Consumer medicine information

Akamin

Minocycline

BRAND INFORMATION

Brand name

Akamin

Active ingredient

Minocycline

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Akamin.

What is in this leaflet

This leaflet answers some common questions about Akamin.

It does not contain all the available information. It does not take the place of talking to your doctor or pharmacist.

All medicines have benefits and risks. Your doctor has weighed the risks of you taking Akamin against the benefits expected 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 Akamin is used for

Akamin is used to:

  • treat certain infections caused by bacteria
  • control acne.

Akamin is an antibiotic that belongs to a group of medicines called tetracyclines. These medicines work by stopping the growth of bacteria which cause infections or make acne worse.

Akamin will not work against infections caused by viruses, such as colds or flu.

Ask your doctor if you have any questions about why Akamin has been prescribed for you. Your doctor may have prescribed Akamin for another reason.

Akamin is available only with a doctor's prescription.

There is no evidence that Akamin is addictive.

Before you take Akamin

When you must not take it

Do not take Akamin if you are allergic to:

  • medicines containing minocycline (e.g. Minomycin)
  • medicines containing any other tetracycline antibiotic (e.g. Doryx, Doxylin, Vibramycin, Vibra-Tabs)
  • any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include skin rash, itching or hives; swelling of the face, lips, tongue or other parts of the body; shortness of breath, wheezing or difficulty breathing.

Do not take Akamin if you are taking preparations containing:

  • vitamin A
  • retinoids, which are medicines used to treat
    - skin problems such as isotretinoin (Roaccutane, Oratane) and acitretin (Neotigason)
    - a certain type of leukaemia such as tretinoin (Vesanoid).

Taking Akamin with any of these preparations may lead to serious unwanted side effects.

Ask your doctor or pharmacist if you are not sure if you are taking one of these medicines.

Do not take Akamin if you are pregnant. Akamin is not recommended in the second and third terms of pregnancy as it may harm your developing baby. This may include enamel loss and staining of your baby's teeth.

Do not take Akamin if you are breastfeeding. Akamin passes into breast milk and may cause enamel loss and staining of your baby's teeth.

Do not take Akamin if you have any of the following medical conditions:

  • severe kidney disease
  • systemic lupus erythematosus (SLE).

Do not give Akamin to a child aged 8 years and under unless directed by the child's doctor. Tetracycline medicines, including Akamin, may cause permanent staining and enamel loss in developing teeth, and reduced bone growth.

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, dyes or preservatives.

Tell your doctor if you have or have had any of the following medical conditions:

  • kidney problems
  • liver problems.

Your doctor may want to take special care if you have any of these conditions.

Tell your doctor if you plan to have surgery, including dental surgery, especially if it requires a general anaesthetic.

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

Taking other medicines

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

Some medicines and Akamin may interfere with each other. These include:

  • preparations containing vitamin A including vitamin supplements
  • retinoids used for skin problems, such as isotretinoin (Roaccutane, Oratane), acitretin (Neotigason) or for leukaemia such as tretinoin (Vesanoid)
  • medicines used to prevent blood clots, such as warfarin (Coumadin, Marevan)
  • penicillins, another group of antibiotics (e.g. Amoxil)
  • diuretics, also called fluid or water tablets (e.g. Lasix, Moduretic, Aldactone)
  • methoxyflurane (Penthrax), an inhalation general anaesthetic
  • the contraceptive pill (birth control pill).

Talk to your doctor about the additional need for a barrier method of contraception (e.g. condom or diaphragm) while taking Akamin. Akamin may decrease the effectiveness of some birth control pills.

Medicines which interfere with the absorption of Akamin include:

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

You can still take these medicines while you are taking Akamin. However, you must take Akamin at least 2 hours before or 2 hours after taking any of these medicines to make sure there is no problem with absorption.

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

How to take Akamin

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 bottle, ask your doctor or pharmacist.

How much to take

For treating infections, the usual dose for adults is 200 mg initially, followed by 100 mg every 12 hours.

