Consumer medicine information

Rifadin Oral

Rifampicin

BRAND INFORMATION

Brand name

Rifadin

Active ingredient

Rifampicin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Rifadin Oral.

What is in this leaflet

This leaflet answers some common questions about Rifadin.

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 Rifadin against the benefits he/she expects 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 Rifadin is used for

Rifadin is an antibiotic that is used in combination with other medicines to treat tuberculosis, also known as TB. TB is a bacterial infection, which mainly affects the lungs, but it can also spread to other organs in the body.

Rifadin is also used to treat leprosy, a skin condition that has many forms.

Rifadin is also used to prevent certain diseases occurring where you may be in contact with, or have had contact with, a person known to have the disease or is known to be able to pass it on to others. Examples of such diseases are meningitis, a serious infectious disease (an inflammation of the membranes that cover the brain and spinal cord), affecting children and young adults, and pneumonia, conjunctivitis and meningitis caused by Haemophilus influenzae, a bacterium in the respiratory tract.

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

Before you take it

When you must not take it

Do not use Rifadin if:

You have an allergy to Rifadin (rifampicin) or any other rifamycin antibiotics or any of the ingredients listed at the end of this leaflet. Symptoms of an allergic reaction may include skin rash, itching, difficulty breathing or swallowing, and swelling of the face, lips, tongue and throat.

You have jaundice (yellowing of the eyes and skin).

You are taking combination saquinavir/ritonavir medications.

You are breast-feeding or planning to breastfeed. Rifadin passes into breast milk and there is a possibility your baby may be affected.

If the packaging is torn or shows signs of tampering.

If the expiry date (exp) printed on the pack has passed. If you use this medicine after the expiry date has passed, it may not work as well.

If you are not sure whether you should start using Rifadin, talk to your doctor.

Before you start to take it

Tell your doctor if:

You have any type of liver disease.

You have any allergies to any other medicines or any other substances, such as foods, preservatives or dyes.

You have a problem with bleeding or tendency to bruise easily.

You are taking other antibiotics at the same time.

You have diabetes.

You are pregnant or intend to become pregnant. Your doctor will discuss the possible risks and benefits of using Rifadin during pregnancy.

You are breast-feeding or plan to breast-feed. Rifadin should not be used while breast-feeding.

If you have not told your doctor about any of the above, tell them before you are given Rifadin.

Urine, faeces, saliva, sputum, sweat, tears and teeth may be coloured red-orange, yellow or brown by Rifadin. Soft contact lenses may be permanently stained.

Taking other medicines

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

Some drugs should not be taken with Rifadin. These include:

  • The combination of saquinavir and ritonavir, antiviral agents used to treat acquired immune deficiency syndrome (AIDS) and human immunodeficiency virus (HIV) infections.
  • Halothane, a general anaesthetic (a sleep inducing drug)
  • Daclatasvir, simeprevir, sofosbuvir and telaprevir, antiviral agents used to treat Hepatitis C
  • Cephazolin and other cephalosporin antibiotics used to treat infection.

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

  • Antacids, used for heart burn and indigestion
  • Atovaquone, used to treat a respiratory infection in acquired immune deficiency syndrome (AIDS)
  • Ketoconazole, used for fungal infections
  • Enalapril, used to treat high blood pressure and heart problems
  • Isoniazid and p-aminosalicylic acid (PAS), used for TB (tuberculosis).

Rifadin may reduce the effectiveness of a wide variety of medicines or they may affect how well Rifadin works. These include certain medicines used for:

  • Decreasing the clotting of the blood
  • Controlling and preventing seizures
  • Heart disease and high blood pressure
  • Breast cancer treatment or prevention
  • Sedation
  • Bacterial infections
  • Fungal infections
  • Inflammatory conditions
  • Contraception
  • High blood cholesterol
  • Diabetes
  • TB and leprosy
  • Malaria
  • Rejection of transplanted organs
  • Thyroid deficiency states
  • Pain
  • Nocturnal cramps
  • Breathing difficulties
  • Anxiety or depression
  • Treatment of certain mental illnesses
  • Treatment of HIV (Human Immunodeficiency Virus) infections.
  • Nausea and vomiting

Your doctor or pharmacist may have more information on medicines to be careful with or to avoid while taking Rifadin.

How to take it

How much to take

Your doctor will decide what dose and for how long you will receive Rifadin.

