Consumer medicine information

Doxycycline Sandoz

Doxycycline

BRAND INFORMATION

Brand name

Doxycycline Sandoz

Active ingredient

Doxycycline

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Doxycycline Sandoz.

WHAT IS IN THIS LEAFLET

This leaflet answers some common questions about Doxycycline Sandoz.

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 this medicine against the benefits they expect it will 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 DOXYCYCLINE SANDOZ IS USED FOR

This medicine is used to:

  • treat certain infections
  • control acne
  • prevent a form of malaria
  • treat anthrax infection or for use after exposure to anthrax.

It contains the active ingredient doxycycline.

Doxycycline 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. They also work against parasites that cause malaria.

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 available only with a doctor's prescription.

BEFORE YOU TAKE DOXYCYCLINE SANDOZ

When you must not take it

Do not take this medicine if you have an allergy to:

  • doxycycline, the active ingredient, or to any of the other ingredients listed at the end of this leaflet under Product Description
  • any other similar medicines such as tetracyclines.

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 preparations containing isotretinoin, etretinate or Vitamin A. 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 ages eight years or under unless directed by the child’s doctor. Doxycycline 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 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 have or have ever had any other health problems
  • you are scheduled to have surgery under general anaesthetic
  • you work outdoors or you are exposed to direct sunlight or ultra-violet light.

Tell your doctor if you are pregnant or plan on getting pregnant.

Tell your doctor if you are breastfeeding or plan on breastfeeding. Your doctor can discuss with you the risks and benefits involved.

If you have not told your doctor about any of the above, tell him/her before you start taking Doxycycline Sandoz.

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 Doxycycline Sandoz 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 clots
  • methoxyflurane, an inhaled anaesthetic
  • the contraceptive (birth control) pill.
    Doxycycline Sandoz 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 this medicine.
  • penicillin antibiotics
  • barbiturates such as phenobarbitone
  • anticonvulsant medicines that are used to treat seizures, such as phenytoin and carbamazepine
  • sodium bicarbonate
  • acetazolamide, a medicine used to treat glaucoma.

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

Alcohol and some medicines may interfere with the absorption of Doxycycline Sandoz. These include:

  • iron preparations (including vitamin preparations containing iron)
  • antacids and other medicines containing aluminium, calcium or magnesium.
  • Bismuth salts, found in some medicines used to treat stomach ulcers

Do not drink alcohol or take any of these medicines if you are taking Doxycycline Sandoz.

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

HOW TO TAKE DOXYCYCLINE SANDOZ

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, ask your doctor or pharmacist for help.

How much to take

For treating infections, the usual dose of Doxycycline Sandoz is:

  • two 100 mg tablets on the first day followed by one 100 mg tablet each day from then on.

For controlling acne, the usual dose is:

  • one 50 mg tablet each day.

For the prevention of malaria, the usual dose is:

  • one 100 mg tablet each day, commencing two days before entering the malarious area, during the visit, and two weeks after leaving the area.

Doxycycline Sandoz is normally used in combination with other antimalarial medicine.

For the treatment of anthrax infection or after exposure, the usual dose is:

  • one 100 mg tablet every 12 hours in adults and 2.2 mg/kg every 12 hours for children (8 years or younger and children weighing 45 kg and less).

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

Ask your doctor or pharmacist if you are unsure of the correct dose for you. They will tell you exactly how much to take.

Follow the instructions they give you. If you take the wrong dose, Doxycycline Sandoz may not work as well and your problem may not improve.

How to take it

If you need to break Doxycycline Sandoz 100 mg tablets, hold tablet with both hands and snap along break line.

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

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

When to take Doxycycline Sandoz

Take your medicine during or immediately after a meal, at about the same time each day (usually in the morning).

If you take it on an empty stomach, it may cause stomach upset.

If you need to take an antacid, take it at least 2 hours before or 2 hours after your dose of Doxycycline Sandoz.

