Consumer medicine information

Doryx

Doxycycline

BRAND INFORMATION

Brand name

Doryx

Active ingredient

Doxycycline

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Doryx.

What is in this leaflet

This leaflet answers some common questions about DORYX. 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 DORYX against the benefits this medicine is expected to have for you.

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

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

What DORYX is used for

DORYX is an antibiotic used to:

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

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. 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.

Before you take DORYX

When you must not take it

Do not take DORYX if you have an allergy to:

  • any medicine containing doxycycline
  • 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 troubled 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 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.

Do not take this medicine if you are more than 18 weeks pregnant or are breast-feeding. 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.

Do not give this medicine to children aged eight years or under unless directed by the child's doctor. DORYX 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 DORYX, 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 have any other health problems.

Tell your doctor if you 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.

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

Taking other medicines

Tell your doctor 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 DORYX may interfere with each other. 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). DORYX may decrease the effectiveness of some birth control pills.
    Your doctor may advise you to use an additional method of contraception while taking DORYX and for 7 days after taking DORYX. Refer to your doctor or pharmacist for advice.

These medicines may be affected by DORYX 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 DORYX:

  • 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 DORYX.

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

How to take DORYX

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 capsules you will need to take each day.

For treating infections, the usual dose of doxycycline is two 100 mg capsules on the first day, followed by one 100 mg capsule each day from then on.

For controlling acne, the usual dose is one 50 mg capsule each day.

For the prevention of malaria, the usual dose is one 100 mg capsule 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.

How to take it

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

Do not lie down immediately after swallowing DORYX. 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.

Do not chew the capsules.

When to take it

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.

How long to take it

Continue taking your medicine until you finish the pack or for as long as your doctor recommends.

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, DORYX is usually taken for one to two weeks.

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

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

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

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 double a dose to make up for the dose you have 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 your nearest hospital, if you think that you or anyone else may have taken too much DORYX. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

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

While you are taking DORYX

Things you must do

If you are taking DORYX for an infection and your symptoms do not improve within a few days or 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 DORYX 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.

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 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 DORYX to make sure there is no problem with absorption.

Things you must 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 DORYX 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. DORYX 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 DORYX, tell your doctor. Sometimes the use of this medicine allows fungi to grow as they are not killed by DORYX.

Side effects

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

This medicine is effective against infections/acne and helps prevent malaria for most people, but it may have unwanted side effects in some people. Sometimes they are serious, most of the time they are not. You may need medical attention 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:

  • 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.

The above list includes the more common side effects.

Tell your doctor as soon as possible if you notice any of the following:

  • depression
  • feeling anxious or nervous
  • muscle tenderness or weakness, not caused by exercise
  • painful swollen joints.

The above list includes serious side effects which may require medical attention.

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)
  • 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 swallowing
  • pain when 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.

These are serious side effects. You may need urgent medical attention or hospitalisation.

Tell your doctor if you notice anything else that is making you unwell. Other side effects not listed above 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 DORYX:

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

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

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

After using DORYX

Storage

Keep your capsules in their pack until it is time to take them. Avoid exposure to light. If you take the capsules out of the pack they may not keep as well.

Keep your capsules in a cool dry place where the temperature stays below 25°C.

Do not store DORYX or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car. 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

DORYX capsules come in two strengths:

DORYX 100 mg - clear capsules filled with yellow pellets, marked DORYX 100 in black. It is available in HDPE bottles of 7 or 21 capsules.

DORYX 50 mg - clear capsules filled with yellow pellets, marked DORYX 50 in black. It is available in HDPE bottles of 25 capsules.

Ingredients

Active ingredients:

DORYX 100 mg - contains 100 mg of doxycycline as doxycycline hyclate (hydrochloride) in each capsule.

DORYX 50 mg - contains 50 mg of doxycycline as doxycycline hyclate (hydrochloride) in each capsule.

Other ingredients:

  • lactose monohydrate
  • cellulose (460)
  • povidone
  • hypromellose phthalate
  • hypromellose
  • diethyl phthalate
  • wheat starch (contains gluten)
  • magnesium stearate
  • hyprolose
  • gelatin
  • Opacode Black A-10259 (contains shellac, carbon black, pharmaceutical glaze and ethanol)

This medicine does not contain sucrose, tartrazine or any other azo dyes.