How to take it

Follow all directions given to you by your doctor or pharmacist carefully.

Swallow Rifadin tablets and capsules whole with a glass of water.

Do not crush or chew the tablets. These tablets have a special coating to stop them dissolving until they have gone through the stomach and into the intestines, where they start to work. If you chew them, the coating is destroyed.

Rifadin should be taken on an empty stomach at least 30 minutes before or 2 hours after a meal.

If you need to take an antacid, take it at least 1 hour after your dose of Rifadin.

If you forget to take it

Take the dose as soon as you remember, and then resume taking Rifadin as directed.

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

If you are unsure about taking the next dose, speak to your doctor or pharmacist.

If you have trouble remembering when to take your medication, ask your pharmacist for some hints.

If you take too much (overdose)

Immediately telephone your doctor or Poisons Information Centre (Australia: telephone 13 11 26, New Zealand: telephone 0800 POISON or 0800 764766) for advice, or go to casualty at your nearest hospital, if you think that you or anyone else has taken too much Rifadin.

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

If you take too much Rifadin you may have symptoms of nausea, vomiting, abdominal pain, itchy skin, headache, fatigue, dizziness, swelling and abnormal heart beating.

While you are taking it

Things you must do

Take Rifadin exactly as directed or as your doctor has prescribed. If you miss doses, side effects may occur more often and may be more serious than usual.

You should see your doctor monthly for a check-up.

If you develop itching with swelling or skin rash or difficulty breathing, or if you turn yellow while you are taking Rifadin do not take any more Rifadin and tell your doctor immediately.

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

If you get a sore white mouth or tongue while taking or soon after stopping Rifadin, 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 Rifadin allows fungi to grow and the above symptoms to occur. Rifadin does not work against fungi.

If you become pregnant while you are taking Rifadin tell your doctor.

If you are using oral contraceptives you should change to alternative methods of birth control while you are taking Rifadin.

If you are about to start taking any new medicine, tell your doctor or pharmacist that you are taking Rifadin.

If you have to have any blood or urine tests tell your doctor you are being given Rifadin. Rifadin may affect the results of some blood and urine tests.

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

Things you must not do

Do not stop taking Rifadin because you feel better.

If you do not complete the full treatment prescribed by your doctor, some 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.

Side effects

Check with your doctor as soon as possible if you have any problems while being treated with Rifadin, even if you do not think the problems are connected with the medicine or are not listed in this leaflet.

Like other medicines, Rifadin can cause some side effects. If they occur, most are likely to be minor and temporary. However, some may be serious and need medical attention.

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:

  • Yellow discolouration of skin or eyes
  • Heartburn, loss of appetite, nausea, vomiting, upset stomach, abdominal discomfort, wind, cramps or diarrhoea
  • Drowsiness, fatigue, inability to concentrate, confusion, or mental problems
  • Poor coordination, muscle weakness, pain in the fingers or toes, or numbness
  • Oral thrush - white, furry, sore tongue and mouth
  • Vaginal thrush - sore and itchy vagina and/or discharge
  • Conjunctivitis or visual disturbances
  • Menstrual disturbances.

Tell your doctor immediately if you notice any of the following:

  • Severe red and/or itchy skin, blisters or pimples, bleeding, peeling or bruising of the skin
  • Swelling of the face, lips, tongue or throat which may cause difficulty in breathing or swallowing
  • Itching, weakness, loss of appetite, nausea, vomiting, abdominal pain, yellowing of the eyes or skin or dark urine
  • Shortness of breath and wheezing
  • Blood in the urine or any other urination disturbances
  • Severe bleeding or bruising more easily than normal
  • Fever, chills, headache or dizziness
  • Bone pain.

Some people may get other side effects while taking Rifadin. Some of these side effects (for example changes in liver function) can only be found when your doctor does tests from time to time to check your progress.

Ask your doctor or pharmacist if you don't understand anything in this list.

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

Urine, faeces, saliva, sputum, sweat, tears and teeth may be coloured red-orange, yellow or brown by Rifadin. Soft contact lenses may be permanently stained.

After finishing Rifadin

Tell your doctor immediately if you notice any of the following side effects, particularly if they occur several weeks after stopping treatment with Rifadin:

  • 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, which may need urgent medical attention. However, this side effect is rare.

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

After taking it

Storage

Keep Rifadin 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.

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

Rifadin tablets#
Keep the tablets in a cool dry place where the temperature stays below 25°C.

