MACROPEN 500 (capsules); MACROPEN S (syrup)

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

MACROPEN 500 (capsules)
MACROPEN S (syrup)

SCHEDULING STATUS:
S4

PROPRIETARY NAMES
(and dosage form):

MACROPEN 500 (capsules)
MACROPEN S (syrup)

COMPOSITION:
MACROPEN 500 - Gelatine capsules containing Amoxycillin trihydrate equivalent to 250 mg Amoxycillin and Flucloxacillin sodium equivalent to 250 mg Flucloxacillin.
MACROPEN S - Powder for preparing a fruit-flavoured syrup. When dispensed as directed each 5 mL contains Amoxycillin trihydrate equivalent to 125 mg Amoxycillin and Flucloxacillin sodium equivalent to 125 mg Flucloxacillin. The powder contains 0,13% m/m sodium benzoate as a preservative.

PHARMACOLOGICAL CLASSIFICATION:
A.20.1.2 Penicillins

PHARMACOLOGICAL ACTION:

(a)	Bacteriology
	MACROPEN exhibits in vitro and in experimental animals in vivo, bactericidal activity against some Gram-positive and Gram-negative bacteria.
	In vitro sensitivity does not necessarily imply in vivo efficacy.
(b)	Absorption
	MACROPEN is well absorbed orally. Peak serum levels are achieved 1 to 2 hours after dosing.
(c)	Excretion
	Approximately 50% of the dose is excreted unchanged into the urine within 6 hours, resulting in high urine levels of active drug.

INDICATIONS:
MACROPEN is indicated for the treatment of bacterial infections, caused by susceptible organisms; in particular infections of mixed origin where penicillin-resistant staphylococci may be implicated.

CONTRA-INDICATIONS:
MACROPEN should not be given to those subjects hypersensitive to penicillin. As there is currently no neonatal formulation MACROPEN should not be given to neonates.

DOSAGE AND DIRECTIONS FOR USE:
Adults: One 500 mg capsule three times a day.
Children 2 - 12: 5 mL of syrup (containing 250 mg MACROPEN) three times a day.
Children under 2: 2,5 mL of syrup (containing 125 mg MACROPEN) three times a day.
Neonates: No formulation is available at present.
In severe infections these dosages may be increased
To ensure maximal absorption MACROPEN should be given in the fasting state, i.e. approximately 1 hour before a meal.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Amoxycillin
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 reaction may occur when treating patients with syphilis. Amoxycillin may decrease the efficacy of oestrogen-containing oral contraceptives and it may also affect the absorption of other drugs due to its 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.
Flucloxacillin
As for Amoxycillin, see above. Cholestatic hepatitis has been reported rarely.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
No known symptoms of overdosage.
As with all penicillins, oral administration 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:

MACROPEN 500:	Light grey/dark grey capsules imprinted "Macropen 500".
MACROPEN S:	Free-flowing off-white powder. Yellow syrup.

PRESENTATION:

MACROPEN 500:	Glass bottles containing 15 or 100 capsules.
MACROPEN S:	Glass bottles containing powder for the preparation of 100 mL of 250 mg/5 mL syrup.

STORAGE INSTRUCTIONS:
Containers should be kept tightly closed in a cool, dry place (below 25°C). Once dispensed, MACROPEN S must 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:

MACROPEN 500:	27/20.1.2/0106
MACROPEN S:	27/20.12/0107

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

DATE OF PUBLICATION OF THIS PACKAGE INSERT:

29 January 1993

P1329