Product information

PRODUCT INFORMATION
ACHROMYCIN
DESCRIPTION
Composition ACHROMYCIN

Tetracycline HCl is a broad spectrum antibiotic isolated from Streptomyces aureofaciens. It
is a yellow, crystalline, hygroscopic powder soluble 1 in 10 parts of water.
CLINICAL PHARMACOLOGY
Tetracycline is rapidly but incompletely absorbed from the stomach and small intestine.
Absorption is impaired by administration with food, milk, antacids and di- and trivalent
cations.
A single dose of 250 mg produces a peak serum level of 1-2 mg/L in 2-4 hours. The
administration of 250 mg every 6 hours for 24 hours produces a peak plasma concentration of
approximately 3 mg/L. The administration of 500 mg every 6 hours produces serum levels of
4-5 mg/L. Doses larger than 500 mg every 6 hours usually do not result in higher serum
levels, due to diminished absorption.
Most of the absorbed dose of tetracycline is eliminated unchanged in urine and bile. The
remainder, a relatively small amount, is metabolised in the liver. Urinary excretion accounts
for approximately 20% of the orally administered dose; the unabsorbed fraction is excreted in
the faeces.
The protein binding of tetracycline ranges from 24 to 64%.
MICROBIOLOGY AND INDICATIONS
The tetracyclines are primarily bacteriostatic and are thought to exert their antimicrobial
effect by the inhibition of protein synthesis.
Tetracyclines are active against a wide range of Gram-negative and Gram-positive organisms.
The drugs in the tetracycline class have similar antimicrobial spectra and cross resistance
among them is common.
Indications: Tetracycline hydrochloride is indicated in infections caused by the following
micro organisms: Rickettsiae (Rocky Mountain spotted fever, typhus fever and the typhus
group, Q fever, rickettsial pox, tick fever). Mycoplasma pneumoniae (PPLO, Eaton agent).
Agents of psittacosis. Agents of lymphogranuloma venereum and granuloma inguinale. The
spirochaetal agent of relapsing fever (Borrelia recurrentis).
The following Gram-negative micro organism: Haemophilus ducreyi (chancroid),
Pasteurella pestis and Pasteurella tularensis, Bartonella bacilliformis, Bacteroides species.
Vibrio comma an Vibrio foetus. Brucella species (in conjection with streptomycin).
Because many strains of the following groups of micro organisms have been shown to be
resistant to tetracyclines, culture and susceptibility testing are recommended prior to initiation
of therapy.
Tetracycline may be used for treatment of infections caused by the following Gram-negative
micro organisms only when bacteriological testing indicates appropriate susceptibility to the
drug: Escherichia coli, Enterobacter aerogenes (formerly Aerobacter aerogenes), Shigella
species, Mima species and Herellea species, Haemophilus influenzae (respiratory infections),
Klebsiella species (respiratory and urinary infections).
Tetracycline may be used for the treatment of infections caused by the following Gram-
positive micro organisms when bacteriological testing indicates appropriate susceptibility to
the drug:
Streptococcus species: Up to 44% of strains of Streptococcus pyogenes and 74% of
Streptococcus faecalis have been found to be resistant to tetracyclines. Therefore,
tetracycline should not be used for streptococcal disease unless the organism has been
demonstrated to be sensitive For upper respiratory infection due to group A β-haemolytic
streptococci (Streptococcus pyogenes), penicillin is the usual drug of choice, including
prophylaxis of rheumatic fever. Streptococcus pneumoniae, Staphylococcus aureus in skin
and soft tissue infections.
Tetracyclines are not the drug of choice in the treatment of any type of staphylococcal
infection.
When penicillin is contraindicated, tetracyclines are alternative drugs in the treatment of
infections due to: Treponema pallidum and Treponema pertenue (syphilis and yaws), Listeria
monocytogenes, Clostridium species, Bacillus anthracis, Fusobacterium fusiforme (Vincent's
infection), Actinomyces species.
In acute intestinal amoebiasis, the tetracyclines may be a useful adjunct to amoebicides. In
severe acne, the tetracyclines may be useful adjunctive therapy.
Tetracycline is indicated in the treatment of trachoma, although the infectious agent is not
always eliminated, as judged by immunofluorescence.
Inclusion conjunctivitis may be treated with oral tetracyclines or with a combination of oral
and topical agents.
SUSCEPTIBILITY TESTING
Micro organisms may be considered susceptible if the MIC (minimum inhibitory
concentration) is not more than 4 µg/mL and intermediate if the MIC is 4 to 12.5 µg/mL.