Manufacturer/Distributor

Mayne Pharma International Pty Ltd
ABN 88 007 870 984
1538 Main North Road
Salisbury South SA 5106

Doryx® is a registered trademark of Mayne Pharma International Pty Ltd.

AUST R numbers

  • DORYX 100 mg - AUST R 30100
  • DORYX 50 mg - AUST R 29728

This leaflet was prepared in May 2019.

CMI Version Number: 8.0

Published by MIMS August 2019

BRAND INFORMATION

Brand name

Doryx

Active ingredient

Doxycycline

Schedule

S4

 

1 Name of Medicine

Doxycycline hyclate (hydrochloride).

6.7 Physicochemical Properties

The chemical designation of this light-yellow crystalline powder is 6-deoxy-5-oxytetracycline.
Molecular Formula: C22H24N2O8.HCl,½[C2H5OH.H2O]. MW: 512.9.

Chemical structure.

The chemical structure of doxycycline hyclate (hydrochloride) is:

CAS number.

24390-14-5.
Doxycycline has a high degree of lipid solubility and a low affinity for calcium binding. It is highly stable in normal human serum. Doxycycline will not degrade into an epianhydro form.

2 Qualitative and Quantitative Composition

Doryx Capsules contain either 50 mg or 100 mg of doxycycline (as doxycycline hyclate (hydrochloride)).
Doryx Capsules also contain lactose and wheat starch. For the full list of excipients see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Doryx capsules contain modified release pellets of doxycycline hyclate (hydrochloride). The capsule contains pellets which are coated so as to retard but not prevent release in acid media.
Doryx 50 mg capsules are clear capsules marked Doryx 50, containing yellow pellets.
Doryx 100 mg capsules are clear capsules marked Doryx 100, containing yellow pellets.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Doxycycline is a broad spectrum antibiotic synthetically derived from oxytetracycline. Doxycycline is primarily bacteriostatic and is thought to exert its antimicrobial effect by the inhibition of protein synthesis. Doxycycline is active against a wide range of gram positive and gram negative organisms.

Susceptibility testing.

The drugs in the tetracycline class have closely similar antimicrobial spectra, and cross resistance among them is common. Microorganisms may be considered susceptible if the MIC (minimum inhibitory concentration) is less than 1 microgram/mL and intermediate if the MIC is 1.0 to 5.0 microgram/mL.

Susceptibility plate testing.

A tetracycline disc may be used to determine microbial susceptibility to drugs in the tetracycline class. If the Kirby-Bauer method of disc susceptibility testing is used, a 30 microgram tetracycline disc should give a zone of at least 19 mm when tested against a tetracycline susceptible bacterial strain.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Doxycycline is virtually completely absorbed after oral administration. Its absorption is not significantly affected by the presence of food or milk. Following a 200 mg dose, normal adult volunteers averaged peak serum levels of 2.6 microgram/mL of doxycycline at 2 hours, decreasing to 1.45 microgram/mL at 24 hours.

Distribution.

In vitro serum protein binding of doxycycline varies from 23 to 93%.

Metabolism.

The metabolism of doxycycline in the human body has not been investigated.

Excretion.

Excretion of doxycycline by the kidney is about 40%/72 hours in individuals with normal renal function (creatinine clearance above 75 mL/min). This percentage may fall as low as 1 to 5%/72 hours in individuals with severe renal insufficiency (creatinine clearance below 10 mL/min). Studies have shown no significant difference in serum half-life of doxycycline range (18 to 22 hours) in individuals with normal and impaired renal function. The proportion of drug that is not eliminated within 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. Haemodialysis does not alter serum half life.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

4 Clinical Particulars

4.1 Therapeutic Indications

Note.

