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

Logo AMOXIL 250 (capsules)
AMOXIL 500 (capsules)
AMOXIL S (syrup)
AMOXIL SF (syrup)
AMOXIL D (paediatric drops)
AMOXIL 250 I (injection)
AMOXIL 500 I (injection)

SCHEDULING STATUS
S4

PROPRIETARY NAME
(and dosage form)

AMOXIL 250 (capsules)
AMOXIL 500 (capsules)
AMOXIL S (syrup)
AMOXIL SF (syrup)
AMOXIL D (paediatric drops)
AMOXIL 250 I (injection)
AMOXIL 500 I (injection)

COMPOSITION:
(a) Oral   Amoxycillin trihydrate B.P. available as:
  Amoxil 250 –– Gelatin capsules containing the equivalent of 250 mg amoxycillin.
  Amoxil 500 –– Gelatin capsules containing the equivalent of 500 mg amoxycillin.
  Amoxil S –– Powder for preparing a fruit flavoured syrup. When reconstituted as directed, each 5 mL of the suspension contains the equivalent of 125 mg amoxycillin. The powder contains 0,295% m/m sodium benzoate B.P. as a preservative.
  Amoxil SF –– Powder for preparing a fruit-flavoured syrup. When reconstituted as directed, each 5 mL of the suspension contains the equivalent of 250 mg amoxycillin. The powder contains 0,295% m/m sodium benzoate B.P. as a preservative.
  Amoxil D –– Powder for preparing a fruit flavoured suspension of paediatric drops. When dispensed as directed each 1,25 mL of the suspension, as measured by the pipette provided, contains the equivalent of 125 mg amoxycillin. The powder contains 0,27 % m/m sodium benzoate B.P. as a preservative.
(b) Parenteral –– Amoxycillin sodium available as:
  Amoxil 250 I –– Sterile powder for preparing the equivalent of 250 mg amoxycillin.
  Amoxil 500 I –– Sterile powder for preparing the equivalent of 500 mg amoxycillin.

PHARMACOLOGICAL CLASSIFICATION:
A 20.1.2 Penicillins

PHARMACOLOGICAL ACTION:
(a)        Bacteriology:
  (i)        Spectrum
    Amoxycillin is a penicillinase-susceptible penicillin. Amoxycillin exhibits in vitro, bactericidal activity against a wide range of Gram-negative and Gram-positive organisms including:

Gram-positive bacteria Gram-negative bacteria
Staphylococcus aureus (penicillin*-sensitive) Neisseria gonorrhoea*
Streptococcus pyogenes Neisseria meningitidis
Streptococcus viridans* Haemophilus influenzae**
Streptococcus faecalis Bordetella pertussis
Diplococcus pneumoniae* Escherichia coli*
Corynebacterium species* Salmonella typhi
Clostridium species* Salmonella species
Bacillus anthracis* Shigella species
  Proteus mirabilis
  Brucella species
*         Sensitivity tests must be performed,
**        except type b-strains causing meningitis in children.

  (ii)        Bactericidal Action
    Amoxycillin exerts a rapid bactericidal activity at normal dosage levels against all susceptible organisms.

(b)        Absorption
  Amoxycillin is extremely well absorbed orally. A single 250 mg oral dose achieves an average peak serum level virtually equal to that achieved by IM injection viz. 5,3 µg/mL oral and 5,6 µg/mL IM. The peak serum level is achieved within 1,5 ––2 hours after oral and 15 minutes after IM or IV administration.
  After oral administration, there is no significant difference between the peak serum levels in fasting and non-fasting subjects. The presence of food does not interfere with the absorption of Amoxil. Amoxil may, therefore, be taken with meals.
  There is a linear/dose response in peak serum levels after both oral and parenteral administration.
(c)        Distribution
  (i) Sputum: The concentration of amoxycillin in sputum does not decrease as occurs with ampicillin as purulence subsides.
  (ii) Bile: Amoxil is present in bile obtained from a common bile duct drain of a healthy gall-bladder, however, biliary levels are lower when the gall-bladder is diseased and absent in the presence of biliary tract obstruction. 
  (iii) Urine: the average concentration of Amoxil in urine collected during the first six hours after 250 mg oral dose, is 580 mg/mL. 
(d)        Excretion
  (i) Renal: Approximately 60% of an oral dose of Amoxycillin is excreted unchanged in the active form into the urine within six hours. Approximately 70% - 80% of an intramuscular dose and 90% of an intravenous dose is excreted unchanged in the active form, into the urine within 12 hours.
  (ii) Biliary: A variable percentage of Amoxil is excreted into the bile.
(e)        Probenecid
  Even higher Amoxil serum levels may be achieved after oral administration to patients with normal renal function, by the simultaneous administration of a renal blocking agent such as probenecid. Probenecid should not be given in the presence of abnormal renal function. No data on the effect of probenecid on parenteral Amoxil are yet available.

INDICATIONS:
Infections caused by susceptible, non-penicillinase-producing organisms including:

Upper respiratory tract infections Lower respiratory tract infections
Otitis media Typhoid Fever
Upper urinary tract infections Lower urinary tract infections
Skin and soft tissue infections Gastro-intestinal tract infections
Gonorrhoea Non-specific urethritis

CONTRA-INDICATIONS:
Allergy to penicillins or any of the cephalosporins is an absolute contra-indication to the use of Amoxil.

