Consumer medicine information

Doxsig Tablets

Doxycycline

BRAND INFORMATION

Brand name

Doxsig

Active ingredient

Doxycycline

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Doxsig Tablets.

What is in this leaflet

This leaflet answers some common questions about DOXSIG.

It does not contain all of the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have benefits and risks. Your doctor has weighed the risks of you taking DOXSIG against the benefits they expect it will have for you.

If you have any concerns about taking this medicine, talk to your doctor or pharmacist.

Keep this leaflet with your medicine.

You may need to read it again.

What DOXSIG is used for

DOXSIG is an antibiotic used to

  • Treat certain infections
  • Control acne
  • Prevent malaria

DOXSIG tablets belong to a class of medicines called tetracyclines.

These medicines work by killing or stopping the growth of bacteria which cause infections or make acne worse. They also work against parasites which cause malaria.Tetracyclines will not work against viral infections such as colds or the ‘flu’.

Your doctor, however, may prescribe DOXSIG for another purpose. Ask your doctor if you have any questions about why DOXSIG has been prescribed for you.

This medicine is only available with a doctor’s prescription.

There is no evidence that DOXSIG is addictive.

Before You Take DOXSIG

When you must not take DOXSIG

Do not take DOXSIG if:

  1. You have ever had an allergic reaction to
  • Medicines containing doxycycline, or doxycycline hydrochloride
  • Medicines containing other tetracyclines
  • Any of the ingredients listed at the end of this leaflet
Some of the symptoms of an allergic reaction to tetracyclines may include: rash, itching or hives of the skin, swelling of the face, lops and tongue or other parts of the body, shortness of breath, wheezing or troubled breathing
  1. You are taking preparations containing Vitamin A, isotretinoin or etretinate
Ask your doctor or pharmacist if you are not sure if you are taking one of these medicines
  1. You are in the second or third trimester of pregnancy or breastfeeding
As with many medicines, tetracyclines can harm the developing or breastfeeding baby. This may include enamel loss and staining of the child’s teeth and increase the pressure on your child’s brain.
High doses of tetracyclines may also cause liver problems in pregnant women.

If you are not sure whether you should be taking DOXSIG, talk to your doctor.

Do not take DOXSIG if:

  • The expiry date on the pack has passed
    If you take this medicine after the expiry date has passed it may have no effect at all, or worse, an entirely unexpected effect.
  • The packaging is torn or shows signs of tampering.

Do not give DOXSIG to children of eight years and under unless directed by the child’s doctor. DOXSIG like all other tetracyclines may cause enamel loss and staining in developing teeth.

Before you start to take DOXSIG

You must tell your doctor if:

  1. You are allergic to any other medicines or substances such as foods, dyes or preservatives
  2. You have or have ever had any other health problems
  3. You plan to become pregnant or breastfeed
  4. You are scheduled to have surgery under general anaesthetic
  5. You are exposed to direct sunlight or ultra violet light

If you have not told your doctor or pharmacist about any of the above, tell them before you start taking DOXSIG.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you buy without a prescription from a pharmacy, supermarket or health food shop.

Some medicines and DOXSIG may interfere with each other, including:

  • preparations containing Vitamin A
  • some medicines used for skin problems such as isotretinoin or etretinate
  • warfarin, a medicine used to stop blood clotting
  • another group of antibiotics called penicillins
  • Methoxyflurane, an inhaled anaesthetic
  • Barbiturates such as phenobarbitone
  • Medicines containing sodium bicarbonate
  • Acetazolamide and ethoxzolamide, a medicine used to treat glaucoma
  • The contraceptive pill (birth control pill). DOXSIG may decrease the effectiveness of some birth control pills.
    Your doctor may advise you to use an alternative method of contraception while taking DOXSIG
  • some medicines for epilepsy such as phenytoin, carbemazepine or phenobarbitone

These medicines may be affected by DOXSIG or may affect how well it works. You may need different amounts of your medicine.

Some medicines may interfere with the absorption of DOXSIG tablets. These include:

  • iron preparations, including vitamin preparations which contain iron
  • antacids used for indigestion containing aluminium, calcium or magnesium
  • do not drink alcohol or take any of these medicines if you are taking DOXSIG tablets.