The 50 mg capsule is not a paediatric formulation.
Doryx is indicated in the treatment of infections caused by the following microorganisms.
Mycoplasma pneumoniae: primary atypical pneumonia.
Rickettsiae: Queensland tick typhus, typhus fever and Q fever.
Agents of psittacosis.
Calymmatobacterium (Donovania) granulomitis: granuloma inguinale.
Agents of lymphogranuloma venereum.
Borreliae: relapsing fever.
Chlamydia trachomatis.
Doryx 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 Doryx alone, or in combination with topical agents.
Doryx 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: tularemia.
Bartonella bacilliformis: bartonellosis.
Bacteroides species.
When penicillin is contraindicated, doxycycline is an alternative medicine 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).
Doryx is not the medicine of choice in the treatment of any type of staphylococcal infection or infections caused by Streptococcus pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, Streptococcus 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 tract infections due to group A β-haemolytic Streptococci (including prophylaxis of rheumatic fever) penicillin is the usual medicine of choice.
Doxycycline is active against both pre-erythrocytic and asexual bloodstages of Plasmodium falciparum. The tetracyclines are only partially active against the pre-erythrocytic stages of Plasmodium vivax, and protection depends on drug suppression of the blood stages. Doxycycline has no activity against the relapsing forms (hypnozoites) of Plasmodium vivax.
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 co-exist to some extent with P. falciparum, it is recommended that doxycycline should be used routinely with other agents, for example chloroquine.
In acute intestinal amoebiasis Doryx may be a useful adjunct to amoebicides.
In severe acne Doryx may be a useful adjunctive therapy.

4.3 Contraindications

This medicine is contraindicated in persons who have shown hypersensitivity to any of the tetracyclines or any of the excipients of Doryx capsules.
Use in pregnancy (16 weeks post conception) and use in lactation are contraindicated (see Section 4.4 Special Warnings and Precautions for Use).
Rare cases of benign intracranial hypertension have been reported after tetracyclines and after vitamin A or retinoids such as isotretinoin and etretinate. Concomitant treatment of tetracyclines with vitamin A or retinoids 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

Oesophageal injury.

If Doryx capsules are ingested in an incorrect manner there is a risk of adhesion of the capsule 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, Doryx 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. Most of these patients took medication immediately before going to bed. Administration of adequate amounts of fluid with the antibiotic is recommended to reduce the risk of oesophageal irritation and ulceration. It also is recommended that the antibiotic be administered in the morning (rather than late night), where practical, in an attempt to avoid this adverse effect.

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.

Photosensitivity.

Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. Patients likely to be exposed to direct sunlight or ultraviolet light should be advised that this reaction can occur with tetracycline medicines, and treatment should be discontinued at the first evidence of skin erythema.

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.
Antibiotic associated pseudomembranous colitis has been reported with many antibiotics including Doryx. 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 medicine discontinuation alone. This may be sufficient in the early stages, although cholestyramine orally may help by binding the toxin in the colonic lumen. 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. Medicines which delay peristalsis, e.g. opiates and diphenoxylate with atropine (Lomotil) may prolong and/or worsen the condition and should not be used.

Venereal disease.

In venereal disease when co-existent 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.

Gastric irritation.

If gastric irritation occurs, it is recommended that Doryx be given with food or milk. The absorption of Doryx is not markedly influenced by simultaneous ingestion of food or milk.

Beta-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. Infections due to group A β-haemolytic Streptococci should be treated for at least 10 days (see Section 4.1 Therapeutic Indications).

Hepatic function.

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

Increased serum urea.

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

Use in the elderly.

No data available.

Paediatric use.

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 prematures given oral tetracycline in doses of 25 mg/kg every six hours. This reaction was shown to be reversible when the medicine was discontinued.
The use of the medicines of the tetracycline class (including Doryx) 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 medicines but has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. Doryx, therefore, should not be used in this age group unless other medicines 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.

Effects on laboratory tests.

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

4.5 Interactions with Other Medicines and Other Forms of Interactions

Because the tetracyclines have been shown to depress plasma prothrombin activity, patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage.
Antacids containing aluminium, calcium, magnesium or bismuth salts and preparations containing iron impair absorption and should not be given to patients taking Doryx.
Since bacteriostatic medicines may interfere with the bactericidal action of penicillin, it is advisable to avoid giving tetracycline in conjunction with penicillin.
Plasma levels of doxycycline are reduced by the administration of barbiturates, anticonvulsants (phenytoin, carbamazepine), disodium hydrogen citrate, sodium bicarbonate, sodium lactate, acetazolamide and ethoxzolamide.
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 Doryx and for seven days following completion of the course of Doryx.
The concurrent use of tetracycline and methoxyflurane has been reported to result in fatal renal toxicity.

