Clasynmo

Clasynmo 875 mg /125 mg F.C. Tablet

Composition

 Each F.C. tablet contains :

Amoxicillin trihydrate 1004.43 mg (Eq. to Amoxicillin 875 mg)

Clavulanic acid 125 mg

 

Pharmacological action:

Amoxicillin is a semi-synthetic antibiotic with broad spectrum of antibactericidal activity against many Gram-positive and Gram-negative microorganisms. Amoxicillin is, however, susceptible to degradation by beta-lactamases, and therefore, the spectrum of activity does not include organisms which produce these enzymes.

Clavulanic acid is a beta-lactam, structurally related to the penicillins, which possesses the ability to inactivate a wide range of beta-lactamase enzymes commonly found in microorganisms resistant to penicillins and cephalosporins.

The presence of clavulanic acid protects amoxicillin from degradation by beta-lactamase enzymes and effectively extends the antibacterial spectrum of amoxicillin to include many bacteria normally resistant to amoxicillin and other penicillins and cephalosporins. Thus Clasynmo possesses the distinctive properties of broad spectrum antibiotic and beta-lactamase inhibitor.

Clasynmo is bactericidal to a wide range of organisms including:

Gram-positive:

Aerobes: Enterococcus faecalis, Streptococcus pneumoniae, Streptococcus pyogenes,

Streptococcus Viridans, Staphylococcus aureus, Coagulase negative staphylococci (including Staphylococcus epidermidis), Corynebacterium species, Bacillus anthracis, Listeria monocytogenes.

Anaerobes: Clostridium species, Peptococcus species, Peptostreptococcus.

Gram-negative:

Aerobes: Haemophilus influenzae, Escherichia coli, Proteus mirabilis, Proteus vulgaris, Klebsiella species, Moraxella catarrhalis, Salmonella species, Shigella species, Bordetella pertussis, Brucella species, Neisseria gonorrhoeae, Neisseria meningitides, Vibro cholerae, Pasteurella multocida.

Anaerobes: Bacteroides spp. including B. fragilis

Including beta-lactamase producing strains resistant to ampicillin and amoxicillin.

 

Pharmacokinetics

The pharmacokinetics of the two components is closely matched. Both Clavulanate and Amoxicillin have low levels of serum binding about 70% remains free in serum.

Doubling the dosage of Clasynmo approximately double the serum levels achieved.

Peak serum levels of both occur about 1 hour after oral administration. Absorption of Clasynmo is optimized at the start of meal

 

Indication:

Clasynmo is indicated for short-term treatment infections at the following sites when caused by Amoxicillin- Clavulanate susceptible organisms.

Upper Respiratory Tract Infections (including ENT) e.g. recurrent tonsillitis, sinusitis, otitis media, typically caused by Staphylococcus pneumonia, Haemophilus influenzae and Moraxella catarrhalis.

Lower Respiratory Tract Infections: e.g. acute exacerbations of chronic bronchitis, lobar and bronchopneumonia, typically caused by Staphylococcus pneumonia, Haemophilus influenzae and  Moraxella catarrhalis

Genito-urinary tract infections: e.g. cystitis, urethritis, pyelonephritis, female genital infections, typically caused by enterobacteriaceae ( mainly Escherichia Coli), Staphylococcus saprophyticus and enterococcus species, and gonorrohoea caused by Neisseria gonorrhoeae.

Skin and soft tissue Infections – typically caused by Staphylococcus aureus, Staphylococcus pyogens and bacteroides species.

Bones and joint infections: e.g. Osteomyelitis, typically caused by Staphylococcus aureus where more prolonged therapy may be appropriate

Other infections: e.g. Septic abortion, puerperal sepsis, intra-abdominal sepsis

 

Dosage and administration:

Depends on the age, weight, renal function of the patient, the severity of the infection and physician's instructions.

Adults:

Mild to moderate infection: 375mg given 3 times daily, or 1g 2 times daily.

Severe infection: (including chronic and recurrent urinary tract infections and those of the lower respiratory tract) two tablets 375mg given 3 times daily or 1 g 3times daily.

Renal Impairment:

Dosage adjustment is based on the maximum recommended level of Amoxicillin.

Adults:

Creatinine- clearance  <30 mL/min: No adjustment necessary.

Creatinine- clearance 10- 30 mL/min: one or two tablets of 375mg, depending upon severity of infection,  given 2 times daily

Creatinine- clearance > 10 mL/min: one or two tablets of 375mg, depending upon severity of infection, given once daily

Haemodialysis:

Adults:

Two tablets of 375mg every 24 hours

Plus one dose during dialysis, to be repeated at the end of dialysis ( as serum concentrations of both Amoxocillin and Clavulanic acid are decreased).

The 1 g presentation should only be used in patients with creatinine clearance < 30ml/min

Hepatic Impairment:

Dose with caution,  monitor hepatic function at regular intervals.

There are insufficient data on which to base dosage recommendation.

 

Method of Administration:

Oral route:

To minimize Potential gastrointestinal intolerance, administer at the start of meal

The absorption of Clasynmo is optimized when taken at the start of meal

Treatment should not be extended beyond 14 days without review

Therapy can be started parenterally and continued with an oral preparation.