Rifadin syrup
Keep the syrup in a cool dry place where the temperature stays below 25°C.

Disposal

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

Product description

What it looks like

Rifadin capsules
Rifadin 150 mg capsules are blue/red capsules. They come in packs of 100 capsules.

Rifadin 300 mg capsules are red capsules. They come in packs of 100 capsules.

Rifadin tablets#
Rifadin 600 mg tablets are cyclamen red capsule shaped sugar coated tablets. They come in packs of 30 tablets.

Rifadin syrup
Rifadin syrup is a red liquid supplied in 60 mL bottles.

Ingredients

Rifadin preparations do not contain azo dyes.

Diabetics should note that Rifadin syrup contains 40% w/v of sugar.

Rifadin syrup contains potassium metabisulfite.

Rifadin capsules

Active Ingredient:

Rifadin 150 mg - 150 mg active per capsule

Rifadin 300 mg - 300 mg active per capsule

Inactive Ingredients:

The 150 mg and 300 mg capsules also contain:

  • maize starch
  • magnesium stearate

The capsule shell also contains

  • titanium dioxide
  • erythrosine
  • indigo carmine
  • gelatin

Rifadin tablets#

Active Ingredient:

Rifadin 600 mg - 600 mg active per tablet

Inactive Ingredients:

  • sodium lauryl sulfate
  • microcrystalline cellulose
  • lactose monohydrate
  • calcium stearate
  • carmellose sodium
  • maize starch
  • magnesium stearate

The sugar coating also contains:

  • acacia
  • povidone
  • erythrosine
  • titanium dioxide
  • sucrose
  • purified talc
  • magnesium carbonate hydrate
  • kaolin
  • colloidal anhydrous silica
  • gelatin

Rifadin syrup

Active Ingredient:

Rifadin 100 mg/5mL - 100 mg active per 5 mL of syrup

Inactive Ingredients:

  • agar
  • sucrose
  • methyl hydroxybenzoate
  • propyl hydroxybenzoate
  • potassium sorbate
  • saccharin
  • sodium metabisulfite
  • polysorbate 80
  • raspberry essence (PI 458)
  • diethanolamine
  • purified water

Manufacturer/Sponsor

Rifadin is supplied in Australia by:

sanofi-aventis australia pty ltd
12-24 Talavera Road
Macquarie Park NSW 2113

Australian Registration Numbers:

AUST R 233442 (150 mg capsules blister pack)

AUST R 233443 (300 mg capsules blister pack)

AUST R 227519 (600 mg tablet blister pack) #

AUST R 10114 (150 mg capsules)#

AUST R 10111 (300 mg capsules)#

AUST R 10112 (600 mg tablets)#

AUST R 10113 (syrup)

#Not marketed

Rifadin is supplied in New Zealand by:

sanofi-aventis new zealand limited
Level 8, 56 Cawley Street
Ellerslie
Auckland

This leaflet was prepared in: April 2020

® Registered Trademark

rifadin-ccdsv12-cmi11-apr20

Published by MIMS June 2020

BRAND INFORMATION

Brand name

Rifadin

Active ingredient

Rifampicin

Schedule

S4

 

1 Name of Medicine

Rifampicin.

2 Qualitative and Quantitative Composition

Rifadin 150 mg capsules contain 150 mg of rifampicin per capsule.
Rifadin 300 mg capsules contain 300 mg of rifampicin per capsule.
Rifadin syrup contains 100 mg of rifampicin per 5 mL of syrup.

Excipients with known effect.

Syrup also contains methyl hydroxybenzoate, propyl hydroxybenzoate, potassium sorbate, sodium metabisulfite and saccharin.
Rifadin IV infusion contains 600 mg rifampicin per vial.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Capsules: 150 mg (blue/red, marked R-150).
300 mg (red, marked R-300).
Syrup: 100 mg/5 mL (red, raspberry flavoured).
IV infusion: 600 mg (spongy, fragile amorphous red powder) with 10 mL sterile water for injection solvent.

4 Clinical Particulars

4.1 Therapeutic Indications

Tuberculosis.

In the initial treatment and in re-treatment of patients with tuberculosis, Rifadin must be used in conjunction with at least one other antituberculosis drug.

Leprosy.

