Consumer medicine information

Doxylin

Doxycycline

BRAND INFORMATION

Brand name

Doxylin

Active ingredient

Doxycycline

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Doxylin.

SUMMARY CMI

DOXYLIN®

Consumer Medicine Information (CMI) summary

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

1. Why am I using DOXYLIN?

DOXYLIN contains the active ingredient doxycycline hyclate (hydrochloride). DOXYLIN 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 using DOXYLIN? in the full CMI.

2. What should I know before I use DOXYLIN?

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 use DOXYLIN? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with DOXYLIN 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 use DOXYLIN?

  • Your doctor or pharmacist will tell you how many capsules you will need to take each day.
  • Swallow the capsules 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 use DOXYLIN? in the full CMI.

5. What should I know while using DOXYLIN?

Things you should do
  • Remind any doctor, dentist or pharmacist you visit that you are taking DOXYLIN.
  • 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 DOXYLIN.
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 DOXYLIN 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 DOXYLIN affects you.
Drinking alcohol
  • Tell your doctor if you drink alcohol.
Looking after your medicine
  • Keep your tablets in the pack or bottle until it is time to take them.
  • Store in a cool dry place where the temperature stays below 30°C.

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

6. Are there any side effects?

Some of the 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.

Some of the more serious side effects include depression, anxiety, joint pain, muscle tenderness/ weakness, 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

DOXYLIN®

Active ingredient(s): doxycycline hyclate

Consumer Medicine Information (CMI)

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

Where to find information in this leaflet:

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

1. Why am I using DOXYLIN?

DOXYLIN contains the active ingredient doxycycline hyclate. This medicine belongs to a group of medicines called tetracyclines.

DOXYLIN is an antibiotic used to:

  • treat certain infections caused by bacteria
  • control acne
  • prevent some forms of malaria

It works by killing or stopping the growth of bacteria which cause infections or make acne worse.

DOXYLIN also works against parasites that cause malaria. It is sometimes used in combination with other anti-malarial medicines.

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.

2. What should I know before I use DOXYLIN?

Warnings

Do not use DOXYLIN if:

  • You are allergic to doxycycline hyclate, any medicines containing other tetracyclines, or any of the ingredients listed at the end of this leaflet.
    Some of the symptoms of an allergic reaction may include:
    - shortness of breath
    - wheezing or difficulty breathing
    - swelling of the face, lips, tongue or other parts of the body
    - rash, itching or hives on the skin

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. DOXYLIN 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.

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 (e.g. on a sun bed).
  • 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. High doses of tetracyclines may also cause liver problems in pregnant women.

Talk to your doctor if you are breastfeeding or intend to breastfeed. DOXYLIN, like other 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.

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 may interfere with DOXYLIN and affect how it works. These include:

  • preparations containing vitamin A, including vitamin supplements
  • preparations containing calcium or iron, including vitamin supplements
  • antacids, medicines used for indigestion
  • some medicines used for skin problems such as isotretinoin or etretinate
  • warfarin, a medicine used to prevent blood clots
  • another group of antibiotics called penicillins
  • phenytoin or carbamazepine, anticonvulsant medicines that are used to treat seizures
  • barbiturates, such as phenobarbital (phenobarbitone)
  • methoxyflurane, an anaesthetic
  • acetazolamide, a medicine used to help the body rid of salt and water
  • the contraceptive pill (birth control pill)
    DOXYLIN may decrease the effectiveness of some birth control pills.
    Your doctor may advise you to use an additional method of contraception while you are taking DOXYLIN and for 7 days after taking DOXYLIN

These medicines may be affected by DOXYLIN or may affect how well it works. You may need different amounts of your medicines, 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 DOXYLIN:

  • antacids (containing aluminium, calcium, magnesium or bismuth) used for indigestion
  • preparations that contain iron including vitamin preparations.

These medicines may interfere with the absorption of DOXYLIN.

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

4. How do I use DOXYLIN?

Your doctor will tell you how much you need to take each day and when to take it. This depends on your condition and whether or not you are taking any other medicines.

