoside can occur under these conditions

Storage and Handling Instructions

Store below 25^ºC. Protect from moisture

Packaging Information

NOVAMOX CV 1.2 g I.V: Vial of 20 mL plus 20 mL of Sterile Water for Injection, IP
NOVAMOX CV 375: Alu-Alu pack of 6 tablets
NOVAMOX CV 625: Alu-Alu pack of 6 tablets
NOVAMOX CV 457: Alu-Alupack of 6 dispersible tablets
NOVAMOX CV 228.5: Alu-Alupack of 10 dispersible tablets
NOVAMOX CV: Bottle of 30 ml forte syrup
NOVAMOX CV 228.5: Bottle of 30/60 ml syrup
NOVAMOX CV 91.4: Bottle of 10 ml drops