Triclav 625 Amoxicillin and Clavulanate Potassium Tablets

TRICLAV®-625
AMOXICILLIN & CLAVULANATE POTASSIUM TABETS USP

 

Each film coated Tablet contains:

Amoxicillin Trihydrate BP Eq. to Amoxicillin 500 mg

Potassium Clavulanate BP

(As Potassium Clavulanate Diluted BP)

Eq. to Clavulanic Acid 125 mg

Excipients Q.S.

Colour: Titanium Dioxide

 

PHARMACOLOGICAL ACTION

(a) Bacteriology

(i) Spectrum

AMOXYCILLIN AND POTASSIUM CLAVULANATE is the group name for formulations containing 2, 4 and 7 parts of a broad spectrum penicillin, amoxycillin and 1 part of potassium clavulanate. Potassium clavulanate has been shown in vitro to be an irreversible inhibitor of beta-lactamases produced by: Staphylococcus aureus, Escherichla coli, Kiebsiella pneumoniae, Proteus mirabilis, Proteus vulgaris, Heemophilus influenzae, Neisseria gonorrhoea and Bacteroides fragilis. Potassium clavulanate does not inactivate the chromosomally mediated (Sykes Type 1 Cephalosporinase) beta-lactamases produced by Acinetobacter species, Citrobacter species, Enterobacter, Indole positive Proteus, Providencia species and Serratia marcescens. In vitro the formulation showed synergism against amoxycillin-resistant organisms, with no evidence of antagonism and the activity was not reduced in the presence of serum. (In vitro activity does not necessarily imply in vivo efficacy).

(ii) Bactericidal action

The amoxycillin component of the formulations exert a bactericidal action against many strains of Gram-positive and Gram-negative organisms: The clavulanic acid component has very little bactericidal action. It does however, by inactivation of susceptible beta-Iactamases protect amoxycillin from degradation by a large number of beta-lactamase enzymes produced by penicillin resistant Strains of organisms.

(b) Absorption

The pharmacokinetics of amoxycillin and clavulanic acid are closely allied and neither are adversely affected by the presence of food in the stomach. After an oral dose of the 2 parts amoxycillin and 1 part clavulanic acid AMOXYCILLIN AND POTASSIUM CLAVULANATE 375 tablet, taken at the start of a meal, a mean peak serum level of 5.7 micrograms amoxcillin and 3.8 micrograms clavulanic acid per milliliter was achieved within one hour in healthy volunteers. Doubling the dose virtually doubles the peak serum level.

(C) Excretion

64.9% of amoxycillin and 37.5%. of clavulanic acid are excreted unchanged in the urine in the first 6 hours after an oral dose of 1 AMOXYCILLIN AND POTASSIUM CLAVULANATE 625 tablet. Co-administration of probenecid has little effect on the excretion of the clavulanic acid component of the formulation.

 

INDICATIONS

AMOXYCILLIN AND POTASSIUM-CLAVULANATE formulations are indicated for the treatment of infections caused by amoxicillin resistant organisms producing beta-lactamases sensitive to clavulanic acid:

Upper respiratory tract infections, such as sinusitis, recurrent otitis media, tonsillitis.

Lower respiratory tract infections, such as bronchitis caused by amoxycillin resistant beta-lactamase producing Escherichia coli, Haemophilus influenzae and Haemophilus para-influenzae); bronchopneumonia.

Genito-urinary tract infections, such as cystitis, urethritis, pyelonephritis.

Skin and soft tissue infections.

AMOXYCILLIN AND POTASSIUM CLAVULANATE formulations will also be effective in the treatment of infections caused by amoxycillin sensitive organisms at the appropriate amoxycillin dosage since in this situation the clavulanic acid component does not contribute to the therapeutic effect.

 

CONTRAINDICATIONS

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

Safety in pregnancy has not been established. There is limited information on the use of AMOXYCILLIN AND POTASSIUM CLAVULANATE in human pregnancy.

Use should be avoided in pregnancy unless considered essential by the physician.
AMOXYCILLIN AND POTASSIUM CLAVULANATE is contra-indicated in patients with a previous history of AMOXYCILLIN AND POTASSIUM CLAVULANATE-associated jaundice/hepatic dysfunction.

 

WARNINGS

Serious and occasionally fatal hypersensitivity (anaphylactoid) 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 any penicillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other allergens. If an allergic reaction occurs, AMOXYCILLIN AND POTASSIUM CLAVULANATE should be discontinued and the appropriate therapy instituted: adrenaline corticosteroids and antihistamines.

AMOXYCILLIN AND POTASSIUM CLAVULANATE 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.