How long to take Doxycycline Sandoz

Continue taking your medicine for as long as your doctor tells you, 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, Doxycycline Sandoz is usually taken for one or two weeks.

For controlling acne, Doxycycline Sandoz is usually taken for a period up to 12 weeks.

For preventing malaria, Doxycycline Sandoz is normally recommended to be taken up to a maximum of 8 weeks.

For treating or after exposure to anthrax, Doxycycline Sandoz is usually taken for at least 60 days.

If you forget to take it

Take your dose as soon as you remember, and continue to take it as you would normally.

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

Do not take a double dose to make up for the dose that 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 Australia 13 11 26 or New Zealand 0800 POISON or 0800 764766) for advice, or go to Accident and Emergency at the nearest hospital, if you think that you or anyone else may have taken too much Doxycycline Sandoz. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Symptoms of an overdose may include nausea and vomiting.

WHILE YOU ARE TAKING DOXYCYCLINE SANDOZ

Things you must do

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

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

If you are going to have surgery, tell the surgeon or anaesthetist that you are taking this medicine. It may affect other medicines used during surgery.

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

If you are taking Doxycycline Sandoz 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 stopping this medicine. Diarrhoea may mean 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.

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 vitamins that contain iron, bismuth salts or antacids (containing aluminium, calcium or magnesium), you must take them at least two hours before or two hours after this medicine, to make sure there is no problem with absorption.

Things you must not do

Do not take Doxycycline Sandoz 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 10 am and 3 pm. Do not use a sunlamp while taking this medicine.

Doxycycline Sandoz 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 severe sunburn.

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.

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 doxycycline, tell your doctor. Sometimes the use of this medicine allows fungi to grow as they are not killed by doxcycline.

SIDE EFFECTS

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

All medicines can have side effects. 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.

While taking it

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 and/or discharge)
  • rash or itching
  • nail changes
  • stomach upset or vomiting
  • difficulty in swallowing
  • mild irritation of the oesophagus (food pipe)
  • taste loss
  • ringing or other persistent noise in the ears.

These are the more common side effects of your medicine. These side effects are usually mild.

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

If any of the following happen, stop taking Doxycycline Sandoz and 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 larger blisters and ends with peeling layers of skin
  • difficulty swallowing
  • pain when swallowing
  • flaking of the skin
  • dizziness
  • fast heart rate
  • frequent bruising
  • passing less urine
  • yellowing of the eyes or skin (jaundice)
  • sever 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 (eg. Liver, kidney, lung)
  • a reaction that can happen after starting doxycycline therapy for a particular bacterial infection (spirochete infections, eg. Lyme disease); symptoms include fever, chills, muscle pain or worsening of skin rash.

The above list includes serious side effects. You may need urgent medical attention or hospitalisation.

Tell your doctor or pharmacist if you notice anything else that is making you feel unwell. Other side effects not listed above may also 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 Doxycycline Sandoz:

  • severe abdominal cramps or stomach cramps
  • watery and severe diarrhoea, which may 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. Doxycycline Sandoz can cause some bacteria that are normally harmless and present in the bowel to multiply and cause the above symptoms. Therefore you may need urgent medical attention.

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

AFTER TAKING DOXYCYCLINE SANDOZ

Storage

Keep your medicine in the original container.

If you take it out of its original container it may not keep well.

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

Keep your medicine where it is protected from light.

Do not store Doxycycline Sandoz 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

Doxycycline Sandoz comes in two types of tablets:

Doxycycline Sandoz 50 mg - dull yellow, round, biconvex tablet.

Available in blisters of 25 tablets.

Doxycycline Sandoz 100 mg - dull yellow, round, biplane tablet with a single sided score notch.

Available in blisters of 7 tablets.

Ingredients

Active ingredient:

  • Doxycycline Sandoz 50 mg - 50 mg doxycycline (as monohydrate)
  • Doxycycline Sandoz 100 mg - 100 mg doxycycline (as monohydrate).

