APEN 500 (capsules); APEN S (syrup)

INDICATIONS CONTRA-INDICATIONS DOSAGE SIDE-EFFECTS PREGNANCY OVERDOSE IDENTIFICATION PATIENT INFORMATION

APEN 500 (capsules)
APEN S (syrup)

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

APEN 500 (capsules)
APEN S (syrup)

COMPOSITION:
Ampicillin trihydrate B.P. and cloxacillin sodium B.P. available as:
APEN 500 –Gelatin capsules containing the equivalent of 250 mg ampicillin and 250 mg cloxacillin.
APEN S –Powder for preparing a fruit-flavoured suspension. When dispensed as directed each 5 mL of the suspension contains the equivalent of 125 mg ampicillin and 125 mg cloxacillin. The powder contains 0,13% m/m sodium benzoate B.P. as a preservative.

PHARMACOLOGICAL CLASSIFICATION:
A.20.1.2 Penicillins

PHARMACOLOGICAL ACTION:

(a)	Bacteriology APEN exhibits in vivo and in vitro bactericidal activity against some Gram-positive and Gram-negative organisms, in vitro sensitivity does not necessarily imply in vivo efficacy.
(b)	Absorption Both ampicillin and cloxacillin are acid stable and well absorbed orally, giving peak serum levels two hours after dosing. As there is a linear dose/response in peak serum levels after oral administration of both components, doubling the dose virtually doubles the peak serum levels.
(c)	Excretion Both components are excreted primarily by the kidneys by glomerular filtration and tubular secretion. Bile: Bile concentrations of APEN vary from 3 to 48 times the serum concentration, according to the condition of the biliary tract.
(d)	Probenecid Higher APEN serum levels can be achieved in patients with normal renal function by the concurrent administration of a renal blocking agent such as probenecid. In adults, a dose of 500 mg of probenecid four times daily will result in 1,5 - 2 fold increase in APEN serum levels.

INDICATIONS:
Infections caused by susceptible organisms where a mixed infection is present and includes penicillin-resistant staphylococci.

CONTRA-INDICATIONS:
Allergy to penicillins is an absolute contra-indication to the use of APEN. APEN must not be used in the eye either subconjunctivally or locally.

DOSAGE AND DIRECTIONS FOR USE:
The average adult dose for APEN is 2 - 4 g per day. In severe infections, dosages may be safely increased.
Adults and children over 10 years: 500 mg - 1 g (1 - 2 x 500 mg capsules) every 6 hours.
Children 2 - 10 years: 250 - 500 mg (5 - 10 mL of 250 mg/5 mL syrup) every 6 hours.
Children up to 2 years: 250 mg (5 mL of 250 mg/5 mL syrup) every 6 hours.
Note:

(1)	Best results are obtained if dosages are administered half to one hour prior to meals.
(2)	Patients with renal insufficiency may require a reduced dosage.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Ampicillin
The most common adverse effects associated with penicillins are allergic reactions. Of these, skin rashes occur most frequently and are either urticarial or maculopapular. The incidence of this occurring is especially high in patients suffering from mononucleosis.
Patients with lymphatic leukaemia and patients with hyperuricaemia being treated with allopurinol may also be at increased risk of developing skin rashes. Administration of penicillins to a hypersensitive patient may occasionally result in anaphylactic shock with collapse and sometimes death. Angioedema or bronchospasm may also occur.
Gastro-intestinal adverse effects particularly diarrhoea, nausea and vomiting occur quite frequently.
Pseudomembranous colitis has also been reported. Supra-infections with non-susceptible organisms may occur particularly with prolonged use. Renal and haematological systems should be monitored during prolonged high dose therapy. Jarisch-Herxheimer's reaction may occur when treating patients with syphilis.
Ampicillin may decrease the efficacy of oestrogen containing oral contraceptives and it may also affect the absorption of other drugs due to ifs effect on gastro-intestinal flora.
The use of this antibiotic may lead to the appearance of resistant strains of organisms and sensitivity testing should therefore be carried out whenever possible, to ensure the appropriateness of the therapy.
Cloxacillin
As for ampicillin, see above.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
No known symptoms of overdosage.
As with all penicillins, oral administration of APEN can cause gastro-intestinal symptoms such as transient diarrhoea, nausea and colic which are dose related and a result of local irritation, not toxicity.

IDENTIFICATION:
APEN 500: Grey/Aubergine capsules imprinted "Apen 500".
APEN S: Free-flowing off-white powder. Ivory suspension.

PRESENTATION:
APEN 500: Glass bottles containing 20 or 100 capsules.
APEN S: Glass bottles containing powder for the preparation of 100 mL of suspension.

STORAGE INSTRUCTIONS:
Containers of APEN should be kept tightly closed in a cool, dry place (below 25°C). Once reconstituted, APEN S should be used within 7 days if stored in a cool place (below 25°C), or 14 days if stored in a refrigerator (5°C).
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBERS:
APEN 500: 27/20.1.2/0108
APEN S: 27/2012/0109

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
XIXIA Pharmaceuticals (Pty) Ltd
15 Thora Crescent,
Wynberg Ext. 3,
Sandton
P.O. Box 2080, Gallo Manor, 2052

DATE OF PUBLICATION OF THIS PACKAGE INSERT:

4 May 1993

P1334