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.

SUMMARY CMI

DOXSIG

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about taking this medicine, speak to your doctor or pharmacist.

1. Why am I taking DOXSIG?

DOXSIG contains the active ingredient doxycycline hyclate (hydrochloride). DOXSIG is an antibiotic used to treat certain types of infections, control acne and prevent some forms of malaria, sometimes in combination with another antimalarial medicine.

For more information, see Section 1. Why am I taking DOXSIG? in the full CMI.

2. What should I know before I take DOXSIG?

Do not use if you have ever had an allergic reaction to doxycycline hyclate (hydrochloride), other tetracyclines, or any of the ingredients listed at the end of the CMI. Talk to your doctor if you have allergies to any medicines, have any other medical conditions, take any other medicines, work outdoors or are likely to be exposed to strong sunlight or ultra-violet light, are scheduled to have surgery under general anaesthetic, or are pregnant or plan to become pregnant or are breastfeeding.

For more information, see Section 2. What should I know before I take DOXSIG? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with DOXSIG and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I take DOXSIG?

  • Your doctor or pharmacist will tell you how many tablets you will need to take each day.
  • Swallow the tablets whole with a full glass of water or milk while sitting or standing upright.

More instructions can be found in Section 4. How do I take DOXSIG? in the full CMI.

5. What should I know while taking DOXSIG?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are taking DOXSIG.
  • Tell your doctor if your symptoms do not improve or worsen, you get severe diarrhoea, you become pregnant while taking this medicine, or you are about to have any blood tests.
  • If you are taking iron preparations you must take them at least two hours before or two hours after DOXSIG.
Things you should not do
  • Do not stop taking your medicine because you are feeling better unless advised by your doctor.
  • Do not give your medicine 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.
Driving or using machines
  • Be careful before you drive or use any machines or tools until you know how DOXSIG affects you.
Drinking alcohol
  • Tell your doctor if you drink alcohol.
Looking after your medicine
  • Keep your tablets in their pack until it is time to take them.
  • Store below 25°C. Protect from light.

For more information, see Section 5. What should I know while taking DOXSIG? in the full CMI.

6. Are there any side effects?

Less serious side effects include: oral/vaginal thrush, rash/itching, nail changes, stomach upset/vomiting, mild irritation of the oesophagus, taste loss, ringing in ears. Serious side effects include: depression, feeling anxious/nervous, muscle tenderness/ weakness, painful swollen joints, increased pressure in brain, severe blisters and bleeding in lips, eyes, mouth, nose and genitals, severe skin reactions, difficulty in/pain with swallowing, dizziness, fast heart rate, frequent bruising, passing less urine, yellowing of eyes/skin, severe upper stomach pain often with nausea and vomiting.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

DOXSIG (dox-IG)

Active ingredient(s): doxycycline hyclate (hydrochloride) (dox-I-SYE-kleen)

Consumer Medicine Information (CMI)

This leaflet provides important information about taking DOXSIG. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about taking DOXSIG.

Where to find information in this leaflet:

1. Why am I taking DOXSIG?
2. What should I know before I take DOXSIG?
3. What if I am taking other medicines?
4. How do I take DOXSIG?
5. What should I know while taking DOXSIG?
6. Are there any side effects?
7. Product details

1. Why am I taking DOXSIG?

DOXSIG contains the active ingredient doxycycline hyclate (hydrochloride). This medicine belongs to a group of medicines called tetracyclines.

DOXSIG is an antibiotic used to:

  • treat certain types of infections
  • control acne
  • prevent some forms of malaria, sometimes in combination with another antimalarial medicine.

It works by killing or stopping the growth of bacteria which cause infections or make acne worse. It also works against parasites that cause malaria.

Tetracyclines will not work against viral infections such as colds or flu.

Ask your doctor if you have any questions about why this medicine has been prescribed for you.

Your doctor may have prescribed it for another reason.

This medicine is not addictive.

It is available only with a doctor's prescription.

