Nosclav 1000 Amoxicillin and Potassium Clavulanate Tablets

Nosclav-1000 Tablets

(Amoxicillin and Potassium Clavulanate BP)

For the use of a Registered Medical Practitioner or a Hospital or a Laboratory only.

 

COMPOSITION

Each film coated tablet contains:

Amoxicillin Trihydrate BP eq. to Amoxicillin 75 mg

Diluted Potassium Clavulanate BP eq. to Clavulanic Acid 125mg

Excipients Q.S.

Colour: Titanium Dioxide BP

 

MECHANISM OF ACTION

Nosclav-1000 is a combination of Amoxicillin and Potassium Clavulanate. The Amoxicillin component of the formulation exerts a bactericidal action against many strains of Gram-positive and Gram-negative organisms. The Clavulanic acid component has little or no antimicrobial action. It does, however, by inactivation of susceptible β-lactamase, protect Amoxicillin from degradation by β-lactamase enzymes produced by penicillin resistant strains of microorganisms.

 

Antibacterial Activity

Clavulanic acid is an irreversible inhibitor of β-lactamases produced by Staphylococcus aureas, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis and Proteus vulgaris, H. influenzae, N. gonorrhoeae and B. fragilis (In vitro activity does not necessarily imply in-vivo efficacy). Potassium clavulanate does not inactivate the chromosamally mediated (Sykes Type 1 Cephalosporinase) β -lactamases produced by Acinetobacter species, Citrobacter species, Enterobacter, indole positive Proteus, Providencia species and Serratia marcencens.

 

Pharmacokinetics

The pharmacokinetics of Amoxicillin and Clavulanic acid are closely allied and neither are adversely affected by the presence of food in the stomach, and are stable in the presence of gastric acid. The oral bioavailability of Amoxicillin and Potassium Clavulante is approximately 90% and 75% respectively.

Peak serum levels of both occur about 1-2 hours after oral administration. Clavulanic acid has about the same plasma elimination half-life (1 hour) as that of Amoxicillin (1.3 hours). Nosclav-1000 is eliminated primarily unchanged through the renal route (glomerular filtration and tubular secretion). Approximately 50- 78% of Amoxicillin and 25-40% of Clavulanic acid are excreted unchanged in urine within the first 6 hours after administration.

 

INDICATIONS

Nosclav-1000 is indicated for the treatment of infections caused by Amoxicillin resistant organisms producing β -Iactamases sensitive to Clavulanic acid:

Upper respiratory tract infections: Otitis media, tonsillitis, sinusitis.

Lower respiratory tract infections: Pneumonia, bronchitis (caused by Amoxicillin resistant β -lactamases producing E. coli, H. influenzae and Haemophilus parainfluenzae).

Urinary tract infections: Cystitis, urethritis, pyelonephritis.

Skin and soft tissue infections: Nosclav-1000 formulations will also be effective in the treatment of infections caused by Amoxicillin sensitive organisms at the appropriate Amoxicillin dosage since in this situation the Clavulenic acid component does not contribute to the therapeutic effect.

 

CONTRAINDICATIONS

Allergy to penicillins and cephalosporins.

Safety in pregnancy has not been established.

Nosclav-1000 is contraindicated in patients with a previous history of Amoxicillin and Potassium Clavulanate associated jaundice/hepatic dysfunction. Nosclav-1000 is also contraindicated in infectious mononucleosis. Patients with lymphatic leukemia and patients with hyperuricaemia having been treated with allopurinol may also be at an increased risk of developing skin rashes.

 

WARNINGS

Transient hepatitis and cholestatic jaundice has been reported, hence, Nosclav-1000 should be used with caution in patients with evidence of hepatic dysfunction. 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 esperienced severe reactions when treated with cephalosponins. 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, Nosclav-1000 should be discontinued and the appropriate therapy instituted: adrenaline, corticosteroids, and antihistamines.

 

DOSAGE

Tablets should be taken with meal or as directed by the physician.

Adults

Nosclav-1000: 1 Tablet every 12 hours or as directed by the physician.

 

Dosage In renal failure

Both Amoxicillin 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.

 

SIDE EFFECTS AND SPECIAL PRECAUTIONS

Amoxicillin

Sensitivity reactions 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 hypersensitivity reactions reported are erythernutous maculopapular rashes, urticaria, fever and joint pains. Anaphylactic shock may occur.

 

Gastrointestinal

Nausea, heartburn, vomiting and diarrhoea.

Pseudomembranous colitis has been reported.