In the management of lepromatous leprosy and dimorphous leprosy to effect speedy conversion of the infectious state to the noninfectious state which may be expected to occur in 3 to 4 months of treatment.
As an alternative drug in lepromatous, dimorphous, indeterminate and tuberculoid leprosy resistant to sulfones and other antileprosy drugs.
As an alternative drug in all those patients having true drug allergy to the more commonly used antileprosy drugs.

Meningococcal disease.

Prophylaxis of meningococcal disease in close contacts of known cases and in carriers (Rifadin is not indicated for the treatment of meningococcal infections).

Haemophilus influenzae.

Prophylaxis of household contacts of patients with H. influenzae type B.

4.2 Dose and Method of Administration

Oral.

It is recommended that oral Rifadin be administered once daily, on an empty stomach either 30 minutes before or two hours after a meal.

Pulmonary tuberculosis.

Adults.

600 mg in a single daily administration.

Children.

10 to 20 mg/kg, not to exceed 600 mg/day.

Leprosy.

Adults.

450 to 600 mg in a single daily administration.

Prophylaxis of meningococcal disease (see Section 4.1 Therapeutic Indications).

Adults.

600 mg/day for 4 days.

Children over 5 years.

10 mg/kg/day for 4 days, not to exceed 600 mg/day.
Data are not available for determination of dosage for children under 5 years.
The NHMRC recommend that in any household in which a case of H. influenzae type B infection has occurred and in which another child less than 4 years resides, all members of the family, including adults, should receive rifampicin in a dose of 20 mg/kg per dose once daily (maximum dose 600 mg/day) for 4 days; the dose for neonates (less than 1 month) is 10 mg/kg once daily for 4 days.
In the treatment of pulmonary tuberculosis, Rifadin must be used in conjunction with at least one other antituberculous agent. Similarly, in the treatment of leprosy, rifampicin should always be used in conjunction with at least one other antileprosy drug.
In general, therapy should be continued until bacterial conversion and maximal improvement have occurred.
Continuous daily treatment with Rifadin is usually better tolerated than intermittent medication (see Section 4.4 Special Warnings and Precautions for Use). The termination of long-term therapy with rifampicin and a subsequent resumption of medication may lead to immunopathological effects (see Section 4.8 Adverse Effects (Undesirable Effects)). Intermittent therapy should be avoided but if this alternative is not possible, therapy should be initiated with small incremental (150 mg/day) doses. Renal function should be monitored and corticosteroids may be useful.

Intravenous infusion.

Rifadin IV infusion is indicated in patients who are unable to tolerate oral therapy, e.g. postoperative or comatose patients, or patients in whom gastrointestinal absorption is impaired. Serum concentrations following single daily administration of 600 mg rifampicin given in an intravenous infusion drip over 1 to 3 hours are similar to those obtained after 600 mg by mouth.

Adults.

Usual dose is 600 mg infused daily.

Children.

10 to 20 mg/kg/day, up to 600 mg/day.
In general, therapy should be continued until bacterial conversion and maximal improvement have occurred.

Preparation of intravenous infusion.

Rifadin IV is only intended to be administered via intravenous infusion and must not be administered by intramuscular or subcutaneous route. It should be freshly prepared by aseptically adding the solvent to the vial of rifampicin powder and swirling gently and continuously until the powder has completely dissolved. When the powder has completely dissolved, the solution is stable for up to 30 hours.
The solution should be diluted in 500 mL of 5% glucose solution or normal saline. It is suggested that the infusion is administered over a period of 1 to 3 hours.
Dilutions in glucose 5% for injections are stable for up to 8 hours at room temperature and should be prepared and used within this time. Precipitation of rifampicin from the infusion solution may occur beyond this time.
Rifadin IV infusion is compatible with normal saline for up to 6 hours. Other infusion solutions are not recommended.

4.3 Contraindications

Jaundice.
History of hypersensitivity to any of the rifamycins.
Rifadin use is contraindicated when given concurrently with the combination of saquinavir/ ritonavir (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