For controlling acne, the usual dose is 50 mg twice a day.

However, depending on your condition and your response to this medicine, your doctor may ask you to take a different dose.

People with kidney problems may require smaller doses.

How to take it

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

Stay upright for at least 30 minutes. Do not lie down immediately after taking Akamin. This is to help avoid irritation to your oesophagus (food pipe), which you may feel as heartburn or indigestion.

When to take it

Take Akamin during or immediately after a meal. This will reduce the chances of stomach upset.

Take Akamin 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 for

Keep taking Akamin until you finish the tablets or capsules, or for as long as your doctor recommends.

For infections, your doctor will tell you when to stop taking Akamin, as the length of treatment varies depending on the condition you have. This is usually 24 to 48 hours after the fever and signs of infection have gone.

Do not stop taking Akamin, even if you feel better after a few days, unless advised by your doctor. Your infection may not clear completely if you stop taking your medicine too soon.

For controlling acne, Akamin is normally taken for a few months.

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 the missed dose as soon as you remember, and then go back to taking your tablets or capsules as you would normally.

Do not take a double dose to make up for the dose you missed.

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

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 Akamin. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

If you take too much Akamin you may experience the following symptoms: nausea, vomiting, stomach pain, fall in blood pressure, tiredness.

While you are taking Akamin

Things you must do

If you develop a persistent headache with one or more of the following symptoms - nausea, vomiting, blurred vision or dizziness; see your doctor immediately. These may be signs of a rare condition associated with the use of minocycline called benign intracranial hypertension (increased pressure within the skull).

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

If you become pregnant while you are taking Akamin, tell your doctor immediately.

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

If you get a sore, white mouth or tongue while taking or soon after stopping Akamin, tell your doctor. Also tell your doctor if you get vaginal itching or discharge. This may mean you have a fungal infection called thrush. Sometimes the use of Akamin allows fungi to grow and the above symptoms to occur. Akamin does not work against fungi.

Before starting any new medicine, tell your doctor or pharmacist that you are taking Akamin.

Tell all the doctors, dentists and pharmacists who are treating you that you are taking Akamin.

If you are taking Akamin for a long time, visit your doctor regularly so that they can check on your progress. Your doctor may want you to have some blood tests from time to time.

Things you must not do

Do not stop taking Akamin or change the dose, without checking with your doctor. If you do not complete the full course prescribed by your doctor, all of the bacteria causing your infection may not be killed. Your infection may not clear completely or may return.

Do not let yourself run out of Akamin over the weekend or on holidays.

Do not use Akamin to treat any other conditions unless your doctor tells you to.

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

Things to be careful of

Protect your skin when you are in the sun, especially between 10 am and 3 pm. If outdoors, wear protective clothing and use a SPF 30+ sunscreen. Akamin may cause your skin to be much more sensitive to sunlight than it is normally. This may cause a skin rash, itching, redness or severe sunburn.

If your skin does appear to be burning, stop taking Akamin and tell your doctor.

Be careful driving or operating machinery until you know how Akamin affects you. Akamin may cause dizziness or lightheadedness in some people. If you have any of these symptoms, do not drive, operate machinery or do anything else that could be dangerous.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Akamin. Akamin helps most people with their infections or acne, but it may have unwanted side effects in some people.

All medicines can have side effects. 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 this list of possible side effects. You may not experience any of them.

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

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

  • dizziness, lightheadedness, unsteadiness
  • headache
  • blurred vision, hearing loss
  • feeling sick (nausea), vomiting, diarrhoea
  • loss of appetite
  • sore mouth or tongue
  • difficulty in swallowing
  • oral thrush (white, furry sore tongue and mouth)
  • vaginal thrush (sore and itchy vagina, vaginal discharge)
  • swelling and itching in the anal and genital areas
  • heartburn, which may be due to irritation and ulceration of the oesophagus (food pipe).

The above list includes the milder side effects of Akamin.