You can still take these medicines while you are taking DOXSIG. However, you must take your DOXSIG Tablets at least two hours before or two hours after taking any of these medicines to make sure that there is no problem with absorption.

How to take DOXSIG

Follow all directions given to you by your doctor and pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the pack, ask your doctor or pharmacist for help

How much to take

Depending on your condition, your doctor will tell you how much DOXSIG to take. Follow all instructions carefully.

How to take it

Swallow the prescribed dose of DOXSIG whole with a full glass of water or milk while standing upright. Do not lie down immediately after swallowing DOXSIG. It is important to drink adequate amounts of fluid and to stay upright, for example sitting, standing or walking for at least half an hour after swallowing your tablet. This is to help avoid irritation and ulceration oesophagus (foodpipe).

When to take it

Take DOXSIG tablets during or immediately after a meal, at about the same time each day (usually in the morning). If taken on an empty stomach, DOXSIG may cause a stomach upset.

Late evening ingestion of the tablet should be avoided.

How long to take it

For controlling acne, DOXSIG tablets should be taken as prescribed by your doctor. For severe acne the tablets may be taken up to a maximum of 12 weeks.

For treating infections DOXSIG tablets are usually taken for one to two weeks. Do not stop taking DOXSIG because you are feeling better. If you do not complete the full course prescribed by your doctor, the infection may not clear completely or your symptoms may return.

For preventing malaria, DOXSIG tablets are normally recommended to be taken for up to a maximum of eight weeks.

However, your doctor may prescribe DOXSIG tablets for longer periods. Check with your doctor if you are not sure how long you should be taking it.

Continue taking DOXSIG tablets until you finish the pack or until your doctor recommends.

Follow all directions given to you by your doctor and pharmacist carefully.

If you forget to take DOXSIG

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to.

Otherwise, take the missed dose as soon as you remember, and then go back to taking your tablets as you would normally.

Do not take a double dose to make up for the dose you missed.

If you are not sure what to do, ask your doctor or pharmacist.

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (telephone 13 11 26) for advice, or go to Accident and Emergency at the nearest hospital, if you think you or anyone else may have taken too much DOXSIG. Do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention.

Symptoms of an overdose may include nausea, vomiting and diarrhoea.

While you are taking DOXSIG

Things you must do

If the symptoms of your infection do not improve within a few days, or if they become worse, tell your doctor.

If you get severe diarrhoea tell your doctor, pharmacist or nurse immediately. Do this even if this occurs several weeks after you have stopped taking DOXSIG. Diarrhoea may mean that you have a serious condition affecting your bowel. You may need urgent medical care. Do not take any diarrhoea medicine without first checking with your doctor.

If you get a sore white mouth or tongue while taking or soon after stopping DOXSIG tell your doctor. Also tell your doctor if you get vaginal itching or discharge. This may mean you have a fungal infection called thrush. Sometimes the use of DOXSIG allows fungi to grow and the above symptoms to occur. DOXSIG do not work against fungi.

If you become pregnant while you are taking DOXSIG, tell your doctor.

If you are about to start taking a new medicine tell your doctor and pharmacist that you are taking DOXSIG.

Things you must not do

Do not stop taking your tablets because you are feeling better, unless advised to do so by your doctor. If you do not complete the full course prescribed by your doctor, the infection may not clear completely or your symptoms may return.

Do not give DOXSIG to anyone else even if they have the same condition as you.

Do not use DOXSIG to treat any other complaints unless your doctor tells you to.

Things to be careful of

Protect your skin when you are in the sun, especially between 10am and 3pm. Doxycycline may cause your skin to be much more sensitive to sunlight than it is normally.

Exposure to sunlight may cause a skin rash, itching, redness, or a severe sunburn. If outdoors, wear protective clothing and use a 30+ sunscreen. If your skin does appear to be burning, stop taking DOXSIGd tell your doctor.

Be careful of driving or operating machinery until you know how DOXSIG affects you. DOXSIG does not normally cause any problems with your ability to drive a car or operate machinery. However, as with many other medicines Doxycycline tablets may cause tiredness in some people.

Side Effects

Tell your doctor or pharmacist as soon as possible if you have any problems while you are taking DOXSIG, even if you do not think that the problems are connected with the medicine or are not listed in this leaflet. Like all medicines, DOXSIG can cause side effects. If they occur, most are likely to be minor and temporary. However, some may be serious and need medical attention.

