INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
AMPICLOX 500 (capsules)
AMPICLOX S (syrup)
AMPICLOX 500 I (injection)
AMPICLOX 75 I (neonatal injection)
AMPICLOX D (neonatal drops)

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

AMPICLOX 500 (capsules)
AMPICLOX S (syrup)
AMPICLOX 500 I (injection)
AMPICLOX 75 I (neonatal injection)
AMPICLOX D (neonatal drops)

COMPOSITION:
(a) Oral:
Ampicillin trihydrate B.P. and cloxacillin sodium B.P. available as:

AMPICLOX 500	:	Gelatin capsules containing the equivalent of 250 mg ampicillin and 250 mg cloxacillin.
AMPICLOX S	:	Powder for preparing 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 of sodium benzoate B.P. as a preservative.
AMPICLOX D	:	Powder for preparing neonatal drops. When dispensed as directed, each 0,6 mL of the suspension contains the equivalent of 60 mg ampicillin and 30 mg cloxacillin. The powder contains 0,525% m/m sodium benzoate B.P. as a preservative.

(b) Parenteral
Ampicillin sodium B P. and cloxacillin sodium B.P. available as:

AMPICLOX 75 I	:	Sterile powder for preparing the equivalent of 50 mg ampicillin and 25 mg cloxacillin per neonatal vial.
AMPICLOX 500 I	:	Sterile powder for preparing the equivalent of 250 mg ampicillin and 250 mg cloxacillin per vial.

PHARMACOLOGICAL CLASSIFICATION:
A.20.1.2 Penicillins

PHARMACOLOGICAL ACTION:
(a) Bacteriology:
AMPICLOX exhibits in vivo and in vitro bactericidal activity against Gram-positive and Gram-negative organisms.
In vitro sensitivity does not necessarily imply in vivo activity.

(b) Absorption:
Both ampicillin and cloxacillin are acid stable and well absorbed orally, giving peak serum levels about two hours after dosing. As there is a linear dose/response in peak serum level 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 AMPICLOX vary from 3 –48 times the serum concentration, according to the condition of the biliary tract.

(d) Probenecid:
Higher AMPICLOX 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 q.d.s. will result in 1,5 –2 fold increase in AMPICLOX serum levels.

INDICATIONS:
The use of this antibiotic may lead to the appearance of resistant strains of organisms and sensitivity resting should, therefore, be carried out wherever possible, to ensure the appropriateness of the therapy.
Infections caused by susceptible organisms where a mixed infection is present and includes penicillin-resistant staphylococci.

CONTRA-INDICATIONS:
Known allergy to penicillin or cephalosporins. Cases of cross sensitivity have been reported.
Babies born of hypersensitive mothers in the neonatal period.
The oral dosage forms are not recommended for chronic, severe, or deep-seated infections such as subacute bacterial endocarditis, meningitis or syphilis. AMPICLOX should not be administered by sub-conjunctival injection or used as an eye drop as it contains cloxacillin.

WARNINGS:
When administered to a patient with penicillin allergy anaphylactic shock may occur. Adrenaline, corticosteroids and antihistamines should be used to treat anaphylaxis. Use with caution in patients with a known history of allergy.
Because of the variability in intestinal absorption of cloxacillin containing products, oral administration is not a suitable substitute for the parenteral route in treatment of severe infections.

DOSAGE AND DIRECTIONS FOR USE:
The average adult dose for AMPICLOX is 2 –4g per day. In severe infections, dosages may be safely increased.

(i) ORAL:

Adults and children over 10	:	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.
Neonates	:	90 mg (0,6 mL i.e. to mark on pipette) every 4 hours.

Note: Best results are obtained if dosages are administered half to one hour prior to meals or at least two hours after meals.

(ii) PARENTERAL

Adults and children over 10	:	500 mg –1 g intravenously or intramuscularly every 4 – 6 hours or as dictated by the severity of the infection.
Children 2 –10 years*	:	Half the adult dose.
Children up to 2 years*	:	Quarter the adult dose.
Neonates*	:	75 mg (i.e. 1 neonatal vial) every 8 hours.

* These dosages should correspond to a daily dosage of 50 –150 mg/kg.
Note: Patients with renal insufficiency may require a reduced dosage.

DIRECTIONS FOR USE:
Intramuscular injection:

500 mg vial	–	add 1,5 mL of Water for Injections B.P. and shake vigorously.
75 mg vial	–	add 0,5 –1,0 mL of Water for Injections B.P. and shake vigorously.

Intravenous injection:
Normally given by slow intravenous injection.

500 mg vial	–	dissolve in 10 mL of Water for Injections B.P. by first dissolving the contents of the vial in approximately 3 mL of the Water for Injections B.P. and then withdrawing the dissolved contents into a 10 mL syringe containing the remaining Water for Injections B.P.
75 mg vial	–	dissolve in 5 mL of Water for Injections B.P.

