INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
AMOXICAP 250 (CAPSULE)

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

AMOXICAP 250 (CAPSULE)

COMPOSITION:
Each capsule contains:
Amoxycillin Trihydrate equivalent to Amoxycillin 250 mg

PHARMACOLOGICAL CLASSIFICATION:
A 20.1.2 Penicillins

PHARMACOLOGICAL ACTION:
Amoxycillin is a semisynthetic beta-lactamase-susceptible penicillin, which has in vitro bactericidal activity against broad spectrum of non beta-lactamase producing Gram positive, and Gram negative organisms. The spectrum of activity does not include those organisms that produce beta lactamases, namely resistant staphylococci, and all strains of Pseudomonas, Klebsiella and Enterobacter.
The following organisms are generally sensitive to the bactericidal action of amoxycillin in vitro. In vitro sensitivity does not mean in vivo efficacy
[(*) denotes sensitivity tests must be performed]
Gram positive bacteria
Staphylococcus aureus (penicillin sensitive)*
Streptococcus pyogenes
Streptococcus viridans*
Streptococcus faecalis*
Streptococcus pneumoniae*
Corynebacterium species*
Clostridium species*
Bacillus anthracis*
Listeria monocytogenes
Gram negative bacteria
Neisseria meningitides* (except the carrier state)
Neisseria gonorrhoeae*
Haemophilus influenza*
Bordetella pertussis
Escherichia coli*
Salmonella species*
Shigella species*
Proteus mirabilis*
Pasteurella multocida*
Fusabacterium species*
Helicobacter pylori
Leptospira species

PHARMACOKINETICS:
Absorption:
Amoxycillin is stable in the presence of acidic gastric secretions. Peak blood levels are achieved 1-2 hr after administration. There is a linear dose response in peak serum levels.
Food does not interfere with the absorption of amoxycillin.
Distribution:
Approximately 18% of the total plasma amoxycillin content is protein bound. Amoxycillin diffuses readily into most body tissues with the exception of the brain and spinal fluid. Inflammation generally increases the permeability of the meninges to penicillins and this may apply to amoxycillin.
Excretion:
The elimination half-life is approximately 1 hour. Amoxycillin is primarily excreted via the kidneys.
Small amounts of the drug are also excreted in the faeces and bile.
Amoxycillin crosses the placenta and is distributed into breast milk.

INDICATIONS:
Amoxicap 250 formulations are indicated for the treatment of mild to moderately severe infections caused by susceptible organisms:

1.	Upper Respiratory tract infections such as sinusitis, otitis media, tonsillitis
2.	Lower respiratory tract infections such as bronchitis, lobar and bronchopneumonia
3.	Gastro-intestinal infections such as typhoid fever
4.	Other infections including Borreliosis (Lyme disease)
5.	In the following infections, amoxycillin therapy should be initiated only if there is microbiological evidence that the causative organism is sensitive to amoxycillin:
	Skin and soft tissue infections
	Urinary tract infections: cystitis, urethritis, pyelonephritis, bacteriuria in pregnancy
6.	“As part of combination therapy in established Helicobacter pylori infection, associated with duodenal ulceration.”
7.	Prophylaxis of endocarditis

CONTRA-INDICATIONS:
Hypersensitivity to penicillins or to cephalosporins. Cross-sensitivity between penicillins and cephalosporins is well documented.

WARNINGS:
Serious and occasionally fatal hypersensitivity (anaphylactic) reactions have been reported in patients on penicillin therapy. Before initiating therapy with Amoxicap 250, careful enquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins or other allergens. 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 sensitivity to multiple allergens. There have been reports of 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.
If an allergic reaction occurs, Amoxicap 250 should be discontinued and the appropriate therapy instituted. Serious anaphylactic reactions may require immediate emergency treatment with adrenaline. Oxygen, intravenous steroids and airway management, including intubation may also be required.
Amoxicap 250 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.
Prolonged use may result in overgrowth of non-susceptible organisms. Pseudomembranous enterocolitis has been reported.
Prolongation of prothrombin time has been reported rarely in patients receiving Amoxicap 250. Appropriate monitoring should be undertaken when anticoagulants are prescribed concurrently.
Periodic assessment of organ function, including renal, hepatic and haematopoietic functions, is advisable during prolonged therapy.
Transient hepatitis and cholestatic jaundice has been reported. Amoxicap 250 should be used with caution in patients with evidence of hepatic dysfunction.