Ask your doctor or pharmacist to answer any questions you may have.

While taking DOXSIG

Tell your doctor if you notice any of the following and they worry you:

  • oral thrush - white, furry, sore tongue and mouth
  • vaginal thrush - sore and itchy vagina and/or discharge
  • nausea
  • vomiting
  • loss of appetite
  • stomach pain
  • darkened tongue
  • taste loss
  • tooth discolouration

Tell your doctor immediately, or go to the nearest casualty at your local hospital if you notice any of the following:

  • skin rash/hives/itchy skin
  • joint pain
  • difficulty breathing
  • fever
  • sore throat
  • more frequent bruising than normal
  • severe sunburn
  • yellowing of the eyes or skin (jaundice).

After finishing DOXSIG

Tell you doctor immediately if you notice any of the following side effects, particularly if they occur several weeks after stopping treatment with DOXSIG

  • severe abdominal cramps or stomach cramps
  • watery and severe diarrhoea, which may also be bloody
  • fever in combination with one or both of the above

These are rare but serious side effects. You may have a serious condition affecting your bowel.

Therefore you may need urgent medical attention.

However, this side effect is very rare.

Do not take any diarrhoea medicine without checking with your doctor first.

Some people may experience other side effects while taking DOXSIG.

Tell your doctor if you notice any other effects.

Do not be alarmed by this list of possible side effects you may not experience any of them.

After taking DOXSIG

Storage

Keep your tablets in the blister pack until it is time to take them. If you take the tablets out of the blister pack they may not keep well.

Keep your tablets in a cool dry place where the temperature stays below 30°C.

Do not store DOXSIG or any other medicine in the bathroom or near a sink.

Do not leave DOXSIG in the car or on window sills. Heat and dampness can destroy some medicines.

Keep DOXSIG where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking DOXSIG, or your tablets have passed their expiry date, ask your pharmacist what to do with any that are left over.

Product description

What it looks like

DOXSIG 50 mg and 100 mg tablets contain 50 or 100 mg of doxycycline respectively as doxycycline hyclate (hydrochloride).

DOXSIG 50 mg tablets
White film-coated, circular, biconvex tablet having a diameter of approximately 6.3mm.
Presented in PVC/PVDC/Al blister packs of 25 tablets (AUST R 148807)

DOXSIG 100 mg tablets
White, film-coated, biconvex tablets with a breakline on one face, for oral use, diameter 9.1mm.
Presented in PVC/PVDC/Al blister packs of 7 or 21 tablets (AUST R 148808),

Ingredients

Active Ingredient:

Doxycycline (as doxycycline hydrochloride)

Other Ingredients:

  • microcrystalline cellulose
  • magnesium stearate
  • colloidal anhydrous silica
  • maize starch
  • Opadry White Y-7000B

DOXSIG tablets do not contain any gluten, lactose, sucrose, tartrazine or any other azo food dyes.

Name and Address of the Sponsor

Arrow Pharma Pty Ltd
15-17 Chapel St
Cremorne VIC 3121

Date of Preparation

July 2019

Published by MIMS November 2019

BRAND INFORMATION

Brand name

Doxsig

Active ingredient

Doxycycline

Schedule

S4

 

1 Name of Medicine

Doxycycline hyclate (hydrochloride).

6.7 Physicochemical Properties

Chemical name: 6-deoxy-5- oxytetracycline. It is a light yellow crystalline powder which has a high lipid solubility and a low affinity for calcium binding. It is highly stable in normal human serum. It will not degrade into an epianhydro form.

Chemical name.

Hydrochloride hemiethanolate hemihydrate of (4S,4aR,5S,5aR,6R,12aS)-4-(dimethylamino)- 3,5,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene- 2-carboxamide.
Molecular formula: C22H25ClN208. Molecular weight: 512.9.

Chemical structure.


CAS number.

24390-14-5.

2 Qualitative and Quantitative Composition

Doxycycline is a broad spectrum antibiotic synthetically derived from oxytetracycline.
Doxsig tablets contain doxycycline 50 mg or 100 mg as doxycycline hyclate (hydrochloride).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Doxsig 50 mg tablets: White film-coated circular biconvex tablet having a diameter of 6.3 mm.
Doxsig 100 mg tablets: White film-coated, biconvex tablet, with a breakline on one face.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Microbiology.

