Amoxicillin Capsules BP

Name of Medicinal Product

Amoxicillin Capsules BP

Pharmaceutical form – Strength and Pack size

Pharmaceutical form: CAPSULES

Description: White to off-white powder filled in ‘0’ size hard gelatin capsule having cylindrical opaque maroon colour cap Printed ‘AMOXY’ & cylindrical yellow colour body printed ‘500’.

Strength: Amoxicillin Trihydrate BP equivalent to Amoxicillin …. 500mg, per Capsule

Therapeutic Category

Penicillin Anti-Bacterial

Indications

• Amoxicillin is indicated for the treatment of the following infections in adults and children:

1. Acute bacterial sinusitis
2. Acute streptococcal tonsillitis and pharyngitis
3. Acute exacerbations of chronic bronchitis
4. Community-acquired pneumonia
5. Acute otitis media
6. Acute cystitis
7. Acute pyelonephritis
8. Asymptomatic Bacteriuria in pregnancy
9. Typhoid and paratyphoid fevers
10. Dental abscess with spreading cellulitis
11. Prosthetic joint infections
12. Helicobacter pylori eradication
13. Lyme disease

• Amoxicillin is also indicated for the prophylaxis of endocarditis. Consideration should be given to official guidance on the appropriate use of antibacterial agents.

Contra-indications

• Hypersensitivity to the active substance, to any of the penicillins or to any of the excipients.
• History of a severe immediate hypersensitivity reaction (e.g. anaphylaxis) to another beta-lactam agent (e.g. a cephalosporin, carbapenem or monobactam).

Precautions / Warnings

Hypersensitivity Reactions:

• Before initiating therapy with amoxicillin, careful enquiry should be made concerning previous hypersensitivity reactions to penicillin and cephalosporins or other beta-lactam agents.
• Serious and occasionally fatal hypersensitivity reactions (including anaphylactoid and severe cutaneous adverse reactions) have been reported in patients on penicillin therapy. These reactions are more likely to occur in individuals with a history of penicillin hypersensitivity and in atopic individuals. If an allergic reaction occurs, amoxicillin therapy must be discontinued and appropriate alternative therapy instituted.

Non-Susceptible Microorganisms:

• Amoxicillin is not suitable for the treatment of some types of infection unless the pathogen is already documented and known to be susceptible or there is a very high likelihood that the pathogen would be suitable for treatment with amoxicillin. 
• This particularly applies when considering the treatment of patients with urinary tract infections and severe infections of the ear, nose and throat.

Convulsions:

• Convulsions may occur in patients with impaired renal function or in those receiving high doses or in patients with predisposing factors (e.g. history of seizures, treated epilepsy or meningeal disorders).

Renal Impairment:

• In patients with renal impairment, the dose should be adjusted according to the degree of impairment.

Skin Reactions:

• The occurrence at the treatment initiation of a feverish generalized erythema associated with pustula may be a symptom of acute generalised exanthemous pustulosis (AGEP). This reaction requires amoxicillin discontinuation and contra-indicates any subsequent administration.
• Amoxicillin 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. Patients with lymphatic leukaemia and possibly with HIV infection are particularly prone to developing erythematous rashes with amoxicillin. Amoxicillin should be discontinued if a skin rash occurs.

Jarisch-Herxheimer Reaction:

• The Jarisch-Herxheimer reaction has been seen following amoxicillin treatment of Lyme disease. It results directly from the bactericidal activity of amoxicillin on the causative bacteria of Lyme disease, the spirochaete Borrelia burgdorferi. Patients should be reassured that this is a common and usually self-limiting consequence of antibiotic treatment of Lyme disease.

Overgrowth of Non-Susceptible Microorganisms:

• Prolonged use of an anti-infective may result in the overgrowth of non-susceptible organisms (superinfection).
• Antibiotic-associated colitis has been reported with nearly all antibacterial agents and may range in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during, or subsequent to, the administration of any antibiotics. 
• Should antibiotic-associated colitis occur, amoxicillin should immediately be discontinued, a physician consulted and an appropriate therapy initiated. Anti-peristaltic medicinal products are contra-indicated in this situation.

Prolonged Therapy:

• Periodic assessment of organ system functions; including renal, hepatic and hematopoietic function is advisable during prolonged therapy. Elevated liver enzymes and changes in blood counts have been reported.

Crystalluria:

• In patients with reduced urine output, crystalluria has been observed very rarely, predominantly with parenteral therapy. During the administration of high doses of amoxicillin, it is advisable to maintain adequate fluid intake and urinary output in order to reduce the possibility of amoxicillin crystalluria. In patients with bladder catheters, a regular check of patency should be maintained.