How much to take / use

  • For treating infections, the usual dose of doxycycline for adults is 200 mg on the first day, followed by 100 mg each day from then on.
  • For controlling acne, the usual dose for adults is 50 mg a day.
  • For the prevention of malaria, the usual dose for adults is 100 mg each day, starting two days before entering the malarious area, continuing during the visit, and for four weeks after leaving the area.

Follow the instructions provided when DOXYLIN was prescribed, including the number of days it should be taken. They may differ from the information contained in this leaflet.

Keep taking DOXYLIN for the full length of treatment. Continue taking your medicine even if you begin to feel better after a few days.

If you stop taking your medicine too soon, your infection may not clear completely, or your symptoms may return.

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

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

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

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

When to take / use DOXYLIN

  • Take your medicine during or immediately after a meal. If taken on an empty stomach, it may cause stomach upset.
  • 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.

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

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

If you forget to use DOXYLIN

DOXYLIN should be used regularly at the same time each day.

If you miss your dose at the usual time, 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 use too much DOXYLIN

If you think that you have used too much DOXYLIN, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (Australia telephone 13 11 26) for advice, 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 overdose may include nausea and vomiting.

5. What should I know while using DOXYLIN?

Things you should do

Call your doctor straight away if you:

  • you are taking DOXYLIN for an infection and your symptoms do not improve within a few days or they become worse
  • you become pregnant while taking DOXYLIN
  • you are about to have any blood tests
  • you get severe diarrhoea. Do this even if it occurs several weeks after DOXYLIN 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 using DOXYLIN.

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 DOXYLIN to make sure there is no problem with absorption.

Things you should not do

  • Do not stop taking DOXYLIN because you are feeling better, unless you are advised to by your doctor. If you do not complete the full course, the bacteria causing your infection may not all be killed. 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 DOXYLIN to treat any other complaints unless your doctor tells you to.

Things to be careful of

DOXYLIN 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.

Protect your skin when you are in the sun, especially between 10am and 3pm. If outdoors, wear protective clothing and use a 30+ sunscreen.

If your skin does appear to be burning, see your doctor as soon as possible. You may need alternative treatment.

Sometimes the use of this medicine allows fungi to grow as they are not killed by DOXYLIN.

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 DOXYLIN, tell your doctor.

Driving or using machines

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

Drinking alcohol

Tell your doctor if you drink alcohol.

Alcohol may interfere with the absorption of DOXYLIN.

Looking after your medicine

  • Keep your tablets in the original container until it is time to take them.
  • 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 window sills.

Keep your medicine where young children cannot reach it.

Getting rid of any unwanted medicine

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

Do not use 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
  • Stomach upset, feeling sick, vomiting, diarrhoea
  • mild irritation of the oesophagus (food-pipe)
  • taste loss
  • oral thrush (white, furry sore tongue and mouth)
  • vaginal thrush (sore and itchy vagina, vaginal discharge)
  • rash or itching
  • nail changes
  • persistent ringing or 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
  • swollen painful joints, muscle tenderness or weakness (not related to exercise)
  • 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 of layers of skin
  • severe sunburn that occurs more quickly than normal
  • pain or difficulty in swallowing
  • flaking of the skin
  • dizziness
  • fast heart rate
  • bleeding or bruising more easily than normal
  • passing little or no urine
  • signs of liver disease such as feeling generally unwell, fever, itching, yellowing of the skin and/or eyes, and dark coloured urine
  • severe upper stomach pain often with nausea and vomiting (pancreatitis)
  • severe diarrhoea, usually with blood and mucus, stomach pain and fever
  • signs of an allergic reaction such as skin rash, itching or hives; shortness of breath, wheezing or trouble breathing; swelling of the face, lips, tongue or other parts of the body
  • 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 DOXYLIN

See your doctor immediately if you notice any of the following, particularly if they occur several weeks after stopping treatment with DOXYLIN:

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

DOXYLIN can cause some bacteria that are normally harmless and present in the bowel to multiply and cause the above symptoms.

You may have a serious condition affecting your bowels. Therefore, it is important to tell your doctor as you may need urgent medical attention.