Susceptibility plate testing: A tetracycline disc may be used to determine microbial
susceptibility to drugs in the tetracycline class. If the Kirby-Bauer method of disc
susceptibility testing is used a 30 ?g tetracycline HCl disc should give a zone of at least 19
mm when tested against a tetracycline-susceptible bacterial strain.
CONTRAINDICATIONS
In persons who have shown hypersensitivity to any of the tetracyclines.
Severe renal insufficiency.
Systemic lupus erythematosus.
WARNINGS
If renal impairment exists, even usual oral or parenteral doses may lead to excessive systemic
accumulation of the drug and possible liver toxicity. Under such conditions, lower than usual
total doses are indicated and, if therapy is prolonged, serum level determinations of the drug
may be advisable.
The anti anabolic action of the tetracyclines may cause an increase in BUN. This effect may
be enhanced by diuretics.
In patients with significantly impaired function, higher serum levels of tetracycline may lead
to azotaemia, hyperphosphataemia and acidosis.
The use of tetracyclines during tooth development (last half of pregnancy, infancy and
childhood to the age of 8 years) may cause permanent discolouration of the teeth
(yellow/grey/brown). This adverse reaction is more common during long term use of the
drugs, but has been observed following repeated short term courses. Enamel hypoplasia has
also been reported. Tetracycline drugs, therefore, should not be used in this age group, unless
other drugs are not likely to be effective or are contraindicated.
Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some
individuals taking tetracycline. Patients apt to be exposed to direct sunlight or ultraviolet
light should be advised that this reaction can occur with tetracycline drugs and treatment
should be discontinued at the first evidence of skin erythema.
Patients should be advised to avoid direct sunlight or UV light exposure if possible.
The use of tetracycline can cause severe enterococolitis due to resistant staphylococci.
Antibiotic associated Pseudomembranous colitis has been reported with many antibiotics
including tetracycline. A toxin produced by Clostridium difficile appears to be the primary
cause. The severity of the colitis may range from mild to life threatening. It is important to
consider this diagnosis in patients who develop diarrhoea or colitis in association with
antibiotic use (this may occur up to several weeks after cessation of antibiotic therapy). Mild
cases usually respond to drug discontinuation alone. However, in moderate to severe cases,
appropriate therapy with a suitable oral antibacterial agent effective against C. difficile should
be considered. Fluids, electrolytes and protein replacement should be provided when
indicated. Drugs that delay peristalsis e.g. opiates and diphenoxylate with atropine (Lomotil)
may prolong and/or worsen the condition and should not be used.
Use in Pregnancy
Pregnancy Category D
Tetracyclines are safe for use during the first 18 weeks (16 weeks post conception) of
pregnancy, after which they cause discolouration of the baby's teeth. During the period of
mineralisation of teeth (the second and third trimesters of pregnancy, the neonatal period and
the first 8 years of life), tetracyclines may induce hypoplasia of the enamel and discolouration
of the teeth. Tetracyclines also accumulate in the growing skeleton. These products should
be avoided during the second and third trimesters of pregnancy. (See above WARNINGS
about use during tooth development.)
Safe use in pregnancy has not been established. Results of animal studies indicate that
tetracyclines cross the placenta, are found in foetal tissues and can have toxic effects on the
developing foetus (often related to retardation of skeletal development). Evidence of
embryotoxicity has also been noted in animals treated early in pregnancy.
High doses of tetracycline, especially if given intravenously, have been reported to cause
severe fatty necrosis of the liver. Because of this and the effect on foetal bone and tooth
development, tetracycline should not be given after the first 18 weeks of pregnancy.
Use in Lactation
Tetracyclines are present in the milk of lactating women who are taking a drug in this class.
Use in Newborns, Infants and Children
(See above WARNINGS about use during tooth development.) All tetracyclines form a
stable calcium complex in any bone forming tissue. A decrease in the fibula growth rate has
been observed in prematures given oral tetracycline in doses of 25 mg/kg every six hours.
This reaction was shown to be reversible when the drug was discontinued.
PRECAUTIONS