Inactive ingredients:

  • microcrystalline cellulose
  • sodium starch glycollate type A
  • hydrogenated castor oil
  • povidone
  • colloidal anhydrous silica
  • magnesium stearate.

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

Supplier

Sandoz Pty Ltd
ABN 60 075 449 553
54 Waterloo Road
Macquarie Park, NSW 2113
Australia
Tel: 1800 726 369

Novartis New Zealand Ltd
PO Box 99102
Newmarket, Auckland 0754
New Zealand
Tel: 0800 354 335

This leaflet was revised in August 2019.

Australian Register Numbers

Doxycycline Sandoz 50 mg tablets: AUST R 69049 (blisters)

Doxycycline Sandoz 100 mg tablets: AUST R 66302 (blisters)

Published by MIMS October 2019

BRAND INFORMATION

Brand name

Doxycycline Sandoz

Active ingredient

Doxycycline

Schedule

S4

 

1 Name of Medicine

Doxycycline monohydrate.

2 Qualitative and Quantitative Composition

Each Doxycycline Sandoz 50 mg tablets contains 50 mg doxycycline (as monohydrate).
Each Doxycycline Sandoz 100 mg tablets contains 100 mg doxycycline (as monohydrate).
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Doxycycline Sandoz 50 mg tablets - dull yellow, round, biconvex tablets.
Doxycycline Sandoz 100 mg tablets - dull yellow, round, biplane tablets with a single-sided score notch.

4 Clinical Particulars

4.1 Therapeutic Indications

Infections caused by the following micro-organisms: Mycoplasma pneumoniae (primary atypical pneumonia); Rickettsiae (Queensland tick typhus, epidemic typhus fever, Q fever, murine endemic typhus fever, Australo-Pacific endemic scrub typhus); Chlamydia psittaci (psittacosis); Chlamydia trachomatis (lymphogranuloma venereum, trachoma, inclusion conjunctivitis).
(Doxycycline is indicated in the treatment of trachoma, although the infectious agent is not always eliminated, as judged by immunofluorescence. Inclusion conjunctivitis may be treated with oral doxycycline, or in combination with topical agents.)
Borreliae (relapsing fever); Calymmatobacterium (Donovania) granulomatis (granuloma inguinale).
Doxycycline Sandoz is indicated for the treatment of Anthrax due to Bacillus anthracis, including inhalational anthrax (post-exposure) to reduce the incidence or progression of disease following exposure to aerosolized Bacillus anthracis (see Section 4.2 Dose and Method of Administration).
Infections caused by the following Gram negative micro-organisms: Vibrio sp. (cholera); Brucella sp. (brucellosis; in conjunction with streptomycin); Yersinia pestis (plague); Francisella tularensis (tularaemia); Bartonella bacilliformis (bartonellosis); Bacteroides sp.
When penicillin is contraindicated, doxycycline is an alternative medicine in the treatment of infections due to: Treponema pallidum (syphilis); Treponema pertenue (yaws); Neisseria gonorrhoea (see Section 4.2 Dose and Method of Administration).

Note.

Doxycycline Sandoz 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 Sandoz should not be used in these infections unless the organism has been shown to be sensitive. For upper respiratory infections due to group A beta-haemolytic streptococci (including prophylaxis of rheumatic fever), penicillin is the usual medicine of choice.
In acute intestinal amoebiasis Doxycycline Sandoz may be a useful adjunct to amoebicides.
In severe acne, doxycycline may be a useful adjunctive therapy.
Doxycycline is indicated, in adults and children older than 10 years, as chemoprophylaxis for malaria caused by Plasmodium falciparum and, in combination with other antimalarial agents, against malaria caused by Plasmodium vivax. Doxycycline is only able to suppress malaria caused by Plasmodium vivax. As there are relatively few locations where P. vivax does not coexist to some extent with P. falciparum, it is recommended that doxycycline should be used routinely with other agents, for example chloroquine.