Tell your doctor immediately or go to Accident and Emergency at the nearest hospital if you notice any of the following:

  • symptoms of a rare condition called benign intracranial hypertension (increased pressure within the skull) such as persistent headache along with one or more of the following - nausea, vomiting, blurred vision or dizziness
  • severe diarrhoea, usually with blood and mucus, stomach pain and fever
  • severe upper stomach pains, often with nausea and vomiting
  • signs of frequent infections such as fever, chills, sore throat or mouth ulcers
  • bruising or bleeding more easily than normal
  • being short of breath when exercising, often with tiredness, headaches, dizziness and looking pale and yellowing of the skin and/or eyes
  • swollen, stiff or painful joints
  • passing less urine than normal
  • signs of liver disease such as feeling generally unwell, loss of appetite, yellowing of the eyes or skin (jaundice), fever, itching and dark coloured urine
  • skin rash, itching, redness, flaking or blistering
  • symptoms of severe sunburn (such as redness, itching, swelling, blistering) that may occur more quickly than normal
  • convulsions or seizures
  • sudden signs of allergy such as rash, itching or hives on the skin, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or trouble breathing.

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

Contact your doctor if you notice any staining of your skin, teeth, tongue, lips, gums or nails. Slight blue-black colour staining of the skin, teeth, nails, inside of the mouth, eyes, tears, breast milk or sweat has been reported. Staining may appear at any time during Akamin therapy but is more common during long-term treatment. Inform your doctor without delay if you notice any staining so that your treatment can be reviewed.

After finishing Akamin

Tell your doctor immediately if you notice any of the following, even if they occur several weeks after stopping treatment with Akamin:

  • watery and severe diarrhoea, which may also be bloody
  • severe stomach cramps.

These may be signs of a serious condition affecting your bowel.

After taking Akamin

Storage

Keep your tablets/capsules in the bottle until it is time to take them.

If you take the tablets/capsules out of the bottle they may not keep well.

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

Do not store Akamin or any other medicine in the bathroom or near a sink. Do not leave Akamin in the car or on window sills.

Heat and dampness can destroy some medicines.

Keep Akamin 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 Akamin, or your tablets or capsules have passed their expiry date, ask your pharmacist what to do with any that are left over.

Product description

What it looks like

Akamin is available in two strengths:

  • Akamin 50 mg - round, gold coloured, film-coated tablet, marked MC on one side and Greek alpha symbol on the other side. Each bottle contains 60 tablets.
  • Akamin 100 mg - white and grey capsule, marked MC 100 on the white half and Greek alpha symbol on the grey half. Each bottle contains 11 capsules.

Ingredients

The active ingredient in Akamin tablets and capsules is minocycline hydrochloride dihydrate.

Akamin 50 tablets
Each Akamin 50 mg tablet contains 50 mg of minocycline.

The tablets also contain the following inactive ingredients:

  • lactose monohydrate
  • sodium starch glycollate
  • povidone
  • microcrystalline cellulose
  • sodium lauryl sulfate
  • magnesium stearate
  • Opadry Orange OY-23022

Akamin tablets contain sulfites, soy products, galactose and sugars (as lactose). Akamin tablets are gluten free.

Akamin 100 capsules
Each Akamin 100 capsule contains 100 mg of minocycline.

The capsules also contain the following inactive ingredients:

  • lactose monohydrate
  • maize starch
  • magnesium stearate
  • titanium dioxide
  • iron oxide black
  • sodium lauryl sulfate
  • colloidal anhydrous silica
  • potable water
  • gelatin
  • TekPrint SW-9008 Black Ink
  • TekPrint SW-9009 Black Ink

Akamin capsules contain sugars (as lactose). Akamin capsules are gluten free.

Manufacturer

Akamin is made in Australia by:

Alphapharm Pty Limited
Level 1, 30 The Bond
30-34 Hickson Road
Millers Point NSW 2000
www.mylan.com.au

Australian Registration Numbers

50 mg tablets - AUST R 70852

100 mg capsules - AUST R 53641

This leaflet was prepared in
September 2019.