4.4 Special Warnings and Precautions for Use

Adults treated for tuberculosis with rifampicin should have baseline measurements of hepatic enzymes, bilirubin, serum creatinine, a complete blood count and a platelet count (or estimate). Baseline tests are unnecessary in children unless a complicating condition is known or clinically suspected.
Patients should be seen at least monthly during therapy and should be specifically questioned concerning symptoms associated with adverse reactions. All patients with abnormalities should have follow-up, including laboratory testing, if necessary. Routine laboratory monitoring for toxicity in people with normal baseline is generally not necessary.
Rifampicin has been observed to increase the requirement for anticoagulant drugs of the coumarin type. The cause of this phenomenon is unknown. In patients receiving anticoagulants and rifampicin concurrently, it is recommended that the prothrombin time be performed daily or as frequently as necessary to establish and maintain the required dose of anticoagulant.
Urine, faeces, saliva, sputum, sweat, tears and teeth may be coloured red-orange, yellow or brown by rifampicin and its metabolites. Soft contact lenses may be permanently stained. Individuals to be treated should be made aware of these possibilities in order to prevent undue anxiety.
Rifampicin has enzyme induction properties that can enhance the metabolism of endogenous substrates including adrenal hormones, thyroid hormones and vitamin D. Isolated reports have associated porphyria exacerbation with rifampicin administration as a result of induction of delta amino levulinic acid synthetase.
Rifampicin may cause vitamin K dependent coagulopathy and severe bleeding (see Section 4.8 Adverse Effects (Undesirable Effects)). Monitoring of occurrence of coagulopathy is recommended for patients at particular bleeding risk. Supplemental vitamin K administration should be considered when appropriate (vitamin K deficiency, hypoprothrombinaemia).
Rifampicin is a well characterised and potent inducer of drug metabolising enzymes and transporters and might therefore decrease or increase concomitant drug exposure, safety and efficacy (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). Therefore, patients should be advised not to take any other medication without medical advice.
I.V. preparation is for intravenous infusion only and must not be administered by intramuscular or subcutaneous route. Avoid extravasation during injection; local irritation and inflammation due to extravascular infiltration of the infusion have been observed. If these occur, the infusion should be discontinued and restarted at another site.
Antibiotic associated pseudomembranous colitis has been reported with many antibiotics. A toxin produced by 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 severe cases, appropriate therapy such as oral antibacterial agents effective against Clostridium difficile should be considered. Fluids, electrolytes and protein replacement therapy should be provided when indicated.

Hepatotoxicity.

Rifampicin has been shown to produce liver dysfunction. There have been fatalities associated with jaundice in patients with liver disease or receiving rifampicin concomitantly with other hepatotoxic agents. Since an increased risk may exist for individuals with liver disease, rifampicin should only be given to these patients in cases of necessity and under strict medical supervision. Periodic liver function monitoring in these patients, especially ALT and AST, should be carried out prior to therapy and then every 2 to 4 weeks during therapy. Dosage adjustment may be necessary. If signs of hepatocellular damage occur, rifampicin should be discontinued. Similar precautions are recommended for undernourished patients.
Cases of mild to severe cholestasis have been reported with rifampicin therapy. Patients should be instructed to contact their physician immediately if they experience symptoms such as itching, weakness, loss of appetite, nausea, vomiting, abdominal pain, yellowing of the eyes or skin or dark urine. If cholestasis is confirmed, rifampicin should be discontinued.
In some cases, hyperbilirubinaemia resulting from competition between rifampicin and bilirubin for excretory pathways of the liver at the cell level can occur in the early days of treatment. An isolated report showing a moderate rise in bilirubin and/or transaminase level is not in itself an indication for interrupting treatment; rather, the decision should be made after repeating the tests, noting trends in the levels and considering them in conjunction with the patient's clinical condition.

Drug resistance.

Both in the treatment of tuberculosis and in meningococcal prophylaxis, small numbers of resistant cells, present within large populations of susceptible cells, can rapidly become the predominating type. Since rapid emergence of resistance can occur, culture and susceptibility tests should be performed in the event of persistent positive cultures.
Rifadin should not be used for the treatment of meningococcal disease. In the treatment of asymptomatic carriers, it should be reserved for situations where the risk of meningococcal meningitis is high.
The risks of drug resistance with rifampicin when used in leprosy have not been adequately evaluated and, therefore, a second drug should be added to the treatment regimen as is done in the case of tuberculosis.
It is necessary to exclude concomitant tuberculosis in any patient with leprosy who is to be given rifampicin. If tuberculosis exists concurrently, combined chemotherapy must be used.

Immunological reactions/anaphylaxis.