Anticoagulants:

• Prolongation of prothrombin time has been reported rarely in patients receiving amoxicillin. Appropriate monitoring should be undertaken when anticoagulants are prescribed concomitantly. Adjustments in the dose of oral anticoagulants may be necessary to maintain the desired level of anticoagulation.

Interference with Diagnostic Tests:

• Elevated serum and urinary levels of amoxicillin are likely to affect certain laboratory tests. Due to high urinary concentrations of amoxicillin, false positive readings are common with chemical methods.
• It is recommended that when testing for the presence of glucose in urine during amoxicillin treatment, enzymatic glucose oxidase methods should be used.
• The presence of amoxicillin may distort assay results for oestriol in pregnant women.

Pregnancy and Lactation

Pregnancy:

• Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. Limited data on the use of amoxicillin during pregnancy in humans do not indicate an increased risk of congenital malformations. 
• Amoxicillin may be used in pregnancy when the potential benefits outweigh the potential risks associated with treatment.

Breastfeeding:

• Amoxicillin is excreted into breast milk in small quantities with the possible risk of sensitisation. Consequently, diarrhoea and fungus infection of the mucous membranes are possible in the breast-fed infant, so that breast-feeding might have to be discontinued. 
• Amoxicillin should only be used during breast-feeding after benefit/risk assessment by the physician in charge.

Fertility:

• There are no data on the effects of amoxicillin on fertility in humans. Reproductive studies in animals have shown no effects on fertility.

Side effects / Adverse reactions

Infections and infestations

Very Rare: Muco-cutaneous candidiasis

Blood and lymphatic system disorders

Very rare: Reversible leucopenia (including severe neutropenia or agranulocytosis), reversible thrombocytopenia and haemolytic anaemia. Prolonged prothrombin and bleeding times.

Immune system disorders

Very rare: As with other antibiotics, severe allergic reactions, including angioneurotic oedema, anaphylaxis, serum sickness and hypersensitivity vasculitis Not known: Jarisch-Herxheimer reaction

If any hypersensitivity reaction occurs the treatment should be discontinued.

Nervous system disorders

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

Gastrointestinal disorders

Clinical Trial Data

⇾    Common: Diarrhoea and nausea.

⇾    Uncommon: Vomiting.

Post-marketing Data

Very rare: Antibiotic associated colitis (including pseudomembraneous colitis and haemorrhagic colitis). Black hairy tongue.

Hepato-biliary disorders

Very rare: Hepatitis and cholestatic jaundice. A moderate rise in AST and/or ALT. The significance of a rise in AST and/or ALT is unclear.

Skin and subcutaneous tissue disorders

Clinical Trial Data

⇾    Common: Skin rash

⇾    Uncommon: Urticaria and pruritus

Post-marketing Data

Very rare: Skin reactions such as erythema multiforme, Stevens-Johnson syndrome, toxic epidermal necrolysis, bullous and exfoliative dermatitis, acute generalised exanthematous pustulosis (AGEP) and drug reaction with eosinophilia and systemic symptoms (DRESS).

Renal and urinary tract disorders

Very rare: Interstitial nephritis.

Very rare: Crystalluria.

Drug Interactions

Oral Anticoagulants:

• Oral anticoagulants and penicillin antibiotics have been widely used in practice without reports of interaction. However, in the literature there are rare cases of increased international normalised 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 amoxicillin.

Probenecid:

• Concomitant use of probenecid is not recommended. Probencid decreases the renal tubular secretion of amoxicilin. Concurrent use with amoxicillin may result in increased and prolonged blood levels of amoxicillin.

Allopurinol:

• Concurrent administration of allopurinol during treatment with amoxicillin can increase the likelihood of allergic skin reactions.

Tetracyclines:

• Tetracyclines and other bacteriostatic drugs may interfere with the bactericidal effects of amoxicillin.

Methotrexate:

• Penicillins may reduce the excretion of methotrexate causing potential increase in toxicity.

Dosage & Administration

• The dose of Amoxicillin that is selected to treat an individual infection should take into account:

1. The expected pathogens and their likely susceptibility to antibacterial agents
2. The severity and the site of infection
3. The age, weight and renal function of the patient; as shown below

• The duration of therapy should be determined by the type of infection and the response of the patient, and should generally be as short as possible. Some infections require longer periods of treatment.