Akamin_cmi\Sep19/00

Published by MIMS November 2019

BRAND INFORMATION

Brand name

Akamin

Active ingredient

Minocycline

Schedule

S4

 

1 Name of Medicine

Minocycline hydrochloride dihydrate.

2 Qualitative and Quantitative Composition

Each Akamin 50 tablet contains minocycline hydrochloride dihydrate equivalent to 50 mg of minocycline.
Each Akamin 100 capsule contains minocycline hydrochloride dihydrate equivalent to 100 mg of minocycline.
Akamin 50 also contains sulfites, soy products, galactose and sugars (as lactose). Akamin 100 also contains sugars (as lactose). For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Akamin 50.

Minocycline 50 mg tablet: gold film coated, marked MC on one side, α on the reverse.

Akamin 100.

Minocycline 100 mg capsule: white body and light grey cap, printed MC 100 on the body and α on the cap in black ink.

4 Clinical Particulars

4.1 Therapeutic Indications

Infections due to the following organisms, provided that they have been shown by bacteriological testing to be susceptible to minocycline: Escherichia coli; Enterobacter aerogenes; Haemophilus influenzae; Klebsiella and Proteus. In addition, infections due to Streptococcus pyogenes (group A β-haemolytic) and Streptococcus faecalis, however, because a large proportion of these organisms are resistant to tetracyclines, minocycline should be used only if the organisms have definitely been shown to be sensitive.
Tetracyclines, including minocycline, are not the drugs of choice in the treatment of staphylococcal infections. Minocycline may be considered for the treatment of such infections only if other suitable agents are not available and the organism has been shown to be sensitive to minocycline.
Minocycline may be used in the treatment of tetracycline resistant acne.

4.2 Dose and Method of Administration

The usual dosage of minocycline for adults is 200 mg initially followed by 100 mg every twelve hours. Therapy should be continued for at least 24 to 48 hours after symptoms and fever have subsided.
In tetracycline resistant acne the dosage is 100 mg daily, given preferably as 50 mg twice daily. Most cases are likely to resolve within 3 months.

Impaired renal function.

(See Section 4.4 Special Warnings and Precautions for Use). Total dosage should be decreased by reduction of recommended individual doses and/or by extending time intervals between doses.

Streptococcal infections.

If tetracycline is used for streptococcal infections, therapeutic doses should be administered for at least 10 days.

4.3 Contraindications

Hypersensitivity to any of the tetracyclines. Severe renal insufficiency. Systemic lupus erythematosus.
Rare cases of benign intracranial hypertension have been reported after tetracyclines and after vitamin A or retinoids such as isotretinoin or etretinate. Concomitant treatment of tetracyclines and vitamin A or retinoids is, therefore, contraindicated (see Section 4.4 Special Warnings and Precautions for Use; Section 4.8 Adverse Effects (Undesirable Effects)).

4.4 Special Warnings and Precautions for Use

As with other antibiotic preparations, use of this drug may result in overgrowth of non-susceptible organisms, including fungi. If superinfection occurs, the antibiotic should be discontinued and appropriate therapy should be instituted.

Discolouration of teeth.

The use of tetracyclines 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 adverse reaction is more common during long-term use of the drugs but has been observed following repeated short-term courses. Enamel hypoplasia has also been reported. Tetracyclines also accumulate in the growing skeleton. Tetracycline drugs, therefore, should not be used in this age group, unless other drugs are unlikely to be effective or are contraindicated.

Hyperpigmentation.

Minocycline use has been associated with blue-black cutaneous hyperpigmentation. Most areas of the body may be affected, including the face. It has also been reported in nails, mucous membranes, hard palate and bone. The incidence varies but appears more likely to occur in patients with certain immunological conditions (rheumatoid arthritis, pemphigus and pemphigoid in particular), acne vulgaris and with prolonged use and/or higher doses. In many cases the cutaneous pigmentation is reversible or partially reversible on discontinuation of minocycline. Complete resolution may take several months or years.

Photosensitivity.