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

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 DOXYLIN contains

Active ingredient
(main ingredient)		doxycycline hyclate
Other ingredients
(inactive ingredients)
  • microcrystalline cellulose
  • pregelatinised maize starch
  • colloidal anhydrous silica
  • magnesium stearate
  • Opadry Yellow OY-LS-32814 (ARTG PI No. 2734)
Potential allergenslactose and trace amounts of sulfites.

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

What DOXYLIN looks like

DOXYLIN is available in two strengths:

  • DOXYLIN 50 mg are round, yellow tablets marked "DE" over "50" one side and "G" on the reverse. They are available in blister packs of 25 tablets (AUST R 63511).
  • DOXYLIN 100 mg are round, yellow tablets marked "DE" over "100" one side and "G" on the reverse. They are available in blister packs of 7 and 21 tablets (AUST R 63509).

Who distributes DOXYLIN

Alphapharm Pty Ltd trading as Viatris
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.viatris.com.au
Phone: 1800 274 276

This leaflet was prepared in June 2024.

DOXYLIN® is a Viatris company trade mark.

DOXYLIN_cmi\Jun24/01

Published by MIMS August 2024

BRAND INFORMATION

Brand name

Doxylin

Active ingredient

Doxycycline

Schedule

S4

 

1 Name of Medicine

Doxycycline hyclate.

2 Qualitative and Quantitative Composition

Each Doxylin tablet contains doxycycline hyclate equivalent to either 50 mg or 100 mg of doxycycline.

Excipients with known effect.

Lactose and trace amounts of sulfites.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Doxylin 50 mg tablet: round, yellow film coated, marked "DE" over "50" on one side, "G" on the reverse.
Doxylin 100 mg tablet: round, yellow film coated, marked "DE" over "100" on one side "G" on the reverse.

4 Clinical Particulars

4.1 Therapeutic Indications

Note.

The 50 mg tablet is not a paediatric formulation.
Doxycycline is indicated in the treatment of 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;
Calymmatobacterium (Donovania) granulomatis: granuloma inguinale;
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.)
Doxycycline is indicated in the treatment of infections caused by the following Gram negative microorganisms:
Vibrio species: cholera;
Brucella species: brucellosis (in conjunction with streptomycin);
Yersinia pestis: plague;
Francisella tularensis: tularaemia;
Bartonella bacilliformis: bartonellosis;
Bacteroides species.
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, e.g. chloroquine.
When penicillin is contraindicated, doxycycline is an alternative drug in the treatment of infections due to:
Treponema pallidum: syphilis;
Treponema pertenue: yaws;
Neisseria gonorrhoeae: gonorrhoea (see Section 4.2 Dose and Method of Administration);
Doxycycline may be a useful adjunct to amoebicides in the treatment of acute intestinal amoebiasis;
In the treatment of severe acne, doxycycline may be a useful adjunctive therapy.
Doxycycline is not the drug of choice in the following:
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. Doxylin should not be used for these infections unless the organism has been shown to be sensitive. For upper respiratory infections due to group A β-haemolytic streptococci, (including prophylaxis of rheumatic fever), penicillin is the usual drug of choice.

4.2 Dose and Method of Administration

Note.

1. The 50 mg tablet is not a paediatric formulation.
2. 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 Doxylin 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, bismuth salts and preparations containing iron impair absorption and should not be given to patients taking Doxylin.
3. The usual dosage and frequency of administration of Doxylin differs from that of other tetracyclines. Exceeding the recommended dosage may result in an increased incidence of side effects. Therapy should be continued for at least 24 to 48 hours after symptoms and fever have subsided.
4. 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 is 200 mg on the first day of treatment (100 mg every 12 hours), followed by a maintenance dose of 100 mg/day, which may be administered as a single dose or as 50 mg every 12 hours. In the management of more severe infections (particularly chronic infections of the urinary tract), 100 mg every 12 hours is recommended.

Acute uncomplicated gonococcal infections.

100 mg twice daily for 5 to 7 days.
Resistance to 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 mg or 200 mg according to severity.
For the prevention of scrub typhus: 200 mg as a single dose.