Transient hepatitis and cholestatic jaundice has been reported. AMOXYCILUN AND POTASSIUM CLAVULANATE should be used with caution in patients with evidence of hepatic dysfunction. In patients with renal impairment, dosage should be adjusted according to the degree of impairment. AMOXYCILLIN AND POTASSIUM CLAVULANATE BD should not be used in patients with a glomerular filtration rate of less than 30 mL/minute. Prolonged use may occasionally result in overgrowth of non-susceptible organisms.

 

DOSAGE AND DIRECTIONS FOR USE

Tablets should be taken immediately before a meal.

Dosages

General Information

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

Adult

For severe infections and infection of the respiratory tract, the dose should be one AMOXYCILLIN AND POTASSIUM CLAVULANATE 625 tablet every eight hours at the start of a meal.

 

Impaired renal function

Both amoxycillin and clavulanic acid are excreted by the kidneys and the serum half-life of each increases in patients with renal failure. Therefore, the dose may need to be reduced or the interval extended. Dosage adjustments are based on the maximum recommended level of amoxycillin. The following schedule is proposed.

AMOXYCILLIN AND POTASSIUM CLAVULANATE 625:

Mild impairment (creatinine clearance greater than 30 mL/minute): no change in dosage.
Moderate impairment (creatinine clearance 10 to 30 mL/minute): 1 tablet every twelve hours.

Severe impairment (creatinine clearance less than 10 mL/minute) half a tablet every twelve hours.

Haemodialysis decreases serum concentrations of both amoxycillin and clavulanic acid and an additional dose should be administered at the end of dialysis.

 

DOSAGE GUIDE

PRODUCT: AMOXYCILLIN AND POTASSIUM CLAVULANATE 625

AMOXYCILLIN SENSITIVE ORGANISMS

UPPER RESPIRATORY TRACT INFECTIONS LOWER RESPIRATORY TRACT INFECTIONS URINARY TRACT INFECTIONS SKIN AND SOFT TISSUE INFECTIONS
ADULTS      
1 tablet 8 hourly 1 tablet 8 hourly 1 tablet 8 hourly 1 tablet 8 hourly

 

AMOXYCILLIN RESISTANT ORGANISMS

UPPER RESPIRATORY TRACT INFECTIONS (otitis media) H. influenzae, H. para ifluenzae LOWER RESPIRATORY TRACT INFECTIONS (bronchitis) H. influenzae, H. para ifluenzae URINARY TRACT INFECTIONS E. coli, Klebsiella pneumoniae SKIN AND SOFT TISSUE INFECTIONS Staphylococcus aureus
ADULTS      
1 tablet 8 hourly 1 tablet 8 hourly 1 tablet 8 hourly 1 tablet 8 hourly

 

SIDE-EFFECTS AND SPECIAL PRECAUTIONS

The most frequently reported adverse effects are diarrhoea, nausea, vomiting, indigestion, abdominal pain, skin rashes, urticaria and erythema multiforme, vaginitis, abnormal taste, headache, dizziness, tiredness and hot flushes. In addition, as these symptoms are especially related to the potassium clavulanate component where these gastrointestinal symptoms occur and a higher concentration of amoxyciIlin is required, consideration should be given to administering the additional amoxycillin separately.
The following adverse reactions have been reported for ampicillin class antibiotics and they occur with AMOXYCILLIN AND POTASSIUM CLAVULANATE:

Hypersensitivity reactions

Angioneurotic oedema, anaphylaxis, serum sickness-like syndrome and hypersensitivity vasculitis have been observed. Skin rashes, pruritis and urticaria have been occasionally reported. Erythema multiforme, Stevens-Johnson syndrome, and less frequently bullous exfoliative dermatitis, toxic epidermal necrolysis and acute generalised exanthematous pustulosis (AGEP) have been reported. Whenever such reactions occur, AMOXYCILLIN AND POTASSIUM CLAVULANATE should be discontinued. Serious and occasional fatal hypersensitivity (anaphylactic) reactions and angioneurotic oedema can occur with oral penicillin (see WARNINGS). Interstitial nephritis can occur rarely.

Gastrointestinal reactions

Effects include gastritis, stomatitis, glossitis, black hairy tongue and enterocolitis. Mucocutaneous candidiasis and antibiotic-associated colitis (including pseudomembranous colitis and haemorrhagic colitis) have been reported. If gastrointestinal reactions are evident, they may be reduced by taking AMOXYCILLIN AND POTASSIUM CLAVULANATE at the start of a meal.

Hepatic effects

A moderate rise in aspartate transaminase (AST) and/or alanine transaminase (ALT) has been noted in patients treated with AMOXYCILLIN AND POTASSIUM CLAVULANATE, but the significance of these findings is unknown.
Hepatitis and cholestatic jaundice have been reported.

Hepatic events have been reported predominantly in males or elderly patients and may be associated with prolonged treatment. 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, death has been reported. These have almost always occurred in patients with serious underlying disease or taking concomitant medications.