2. What should I know before I take DOXSIG?

Warnings

Do not take DOXSIG if:

  • you are allergic to doxycycline hyclate (hydrochloride), other tetracyclines, or any of the ingredients listed at the end of this leaflet.
    Always check the ingredients to make sure you can take this medicine.
  • 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.
  • if you are more than 18 weeks pregnant or are breast-feeding.

Do not give this medicine to children aged eight years or under (or to children under 50 kg) unless directed by the child's doctor. DOXSIG like other tetracyclines, may cause enamel loss and staining in developing teeth. It may also cause increased pressure on the brain if used in infants.

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

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

Check with your doctor if you:

  • have allergies to any other medicines, foods, preservatives or dyes,
  • have any other medical conditions,
  • take any medicines for any other condition,
  • work outdoors or if you are likely to be exposed to strong sunlight or ultra-violet light. Doxycycline may cause your skin to become more sensitive to UV or sunlight, resulting in severe sunburn.
  • are scheduled to have surgery under general anaesthetic.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

As with many medicines, tetracyclines may harm your developing or breast-feeding baby. Tetracyclines may cause enamel loss and staining of your child's teeth or increase the pressure on your child's brain. High doses of tetracyclines may also cause liver problems in pregnant women.

3. What if I am taking other medicines?

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

Some medicines and DOXSIG may interfere with each other and affect how they work.

These Include:

  • preparations containing Vitamin A
  • some medicines used for skin problems, such as isotretinoin or etretinate
  • warfarin, a medicine used to prevent blood clotting
  • another group of antibiotics called penicillins
  • some medicines used in the treatment of epilepsy such as phenytoin, carbamazepine or phenobarbitone
  • methoxyflurane, an anaesthetic
  • acetazolamide, a medicine used to help the body get rid of salt and water
  • the contraceptive pill (birth control pill). DOXSIG may decrease the effectiveness of some birth control pills. Your doctor may advise you to use an additional method of contraception while taking DOXSIG and for 7 days after taking DOXSIG. Refer to your doctor or pharmacist for advice.

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

If you are taking the following medicines, take them at least two hours before or two hours after taking DOXSIG:

  • antacids (containing aluminium, calcium or magnesium) used for indigestion
  • bismuth salts, found in some medicines used to treat stomach ulcers
  • preparations that contain iron including vitamin preparations.

These medicines may interfere with the absorption of DOXSIG.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect DOXSIG.

4. How do I 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

Your doctor or pharmacist will tell you how many tablets you will need to take each day.

  • For treating infections, the usual dose of doxycycline is two 100 mg tablets on the first day, followed by one 100 mg tablet each day from then on.
  • For controlling acne, the usual dose is one 50 mg tablet each day.
  • For the prevention of malaria, the usual dose is one 100 mg tablet each day, commencing two days before entering the malarious area, during the visit, and for four weeks after leaving the area.

Your doctor may ask you to take a different dose, depending on your condition and how you react to the medicine.

Follow the instructions provided when DOXSIG was prescribed, including the number of days it should be taken.

Keep taking this medicine for the full time of treatment even if you begin to feel better after a few days.

If you do not complete the full course prescribed by your doctor, the infection may not clear completely or your symptoms may return.

For treating infections, DOXSIG is usually taken for one to two weeks.

For controlling acne, DOXSIG is normally taken over a period of 12 weeks.

For preventing malaria, DOXSIG is recommended to be taken for up to a maximum of 8 weeks. However, your doctor may prescribe DOXSIG for longer periods.

If you are not sure how long you should be taking this medicine, talk to your doctor.

How to take DOXSIG

Swallow the tablets whole with a full glass of water or milk while sitting or standing upright.

Do not lie down immediately after swallowing DOXSIG. It is important to stay upright, for example sitting, standing or walking around for at least half an hour after swallowing your tablet. This is to help avoid irritation to your food pipe, also called the oesophagus.

Do not chew the tablets.

When to take DOXSIG

  • Take your medicine at about the same time each day (usually in the morning). Taking it at the same time each day will have the best effect. It will also help you to remember when to take it.
  • Take your medicine during or immediately after a meal. If taken on an empty stomach, it may cause stomach upset.

If you forget to take DOXSIG

DOXSIG should be taken regularly at the same time each day.