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

Children over 8 years of age (and below 50 kg in weight, without skeletal growth retardation).

The adult dose of 100 mg should be recalculated on a weight basis of 2 mg/kg (see Section 4.4 Special Warnings and Precautions for Use, 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.

4.3 Contraindications

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

Photosensitivity.

Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. Patients taking tetracycline drugs should be advised against exposure to direct sunlight or ultraviolet light, and treatment should be discontinued at the first sign of skin erythema.

Increased serum urea.

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.

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.

The use of antibiotics may occasionally result in overgrowth of non-susceptible organisms, including fungi. If superinfection occurs, the antibiotic should be discontinued, and appropriate therapy instituted.
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.

Treatment of venereal disease with coexistent syphilis.

In venereal disease when coexistent syphilis is suspected, proper diagnostic measures including a dark field examination should be performed before treatment is started, and the blood serology repeated monthly for at least four months.

Long-term therapy.

In long-term therapy, periodic laboratory evaluation of organ systems, including haematopoietic, renal and hepatic studies should be performed.

Oesophagitis/oesophageal ulceration.

If doxycycline is ingested in an incorrect manner there is a risk of adhesion of the tablet to the 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, doxycycline 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.

Gastric irritation.

To reduce the possibility of gastric irritation, it is recommended that Doxylin be given with food or milk. The absorption of doxycycline is not markedly influenced by simultaneous ingestion of food or milk.

Treatment of group A β-haemolytic streptococci infections.

Tetracyclines are not the medicines of choice for the treatment of streptococcal infections. However, when used, therapy should be continued for 10 days. All infections due to group A β-haemolytic streptococci should be treated for at least 10 days.

Hepatic effects.

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, Intracranial hypertension.)
Like 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.
The use of tetracyclines, including doxycycline, 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 occurs more commonly 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 unlikely 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.

Effects on laboratory tests.

False elevations of urinary catecholamine levels may occur due to interference with the fluorescence tests.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Anticoagulants.

There have been reports of prolonged prothrombin time in patients taking warfarin and doxycycline. Patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage, as tetracyclines have been shown to depress plasma prothrombin activity.

Antacids.

Antacids containing aluminium, calcium or magnesium, or other drugs containing these cations, bismuth salts and preparations containing iron impair absorption and should not be given to patients taking Doxylin.

Penicillin.

It is advisable to avoid giving tetracyclines concomitantly with penicillin as bacteriostatic drugs may interfere with the bactericidal action of penicillin.

Drugs that reduce plasma levels of doxycycline.

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, acetazolamide and ethoxzolamide.

Oral contraceptives.

There have been anecdotal reports that concurrent use of tetracyclines 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 Doxylin and for seven days following completion of the course of Doxylin.

Methoxyflurane.

The concurrent use of tetracyclines 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)
(See Section 4.4 Special Warnings and Precautions for Use.)
Tetracyclines are safe for use during the first 18 weeks of pregnancy, after which they cause discolouration of the baby's teeth.
During the period of mineralisation of a child's teeth (the last half 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 latter half of pregnancy.
Large doses of tetracyclines have caused acute fatty necrosis of the liver in pregnant women, especially those with pyelonephritis.
 Doxycycline is present in the milk of lactating women. It forms a stable calcium complex in bone-forming tissue and a decrease in the fibula growth has been observed in prematures. The use of medicines 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.
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).
Due to doxycycline's virtually complete absorption, side effects of the lower bowel, particularly diarrhoea, have been infrequent. The following adverse reactions have been observed in patients receiving doxycycline.

More common reactions.

Dermatological.

Photosensitive skin reactions (see Section 4.4 Special Warnings and Precautions for Use), erythematous rash, maculopapular rash, morbilliform rash, pustular rash, urticaria, photo-onycholysis and discolouration of the nails.

Gastrointestinal.

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

Hypersensitivity reactions.

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.

Nervous system disorders.

Dizziness.

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, hepatotoxicity, hepatitis. Abnormal hepatic function has been reported rarely (< 1 in 1000), pancreatitis.

Hepatic.