INTERACTIONS:
Probenecid decreases the renal tubular secretion of Amoxicap 250. Concurrent use with Amoxicap 250 may result in increased and prolonged blood concentrations of Amoxicap 250.
Amoxicap 250 may reduce the efficacy of oral contraceptives and patients should be warned accordingly.
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.
Tetracyclines and other bacteriostatic drugs may interfere with the bactericidal effects of Amoxicap.
Interaction with Laboratory tests:
It is recommended that when testing for the presence of glucose in urine during Amoxicap 250 treatment, enzymatic glucose oxidation methods should be used. Due to the high urinary concentrations of Amoxicap 250, false positive readings are common with chemical methods.

PREGNANCY AND LACTATION:
Use in pregnancy:
The safety of Amoxicap 250 in pregnancy has not been established.
Use in lactation:
Amoxicap 250 is distributed into breast milk. Although significant problems in humans have not been documented, the use of Amoxicap 250 by nursing mothers may lead to sensitisation, diarrhoea, candidiasis and skin rash in the infant.

DOSAGE AND DIRECTIONS FOR USE:
The total daily dose as below is administrated in divided doses. The most common regimen is 8 hourly.

ORAL ADMINISTRATION:
Treatment should be continued for 48 to 72 hours beyond the time that a clinical response has been obtained. It is recommended that at least 10 days treatment be given for any infection caused by beta-haemolytic streptococci to prevent the occurrence of acute rheumatic fever or glomerulonephritis.
The absorption of Amoxicap 250 is not affected significantly when taken with food.
Adults and children over 40 kg:
Total daily dosage of 750 mg to 3 g administered in divided doses
Maximum recommended dose: 6 g/day in divided doses
Respiratory tract infections: 500 mg administered 8 hourly.
Lyme disease: 4 g/day in isolated erythema chrionicum migrans and 6 g/day in the case of generalised manifestations, both for a minimum of 12 days.
Gonorrhoea: 3 g with 1 g probenecid
Eradication of Helicobacter pylori: 750 mg - 1 g in combination treatment given 12 hourly for the eradication of established H pylori infection associated with duodenal ulceration for seven days.

Children under 40 kg:
20 –50 mg/kg/day in divided doses
Maximum recommended dose: 150 mg/kg/day in divided doses
Lyme disease: 25 –50 mg/kg/day in isolated erythema chrionicum migrans and 100 mg/kg/day in the case of generalised manifestations, both for a minimum of 12 days

Elderly:
No adjustments needed: as for adults unless there is evidence of severe renal impairment (see below)

Renal Impairment:

Glomerular filtration rate	> 30 mL/min:	No adjustment needed
Glomerular filtration rate	10-30 mL /min:	Maximum 500 mg 12 hourly
Glomerular filtration rate	< 10 mL/min:	Maximum 500 mg daily

In patients receiving peritoneal dialysis: Maximum 500 mg daily

PROPHYLAXIS OF ENDOCARDITIS:
Prophylaxis with alternative antibiotics should be considered if the patient has received penicillin within the previous month or is allergic to penicillin.
For dental, oral or upper respiratory tract procedures:
Prophylaxis for patients undergoing dental extraction, scaling or surgery involving gingival tissues, tonsillectomy, adenoidectomy, bronchoscopy with a rigid bronchoscope and surgical procedures that involve respiratory mucosa.
For patients NOT having a general anaesthetic:
Adults: 2 g orally, 1 hour before the procedure
Children: 50 mg/kg, 1 hour before the procedure
Children’s dose not to exceed the adult dose.