Doxycycline is primarily bacteriostatic and is thought to exert its antimicrobial effect by the inhibition of protein synthesis. It is active against a wide range of Gram positive and Gram negative organisms (see Section 4.1 Therapeutic Indications).

Disc susceptibility test.

Dilution or diffusion techniques - either quantitative (MIC) or breakpoint, should be used following a regularly updated, recognised and standardized method (e.g. Clinical and Laboratory Standards Institute [CLSI formerly NCCLS]). Standardised susceptibility test procedures require the use of laboratory control microorganisms to control the technical aspects of the laboratory procedures.
A report of "Susceptible" indicates that the pathogen is likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable.
A report of "Intermediate" indicates that the result should be considered equivocal, and if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone, which prevents small-uncontrolled technical factors from causing major discrepancies in interpretation.
A report of "Resistant" indicates that the pathogen is not likely to be inhibited if the antimicrobial compound in the blood reaches the concentrations usually achievable; other therapy should be selected.

Note.

The prevalence of resistance may vary geographically for selected species and local information on resistance is desirable, particularly when treating severe infections.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Tetracyclines are readily absorbed though to a varying extent. They are concentrated by the liver in the bile, and excreted in the urine and faeces at high concentrations and in a biologically active form. Doxycycline is virtually completely absorbed after oral administration. Its absorption is not significantly affected by the presence of food or milk.

Distribution.

Following a 300 mg dose, the mean peak serum concentration of doxycycline in normal adult volunteers was 6.3 microgram/mL and the medium time to peak concentration was 2.7 hours. The mean serum level 24 hours after dosing was 1.8 microgram/mL.
Normalised to a 200 mg dose, the mean peak serum concentration of doxycycline was about 4.3 microgram/mL.

Metabolism.

The metabolism of doxycycline in the human body has not been investigated. In vitro serum protein binding of doxycycline varies from 23 to 93%.
Haemodialysis does not alter serum half-life.

Excretion.

Excretion of doxycycline by the kidney is about 40% in 72 hours in individuals with normal function (creatinine clearance above 75 mL/minute).
This percentage excretion may fall as low as 1 to 5% in 72 hours in individuals with severe renal insufficiency (creatinine clearance below 10 mL/minute). Studies have shown no significant difference in serum half-life of doxycycline (range 18 to 22 hours) in individuals with normal and severely impaired renal function.
The fraction of drug that is not eliminated with urine is mainly excreted in the faeces. More than 90% of an oral dose of doxycycline is eliminated from the body within 72 hours of drug administration.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

4 Clinical Particulars

4.1 Therapeutic Indications

Infections caused by the following microorganisms: Mycoplasma pneumoniae (primary atypical pneumonia); Rickettsiae (Queensland tick typhus, epidemic typhus fever, Q fever, murine endemic typhus fever, Australo-Pacific endemic scrub typhus); Chlamydia psittaci (psittacosis); Chlamydia trachomatis (lymphogranuloma venereum, trachoma, inclusion conjunctivitis).
(Doxycycline 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 doxycycline alone, or in combination with topical agents.)
Borreliae (relapsing fever); Calymmatobacterium (Donovania) granulomatis (granuloma inguinale).
Infections caused by the following Gram negative microorganisms: Vibrio sp. (cholera); Brucella sp. (Brucellosis; in conjunction with streptomycin); Haemophilus ducreyi (chancroid); Yersinia pestis (plague); Francisella tularensis (tularaemia); Bartonella bacilliformis (Bartonellosis); Bacteroides sp. When penicillin is contraindicated, doxycycline is an alternative drug in the treatment of infections due to: Treponema pallidum (syphilis); Treponema perenue (yaws); Neisseria gonorrhoeae (see Section 4.2 Dose and Method of Administration).
Doxycycline is not the drug of choice in the treatment of any type of staphylococcal infection or infections caused by Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, Enterococcus faecalis or any type of enteric bacteria because many strains of these organisms have been shown to be resistant to doxycycline. Doxycycline should not be used in these infections unless the organism has been shown to be sensitive. For upper respiratory infections due to group A haemolytic streptococci (including prophylaxis of rheumatic fever), penicillin is the usual drug of choice.
In acute intestinal amoebiasis doxycycline may be a useful adjunct to amoebicides. In severe acne doxycycline may be a useful adjunctive therapy.
Doxycycline is indicated, in adults and children older than 10 years, as chemoprophylaxis for malaria caused by Plasmodium falciparum and, in combination with other antimalarial agents, against malaria caused by Plasmodium vivax. Doxycycline is only able to suppress malaria caused by P. vivax. As there are relatively few locations where P. vivax does not coexist to some extent with P. falciparum, it is recommended that doxycycline should be used routinely with other agents, for example chloroquine.

