AMOXICILLIN PLUS CLAVULINIC ACID

Dr. Laxman Wagle,B.Pharm .PharmD(PB),

Rajiv Gandhi University of Health Science

Clinical pharmacist

Amoxicillin + Amoxicillin + Clavulinic acid Clavulinic acid

Cocci •Staphylococcus aureus •Streptococcus •Enterococcus •Peptostreptococcus(anaerobic)

•Clostridium (anaerobic)

•Actinomyces (anaerobic)

•Neisseria •Moraxella

•E. Coli •Kleibsella•Serratia •Enterobacter •Shigella•Salmonella •Yersinia •Pseudomonas•Strenotrophomonas•Bacteroides (anaerobic)

Bacilli

Gm +ve

Gm -ve

Pleomorphic (shape is coccobacili)

Gm+ve-Listeria Gm-ve H.influenza,Legionella,Bordetella

Gm variable (changing) Acinetobacter

Classification of bacteria

Other than gram stain: Atypicals• Mycoplasma : lack cell wall• Chlamydia : lack peptidoglycan layer• Ricketssia : intracellular parasites• Legionella: doesnot grow on traditional media

Other than coccus or bacilli shape • Spirochetes: Treponema pallidum

Anti-infectives

1. Antibiotics2. Antiviral drugs3. Antifungal drugs4. Antiprotozoal drugs5. Anthelmintic drugs6. Insecticides for ectoparasites 7. Antiseptics and Disnfectant (Not are drugs)8. Vaccines, Serums, and Immunoglobulins

Antibiotics • Cell wall inhibitors• Nucleic acid synthesis inhibitors

– Inhibit DNA gyrase : quinolones– Inhibit folate syhthesis : cotrimoxazole – Create free radicals: metronidazole

• Protein synthesis inhibitors– Inhibit 50’s subunit: macrolides,

clindamycin,linezolid,chloramphenicol,, streptogramins– Inhibit 30’s subunit:

aminoglycosides,tetracyclines,tigecycline

Cell wall inhibitors

• Cycloserine • Bacitracin • Vancomycin • B lactams

– Penicillin– Cefalosporin– Monobactam– Carbapenam

Classification of penicillinCLASSIFICATION SUBTYPE DRUG NAME Narrow spectrum Natural

penicillin Penicillin G,Penicillin V,Benzathine Penicillin G, Procaine Penicillin G

Very very narrow spectrum

Anti-staphylococcal penicillin

Naficillin,methicillin, cloxacillin, flucloxacillin, dicloxacillin

Broad spectrum Amino-penicillin

Ampicillin /+B lactamase inhibitorsAmoxicillin/+B lactamase inhibitors

Very very broad spectrum antibiotics

Antipsudomonal penicillins

Piperacillin/+B lactamase inhibitorsTicarcillin /+B lactamase inhibitorsCarbenicillin /+B lactamase inhibitorsUreidocillin /+B lactamase inhibitors

Mechanism of action

AMOXICILLIN +CLAVULINIC ACID

CONTENTS • Formulations available• Pharmacokinetics• Rationality of combination • Spectrum of activity• Indication• Contraindication • Precaution • Adverse drug reactions • Drug interaction • Lab interferance • Storage • Competitors in Nepal

Formulations availableDosage form Strength Route

Dispersible tablet 200mg+28.5mg Oral

Tablet 250mg+125mg Oral



Dry syrup 125mg+31.25mg/5ml

in 30 ml Oral

Dry syrup 200mg+28.5mg/5ml in

30 ml Oral

Dry syrup 400mg+57mg/5ml in

30ml Oral Powder for injection 1000mg+200mg I.V

Powder for injection 125mg+25mg I.V

• ORAL: – Powder for oral susp: Reconstitute w/ appropriate amount of

water as specified in the label. Shake vigorously until suspended.

• I.V:– Reconstitution: Powd for inj: Dissolve amoxicillin/clavulanic

acid 500/100 mg in 10 mL solvent and 1,000/200 mg in 20 mL solvent. May further dilute to infusion soln containing either water for inj or NaCl 0.9%.