 

Liver

Hepatotoxicity, hepatitis, cholestatic jaundice may occur. A moderate rise in serum glutamic oxalacetic transaminase (SGOT) has been noted, but the significance of this finding is unknown.

 

Hemic and Lymphatic Systems

Anaemia, thrombocytopenia, thrombocytopenic purpura, eosinophilia, leukopenia and granulocytopenia 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, behavioural changes, and/or dizziness have also been reported. Depression, seizures, or hallucinations.

 

Other

A sore mouth or tongue and a black hairy tongue have been reported.

Allergic reactions which may include exfoliative dermatitis, other skin rashes, interstitial nephritis and vasculitis, may occur. Erythema multiforme (including Stevens Johnson’s syndrome), toxic episodes of necrolysis.

 

Clavuanic acid

Gastro-intestinal: Nausea and diarrhea.

Liver: Cholestatic jaundice and hepatitis.

 

PRECAUTIONS

Allergic reactions may occur, usually manifesting as pruritic skin rash, an erythematous skin reaction, urticaria, angiodema, anaphylaxis or eosinophilia. Coomb’s test may become positive. In this event, withdrawal of Nosclav-1000 and the administration of antihistamine will suffice in most cases. Should a serious anaphylactic reaction occur, Nosclav-1000 should be discontinued and the patient treated with the usual agents: adrenaline, corticosteroids and antihistamines.

Treatment with Nosclav-1000 may give rise to a maculopapular rash during therapy or within a few days after completion. The incidence of maculopapular rash is especially high in patients suffering from infectious mononucleosis and hence should be avoided. 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. Monilial overgrowth such as vaginitis and thrush have been reported.

Treatment with Nosclav-1000 can cause gastrointestinal symptoms such us diarrhoea, nausea and vomiting which can be minimised by administering the medicine at the start of a meal. In addition, as these symptoms are especially related to the Potassium Clavulanate component, where these gastro-intestinal symptoms occur and a higher concentration of Amoxicillin is required, consideration should be given to administering the additional Amoxicillin separately. Caution must be exercised in patients with syphilis as some patients may experience a Jarisch – Herxheimer reaction shortly after starting the treatment. Symptoms include fever, chills, headache and reactions at the site of the lesions. The reactions can be dangerous in cardiovascular syphilis or where there is a serious risk of increased local damage such as optic atrophy. A moderate rise in aspartame tranuaminase/alanine transaminase has been observed in patients treated with this combination.

 

Impaired renal function

Renal function should be monitored in patients with moderate to severe renal impairment and Nosclav-1000 dosage should be adjusted. High dose should be avoided in patients with impaired renal function/heart failure and in patients receiving potassium sparing diuretics.

 

Impaired hepatic function

Nosclav-1000 should be used with caution in patients with underlying hepatic disease as hepatic and cholestatic jaundice have been reported with this combination. The condition is more predominant in adult and elderly patients.

 

Use in lactation

Amoxicillin is excreted in human milk but the excretion of clavulanic acid has not been studied conclusively therefore caution should be exercised when Nosclav-1000 is administered to nursing mothers.

 

DRUG INTERACTIONS

Concurrent use of Nosclav-1000 with probenecid may result in increased and prolonged blood levels of Amoxicillin but since the excretion of Clavulanic acid is unchanged by probenecid, its blood level remains unaffected. Interaction of Nosclav-1000 with coumarin or indandione – derivative anticoagulants, heparin, non-steroidal anti-inflammatory drugs (NSAIDs) especially, aspirin, other platelet aggregation inhibitors or thrombolytic agents may be clinically significant. Nosclav-1000 may decrease the efficacy of oestrogen-containing oral contraceptives.

 

KNOWN SYMPTOMS OF OVERDOSAGE AND TREATMENT

Nausea, vomiting and diarrhoea may occur with overdosing. Treatment is symptomatic and supportive. Amoxicillin and clavulanic acid may be removed from the circulation by haemodialysis.

 

STORAGE

Store below 30oC.

Protect from tight and moisture.

Keep out of reach of children.

 

PRESENTATION

Nosclav-1000: 2 strips of 7 tablets presented in a carton.

 

Manufactured in India by

Finecure Pharmaceuticals Ltd.

Shimla Pistaur, Malsa Road, Kichha,

Udham Singh Nagar, Uttarakhand-263148, India.

 

Marketed by

Geneith PHARM. LIMITED

12 Adewale Crescent, Off Ewenla Street,

Off Oshodi-Apapa Expressway, Oshodi – Lagos,

Nigeria.

www.geneithpharm.com