Note.

The 50 mg tablet is not a paediatric formulation.

4.3 Contraindications

Hypersensitivity to any of the tetracyclines or any of the excipients. Rare cases of benign intracranial hypertension have been reported after tetracyclines and after vitamin A or oral retinoids such as isotretinoin or etretinate. Concomitant treatment is therefore contraindicated (see Section 4.8 Adverse Effects (Undesirable Effects)).
Use in pregnancy (16 weeks postconception) and lactation (see Section 4.6 Fertility, Pregnancy and Lactation).

4.4 Special Warnings and Precautions for Use

Use with caution in the following circumstances.

The use of antibiotics may occasionally result in overgrowth of nonsusceptible organisms, including fungi. If superinfection occurs, the antibiotic should be discontinued and appropriate therapy instituted.
In venereal disease when coexistent syphilis is suspected, proper diagnostic measures including a dark field examination should be done before treatment is started and the blood serology repeated monthly for at least four months.
Rarely, oesophagitis and oesophageal ulceration have been reported in patients receiving doxycycline tablets. Most of these patients took medication immediately before going to bed. Administration of adequate amounts of fluid with the tablets is recommended to reduce the risk of oesophageal irritation and ulceration, and late evening ingestion of the dose should be avoided.
To reduce the possibility of gastric irritation, it is recommended that doxycycline be given with food or milk. The absorption of doxycycline is not markedly influenced by simultaneous ingestion of food or milk.
If doxycycline is used to treat infections due to group A haemolytic streptococci, treatment should continue for at least 10 days.

Intracranial hypertension.

Intracranial hypertension (IH) has been associated with the use of tetracyclines including doxycycline (see Section 4.3 Contraindications; Section 4.8 Adverse Effects (Undesirable Effects)). The use of tetracyclines in infants, even in the usual therapeutic doses, may cause increased intracranial pressure and bulging of the fontanelles. Women of childbearing age who are overweight or have a history of IH are at greater risk for developing tetracycline associated IH. Clinical manifestations include headache, blurred vision, diplopia and vision loss. Although intracranial hypertension typically resolves after discontinuation of treatment, the possibility for permanent visual loss exists. If visual disturbance occurs during treatment, prompt ophthalmologic evaluation is warranted. Discontinuation of therapy typically results in prompt return of the pressure to normal. However, since intracranial pressure can remain elevated for weeks after drug cessation patients should be monitored until they stabilise.

Antibiotic associated pseudomembranous colitis and CDAD.

Clostridium difficile associated diarrhoea (CDAD) and antibiotic associated pseudomembranous colitis have been reported with nearly all antibacterial agents including doxycycline, and may range in severity from mild diarrhoea to fatal colitis.
Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile and C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhoea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.
Mild cases usually respond to drug discontinuation alone. However, in moderate to severe cases, appropriate therapy with a suitable oral antibacterial agent effective against Clostridium difficile should be considered. Fluids, electrolytes and protein replacement should be provided when indicated. Drugs which delay peristalsis, e.g. opiates and diphenoxylate with atropine may prolong and/or worsen the condition and should not be used.

Check the following before use.

In long-term therapy, periodic laboratory evaluation of organ systems, including haemopoietic, renal and hepatic studies should be performed.
The use of the drugs of the tetracycline class, including doxycycline, during tooth development (latter 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. Doxycycline, 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 likely 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.
Antibiotic associated pseudomembranous colitis has been reported with many antibiotics including doxycycline. A toxin produced with 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 such as oral antibacterial agents effective against Clostridium difficile should be considered. Fluids, electrolytes and protein replacement should be provided when indicated.
Drugs which delay peristalsis, e.g. opiates and diphenoxylate with atropine (Lomotil) may prolong and/or worsen the condition and should not be used.