Because tetracyclines have been shown to depress plasma prothrombin activity, patients who
are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage.
In long term therapy, periodic laboratory evaluation of orang systems, including
haematopoietic, renal and hepatic studies should be performed.
Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is
advisable to avoid giving tetracycline in conjunction with penicillin.
In venereal diseases when co-existent syphilis is suspected, darkfield examination should be
done before treatment is started and the blood seriology repeated monthly for at least 4
months.
Tetracycline is not the drug of choice in the treatment of any type of staphylococcal infection.

If tetracycline is used for the treatment of infections due to group A β-haemolytic streptococci
(Streptococcus pyogenes) (see INDICATIONS), treatment should continue for 10 days.
ADVERSE REACTIONS

Gastrointestinal: Anorexia, nausea, vomiting, diarrhoea, glossitis, dysphagia, enterocolitis,
pancreatitis and inflammatory lesions (with monilial overgrowth) in the anogenital region.
These reactions have been caused by both the oral and parenteral administration of
tetracyclines. Rarely, oesophagitis and oesophageal ulceration.
Skin: Maculopapular and erythematous rashes. Exfoliative dermatitis has been reported but
is uncommon. Lesions occurring on the glans penis have caused balanitis. Photosensitivity is
discussed above. (See WARNINGS).
Dental: Discolouration of teeth (yellow-grey-grown) and/or enamel hypoplasia have been
reported in infancy and childhood to the age of 8 years.
Renal toxicity: Rise in BUN has been reported and is apparently dose related (see
WARNINGS). Tetracycline may aggravate pre-existing renal failure. Nephrotoxicity has
also occurred in association with "acute fatty liver" related to the use of tetracycline in high
doses. Degraded tetracycline may result in renal tubular damage and a "Fanconi-like"
syndrome.
Hypersensitivity reactions: Urticaria, angioneurotic oedema, anaphylaxis, anaphylactoid
purpura, pericarditis and exacerbation of systemic lupus erythematosus.
Blood: Haemolytic anaemia, thrombocytopenia, neutropenia and eosinophilia have been
reported.
Superinfections: As with other antibiotic preparations, use of this drug may result in
overgrowth of non-susceptible organisms, including fungi. If superinfection occurs, the
antibiotic should be discontinued and appropriate therapy should be instituted.
CNS: Pseudotumour cerebri (benign intracranial hypertension) in adults has been associated
with the use of tetracyclines. The usual clinical manifestations are headache and blurred
vision. Bulging fontanelles have been associated with the use of tetracyclines in infants.
While both of these conditions and related symptoms usually resolve soon after
discontinuation of the tetracycline, the possibility for permanent sequelae exists.
Other: When given over prolonged periods, tetracyclines have been reported to produce
brown-black microscopic discolouration of the thyroid glands. No abnormalities of thyroid
function studies are known to occur.

INTERACTIONS

Since tetracyclines may depress plasma prothrombin activity, patients who are on
anticoagulant therapy may require downward adjustment of their anticoagulant dosage.
Antacids containing aluminium, calcium or magnesium and preparations containing iron,
impair absorption and should not be given to patients taking oral tetracycline.
Foods and some dairy products also interfere with absorption. Oral forms of tetracycline
should be given 1 hour before or 2 hours after meals. Paediatric oral dosage forms should not
be given with milk formulas and should be given at least 1 hour prior to feeding.
Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is
advisable to avoid giving tetracycline in conjunction with penicillin.
Reduced efficacy and increased incidence of breakthrough bleeding has been suggested with
concomitant use of tetracycline and oral contraceptive preparations.
DOSAGE AND ADMINISTRATION

Therapy should be continued for at least 24 to 48 hours after symptoms and fever have
subsided.
Patients with renal impairment: (See WARNINGS) Total dosage should be decreased by
reduction of recommended individual doses and/or by extending time intervals between
doses.
Treatment of streptococcal infections: If tetracycline is used for streptococcal infections,
therapeutic doses should be administered for at least 10 days.
Adults: Usual daily dose, 1 to 2 g divided into four equal doses, depending on the severity of
the infection.
Children: (See WARNINGS) Tetracyclines are not recommended in children 8 years of age
or less. For children above the age of 8 years, the usual daily dose is 25 to 50 mg/kg of
bodyweight divided into four equal doses. The total dose should not exceed that
recommended for adults.
Brucellosis: 500 mg tetracycline four times daily for 3 weeks accompanied by streptomycin,
1 g intramuscularly twice daily the first week and once daily the second week.
Syphilis: A total of 30 to 40 g in equally divided doses over a period of 10 to 15 days should
be given. Close follow up, including laboratory tests, is recommended.
PRESENTATION

ACHROMYCIN capsules, 250 mg (orange, marked Sigma 250 mg):
SPONSOR

Aspen Pharma Pty Ltd
34-36 Chandos Street
St Leonards NSW 2065
Australia
DOH Approval Date:
Date of most recent amendment 30 August 2004.

Source: http://www.aspenstaging.com/product_info/pi/PI_Achromycin.pdf