Rifadin is not recommended for intermittent therapy (less frequently than 2 to 3 times/week) because of the possibility of immunological reactions including anaphylaxis (see Section 4.8 Adverse Effects (Undesirable Effects)). The patient should be cautioned against intentional or accidental interruption of the daily dosage regimen since rare renal hypersensitivity reactions have been reported when therapy was resumed in such cases. If, as may happen in rare cases, a patient develops thrombocytopenia, purpura, haemolytic anaemia or renal failure, treatment with Rifadin should be stopped at once and not reinstituted at any subsequent time.

Rifampicin syrup.

Rifampicin syrup contains sodium metabisulfite which may cause allergic reactions including anaphylactic symptoms and life threatening or less severe asthmatic episodes in certain susceptible people.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome.

Severe, systemic hypersensitivity reactions, including fatal cases, such as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome have been observed during treatment with anti-tuberculosis therapy (see Section 4.8 Adverse Effects (Undesirable Effects)). It is important to note that early manifestations of hypersensitivity, such as fever, lymphadenopathy or biological abnormalities (including eosinophilia, liver abnormalities) may be present even though rash is not evident. If such signs or symptoms are present, the patient should be advised to consult their physician immediately.
Rifampicin should be discontinued if an alternative etiology for the signs and symptoms cannot be established.

Severe bullous reactions.

Cases of severe bullous skin reactions such as Stevens Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and acute generalised exanthematous pustulosis (AGEP) have been reported with rifampicin. If symptoms or signs of AGEP, SJS or TEN are present, rifampicin treatment must immediately be discontinued.

Use in hepatic impairment.

Patients with impaired liver function should only be given Rifadin in cases of necessity and under strict medical supervision (see Hepatotoxicity).

Use in the elderly.

No data available.

Paediatric use.

Use in premature and newborn infants.

As liver enzymes are not fully developed in this age group, treatment with Rifadin should be considered only in the most grave emergencies.

Effects on laboratory tests.

Cross reactivity and false positive urine screening tests for opiates have been reported in patients receiving rifampicin when using the KIMS (Kinetic Interaction of Microparticles in Solution) method (e.g. Abuscreen On-Line opiates assay; Roche Diagnostic Systems). Confirmatory tests, such as gas chromatography/ mass spectrometry, will distinguish rifampicin from opiates.
Therapeutic levels of rifampicin have been shown to inhibit standard microbiological assays for serum folate and vitamin B12. Thus, alternate assay methods should be considered.
Transient elevations of bromsulfophthalein and serum bilirubin have been reported. Rifampicin may impair biliary excretion of contrast media used for visualization of the gallbladder, due to competition for biliary excretion. Therefore, these tests should be performed before the morning dose of rifampicin.