WARNINGS:
Serious and occasionally fatal hypersensitivity (anaphylactoid) reactions have been reported in patients on penicillin therapy. Although anaphylaxis is more frequent following parenteral therapy, it has occurred in patients on oral penicillins. Before commencing therapy with any penicillin, careful inquiry should be made concerning previous hypersensitivity reactions to penicillins, cephalosporins, or other allergies.
If an allergic reaction occurs, appropriate therapy should be instituted and amoxycillin therapy discontinued.
There is insufficient evidence at present to show that Amoxil penetrates into the cerebro-spinal fluid in therapeutic quantities and it should, therefore, not be used in the treatment of cerebro-spinal infections.

DOSAGE AND DIRECTIONS FOR USE:
The average adult dose for Amoxil is 750 mg ––1,5 g/day, but in serious infections up to 6 g daily has been administered.
(a) General dosages:
  (i) Oral
    Adults: 250 mg ( 1 x 250 mg capsule or 5 mL of 250 mg/5 mL syrup) three times a day.
    *Children 2 ––10 years: 125 mg (5 mL of 125 mg/5 mL syrup) three times a day.
    *Children 6 months ––2 years: 125 mg (one full pipette of paediatric suspension or 5 mL of 125 mg/5 mL syrup) three times a day.
    *Infants 0 ––6 months: 62,5 mg (half pipette measure of paediatric suspension) three times a day.
    *Premature infants 1,0 ––2,5 kg: 30,0 ––62,5 mg (quarter to half pipette measure of paediatric suspension) once daily for the first 1 ––2 weeks depending on the size and maturity of the infant, thereafter dose may be given 2 ––3 times daily.
    In severe infections these dosages may be increased.
  (ii) Parenteral
    Adults: Mild to moderate infections: 250 mg ––500 mg IV or IM three times a day.
    Severe infections: 500 mg ––2 g IV 4 ––6 times a day.
    In particularly severe infections doses of up to 3 g may be administered by rapid intravenous infusion over a period of 30 minutes. This may be repeated every four hours.
    Children 2 ––10 years: Half the adult dose. *
    Children up to 2 years: Quarter the adult dose. *
    * This should correspond to a daily dosage of 35 ––100 mg/kg.
NOTE:
(1) Patients with renal insufficiency may possibly require a reduced dose.
(2) During treatment with high doses of Amoxil particularly by bolus injection an adequate fluid intake and urinary output must be maintained. Indwelling catheters should be checked regularly for potency since at room temperature high urinary concentration of Amoxil may precipitate out of solution.

DIRECTIONS FOR PARENTERAL USE:
On dissolution of the powder, a transient colour change (red to purple) may be seen before a clear solution is obtained. The more concentrated IM solutions will be a pale yellow colour and may show slight opalescence.

Intramuscular injections:
Amoxil
by intramuscular injection is always painful. If deemed necessary, the transient pain can be reduced by the use of 0,5% procaine solution as a diluent.
250 mg vial ––add 1,5 mL Water for Injections B.P. and shake vigorously.
500 mg vial ––add 2,5 mL Water for infections B.P. and shake vigorously.

Intravenous Injections:
Normally given as a bolus injection every 30 seconds (half a minute).
250 mg vial ––dissolve in 10 mL Water for Injections B.P.
500 mg vial ––dissolve in 10 mL Water for Injections B.P.

Intravenous Infusion:
3 g should be dissolved in 50 mL Water for Injections B.P. and given as a rapid intravenous infusion over 30 minutes (half an hour).
Solutions must be used within half an hour after preparation.
When reconstituted at the recommended dilutions, sodium amoxycillin is stable in most commonly used infusion fluids at ambient temperature. It is relatively less stable in solutions containing sugars.

Compatibility:
Amoxil
injections are compatible with commonly used intravenous fluids including: sodium chloride, Ringer's solution, sodium lactate, compound lactate, 5% dextrose and sodium chloride plus 4% dextrose.
Intramuscular Injection of Amoxil is compatible with 0,5% procaine solution and with a 1% lignocaine solution.

Incompatibility:
Amoxil
should not be added to infusion bottles containing proteinaceous fluids such as protein hydrolysates, intravenous lipid emulsions, blood or plasma.

Specific dosages: (oral or parenteral)

Indications Daily Dosages* Duration
  Adults Children 
Gastro-intestinal tract infections 1 ––2 g –– 4 ––5 days
Acute Typhoid Fever 4 g –– 14 days
  –– 100 mg/kg 21 days
Gonorrhoea 2 ––3 g –– Stat
* Either oral or parenteral administration.

SIDE EFFECTS AND SPECIAL PRECAUTIONS:
Precautions:
Allergic reactions presenting as a skin rash, pruritus and urticaria have been reported less frequently. Other reactions including angio-oedema, anaphylaxis, erythema multiforma, Stevens-Johnson syndrome and exfoliative dermatitis may occur in exceptional cases. If a skin rash occurs, treatment should be discontinued. In the event of an anaphylactic reaction, immediate treatment with adrenalin, oxygen, corticosteroids and antihistamines should be initiated.