Photosensitivity manifested by an exaggerated sunburn reaction has been observed in some individuals taking tetracyclines. Patients prone to exposure to direct sunlight or ultraviolet light should be advised that this reaction can occur with tetracycline drugs, and treatment should be discontinued at the first evidence of skin erythema.
Patients should be advised to avoid direct sunlight or ultraviolet light exposure if possible. Some reports suggest that, compared with other tetracyclines, minocycline may be less likely to produce photosensitivity.

Enterocolitis.

The use of tetracyclines can cause severe enterocolitis due to resistant staphylococci.

Colitis.

Antibiotic associated pseudomembranous colitis has been reported with many antibiotics including minocycline. A toxin produced with Clostridium difficile appears to be the primary cause. The severity of the colitis may range from mild to life threatening. It is important to consider this diagnosis in patients who develop diarrhoea or colitis in association with antibiotic use (this may occur up to several weeks after cessation of antibiotic therapy). Mild cases usually respond to drug discontinuation alone. However, in moderate to severe cases, appropriate therapy 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 (Lomotil) may prolong and/or worsen the condition and should not be used.

Central nervous system effects.

Central nervous system side effects including light-headedness, dizziness or vertigo have been reported with minocycline therapy. Patients who experience these symptoms should be cautioned about driving vehicles or using hazardous machinery while on minocycline therapy. These symptoms may disappear during therapy and usually disappear rapidly when the drug is discontinued.

Other CNS.

Pseudotumour cerebri (benign intracranial hypertension) in adults has been associated with the use of tetracyclines including minocycline. The usual clinical manifestations are headache and blurred vision. Bulging fontanelles have been associated with the use of tetracyclines in infants. While both of these conditions and related symptoms usually resolve soon after discontinuation of the tetracycline, the possibility for permanent sequelae exists. Headache (not related to pseudotumour cerebri) has also been reported. Decreased hearing has been reported in patients on minocycline therapy.

Anticoagulant therapy.

Patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage, because tetracyclines have been shown to depress plasma prothrombin activity. In long-term therapy, periodic laboratory evaluation of organ systems, including haematopoietic, renal and hepatic studies, should be performed.

Syphilis.

In venereal diseases when coexistent syphilis is suspected, darkfield examination should be done before treatment is started and the blood serology repeated monthly for at least 4 months.

Staphylococcal infection.

Tetracycline is not the drug of choice in the treatment of any type of staphylococcal infection.

Streptococcal infection.

If a tetracycline is used for the treatment of infections due to group A β-haemolytic streptococci (S. pyogenes) (see Section 4.1 Therapeutic Indications), treatment should continue for 10 days.

Use in hepatic impairment.

Hepatotoxicity.

Hepatotoxicity has been reported with minocycline, therefore, minocycline should be used with caution in patients with hepatic dysfunction and in conjunction with other hepatotoxic drugs.

Use in renal impairment.

If renal impairment exists, even usual doses may lead to excessive systemic accumulation of the drug and possible hepatic toxicity. As with all tetracyclines, (except doxycycline), minocycline should be avoided in patients with renal failure.
The antianabolic action of tetracyclines may cause an increase in serum urea. This effect may be enhanced by diuretics.
In patients with significantly impaired renal function, higher serum levels of tetracyclines may lead to azotaemia, hyperphosphatemia and acidosis.

Use in the elderly.

No data available.

Paediatric use.

(See Section 4.4 Special Warnings and Precautions for Use; Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy about use during tooth development). All tetracyclines form a stable calcium complex in any bone forming tissue. A decrease in the fibula growth rate has been observed in premature infants given oral tetracycline in doses of 25 mg/kg every six hours. This reaction was shown to be reversible when the drug was discontinued.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Anticoagulants.

Patients who are on anticoagulant therapy may require downward adjustment of their anticoagulant dosage, as tetracyclines have been shown to depress plasma prothrombin activity.

Aluminium, calcium, magnesium, iron.