Haematologic effect

Haemolytic anaemia, reversible thrombocytopaenia, thrombocytopaenic purpura, eosinophilia, reversible Ieucopaenia (including neutropaenia or agranulocytosis) have been reported during therapy with penicillins. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena. A slight thrombocytosis was noted in less than 1% of the patients treated with AMOXYCILLIN AND POTASSIUM CLAVULANATE. Prolongations of bleeding time and prothrombin time has also been reported less frequently. Appropriate monitoring should be undertaken when anticoagulants are prescribed concomitantly.

Central Nervous System effects

CNS effects have been seen rarely. These include reversible hyperactivity, dizziness, headache and convulsions. Convulsions may occur with impaired renal function or in those receiving high doses.

Miscellaneous

Superficial tooth discolouration has been reported rarely. It usually can be removed by brushing.

Special Precautions

Periodic assessment of organ system functions, including renal, hepatic and haematopoietic function, is advisable during prolonged therapy. Since AMOXYCILLIN AND POTASSIUM CLAVULANATE contains amoxycillin, an aminopenicillin it is not the treatment of choice in patients presenting with sore throat or pharyngitis because of the possibility that the underlying cause is infectious mononucleosis, in the presence of which there is a high incidence of rash if amoxycillin is used. AMOXYCILUN AND POTASSIUM CLAVULANATE shouId be given with caution to patients with lymphatic leukaemia since they are especially susceptible to amoxycillin induced skin rashes. The possibility of super infections with mycotic or bacterial pathogens should be kept in mind during therapy. If super infections occur (usually involving Aerobacter, Pseudomonas or Candida), the agent should be discontinued and/or appropriate therapy instituted.

Impaired hepatic function

Changes in liver function tests have been observed in some patients receiving AMOXYCILLIN AND POTASSIUM CLAVULANATE. It should be used with care in patients with evidence of severe hepatic dysfunction.

Impaired renal function

In patients with moderate or severe renal impairment the AMOXYCILLIN AND POTASSIUM CLAVULANATE dosage should be adjusted. (see DOSAGE AND DIRECTIONS FOR USE.)

Use in lactation

Amoxycillin is excreted in breast milk; there is no data on the excretion of clavulanic acid in human milk. Trace quantities of clavulanate can be detected in breast milk. With the exception of the risk of sensitisation associated with this excretion, there are no known detrimental effects for the breast-fed infant.

Interactions

Probenecid decreases the renal tubular secretion of amoxycillin, but does not affect clavulanic acid excretion. Concomitant use with AMOXYCILLIN AND POTASSIUM CLAVULANATE may result in increased and prolonged blood levels of amoxycillin but not of clavulanic acid.

The concomitant administration of allopurinol and ampicillin substantially increases the incidence of skin rashes in patients receiving both agents as compared to patients receiving ampicillin alone. It is not known whether this potentiation of ampicillin rashes is due to allopurinol or the hyperuricaemia present in these patients. There is no data on AMOXYCILLIN AND POTASSIUM CLAVULANATE and allopurinol administered concomitantly.

No information is available about the concurrent use of AMOXYCILLIN AND POTASSIUM CLAVULANATE and alcohol. However, the ingestion of alcohol whilst being treated with some other beta-lactam antibiotics has precipitated a disulfiram (Antabuse®)-like reaction in some patients. Therefore, the ingestion of alcohol should be avoided during and for several days after treatment with AMOXYCILLIN AND POTASSIUM CLAVULANATE.

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

AMOXYCILLIN AND POTASSIUM CLAVULANATE may reduce the efficacy of oral contraceptives and patients should be warned accordingly.

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

 

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT

Nausea, vomiting and diarrhoea may occur with overdosing. Treatment is symptomatic and supportive.

Amoxycillin may be removed from circulation by haemodialysis. The molecular weight, degree of protein binding and pharmacokinetic profile of clavulanic acid together with information from a single patient with renal insufficiency all suggest that this compound may also be removed by haemodialysis.

 

PRESENTATION

3 Blisters of 5 Tablets in a pouch, such 1 pouch in a carton.

 

STORAGE INSTRUCTIONS

Store in a cool, dry place below 25°C and Protect from light.

 

KEEP OUT OF REACH OF CHILDREN.

 

Mfg. Lic. No.: G/1605-A

NAFDAC Reg. No.: B4-2430

 

Manufactured by

BAROQUE PHARMACEUTICALS PVT. LTD.

Sokhada, Khambhat 388620,

Dist. Anand, Gujarat, India.

 

Manufactured Under License from

NOVOPHARM FORMULATIONS PVT. LTD.

105, Rajmandir, 62, Alkapuri, R. C. Dutt Road,

Vadodara – 390007, Gujarat India.

 

Manufactured for

TRICARE PHARMA LIMITED.

6 Yusuf Oyero Sfreet, Off Demurin Street,

Ketu, Lagos, Nigeria

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