If you miss a dose and 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 it as soon as you remember, and then go back to taking your medicine as you would normally.

Do not take a double dose to make up for the dose you missed. This may increase the chance of you getting an unwanted side effect.

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

If you have trouble remembering to take your medicine, ask your pharmacist for some hints.

If you take too much DOXSIG

If you think that you have taken too much DOXSIG, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

Symptoms of an overdose may include an upset stomach or vomiting.

5. What should I know while taking DOXSIG?

Things you should do:

Call your doctor straight away if:

  • you are taking DOXSIG for an infection and your symptoms do not improve within a few days or they become worse
  • you get severe diarrhoea. Do this even if it occurs several weeks after DOXSIG has been stopped. Diarrhoea may mean that you have a serious condition affecting your bowel. You may need urgent medical care. Do not take diarrhoea medicine without first checking with your doctor.

Remind any doctor, dentist or pharmacist you visit that you are taking DOXSIG.

If you become pregnant while taking this medicine, tell your doctor immediately.

If you are about to have any blood tests, tell your doctor that you are taking this medicine. It may interfere with the results of some tests.

If you are taking iron preparations, including vitamin preparations containing iron, bismuth salts or antacids (containing aluminium, calcium or magnesium), you must take them at least two hours before or two hours after DOXSIG to make sure there is no problem with absorption.

Things you should not do:

  • Do not stop taking your medicine because you are feeling better unless advised by your doctor. If you do not complete the full course, all of the bacteria causing your infection may not be killed. These bacteria may continue to grow and multiply so that your infection may not clear completely or it may return.
  • Do not give your medicine 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. If outdoors, wear protective clothing and use a 30+ sunscreen. DOXSIG 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 your skin does appear to be burning, see your doctor as soon as possible. You may need alternative treatment.
  • If you get thrush (a fungal infection which can affect the mouth and/or vagina) or any other infection while taking, or soon after stopping DOXSIG, tell your doctor. Sometimes the use of this medicine allows fungi to grow as they are not killed by DOXSIG.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how DOXSIG affects you.

Drinking alcohol

Tell your doctor if you drink alcohol.

Looking after your medicine

  • Keep your tablets in their pack until it is time to take them. Avoid exposure to light. If you take the tablets out of the pack they may not keep as well.
  • Store below 30°C.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on windowsills.

Keep it where young children cannot reach it.

When to discard your medicine

Getting rid of any unwanted medicine

If you no longer need to take this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not take this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
  • oral thrush - white, furry, sore tongue and mouth
  • vaginal thrush - sore and itchy vagina with or without discharge
  • rash or itching
  • nail changes
  • stomach upset or vomiting
  • mild irritation of the oesophagus (food-pipe)
  • taste loss
  • ringing or other persistent noise in the ears
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
  • depression
  • feeling anxious or nervous
  • muscle tenderness or weakness, not caused by exercise
  • painful swollen joints
  • increased pressure in the brain (headache, blurred vision, vomiting)
  • severe blisters and bleeding in the lips, eyes, mouth, nose and genitals
  • severe skin reactions starting as painful red areas then large blisters and ends with peeling layers of skin
  • difficulty in/pain with swallowing
  • flaking of the skin
  • dizziness
  • fast heart rate
  • frequent bruising
  • passing less urine
  • yellowing of the eyes or skin (jaundice)
  • severe upper stomach pain often with nausea and vomiting (pancreatitis)
  • symptoms of an allergic reaction such as shortness of breath, wheezing or troubled breathing; swelling of the face, lips, tongue or other parts of the body; rash, itching or hives on the skin
  • a rare, potentially life-threatening, drug-induced sensitivity reaction that includes skin rashes, blood changes, fever and dysfunction of internal organs (e.g. liver, kidney, lung)
  • a reaction that can happen after starting doxycycline therapy for a particular bacterial infection (spirochete infections, e.g. Lyme disease); symptoms include fever, chills, muscle pain and worsening of skin rash.
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

After finishing it

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

Serious side effectsWhat to do
  • 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.
Call your doctor straight away if you notice any of these serious side effects.