Antacids containing aluminium, calcium or magnesium and preparations containing iron impair absorption and should not be given to patients taking oral tetracycline.

Etretinate and isotretinoin.

Administration of etretinate and isotretinoin should be avoided shortly before, during, and shortly after minocycline therapy. Each drug alone has been associated with psuedotumour cerebri (see Section 4.4 Special Warnings and Precautions for Use).

Methoxyflurane.

The concurrent use of tetracycline and methoxyflurane has been reported to result in fatal renal toxicity.

Food and dairy.

Food and dairy products do not appear to significantly influence the absorption of minocycline.

Penicillin.

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

Oral contraceptives.

Reduced efficacy and increased incidence of breakthrough bleeding has been suggested with concomitant use of tetracycline and oral contraceptive preparations. Consideration should, therefore, be given to the patient using an additional mechanical form of contraception whilst on Akamin therapy.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category D)
Safe use in pregnancy has not been established. Tetracyclines are safe for use during the first 18 weeks of pregnancy, after which they cause discolouration of the baby's teeth. These products should be avoided during the second and third trimesters of pregnancy.
Australian categorisation definition of Category D. Drugs which have caused, are suspected to have caused or may be expected to cause, an increased incidence of human foetal malformations or irreversible damage. These drugs may also have adverse pharmacological effects. Accompanying texts should be consulted for further details.
Tetracyclines are present in the milk of lactating women who are taking a drug in this class.

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)

The adverse reactions profile of minocycline is generally similar to that of tetracyclines, except for a significantly higher incidence of vestibular adverse effects, e.g. dizziness, vertigo and ataxia (see Section 4.4 Special Warnings and Precautions for Use).

Gastrointestinal.

Anorexia, nausea, vomiting, diarrhoea, glossitis, dysphagia, enterocolitis, pancreatitis and inflammatory lesions (with monilial overgrowth) in the anogenital region. These reactions have been caused by both the oral and parenteral administration of tetracyclines. Oesophagitis and oesophageal ulceration have been reported rarely.

Hepatic.

Increases in liver enzymes, hepatitis and acute liver failure have been reported. Autoimmune hepatitis with lupus-like symptoms and acute hypersensitivity hepatitis associated with eosinophilia and dermatitis have been reported rarely.

Dermatological.

Maculopapular and erythematous rashes. Exfoliative dermatitis has been reported but is uncommon. Photosensitivity (see Section 4.4 Special Warnings and Precautions for Use). Lesions occurring on the glans penis have caused balanitis. Fixed drug eruptions, erythema multiforme and Stevens-Johnson Syndrome have been reported. Pigmentation of the skin and mucous membranes, as well as nail discolouration, have been reported (see Section 4.4 Special Warnings and Precautions for Use).

Dental.

Discolouration of teeth (yellow-grey-brown) and/or enamel hypoplasia have been reported in infants and children to the age of 8 years. Tooth discolouration has also been reported in adults.

Renal.

Rise in serum urea has been reported, and is apparently dose related (see Section 4.4 Special Warnings and Precautions for Use). Tetracyclines may aggravate pre-existing renal failure. Nephrotoxicity has also occurred in association with "acute fatty liver" related to the use of tetracycline in high doses. Degraded tetracycline may result in renal tubular damage and a "Fanconi-like" syndrome. Reversible acute renal failure has been reported.

Hypersensitivity.

Urticaria, angioneurotic oedema, anaphylaxis, anaphylactoid purpura, pericarditis, polyarthralgia, pulmonary infiltrates with eosinophilia and exacerbation of systemic lupus erythrematosus have been reported. A reversible lupus-like syndrome has been reported.

Haematological.

Agranulocytosis, haemolytic anaemia, thrombocytopenia, neutropenia and eosinophilia have been reported.

Central nervous system.

Convulsions, hypesthesia, dizziness, paresthesia, sedation, and vertigo. Bulging fontanelles in infants and benign intracranial hypertension (the usual clinical manifestations are headache and blurred vision) in adults have been reported. Decreased hearing and headache (not related to benign intracranial hypertension) have also been reported (see Section 4.4 Special Warnings and Precautions for Use).