4.2 Dose and Method of Administration

Dosage.

The usual dosage and frequency of administration of doxycycline differs from that of other tetracyclines. Exceeding the recommended dosage may result in an increased incidence of side effects. Therapy should be continued at least 24 to 48 hours after symptoms and fever have subsided.
Tetracyclines are not the medicines of choice for the treatment of streptococcal infections (see Section 4.1 Therapeutic Indications). However, when used, therapy should be continued for ten days.
Adults, children over 8 years (and > 50 kg). The usual dose of doxycycline is 200 mg on the first day of treatment (administered as 100 mg every twelve hours) followed by a maintenance dose of 100 mg/day. The maintenance dose may be administered as a single dose or as 50 mg every twelve hours. In the management of more severe infections (particularly chronic infections of the urinary tract), 100 mg every twelve hours is recommended.

Acute uncomplicated gonococcal infections.

100 mg twice daily for five to seven 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/day in divided doses for at least ten days.

Louse borne typhus.

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

Prevention of scrub typhus.

200 mg as a single dose.
Children over 8 years (and < 50 kg, without skeletal growth retardation). The adult dose of 100 mg should be recalculated on a weight basis as 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.

Severe acne.

Some efficacy has been demonstrated in some individuals at a dose of 50 mg/day over a period of 12 weeks. No data showing efficacy beyond 12 weeks have been submitted.
Malaria chemoprophylaxis. 100 mg once a day; commencing two days prior to entering malarious areas, while in the malaria area and for two weeks after leaving the malarious area. A maximum of 100 mg daily for eight weeks is recommended, as safety after eight weeks has not been clearly established (see Section 5 Pharmacological Properties; Section 4.1 Therapeutic Indications about combination with other antimalarial agents for prophylaxis against P. vivax).
Anthrax due to Bacillus anthracis including inhalational anthrax (post exposure).

Adults.

The recommended dose for adults is 100 mg every 12 hours.

Children 8 years or younger and children weighing 45 kg and less.

The recommended dose is 2.2 mg/kg every 12 hours.

Duration of treatment.

It is recommended that treatment be continued for at least 60 days.
Therapy should be modified in light of antimicrobial susceptibility testing results.

Method of administration.

Administration of adequate amounts of fluid with the tablets is recommended to reduce the risk of oesophageal irritation and ulceration. Morning (rather than late night) dosing may be preferable. As the recumbent posture may delay oesophageal transit of the tablets, the patient should not lie down for some time after taking the tablets. To reduce the possibility of gastric irritation, it is recommended that doxycycline be given with food or milk. The absorption of doxycycline is not markedly influenced by simultaneous ingestion of food or milk. Antacids containing aluminium, calcium or magnesium and preparations containing iron impair absorption and should not be given to patients taking doxycycline.

4.3 Contraindications

Hypersensitivity to doxycycline, any of the excipients in Doxycycline Sandoz or to any of the tetracyclines. 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

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

Concomitant diseases.

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

Long-term treatment.

In long-term therapy, periodic laboratory evaluation of organ systems, including haemopoietic, renal and hepatic studies, should be performed.
If doxycycline is used to treat infections due to group A beta-haemolytic streptococci, treatment should continue for at least 10 days.

Gastrointestinal disease.

History of colitis.

Antibiotics should be prescribed with care for individuals with a history of gastrointestinal disease, especially ulcerative colitis, regional enteritis or antibiotic associated colitis.

Pseudomembranous colitis.