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.
The following adverse reactions have been reported and may occur with Amoxicap 250.
Hypersensitivity reactions:
Skin rashes, pruritus and urticaria, serum sickness-like syndrome, erythema multiforme, rare cases of Stevens-Johnson syndrome, hypersensitivity vasculitis and less frequently bullous exfoliative dermatitis and toxic epidermal necrolysis have been reported. Whenever such reactions occur, Amoxicap 250 should be discontinued. Serious and occasional fatal hypersentivity (anaphylactic) reactions and angioneurotic oedema can occur with oral penicillin (see Warnings).
Interstitial nephritis can occur rarely.
Gastrointestinal reactions:
Nausea, vomiting, diarrhoea, gastritis, stomatitis, glossitis, black ‘hairy’ tongue, enterocolitis, mucocutaneous candidiasis and antibiotic-associated colitis (including pseudomembranous colitis and haemorrhagic colitis). If gastro-intestinal reactions are evident, they may be reduced by taking Amoxicap 250 at the start of a meal.
Hepatic effects:
Hepatitis and cholestatic jaundice have been reported. The events may be severe, and occur predominantly in adult or elderly patients. 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. The hepatic effects are usually reversible. However, in extremely rare circumstances, death has been reported. These have almost always been cases associated with serious underlying disease or concomitant medication.
A moderate raise in Aspartate transaminase (AST) and/or Alanine transaminase (ALT) has been noted in patients treated with Amoxicap 250, but the significance of these findings is unknown.
Renal effects:
Crystalluria has been reported.
Haematological effects:
Haemolytic anaemia, reversible thrombocytopenia, thrombocytopenic purpura, eosinophilia, reversible leucopoenia and agranulocytosis have been reported. 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 Amoxicap 250. Prolongation of bleeding time and prothrombin time have been reported less frequently. Appropriate monitoring should be undertaken when anticoagulants are prescribed concomitantly.
Nervous System:
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 especially with the suspension and chewable tablet formulations. It can usually be removed by brushing.
SPECIAL PRECAUTIONS:
Caution is needed when administering amoxycillin to patients with syphilis, as the Jarisch-Herxheimer reaction may occur in these patients.
When high doses are administered, adequate fluid intake and urinary output must be maintained.
The sodium content must be taken into account in patients on a sodium-restricted diet if the administration of high doses is necessary.
Periodic assessment of organ system functions, including renal, hepatic and haematopoietic function, is advisable during prolonged therapy. Since Amoxicap 250 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. Amoxicap 250 should be given with caution to patients with lymphatic leukaemia since they are especially susceptible to amoxycillin induced skin rashes.
The possibility of superinfections with mycotic or bacterial pathogens should be kept in mind during therapy. If superinfections occur, 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 Amoxicap 250. 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 Amoxicap 250 dosage should be adjusted. (See Dosage and Directions for use).
Use in lactation:
Amoxycillin is excreted in the milk. Therefore, caution should be exercised when Amoxicap 250 is administered to a nursing woman.
The use of Amoxicap 250 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:
Overdosage with Amoxicap 250 is usually asymptomatic. However, gastrointestinal effects such as nausea, vomiting and diarrhoea may be evident and symptoms of water and electrolyte imbalance should be treated symptomatically.
Adequate fluid intake and urinary output must be maintained to minimise the possibility of crystalluria.
Amoxicap 250 may be removed from the circulation by haemodialysis.

IDENTIFICATION:
A scarlet and grey capsule with “AX250”on one end and “HD”on the other end printed in black ink.

PRESENTATION:
PVC Blister strips of 10 capsules in a pack of 100 in a unit carton.
Opaque plastic bottles containing 100, 500 and 1000 capsules

STORAGE INSTRUCTIONS:
Store below 25ºC. Protect from light. Do not remove the blisters from the carton until required for use.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBER (OR REFERENCE NUMBER):
37/20.1.2/0446

NAME AND BUSINESS ADDRESS OF THE HOLDER OF THE CERTIFICATE OF REGISTRATION:
Gulf Drug Company (Pty) Ltd
22 Burnside Drive
Old Mill Industrial Park
Mount Edgecombe
4300

DATE OF PUBLICATION OF THE PACKAGE INSERT:
18 March 2005

New addition to this site: July 2010
Source: Pharmaceutical Industry
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