Blood:
Blood dyscrasias have been reported less frequently. These reactions are usually reversible on discontinuation of therapy and are believed to be hypersensitivity phenomena.

Liver:
A moderate rise in SGOT and for SGPT has been reported in exceptional cases.
At high doses of parenteral Amoxil, caution must be exercised in treating patients with dehydration or oliguria because of the possibility of cristalluria.
The use of this antibiotic may lead to the appearance of resistant strains of organisms and sensitivity testing should, therefore be carried out wherever possible, to ensure the appropriateness of the therapy.
Gastro-intestinal disturbance including diarrhoea, nausea and vomiting have been reported. Pseudo-membranous colitis has been reported, if this condition occurs, treatment should be discontinued and appropriate therapy, e.g. vancomycin, should be initiated.
The dose should be reduced in patients with renal failure. Periodic assessment of renal, hepatic, and haematopoietic function should be made during prolonged therapy. Prolonged use may also occasionally result in overgrowth of non-susceptible organisms
Amoxycillin should preferably not be used in patients with infectious mononucleosis and should also be used with caution in patients glandular fever, lymphatic leukaemia, and patients treated with allopurinol since they are especially susceptible to ampicillin-induced skin rashes.
Due to Amoxycillin's effect on intestinal flora, the absorption of other medicine may be affected. Amoxycillin may reduce the efficacy of oral contraceptives and patients should be warned accordingly.
The absorption of concurrently administered digoxin may be increased during treatment with Amoxycillin.
Caution is needed when administering Amoxycillin to patients with syphilis, as the Jarisch-Herxheimer reaction may occur in these patients

Pregnancy and Lactation:
Animal reproduction studies have failed to demonstrate a risk to the foetus. There are no adequate and well controlled studies in pregnant women.
Amoxil is excreted in breast milk, and should be used with caution when administered to lactating women.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
If encountered, gastro-intestinal symptoms and disturbance of the fluid and electrolyte balance may be evident. They may be treated symptomatically and supportive with attention to the water/electrolyte balance. In the absence of an adequate fluid intake and urinary output, crystalluria is a possibility and the antibiotic may be removed from the circulation by haemodialysis.
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:
Amoxil 250 –– Pink/blue capsules overprinted "Amoxil 250".
Amoxil 500 –– Pink/blue capsules overprinted "Amoxil 500".
Amoxil S –– Free-flowing, off-white powder. Yellowish suspension.
Amoxil SF –– Free-flowing, off-white powder. Yellowish suspension.
Amoxil D –– Free-flowing, off-white powder. Yellowish suspension.
Amoxil 250 I –– White powder. Clear solution.
Amoxil 500 I –– White powder. Clear solution.
N.B. Amoxil 250 I and Amoxil 500 I: On dissolution of the powder a transient colour change (red to purple) may be seen before a clear solution is obtained. The more concentrated IM solutions are pale yellow and opalescent.

PRESENTATION:
Amoxil 250 –– Securitainers containing 15, 100 or 500 x 250 mg amoxycillin capsules.
Amoxil 500 –– Securitainers containing l5 or 100 x 500 mg amoxycillin capsules.
Amoxil S –– Bottles containing powder for reconstitution to 100 mL of 125 mg/5 mL syrup.
Amoxil SF –– Bottles containing powder for reconstitution to 100 mL of 250 mg/5 mL syrup.
Amoxil D –– Bottles containing powder for reconstitution to 20 mL of suspension of paediatric drops. Each bottle is supplied with a pipette.
Amoxil 250 I –– Vials containing sterile powder for the preparation of a single dose 250 mg amoxycillin in packs of 5 vials.
Amoxil 500 I –– Vials containing sterile powder for the preparation of a single dose of 500 mg amoxycillin in packs of 5 vials.

STORAGE INSTRUCTIONS
Containers of Amoxil 250 and Amoxil 500 should be kept tightly closed in a cool (below 25°C), dry place.
Once dispensed, Amoxil S and Amoxil SF must be used within 14 days and stored in a cool place (below 25°C), preferably in a refrigerator (5°C). Once dispensed, Amoxil D must be used within 14 days and stored in a cool place (below 25°C), preferably in a refrigerator (5°C).
Vials of Amoxil 250 I and Amoxil 500 I are stable for 24 months if stored in a cool (below 25°C), dry place. Once reconstituted, the contents must be used within 30 minutes.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBERS:
Amoxil 250 –– E/20.1.2/276
Amoxil 500 –– G/20.1.2/66
Amoxil S –– E/20.1.2/75
Amoxil SF –– J/20.1.2/29
Amoxil D –– E/20.l.2/119
Amoxil 250 I –– K/20.1.2/38
Amoxil 500 I –– K/20.1.2/39

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
SmithKline Beecham Pharmaceuticals (Pty) Limited
6 Carey Street, Wynberg Ext. 6, Johannesburg 2090.

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
16.10.1992

Amoxil and the SB logo are trademarks.

P0690

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