Use in renal impairment.

The antianabolic action of the tetracyclines may cause an increase in serum urea. Studies to date indicate that this does not occur with the use of doxycycline in patients with impaired renal function.

Use in the elderly.

No data available.

Paediatric use.

(See Section 4.4 Special Warnings and Precautions for Use about use during tooth development).
As with other tetracyclines, doxycycline forms a stable calcium complex in any bone forming tissue. A decrease in the fibula growth rate has been observed in premature infants given oral tetracycline in doses of 25 mg/kg every six hours. This reaction was shown to be reversible when the drug was discontinued.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Plasma levels of doxycycline are reduced by the ingestion of alcohol or the administration of barbiturates, anticonvulsants (phenytoin, carbamazepine), disodium hydrogen edetate, sodium bicarbonate, sodium lactate and acetazolamide and ethoxzolamide.
Antacids containing aluminium, calcium or magnesium and preparations containing iron impair absorption and should not be given to patients taking doxycycline.
Since bacteriostatic drugs may interfere with the bactericidal action of penicillin, it is advisable to avoid giving tetracyclines in conjunction with penicillin.
Because the tetracyclines have been shown to depress plasma prothrombin activity, patients on anticoagulant therapy may require downward adjustment of their anticoagulant dosage.
Concurrent use of doxycycline may render oral contraceptives less effective and breakthrough bleeding may occur. Unplanned pregnancy may occur with this combination. A barrier method of contraception should be used while taking doxycycline and for seven days following completion of the course of doxycycline.
The concurrent use of tetracycline and methoxyflurane has been reported to result in fatal renal toxicity.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category D)
Tetracyclines are safe for use during the first 18 weeks of pregnancy (16 weeks post conception) after which they cause discolouration of the baby's teeth.
During the period of mineralisation of a child's teeth (the second and third trimester 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. Large doses of tetracyclines have caused acute fatty necrosis of the liver in pregnant women, especially those with pyelonephritis.
Doxycycline appears in the milk of lactating women. It forms a stable calcium complex in any bone forming tissue and a decrease in the fibula growth rate has been observed in premature infants. The use of drugs of the tetracycline class during tooth development may also cause permanent discolouration of the teeth. Doxycycline should not be given to nursing mothers.

4.8 Adverse Effects (Undesirable Effects)

Doxycycline is generally well tolerated. Due to doxycycline's virtually complete absorption, side effects of the lower bowel, particularly diarrhoea, have been infrequent. The following adverse effects have been observed in patients receiving doxycycline.

More common reactions.

Dermatological.

Photosensitive dermatitis, erythematous rash, maculopapular rash, morbilliform rash, pustular rash, urticaria, onycholysis and discolouration of the nails.

Gastrointestinal.

Nausea, anorexia, vomiting, dysphagia, diarrhoea, oesophagitis, oesophageal ulceration, abdominal pain, glossitis, black hairy tongue.

Hypersensitivity.

Urticaria, exacerbation of systemic lupus erythematosus.

Hepatic.

Cholestatic hepatitis, fatty liver degeneration.

Renal.

Dose related increase in serum urea (see Section 4.4 Special Warnings and Precautions for Use).

Musculoskeletal.

Tooth discolouration, enamel hypoplasia.

Others.

Bulging fontanelles have been reported in young infants following full therapeutic dosage. The sign disappeared rapidly when the drug was discontinued.
When given over prolonged periods, tetracyclines have been reported to produce brown black microscopic discolouration of thyroid glands. No abnormalities of thyroid function studies are known to occur.

Less common reactions.

Gastrointestinal.

Enterocolitis (see Section 4.4 Special Warnings and Precautions for Use), inflammatory lesions (with monilial overgrowth) in the anogenital region.

Dermatological.

Exfoliative dermatitis.

Genitourinary.

Acute renal failure.

Hypersensitivity.

Angioneurotic oedema, anaphylaxis, anaphylactoid purpura, pericarditis.

Haematological.

Phlebitis associated with intravenous administration; leucopenia, thrombocytopenia, purpura; increase in prothrombin time, haemolytic anaemia, eosinophilia.

Nervous system.