For suspension:

Reconstitute suspension immediately before use

Shake the bottle well before use

 

Overdose:

Gastrointestinal symptoms and disturbance of the fluid and electrolyte balances may be evident. Gastrointestinal symptoms may be treated symptomatically with attention to the water electrolyte balance.

Amoxicillin crystalluria, in some cases leading to renal failure, has been observed.

Clasynmo may be removed from circulation by hemodialysis.

 

Contraindications:

Patients with a history of hypersensitivity to  Beta-lactams e.g., penicillins and cephalosporins).

A previous history of amoxicillin- clavulanate associated Jaundice/Hepatic Dysfunction.

In patients with phenylketonuria: Clasynmo suspension is contraindicated due to the presence of aspartame since one of its metabolic products is phenylalanine

 

Effects on Ability to drive and use machines:

Adverse effects on the ability to drive or operate machinery have not been observed

 

Side effects:

Data from large clinical trials were used to determine the frequency of very common to rare undesirable effects. The frequencies assigned to all other undesirable effects (i.e. those occurring at  < 1/10000) were mainly determined using post-marketing data and refer to reporting rate rather than true frequency.

The following convention has been used for the classification of frequency:

Very common > 1/10

Common > 1/100 and < 1/10

Uncommon > 1/1000 and < 1/100

Rare > 1/10000 and < 1/1000

Very rare < 1/10000

Infections and infestations:

Common:  Mucocutaneous candidiasis

Blood and lymphatic system disorders

Rare: Reversible leucopenia (including neutropenia) and thrombocytopenia.

Very rare: Reversible agranulocytosis and haemolytic anaemia. Prolongation of bleeding time and prothrombin time.

Immune system disorders:

Very rare: Angioneurotic oedema, anaphylaxis, serum sickness-like syndrome, hypersensitivity vasculitis.

Nervous system disorders:

Uncommon: Dizziness, headache

Very rare: Reversible hyperactivity and convulsions. Convulsions may occur in patients with impaired renal function or in those receiving high doses

Gastrointestinal disorders:

Adults:

Very common: Diarrhoea

Common: Nausea, vomiting

Children:

Common: Diarrhoea, Nausea, vomiting

All populations:

Nausea is more often associated with higher oral dosages. If gastrointestinal reactions are evident, they may be reduced by taking Clasynmo at the start of meal.

Uncommon: Indigestion

Very rare: Antibiotic-associated colitis (including pseudomembranous colitis and haemorrhagic colitis)

Black hairy tongue

Hepatobiliary disorders:

Uncommon: 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.

Very rare: Hepatitis and cholestatic jaundice. These events have been noted with other penicillins and cephalosporins

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.

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 medications known to have the potential for hepatic effects.

Skin and subcutaneous tissue disorders:

Uncommon: Skin rash, pruritus, urticaria

Rare: Erythema multiforme

Very rare: Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous exfoliative-dermatitis, acute generalized exanthemous pustulosis (AGEP)

If any hypersensitivity dermatitis reaction occurs, treatment should be discontinued.

Renal and urinary disorders:

Very rare: Interstitial nephritis, crystalluria.

 

Drug Interactions:

Probenecid: Avoid concomitant use with amoxicillin-clavulanic acid as Probenecid  decreases the renal tubular secretion of amoxicillin and may result in increased and prolonged blood levels of amoxicillin but  not of clavulanic acid.

Concomitant use of allopurinol during treatment with amoxicillin can increases the

Likelihood of allergic skin reactions. There are no data on the Concomitant use of

amoxicillin-clavulanic acid and allopurinol

In common with other broad-spectrum antibiotics, Amoxicillin clavulanate may reduce the efficancy of oral contraceptives and patients should be warned accordingly.

In the literature there are rare cases of increased international normalized 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 Clasynmo.

Concomitant administration of amoxicillin and anticoaglants from the coumarin class may prolong the bleeding time. A dose adjustment of anticoagulants may be necessary.

 

Pregnancy and lactation:

Pregnancy: As with all medicines, use should be avoided in pregnancy, unless considered essential by the physician.

Lactation: Clasynmo may be administered during the period of lactation

 

Warning and precautions:

Concomitant administration of amoxicillin and anticoagulants from the coumarin class may prolong the bleeding time. A dose adjustment of anticoagulants may be necessary.

Before initiating therapy with Clasynmo, careful enquiry should be made concerning previous hypersensitivity reactions to Penicillins, Cephalosporins, or other allergens.

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. If an allergic reation occurs, therapy should be discontinued and appropriate alternative therapy instituted. Serious anaphylactoid reactions require immediate emergency treatment with adrenaline. Oxygen, I.V. steroids and airway management, including intubation may also be required.

Clasynmo 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.

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

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

 

Patient instructions:

Keep out of reach of children

 

 

Package and Storage:

 

Carton box containing 1or 2 (Al/Al ) blisters each of 8 Film coated tablets enclosed in aluminum pouch containing silica gel & insert leaflet

 

Storage: To be stored at temperature not exceeding 30°C in dry place

 

Manufactured by Sigmatec pharmaceutical industries for Cardinal Pharmaceutical