– Incompatibility: Incompatible w/ blood products, other proteinaceous fluids (e.g. protein hydrolysates), IV lipid emulsions, aminoglycosides, infusions containing glucose, dextran or bicarbonate

Pharmacokinetics • Absorption: Rapidly and well absorbed from GI tract.

Bioavailability: Approx 70%. Time to peak plasma concentration: W/in 1-2.5 hr.

• Distribution: It crosses the placental barrier(category B); enters breast milk (small amounts); readily distributes into most body tissues and fluid. Amoxicillin: Readily distributes except into cerebrospinal fluid. Volume of distribution: Approx 0.3-0.4 L/kg (amoxicillin); approx 0.2 L/kg (clavulanic acid). Plasma protein binding: Approx 18% (amoxicillin); approx 25% (clavulanic acid).

• Excretion: Via urine (amoxicillin: Approx 50-70% ; clavulanic acid: Approx 25-40%) as unchanged drug during the 1st 6 hr after admininistration. Mean elimination half-life: Approx 1 hr.

Rationality of combination • Amoxicillin is susceptible to degradation by β-lactamases. • The clavulanic acid component of enhancin protects amoxicillin

from degradation by β-lactamase enzymes and effectively extends the antibiotic spectrum of amoxicillin to include many bacteria normally resistant to amoxicillin and other β-lactam antibiotics.

• Taking 500mg/125mg O.D and 250mg/125mg B.D are not the same!!!

• Maximum daily dose of clavulanic acid 250mg.

Spectrum of activity in comparison to other penicillin

ORGANISMS Natural penicillin

Antistaphyloccocus penicillin

Amino+/Blactamase(enhancin)

Antipsudomonal penicillin +/Blactamase

Staph. Aereus (Methicillin sensitive)

+ ++ + +

Staph. Aereus (Methicillin resistant) MRSA

- - - -

Streptococcus ++ - ++ +

Enterococcus + - + +

Gram negetives - - ++ ++

Anaerobics + - ++ ++

Pseudomonas - - - ++

Spectrum of activity of Amoxicillin+ Cavulinic acid among drugs to treat gram-ve infections.

Gram negetive organisms

Aminopenicillin :amoxicillin+clavulinic acid

Anti-pseudomonal

2nd gen.cepha.

3rd gen.cepha

4th generation. cefa :cefepime

aztreonams

carbapenams

Quinolones

aminoglycosides

E.coli, Kleibsella, Proteus

++ ++ ++ ++ ++ ++ ++ ++ ++

Enterobacter, Serratia ,citrobacter

- ++ - + ++ + ++ ++ ++

H.Influenza ++ ++ ++ ++ ++ ++ ++ ++ ++

Neisseria ++ ++ +/- ++ ++ ++ ++ +/- -

Pseudomonas - ++ - Ceftazidime only

++ + ++ Moxifloxacin only

++

Indication and dosage Route Adult dose Child

dose Renal impairement dose

Indication

Oral 250-500 mg 8 hrly or 500-875 mg 12 hrly.

<40 kg: 20-60 mg/kg tid.

Cr cl<10: 500mg 24 hrlyCr cl:10-30:500mg 12 hrly

Respiratory tract infection, Melioidosis; Infected animal bites; Susceptible infections

Oral 3 g as a single dose, repeated once after 8 hr.

<40 kg: 20-60 mg/kg tid.


Dental abscesses

Oral 3 g as a single dose, repeated once after 10-12 hr.

<40 kg: 20-60 mg/kg tid.


Acute uncomplicated urinary tract infections

Oral 3 g bid. <40 kg: 20-60 mg/kg tid.


Severe or recurrent respiratory tract infections

Oral: 2 or 3 g as a single dose to be taken 1 hr before dental procedure.

<40 kg: 20-60 mg/kg tid.


Prophylaxis of endocarditis

775 mg daily for 10 days.