4.6 Fertility, Pregnancy and Lactation

Effects of fertility.

No data available.
(Category D)
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 teeth (the latter 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 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.

4.8 Adverse Effects (Undesirable Effects)

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

Hypersensitivity reactions.

Urticaria, exacerbation of systemic lupus erythematosus and Jarisch-Herxheimer reaction has been reported in the setting of spirochete infections treated with doxycycline.

Gastrointestinal.

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

Hepatic.

Cholestatic hepatitis, fatty liver degeneration.

Renal.

Dose related increase in serum urea.

Musculoskeletal.

Tooth discolouration, enamel hypoplasia.

Nervous system disorders.

Dizziness.

Other.

Bulging fontanelles have been reported in young infants following full therapeutic dosage. This sign disappeared rapidly when the medicine 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.

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, pericarditis, anaphylactoid purpura, serum sickness, hypotension, dyspnoea, peripheral oedema, tachycardia.

Haematological and reticuloendothelial.

Phlebitis associated with IV administration, leucopenia, thrombocytopenia, 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.

4.2 Dose and Method of Administration

Note.

The 50 mg capsule is not a paediatric formulation.
Doryx capsules must be ingested whole with at least 100 mL of liquid (half a glass), preferably in the morning when the patient can remain upright for at least 30 minutes. If gastric irritation occurs, Doryx capsules can be taken with food or milk, since studies indicate that the absorption of doxycycline is not markedly influenced by simultaneous ingestion of food or milk.
Administration of adequate amounts of fluid with the capsules and morning (rather than late night) dosage of the medicine, where practical, is recommended to reduce the risk of oesophageal irritation and ulceration. If gastric irritation occurs, it is recommended that Doryx be given with food or milk. The absorption of Doryx is not markedly influenced by simultaneous ingestion of food or milk. Antacids containing aluminium, calcium, magnesium or bismuth salts and preparations containing iron impair absorption and should not be given to patients taking Doryx (see Section 4.4 Special Warnings and Precautions for Use).
The usual dosage and frequency of administration of Doryx 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 medicines 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 of age (and above 50 kg in weight).

The usual dose of Doryx is 200 mg on the first day of treatment (administered as 100 mg every 12 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 12 hours. In the management of more severe infections (particularly chronic infections of the urinary tract) 100 mg every 12 hours is recommended.
For treatment of 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.

Doryx 100 mg once a day; commencing 2 days prior to entering malarious areas, while in the malarious area and for 4 weeks after leaving the malarious area. A maximum of Doryx 100 mg daily for 8 weeks is recommended, as safety after 8 weeks has not been clearly established (see Section 4.1 Therapeutic Indications) about combination with other antimalarial agents for prophylaxis against P. vivax).

Acute uncomplicated gonococcal infections.

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

Primary and secondary syphilis.

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

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 calculated on a weight basis of 2 mg/kg. (See Section 4.4 Special Warnings and Precautions for Use).
Studies to date have indicated that administration of Doryx at the usual recommended doses does not lead to excessive accumulation of the antibiotic in patients with renal impairment.
In long term therapy, periodic laboratory evaluation of organ systems, including haemopoietic, renal and hepatic studies should be performed.

4.7 Effects on Ability to Drive and Use Machines

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

4.9 Overdose

For information on the management of overdose, contact the Poisons Information Centre on 131126 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Excipients include lactose monohydrate, cellulose, povidone, hypromellose phthalate, hypromellose, diethyl phthalate, wheat starch, magnesium stearate, hyprolose, gelatin and Opacode Black A-10259 [Proprietary Ingredient ID 1659, contains shellac, carbon black, Pharmaceutical glaze and ethanol].

6.2 Incompatibilities

Incompatibilities were not assessed 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 25°C. Avoid exposure to light.

6.5 Nature and Contents of Container

Doryx 100 mg: available in HDPE bottles of 7 and 21.
Doryx 50 mg: available in a HDPE bottle of 25.

6.6 Special Precautions for Disposal

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

Summary Table of Changes