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 medicine 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. Medicines, which delay peristalsis, e.g. opiates and diphenoxylate with atropine may prolong and/or worsen the condition and should not be used.
Rarely, oesophagitis and oesophageal ulceration have been reported in patients receiving doxycycline tablets. Most of these patients took medication immediately before going to bed. Patients should be instructed to take doxycycline with plenty of water (at least 100 mL), remain upright and not take their treatment before going to bed. Withdrawal of doxycycline and investigation of oesophageal disorder should be considered if symptoms such as dyspepsia or retrosternal pain occur. Caution is required in the treatment of patients with known oesophageal reflux disorders. To reduce the possibility of gastric irritation it is recommended that doxycycline be given with food or milk. The absorption of doxycycline is not markedly influenced by simultaneous ingestion of food or milk.

Bacillus anthracis infection.

In the treatment of severe disease due to Bacillus anthracis initial IV therapy is recommended. Doxycycline should not be used as a single agent for treatment of severe disease due to Bacillus anthracis, including meningitis. Doxycycline may be less effective in anthrax meningitis due to poor CNS penetration.

Use in hepatic impairment.

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

Use in renal impairment.

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 premature infants given oral tetracycline in doses of 25 mg/kg every six hours. This effect was shown to be reversible when the medicine was discontinued.
Tetracyclines also interfere with tooth development (see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy). The use of the medicines of the tetracycline class, including Doxycycline Sandoz, 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 effect 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. Therefore, doxycycline should not be used in children younger than 8 years of age 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

There have been reports of prolonged prothrombin time in patients taking warfarin and doxycycline. 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 or magnesium or other medicines containing these cations, bismuth salts, and preparations containing iron impair absorption and should not be given to patients taking doxycycline.
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 ingestion of alcohol or the administration of barbiturates, anticonvulsants (phenytoin, carbamazepine), disodium hydrogen edetate, sodium bicarbonate, sodium lactate, acetazolamide and ethoxzolamide.
There are anecdotal reports that concurrent use of tetracyclines may render oral contraceptives less effective. Unplanned pregnancy may occur with this combination. A barrier method of contraception should be used while taking doxycycline and for seven days following completion of the course of Doxycycline Sandoz.
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)
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.
There are no adequate and well controlled studies on the use of doxycycline in pregnant women. The vast majority of reported experience with doxycycline during human pregnancy is short-term, first trimester exposure. An expert review of published data on experiences with doxycycline use during pregnancy by TERIS (the Teratogen Information System) concluded that therapeutic doses during pregnancy are unlikely to pose a substantial teratogenic risk (the quantity and quality of data were assessed as limited to fair), but the data are insufficient to state that there is no risk. A case control study (18,515 mothers of infants with congenital anomalies and 32,804 mothers of infants with no congenital anomalies) shows a weak but marginally statistically significant association with total malformations and use of doxycycline anytime during pregnancy. Sixty three (0.19%) of the controls and fifty six (0.30%) of the cases were treated with doxycycline. This association was not seen when the analysis was confined to maternal treatment during the period organogenesis (i.e. in the second and third months of gestation) with the exception of a marginal relationship with neural tube defect based on only two exposed cases.
A small prospective study of 81 pregnancies describes 43 pregnant women treated for ten days with doxycycline during early first trimester. All mothers reported their exposed infants were normal at 1 year of age.
Results in animal studies indicate that tetracyclines cross the placenta, are found in foetal tissues and can have toxic effects on the developing foetus (often related to retardation of skeletal development). Evidence of embryotoxicity has also been noted in animals treated early in pregnancy.
Large doses of tetracyclines have caused acute fatty necrosis of the liver in pregnant women, especially those with pyelonephritis. Large doses of the medicine should not be used in pregnant women, or those likely to become pregnant.
 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 uses 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. Due to its virtually complete absorption, side effects of the lower bowel, particularly diarrhoea, have been infrequent. The following adverse effects have been observed in patients receiving doxycycline.

More common effects.

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.

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 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 effects.

Gastrointestinal.