<40 kg: 20-60 mg/kg tid.


Pharyngitis ; Tonsillitis

I.V : 500 mg 8 hrly by slow inj over 3-4 min. In severe infections, may increase to 1 g 6 hrly by slow inj over 3-4 min or infusion over 30-60 min.

<3 mth 25 mg/kg 12 hrly; ≥3 mth <40 kg: 25 mg/kg 8 hrly.

Cr cl<10: Iinitially 1000mg, then 500mg 24 hrlyCr cl:10-30: Iinitially 1000mg, 500mg 12 hrly

Susceptible infections

I.V 1,000 mg up to 30 min before the procedure. For high risk procedures, up to 2-3 further doses may be given 8 hrly

<3 mth 25 mg/kg 12 hrly; ≥3 mth <40 kg: 25 mg/kg 8 hrly.

Cr cl<10: Iinitially 1000mg, then 500mg 24 hrlyCr cl:10-30: Iinitially 1000mg, 500mg 12 hrly

Prophylaxis of surgical infections

Note: Dosage are based on amoxicillin.

Contraindication • Hypersensitivity to penicillins. • History of severe immediate hypersensitivity

reaction to another β-lactam agent (e.g. cephalosporins, carbapenem or monobactam),

• History of cholestatic jaundice/hepatic dysfunction associated w/ amoxicillin and clavulanic acid therapy.

Precaution

• Renal and hepatic impairment.• Children• Pregnancy and lactation. • Monitoring Parameters : Periodically monitor renal,

hepatic and haematologic function. • Monitor for signs of anaphylaxis during 1st dose.

Adverse drug reactions• Diarrhoea/loose stools, Clostridium difficile-

associated diarrhoea, pseudomembranous colitis, nausea, vomiting, skin rashes, urticaria, vaginitis.

• Potentially Fatal: Anaphylaxis, Stevens-Johnson syndrome.

Drug interactions• May increase plasma concentration of amoxicillin w/

probenecid. • May increase allergic or hypersensitivity reaction w/

concomitant use of allopurinol and amoxicillin. • May reduce efficacy of oral oestrogen/progesterone

contraceptives.

Lab interaction • False-positive urinary glucose test using cupric

sulfate (e.g. Benedict's or Fehling's soln, Clinitest)

Storage

• Intravenous: Store at or below 25°C. • Oral: Store at or below 25°C.• Reconstituted oral suspension: Store

between 2-8°C.

COMPETITORS AND THEIR PRICE (PER TAB)

DOSAGE FORM STRENGTH AMX (NPL)

RANBAXY(ENHANCI

N)

ARISTO (MEGA

CV )

SUPER CV(NHC)

INDCLAV(INDCH

EMIE HEALTH SPECIALI

TIES)

AUGMENTIN(GSK)

CLAVAM (ALKEM)

BACTOCLAV(MICROLABS)

CLEDOMOX

(MEDOPHARM)

Dispersible tab 400mg+57mg 14.333 Dispersible tab 200mg+28.5mg 14.16667 8.1667 8.083 6.5

Tablet 250mg+125mg 27.5 13.167 18.6 41.75 17.5Tablet 500mg+125mg 40.3 16.5 43.91667 19Tablet 875mg+125mg 44 29.128 5.465

Dry syrup 125mg+31.25mg/5ml in 30 ml 60

Dry syrup : oral drops

80mg+11.4mg/1ml in 10ml 48 76

Dry syrup 200mg+28.5mg/5ml in 30 ml + 85 52.92 + 55.8 109.1 75 54

Dry syrup 200mg+28.5mg/5ml in 60 ml 102.14

Powder for injection 1000mg+200mg 169 214.4

Powder for injection 500mg+125mg 121.8

Powder for injection 250mg+50mg 67.5

Dry syrup 400mg+57mg/5ml in 30ml 90 130

Powder for injection 125mg+25mg 41

THANK YOU

Health & Medicine

AMOXICILLIN PLUS CLAVULINIC ACID