Malaise, confusion, taste loss, stupor, hypoaesthesia, paraesthesia, somnolence, increased intracranial pressure in infants.

Ocular.

Conjunctivitis, periorbital oedema.

Psychiatric.

Depression, anxiety, hallucination.

Respiratory.

Bronchospasm.
Cases of benign intracranial hypertension have been reported with tetracyclines. It has also occurred with concomitant vitamin A or retinoids such as isotretinoin and etretinate (see Section 4.3 Contraindications).

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

Note.

The 50 mg tablet is not a paediatric formulation.
Administration of adequate amounts of fluid with the tablets is recommended to reduce the risk of oesophageal irritation and ulceration. Morning, rather than late night dosing, may be preferable. As the recumbent posture may delay oesophageal transit of the tablets, the patient should not lie down for some time after taking the tablets. To reduce the possibility of gastric irritation, it is recommended that doxycycline be given with food or milk. The absorption of doxycycline is not markedly influenced by simultaneous ingestion of food or milk. Antacids containing aluminium, calcium or magnesium and preparations containing iron impair absorption and should not be given to patients taking doxycycline.
The usual dosage and frequency of administration of doxycycline differs from that of other tetracyclines. Exceeding the recommended dosage may result in an increased incidence of side effects. Therapy should be continued at least 24 to 48 hours after symptoms and fever have subsided.
Tetracyclines are not the drugs of choice for the treatment of streptococcal infections (see Section 4.1 Therapeutic Indications). However when used, therapy should be continued for 10 days.

Adults and children over 8 years (and above 50 kg in weight).

The usual dose of doxycycline is 200 mg on the first day of treatment (administered as 100 mg every twelve hours) followed by a maintenance dose of 100 mg/day. The maintenance dose may be administered as a single dose or as 50 mg every twelve hours. In the management of more severe infections (particularly chronic infections of the urinary tract), 100 mg every twelve hours is recommended.

Acute uncomplicated gonococcal infections.

100 mg twice daily for 5 to 7 days.
Resistance of tetracyclines is not uncommon amongst gonococci. The use of tetracycline in the treatment of gonorrhoea should, therefore, be accompanied by monitoring of efficacy.

Primary and secondary syphilis.

300 mg a day in divided doses for at least 10 days.

Louse borne typhus.

This has been successfully treated with a single oral dose of 100 or 200 mg according to severity.

For the prevention of scrub typhus.

200 mg as a single dose.

For children above 8 years of age without skeletal growth retardation but weighing less than 50 kg.

The adult dose of 100 mg should be recalculated on a weight basis as 2 mg/kg (See Paediatric use).
Studies to date have indicated that administration of doxycycline at the usual recommended doses does not lead to excessive accumulation of the antibiotic in patients with renal impairment.

Severe acne.

Some efficacy has been demonstrated in some individuals at a dose of 50 mg/day over a period of 12 weeks. No data showing efficacy beyond 12 weeks have been submitted.

Malaria chemoprophylaxis.

100 mg once a day; commencing two days prior to entering malarious areas, while in the malarious area and for two weeks after leaving the malarious area. A maximum of doxycycline 100 mg daily for 8 weeks is recommended, as safety after 8 weeks has not been clearly established (see Mechanism of action, Microbiology; Section 4.1 Therapeutic Indications about combination with other antimalarial agents for prophylaxis against P. vivax).

4.7 Effects on Ability to Drive and Use Machines

The effects of this medicine on a person's ability to drive and use machines were not assessed as part of its registration.

4.9 Overdose

The symptoms of overdosage may be an exaggeration of the gastrointestinal side effects, the main ones being nausea, vomiting and diarrhoea. High doses of tetracyclines have been shown to cause an increase in serum urea so after a large overdosage a medical examination is advised.
Treatment of overdosage should be symptomatic and supportive.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Doxsig 100 mg and Doxsig 50 mg tablets also contain microcrystalline cellulose, maize starch, colloidal anhydrous silica, magnesium stearate and Opadry white Y-1-7000B.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 30°C. Protect from light and moisture.

6.5 Nature and Contents of Container

Doxsig 100 mg tablets.

Available in PVC/PVDC/Al blister packs of 7 or 21 tablets.

Doxsig 50 mg tablets.

Available in PVC/PVDC/Al blister packs of 25 tablets.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

Summary Table of Changes