These are rare but serious side effects. You may have a serious condition affecting your bowel. DOXSIG may cause the bacteria which are normally harmless and present in the bowel to multiply, resulting in the above symptoms. Therefore you may need urgent medical attention.

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

Ask your doctor or pharmacist to answer any questions you may have about the side effects.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

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

What DOXSIG contains

Active ingredient
(main ingredient)		doxycycline hyclate (hydrochloride)
Other ingredients
(inactive ingredients)
  • microcrystalline cellulose
  • maize starch
  • magnesium stearate
  • colloidal anhydrous silica
  • Opadry White Y-7000B
Potential allergensThis medicine does not contain sucrose, tartrazine or any other azo dyes

Do not take this medicine if you are allergic to any of these ingredients.

What DOXSIG looks like

DOXSIG tablets come in two strengths:

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, diameter 9.1mm. Presented in PVC/PVDC/Al blister packs of 7 or 21 tablets (AUST R 148808),

*Not all pack sizes may be marketed.

Who distributes DOXSIG?

Arrotex Pharmaceuticals pty ltd
15-17 Chapel St
Cremorne VIC 3121
Ph: 1800 195 055

This leaflet was prepared in June 2023.

Published by MIMS August 2023

BRAND INFORMATION

Brand name

Doxsig

Active ingredient

Doxycycline

Schedule

S4

 

1 Name of Medicine

Doxycycline hyclate (hydrochloride).

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.

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 pertenue (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.

4.2 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).

4.3 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).
The concurrent use of tetracycline and methoxyflurane has been reported to result in fatal renal toxicity (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

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.

Venereal disease.

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.

Oesophageal injury.

If Doxsig capsules are ingested in an incorrect manner, there is a risk of adhesion of the capsule to oesophagus. If this happens, oesophageal injury may occur. Dysphagia, retrosternal pain, new or worsening heartburn are possible symptoms of such injury. In order to avoid oesophageal injury, Doxsig capsules must be ingested with at least 100 mL of fluid (half a glass) and the patient must remain upright for at least 30 minutes. Administration in the morning is recommended rather than in the evening.
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. The use of tetracyclines in infants, even in the usual therapeutic doses, may cause increased intracranial pressure and bulging of the fontanelles. Discontinuation of therapy results in prompt return of the pressure to normal.

Photosensitivity.

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.

Hepatic function.

Abnormal hepatic function has been reported rarely and has been caused by both the oral and parenteral administration of tetracyclines, including doxycycline.

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.

4.7 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.

4.8 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.
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).

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 and Jarisch-Herxheimer reaction has been reported in the setting of spirochete infections treated with doxycycline.

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 dyspepsia and pseudomembranous colitis enterocolitis (see Section 4.4 Special Warnings and Precautions for Use), C. difficile diarrhoea. Abnormal hepatic function has been reported rarely (< 1/1000), pancreatitis.

Dermatological.

Exfoliative dermatitis Steven-Johnson syndrome, toxic epidermal necrolysis (TEN).

Musculoskeletal.

Arthralgia, myalgia.

Genitourinary.

Acute renal failure.

Hypersensitivity.

Angioneurotic oedema, anaphylaxis, anaphylactoid purpura, pericarditis anaphylactic reaction, serum sickness, hypotension, dyspnoea, peripheral oedema, tachycardia.

Haematological and reticuloendothelial.

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

Nervous system.

Malaise, flushing, headache, confusion, taste loss, stupor, hypoaesthesia, paraesthesia, somnolence, benign intracranial hypertension in adults, increased intracranial pressure in infants. In relation to benign intracranial hypertension, symptoms included blurring of vision, scotomata and diplopia. Permanent visual loss has been reported.

Ocular.

Conjunctivitis, periorbital oedema.

Hearing/ vestibular.

Tinnitus.

Psychiatric.

Depression, anxiety, hallucination.

Respiratory.

Bronchospasm.

Rare reactions.

Retrosternal pain.

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.

4.9 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).

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.

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.

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 structure.


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.

CAS number.

24390-14-5.

7 Medicine Schedule (Poisons Standard)

Schedule 4 (Prescription only medicine).

Summary Table of Changes