Intravenous infusion:
Vial contents should be dissolved in a suitable volume of fluid and given as a rapid intravenous infusion over 30 minutes or suitably diluted into the drip tubing. Solutions must be used within 30 minutes of preparation.

Compatibility:
AMPICLOX injectable is compatible with commonly used intravenous fluids including: normal saline, 5% dextrose, dextrose saline, M/6 sodium lactate, Ringer's solution, 1,4% sodium bicarbonate, Dextran 40 injection in normal saline.

Incompatibility:
AMPICLOX should not be added to infusion bottles containing Dextran 40 injection in 5% dextrose, but may be injected into the drip tubing of such an infusion. Cloxacillin has been reported to be incompatible with aminoglycosides, tetracyclines, and other antimicrobial agents including erythromycin and polymyxin B sulphate.
Should not be mixed with blood products or other proteinaceous fluids.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
AMPICLOX may produce diarrhoea, nausea and heartburn. Allergic reactions which may include exfoliative dermatitis, other skin rashes, interstitial nephritis and vasculitis may occur. In this event, withdrawal of AMPICLOX and administration of an antihistamine will suffice in most cases. Should a serious anaphylactic reaction occur. AMPICLOX should be discontinued and the patient treated with the usual agents (adrenalin, corticosteroids or antihistamines).
A generalised sensitivity reaction with urticaria, fever, joint pains and eosinophilia can develop within a few hours to several weeks after starting treatment.
Superinfections by resistant species, such as Pseudomonas or Candida, which do not respond to penicillin therapy may occur.
A sore mouth or tongue and a black hairy tongue have been reported.
Increase in liver enzyme values have been reported.
Care should be taken when high doses are given to patients with renal impairment (because of the risk of neurotoxicity) or congestive heart failure. Renal and haematological systems should be monitored during prolonged and high dose therapy.
Care should be taken when treating patients with syphilis, as the Jarisch-Herxheimer reaction may occur shortly after starting treatment. This reaction, manifesting as fever, chills, headache and reactions at the site of the lesion, can be dangerous in cardiovascular syphilis or where there is a serious risk of increased local damage such as with optic atrophy.
Haemolytic anaemia and leucopenia, prolongation of bleeding time and detective platelet function have been observed usually following high intravenous doses. Convulsions and other signs of toxicity to the CNS may occur particularly with intravenous administration or in patients with renal failure.
Intrathecal administration of penicillins is not recommended, because it is a potent convulsant when given by this route.
AMPICLOX contains ampicillin and should preferably not be given to patients with infectious mononucleosis, lymphatic leukaemia and patients receiving allopurinol treatment because of an increased risk of developing skin rashes.
AMPICLOX may decrease the efficacy of oestrogen-containing oral contraceptives.
AMPICLOX contains cloxacillin sodium, therefore disturbances of blood electrolytes may follow the administration of large doses.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
See Side-Effects and Special Precautions. Treatment is symptomatic and supportive.

IDENTIFICATION:

(a)	AMPICLOX 500	:	Amethyst/black capsules overprinted "AMPICLOX 500".
(b)	AMPICLOX S	:	Free-flowing off-white powder. White suspension.
(c)	AMPICLOX D	:	Free-flowing, off-white powder. White suspension.
(d)	AMPICLOX 75 I	:	White powder. Clear solution.
(e)	AMPICLOX 500 I	:	White powder. Clear solution.

PRESENTATION:

(a)	AMPICLOX 500	:	Glass bottles containing 20 or 100 capsules.
(b)	AMPICLOX S	:	Glass bottles containing powder for reconstitution of 100 mL of suspension.
(c)	AMPICLOX D	:	Glass bottles containing powder for reconstitution of 8 mL of suspension. Each bottle is supplied with a pipette.
(d)	AMPICLOX 75 I	:	Glass vials in packs of 5.
(e)	AMPICLOX 500 I	:	Glass vials in packs of 5.

STORAGE INSTRUCTIONS:
Containers of AMPICLOX 500 should be kept tightly closed in a cool (below 25°C), dry place.
AMPICLOX S, AMPICLOX D, AMPICLOX 75 I and AMPICLOX 500 I preparations should be stored in a cool (below 25°C), dry place.
Once reconstituted AMPICLOX 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).
Once reconstituted, AMPICLOX D should be used within 2 days if stored in a cool place (below 25°C) or within 7 days if stored in a refrigerator (5°C).
Once prepared, AMPICLOX 500 I and AMPICLOX 75 I must be used immediately.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBERS:

AMPICLOX 500	:	B/20.1.2/57
AMPICLOX S	:	E/20.1.2/6
AMPICLOX 500 I	:	B/20.1.2/45
AMPICLOX 75 I	:	A/20.1.2/616
AMPICLOX D	:	A./20.1.2/612

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
SmithKline Beecham Pharmaceuticals (Pty) Ltd
39 Hawkins Avenue
Epping Industria 1
Cape Town
7460

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
02.09.1994

AMPICLOX and theSB logo are trademarks.

P2209
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