Hepatotoxicity.

Skin.

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

Musculoskeletal.

Arthralgia; myalgia.

Genitourinary.

Acute renal failure.

Hypersensitivity reactions.

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

Haematological and reticuloendothelial.

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

Nervous system.

Flushing, malaise, 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

Signs and symptoms.

Tetracyclines, including doxycycline, generally have low toxicity. Severe toxicity following acute overdosage is unlikely, with nausea and vomiting being the most common effects after ingestion of therapeutic and overdose amounts.

Treatment.

Treatment may include immediate discontinuation of medication, dilution with water or milk and general supportive care. Antacids may be useful in managing gastric irritation. In most cases, gastrointestinal decontamination is not required. Plasma levels are not clinically useful and specific laboratory monitoring is not needed unless otherwise indicated.
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 active against a wide range of Gram positive and Gram negative organisms. It is thought to exert its antimicrobial effect by the inhibition of protein synthesis.

Susceptibility testing.

Dilution or diffusion techniques. Either quantitative (MIC) or breakpoint, should be used following a regularly updated, recognised and standardised method (e.g. 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, but to a varying extent.
Doxycycline is almost completely absorbed following oral administration. Its absorption is not significantly affected by the presence of food or milk.

Distribution.

Tetracyclines are concentrated by the liver in the bile, and excreted in the urine and faeces at high concentrations and in a biologically active form.

Metabolism.

Following a 200 mg dose to normal adult volunteers, average peak plasma levels of 4.5 microgram/mL of doxycycline occur at approximately 2 hours, decreasing to 1.2 microgram/mL at 24 hours.
The plasma half-life of doxycycline ranges from 10 to 24 hours. No significant difference in serum half-life has been seen in individuals with normal and severely impaired renal function. Haemodialysis does not alter serum half-life.
The metabolism of doxycycline in humans has not been investigated. In vitro serum protein binding of doxycycline varies from 23 to 93%.

Excretion.

More than 90% of an oral dose of doxycycline is eliminated from the body within 72 hours of drug administration. The fraction of drug that is not eliminated with urine is mainly excreted in the faeces.
Excretion of doxycycline by the kidney is about 40% in 72 hours in individuals with normal renal function (creatinine clearance above 75 mL/min). Excretion may fall to as low as 1 to 5% in 72 hours in individuals with severe renal insufficiency (creatinine clearance below 10 mL/min).

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Doxylin 50 tablets contain colloidal anhydrous silica, magnesium stearate, microcrystalline cellulose, Opadry Yellow OY-LS-32814 (ARTG PI No. 2734), pregelatinised maize starch.
Doxylin 100 tablets contain colloidal anhydrous silica, magnesium stearate, microcrystalline cellulose, Opadry Yellow OY-LS-32814 (ARTG PI No. 2734), pregelatinised maize starch.

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.

6.5 Nature and Contents of Container

Container type.

Blister pack (PVC/PVDC/Al).

Pack sizes.

50 mg: blister pack: 25 tablets.
100 mg: blister packs: 7 and 21 tablets.
Some strengths, pack sizes and/or pack types may not be marketed.

Australian Register of Therapeutic Goods (ARTG).

AUST R 63511 - Doxylin 50 doxycycline 50 mg (as hyclate) tablet blister pack.
AUST R 63509 - Doxylin 100 doxycycline 100 mg (as hyclate) tablet blister pack.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking it to your local pharmacy.

6.7 Physicochemical Properties

Chemical structure.

Doxycycline is a yellow, crystalline powder hygroscopic. It is freely soluble in water and in methanol, sparingly soluble in ethanol (96%). It dissolves in solutions of alkali hydroxides and carbonates.
Doxycycline is a broad-spectrum antibiotic synthetically derived from oxytetracycline. It has a high lipid solubility and a low affinity for calcium binding, is highly stable in normal human serum, and will not degrade into an epianhydro form.
Chemical name: hemiethanol 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: C22H24N2O8.HCl.½C2H6O. ½H2O.
Molecular weight: 512.9.

CAS number.

24390-14-5.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

Summary Table of Changes