Enterocolitis (see Section 4.4 Special Warnings and Precautions for Use), inflammatory lesions (with monilial overgrowth) in the ano-genital region; dyspepsia and pseudomembranous colitis (see Section 4.4 Special Warnings and Precautions for Use), C. difficile diarrhoea, hepatotoxicity, hepatitis. Abnormal hepatic function has been reported rarely (< 1/1,000), pancreatitis.

Dermatological.

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

Musculoskeletal.

Arthralgia, myalgia.

Genitourinary.

Acute renal failure.

Hypersensitivity.

Angioneurotic oedema, anaphylaxis, anaphylactic shock, anaphylactic reaction, anaphylactoid purpura, pericarditis, serum sickness, hypotension, dyspnoea, peripheral oedema, tachycardia, erythema multiforme, drug rash with eosinophilia and systemic symptoms (DRESS).

Haematological and reticuloendothelial.

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

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.

Hepatic.

Hepatotoxicity.

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

Tetracyclines, including doxycycline, generally have low toxicity.

Symptoms.

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.
In case of an oral overdose with doxycycline, gastric lavage should be considered to remove unabsorbed portions of the substance. Remaining residues of doxycycline should be minimised by administering antacids or calcium or magnesium salt in order to produce non-absorbable chelates.
Doxycycline is not sufficiently dialysable. Thus, haemodialysis or peritoneal dialysis is not very effective.
In massive overdose, there is a risk of liver damage sometimes accompanied by pancreatitis.
For information on the management of overdose, contact the Poison Information Centre on 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Doxycycline is a broad spectrum antibiotic synthetically derived from oxytetracycline.

Mechanism of action.

Microbiology. Doxycycline is primarily bacteriostatic and is thought to exert its antimicrobial effect through inhibition of protein synthesis. It is active against a wide range of Gram-positive and Gram-negative organisms (see Section 4.1 Therapeutic Indications).
Strains of Bacillus anthracis isolated from the environment are generally sensitive to doxycycline. Because of the potential for laboratory manipulation of B. anthracis, in the treatment of anthrax, clinical isolates should be tested for antibiotic susceptibility by validated test methods. Therapy should be modified in light of antimicrobial susceptibility testing results.

Susceptibility testing.

Medicines 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 1.0 microgram/mL, and intermediate if the MIC is 1.0 to 5.0 microgram/mL.
A tetracycline disc may be used to determine microbial susceptibility to medicines in the tetracycline class. If the Kirby-Bauer method of disc susceptibility is used, a 30 microgram tetracycline disc should give a zone of at least 19 mm when tested against a tetracycline susceptible bacterial strain.

Disc susceptibility testing.

Dilution or diffusion techniques - either quantitative (MIC) or breakpoint, should be used following a regularly updated, recognised and standardised method (e.g. 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 the alternative, clinically feasible drugs, the tests 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 reached concentrations usually achievable; other therapy should be selected.

Note.

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

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Tetracyclines are readily absorbed though to a varying extent. 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.

There is limited diffusion of doxycycline into CSF after oral administration.

Metabolism.

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

Excretion.

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

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Microcrystalline cellulose, sodium starch glycollate type A, hydrogenated castor oil, povidone, colloidal anhydrous silica and magnesium stearate.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.
For information on interactions with other medicines and other forms of interactions, see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

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.
Protect from light.

6.5 Nature and Contents of Container

Doxycycline Sandoz 50 mg tablets are available in PP/Al blister packs of 25 tablets.
Doxycycline Sandoz 100 mg tablets are available in PP/Al blister packs of 7 tablets.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Doxycycline is a light yellow crystalline powder, which has a high lipid solubility and a low affinity for calcium binding. It is highly stable in normal human serum. It will not degrade into an epianhydro form.
Chemical formula: (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 monohydrate.
Molecular formula: C22H24N2O8.H2O.
Molecular weight: 462.5.

Chemical structure.


CAS number.

17086-28-1.

7 Medicine Schedule (Poisons Standard)

S4.

Summary Table of Changes