Adults and children ≥ 40 kg

* Consideration should be given to the official treatment guidelines for each indication

Children < 40 kg

• Children may be treated with Amoxicillin capsules, dispersible tablets, suspensions or sachets.
• Amoxicillin Paediatric Suspension is recommended for children under six months of age.
• Children weighing 40kg or more should be prescribed the adult dosage.

Recommended doses:

+ Consideration should be given to the official treatment guidelines for each indication.

* Twice daily dosing regimens should only be considered when the dose is in the upper range.

Elderly

No dose adjustment is considered necessary.

Renal impairment

In patients receiving Haemodialysis

Amoxicillin may be removed from the circulation by haemodialysis

In patients receiving peritoneal dialysis

Amoxicillin maximum 500mg/day

Hepatic impairment

Dose with caution and monitor hepatic function at regular intervals.

Method of administration

• Amoxicillin is for oral use.
• Absorption of amoxicillin is impaired by food.
• Therapy can be started parenterally according to the dosing recommendations of the intravenous formulation and continued with an oral preparation.
• Swallow with water without opening capsule.

Over dosage

Symptoms and signs of overdose

• Problems of overdosage with amoxicillin are unlikely to occur. Gastrointestinal symptoms (such as nausea, vomiting and diarrhoea) and disturbances of the fluid and electrolyte balances may be evident. Amoxicillin crystalluria, in some cases leading to renal failure, has been observed. Convulsions may occur in patients with impaired renal function or in those receiving high doses.

Treatment of intoxication:

• Gastrointestinal symptoms may be treated symptomatically, with attention to the water/electrolyte balance.
• Amoxicillin can be removed from the circulation by haemodialysis.

Effects on ability to drive and use machines

No data available on the effects of ability to drive and use machines.

However, undesirable effects may occur (e.g. allergic reactions, dizziness, convulsions), which may influence the ability to drive and use machines

Shelf life

24 months from the date of manufacturing

Special precautions for storage

Store in a cool and dry place. Protect from light, heat and moisture.

Keep out of reach of Children.

Mechanism of Action

• Amoxicillin is a semisynthetic penicillin (beta-lactam antibiotic) that inhibits one or more enzymes (often referred to as penicillin-binding proteins, PBPs) in the biosynthetic pathway of bacterial peptidoglycan, which is an integral structural component of the bacterial cell wall. Inhibition of peptidoglycan synthesis leads to weakening of the cell wall, which is usually followed by cell lysis and death.
• Amoxicillin is susceptible to degradation by beta-lactamases produced by resistant bacteria and therefore the spectrum of activity of amoxicillin alone does not include organisms which produce these enzymes.

Pharmacokinetic Properties

Absorption:

• Amoxicillin fully dissociates in aqueous solution at physiological pH. It is rapidly and well absorbed by the oral route of administration. Following oral administration, amoxicillin is approximately 70% bioavailable. The time to peak plasma concentration (Tmax) is approximately one hour.
• The pharmacokinetic results for a study, in which an amoxicillin dose of 250 mg three times daily was administered in the fasting state to groups of healthy volunteers are presented below.

• In the range 250 to 3000 mg the bioavailability is linear in proportion to dose (measured as Cmax and AUC). The absorption is not influenced by simultaneous food intake.
• Haemodialysis can be used for elimination of amoxicillin.

Distribution:

• About 18% of total plasma amoxicillin is bound to protein and the apparent volume of distribution is around 0.3 to 0.4 l/kg.
• Following intravenous administration, amoxicillin has been found in gall bladder, abdominal tissue, skin, fat, muscle tissues, synovial and peritoneal fluids, bile and pus. Amoxicillin does not adequately distribute into the cerebrospinal fluid.
• From animal studies there is no evidence for significant tissue retention of drug-derived material. Amoxicillin, like most penicillins, can be detected in breast milk.
• Amoxicillin has been shown to cross the placental barrier.

Biotransformation:

• Amoxicillin is partly excreted in the urine as the inactive penicilloic acid in quantities equivalent to up to 10 to 25% of the initial dose.

Elimination

• The major route of elimination for amoxicillin is via the kidney.
• Amoxicillin has a mean elimination half-life of approximately one hour and a mean total clearance of approximately 25 l/hour in healthy subjects. Approximately 60 to 70% of the amoxicillin is excreted unchanged in urine during the first 6 hours after administration of a single 250 mg or 500 mg dose of amoxicillin. 
• Various studies have found the urinary excretion to be 50-85% for amoxicillin over a 24 hour period.