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.

What is in this leaflet?

This leaflet answers some common questions about DOXYLIN. It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

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

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

Keep this leaflet with your medicine. You may need to read it again.

What DOXYLIN is used for

DOXYLIN is an antibiotic used to:

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

This medicine belongs to a group of medicines called tetracyclines. 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 infections caused by viruses, 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.

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

Before you take DOXYLIN

When you must not take it

Do not take DOXYLIN if you have an allergy to:

  • any medicine containing doxycycline hyclate
  • any medicines containing other tetracyclines
  • 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 take this medicine if you are taking other medicines containing vitamin A, isotretinoin or etretinate.

DOXYLIN should not be taken if you are more than 18 weeks pregnant or are breastfeeding. 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.

Do not give this medicine to children aged eight years or under 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.

Do not take this medicine after the expiry date printed on the pack or if the packaging is torn or show 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 start taking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you are pregnant or plan to become pregnant. High doses of tetracyclines may also cause liver problems in pregnant women.

Tell your doctor if you are breastfeeding or plan to breastfeed.

Tell your doctor if you are scheduled to have surgery under general anaesthetic.

Tell your doctor if you work outdoors or if you are likely to be exposed to strong sunlight or ultra-violet light (e.g. on a sun bed). You should avoid exposure to strong sunlight while taking this medicine as your skin may be more sensitive to sunburn than normal.

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

Taking other medicines

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

Some medicines and DOXYLIN may interfere with each other. 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.

Alcohol may also interfere with the absorption of DOXYLIN.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking this medicine.

How to take DOXYLIN

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

If you do not understand the instructions on the box/bottle, ask your doctor or pharmacist for help.

How much to take

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.

For treating infections, the usual dose of doxycycline hyclate 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.

Children over 8 years of age may need smaller doses, depending on their weight.

How to take it

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

If you are taking iron or calcium medicines (including vitamins that contain iron or calcium) or antacids, you must take them at least two hours before or two hours after taking DOXYLIN to make sure there are no problems with absorption.

Do not lie down immediately after taking DOXYLIN. It is important to not lie down for at least half an hour after swallowing your medicine, so that the tablet can move swiftly into the stomach and prevent irritation of the throat or oesophagus (canal taking food from the mouth to the stomach).

When to take it

Take your medicine during or immediately after a meal, preferably in the morning. This will reduce the chances of stomach upset.

Take your medicine at about the same time each day. Taking it at the same time each day will have the best effect. It will also help you remember when to take it.

How long to take it

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 forget to take it

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

Otherwise, take 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 (overdose)

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

Symptoms of overdose include nausea and vomiting.

While you are taking DOXYLIN

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking DOXYLIN.

Tell any other doctors, dentists and pharmacists who treat you that you are taking this medicine.

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

If you are taking DOXYLIN for an infection and your symptoms do not improve within a few days, or if they become worse, tell your doctor.

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

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.

Keep all of your doctor's appointments so that your progress can be checked. Your doctor may do some tests from time to time to make sure the medicine is working and to prevent unwanted side effects.

Things you must not do

Do not take DOXYLIN to treat any other complaints unless your doctor tells you to.

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

Do not stop taking your medicine or lower the dosage without checking with your doctor.

If you do not complete the full course prescribed by your doctor, all 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 may return.

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 SPF 30+ sunscreen. DOXYLIN may cause your skin to be more sensitive to sunlight than normal. Exposure to sunlight may cause a skin rash, itching, redness, or severe sunburn.

If your skin does appear to be burning, tell your doctor before you take your next dose of 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. Sometimes use of this medicine allows fungi to grow. These fungi are not killed by DOXYLIN.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking DOXYLIN.

This medicine helps most people, but it may have unwanted side effects in a few people. Sometimes they are serious, most of the time they are not. You may need medical treatment if you get some of the side effects.

Do not be alarmed by the following lists of side effects. You may not experience any of them.

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

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

  • feeling sick, vomiting, diarrhoea
  • taste loss
  • stomach upset or vomiting
  • 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

The above side effects are usually mild.

If any of the following happen, tell your doctor immediately or go to Accident and Emergency at your nearest hospital:

  • increased pressure in the brain (headache, blurred vision, vomiting)
  • heartburn or indigestion, which may be due to irritation of the oesophagus (food pipe)
  • severe diarrhoea, usually with blood and mucus, stomach pain and fever
  • bleeding or bruising more easily than normal
  • dizziness
  • fast heart rate
  • severe blisters and bleeding in the lips, eyes, mouth, nose and genitals
  • signs of liver disease such as feeling generally unwell, fever, itching, yellowing of the skin and/or eyes, and dark coloured urine
  • passing little or no urine
  • joint pain, muscle tenderness or weakness
  • pain or difficulty in swallowing
  • severe sunburn that occurs more quickly than normal
  • severe skin reactions starting as painful red areas then large blisters and ends with peeling of layers of skin
  • 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

The above list includes serious side effects that may require medical attention. Serious side effects are rare.

Tell your doctor or pharmacist if you notice anything that is making you feel unwell.

Other side effects not listed above may also 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.

After taking DOXYLIN

Storage

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

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

Do not store DOXYLIN or any other medicine in the bathroom or near a sink. Do not leave it in the car or on a window sill. Heat and dampness can destroy some medicines.

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

Disposal

If your doctor tells you to stop taking this medicine or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

DOXYLIN is available in two strengths:

  • 50 mg - round, yellow tablet marked "DE" over "50" one side and "G" on the reverse
  • 100 mg - round, yellow tablet marked "DE" over "100" one side and "G" on the reverse

DOXYLIN 50 mg is available in blister packs of 25 tablets.

DOXYLIN 100 mg is available in blister packs of 7 and 21 tablets.

Ingredients

DOXYLIN contains doxycycline hyclate equivalent to either 50 mg or 100 mg of doxycycline as the active ingredient.

The tablets also contain the following inactive ingredients:

  • microcrystalline cellulose
  • pregelatinised maize starch
  • colloidal anhydrous silica
  • magnesium stearate
  • Opadry Yellow OY-LS-32814(ARTG PI No. 2734)

DOXYLIN contains lactose and trace amounts of sulfites. This medicine does not contain gluten.

Manufacturer

DOXYLIN is made in Australia by:

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 September 2023.

Australian registration numbers:
Doxylin 50 - AUST R 63511
Doxylin 100 - AUST R 63509

DOXYLIN® is a Viatris company trade mark

DOXYLIN_cmi\Sep23/00

Published by MIMS October 2023

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