Other.

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, but the potential for such an effect cannot be excluded.

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

Maximum dosage should not exceed 400 mg/day.

Symptoms and signs of acute overdosage.

May include nausea, vomiting, abdominal pain, hypotension, lethargy, coma, acidosis and azotaemia without a concomitant rise in creatinine.

Treatment of acute overdose.

No specific antidote. General supportive care includes maintenance of clear airway, adequate respiration, circulation and renal function.
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.

Minocycline hydrochloride dihydrate is a semisynthetic derivative of the broad spectrum antibiotic tetracycline.

Microbiology.

Like other tetracyclines, minocycline is primarily bacteriostatic and is thought to exert its antimicrobial effect by protein synthesis inhibition.
Minocycline is active against a wide range of Gram-negative and Gram-positive organisms. It is active against a proportion of Staphylococcus aureus organisms which are resistant to other tetracyclines. Except for this difference, it shares the antimicrobial spectra and cross resistance common to other tetracyclines.
Because many strains of the Gram-negative and Gram-positive microorganisms have been shown to be resistant to tetracyclines, culture and susceptibility tests are especially recommended. Resistance levels in an individual may also be influenced by previous antibiotic exposure.

Microbiology, susceptibility tests.

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 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.

Following oral administration of a single minocycline 200 mg dose, mean peak plasma levels of approximately 4 microgram/mL were achieved in one to four hours.
With oral doses of 100 mg twice daily, it has been reported that steady state levels were achieved in approximately five days; mean peak serum levels were higher in women (3.4 microgram/mL) than in men (2.45 microgram/mL).

Distribution.

Minocycline is widely distributed in body tissues. Approximately 75% of the minocycline in plasma is protein bound.

Metabolism.

A number of metabolites of minocycline have been isolated from urine. Therefore, metabolism appears to be a significant mechanism of clearance of minocycline in contrast to other tetracycline derivatives.
The plasma half-life of minocycline is approximately 13 hours.

Excretion.

Less than 10% of the administered dose is excreted in the urine. Minocycline is excreted in the bile and undergoes enterohepatic circulation. Approximately 35% of an administered dose is excreted in the faeces.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

No data available.

6 Pharmaceutical Particulars

6.1 List of Excipients

Akamin 50 mg tablets contain the following inactive ingredients: lactose monohydrate, sodium starch glycollate, povidone, microcrystalline cellulose, sodium lauryl sulfate, magnesium stearate and Opadry Orange OY-23022.
Akamin 100 mg capsules contain the following inactive ingredients: lactose monohydrate, maize starch, magnesium stearate, titanium dioxide, iron oxide black, sodium lauryl sulfate, colloidal anhydrous silica, potable water, gelatin, TekPrint SW-9008 Black Ink (ARTG PI 2328) and TekPrint SW-9009 Black Ink (ARTG PI 2343).

6.2 Incompatibilities

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.

6.5 Nature and Contents of Container

Akamin 50.

HDPE bottle containing 60 tablets.

Akamin 100.

HDPE bottle and PVC/PVDC/Al blister pack containing 11 capsules.
Some strengths, pack sizes and/or pack types may not be marketed.

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

Minocycline hydrochloride dihydrate is a yellow crystalline powder which is sparingly soluble in water, slightly soluble in alcohol. It dissolves in solutions of alkali hydroxides and carbonates.

Chemical structure.


Chemical name: (4S,4aS,5aR,12aS)- 4,7-bis(dimethylamino)- 3,10,12,12a-tetrahydroxy-1, 11-dioxo- 1,4,4a,5,5a,6,11,12a- octahydrotetracene-2- carboxamide.
Structural formula:
Molecular formula: C23H27N3O7.HCl.
Molecular weight: 493.95.

CAS number.

13614-98-7.

7 Medicine Schedule (Poisons Standard)

S4 (Prescription Only Medicine).

Summary Table of Changes