4.5 Interactions with Other Medicines and Other Forms of Interactions

When Rifadin is given concomitantly with combination saquinavir/ ritonavir, the potential for hepatotoxicity is increased. Therefore, concomitant use of Rifadin with saquinavir/ ritonavir is contraindicated (see Section 4.3 Contraindications).
Concomitant antacid administration may reduce the absorption of rifampicin. Daily doses of rifampicin should be given at least one hour before the ingestion of antacids.
Rifampicin is a well characterised and potent inducer of drug metabolising enzymes and transporters. Enzymes and transporters reported to be affected by rifampicin include cytochromes P450 (CYP) 1A2, 2B6, 2C8, 2C9, 2C19, and 3A4, UDP-glucuronyltransferases (UGT), sulfotransferases, carboxylesterases, and transporters including P-glycoprotein (P-gp) and multidrug resistance-associated protein 2 (MRP2). Most drugs are substrates for one or more of these enzyme or transporter pathways, and these pathways may be induced by rifampicin simultaneously. Therefore, rifampicin may accelerate the metabolism and decrease the activity of certain co-administered drugs or increase the activity of a coadministered pro-drug (where metabolic activation is required), and has the potential to perpetuate clinically important drug-drug interactions against many drugs and across many drug classes. To maintain optimum therapeutic blood levels dosages of drugs may require adjustment when starting or stopping concomitantly administered rifampicin.
Caution should be used when prescribing rifampicin with drugs metabolised by enzyme and transporters reported to be affected by rifampicin, including cytochrome P-450.
Examples of drugs metabolised by cytochrome P450 enzymes include: oral anticoagulants (e.g. warfarin), anticonvulsants (e.g. phenytoin), antiarrhythmics (e.g. disopyramide, mexiletine, quinidine, tocainide and propafenone), antioestrogens (e.g. tamoxifen, toremifen), antipsychotics (e.g. haloperidol), antifungals (e.g. fluconazole, itraconazole, ketoconazole; see below), antiretroviral drugs (e.g. zidovudine, saquinavir, indinavir, efavirenz), barbiturates, beta-blockers, benzodiazepines (e.g. diazepam), benzodiazepine-related drugs (e.g. zopiclone, zolpidem), calcium channel blockers (e.g. diltiazem, nifedipine, verapamil), chloramphenicol, clarithromycin, corticosteroids, cardiac glycoside preparations, clofibrate, systemic hormonal contraceptives (see below), dapsone, doxycycline, oestrogens, fluoroquinolones, gestrinone, oral hypoglycaemic agents (sulfonylureas), immunosuppressive agents (e.g. ciclosporin, tacrolimus) irinotecan, levothyroxine, narcotic analgesics, methadone, praziquantel, progestins, quinine, riluzole, selective 5-HT3 receptor antagonists (e.g. ondansetron), statins metabolized by CYP3A4, telithromycin, theophylline, thiazolidinediones (e.g. rosiglitazone), tricyclic antidepressants (e.g. amitriptyline, nortriptyline) and losartan. It may be necessary to adjust the dosage of these drugs if they are given concurrently with rifampicin.
Concurrent use of hepatitis-C antiviral drugs (e.g. daclatasvir, simeprevir, sofosbuvir, telaprevir) and rifampicin should be avoided.
When atovaquone and rifampicin were taken concomitantly, decreased concentrations of atovaquone and increased concentrations of rifampicin were observed.
Concomitant use of ketoconazole and rifampicin has resulted in decreased serum concentrations of both drugs.
Concurrent use of rifampicin and enalapril has resulted in decreased concentrations of enalaprilat, the active metabolite of enalapril. Dosage adjustments should be made if indicated by the patient's clinical condition.
When rifampicin is taken with p-aminosalicylic acid (PAS), rifampicin levels in the serum may decrease. Therefore, the drugs should be taken at least 4 hours apart.
Rifampicin treatment reduces the systemic exposure of oral contraceptives. Patients using oral contraceptives should be advised to change to nonhormonal methods of birth control during rifampicin therapy. Diabetes may become more difficult to control in patients treated with rifampicin.
Combined administration of either halothane or isoniazid and rifampicin may give rise to more frequent and marked disorders of liver function than treatment with rifampicin alone. The concomitant use of rifampicin and halothane should be avoided. Patients receiving both rifampicin and isoniazid should be monitored closely for hepatotoxicity.
The concomitant use of rifampicin with other antibiotics causing vitamin K dependent coagulopathy such as cefazolin (or other cephalosporins with N-methyl-thiotetrazole side chain) should be avoided as it may lead to severe coagulation disorders, which may result in fatal outcome (especially with high doses).
Rifadin strongly induces CYP2C19, resulting in both an increased level of clopidogrel active metabolite and platelet inhibition, which in particular might potentiate the risk of bleeding. As a precaution, concomitant use of clopidogrel and rifampicin should be discouraged.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No data available.
(Category C)
There are no well controlled studies with rifampicin in pregnant women. Therefore, rifampicin should be used in pregnant women or in women of childbearing potential only if the potential benefit justifies the potential risk to the foetus.
In animal experiments, rifampicin, given during organ development has caused skeletal malformations.
Although rifampicin has been reported to cross the placental barrier and appear in cord blood, the effect of rifampicin on the human foetus is not known.
Bleeding attributable to hypoprothrombinaemia has been reported in newborn infants and in mothers after the use of rifampicin during late pregnancy. If rifampicin is used during the last few weeks of pregnancy, vitamin K should be given to the mother and the newborn infant.
Rifampicin is excreted in breast milk and infants should not be breastfed by a patient receiving rifampicin.

4.7 Effects on Ability to Drive and Use Machines

Rifadin may cause undesirable effects which may reduce the capacity for the completion of certain tasks. Patients should be informed of the potential for these undesirable effects and if they experience these symptoms, consideration should be given not to drive or operate machinery.

4.8 Adverse Effects (Undesirable Effects)

Gastrointestinal disturbances such as heartburn, epigastric distress, abdominal discomfort, anorexia, decreased appetite, nausea, vomiting, gas, cramps and diarrhoea, have been noted in some patients. Pseudomembranous colitis has been reported (see Section 4.4 Special Warnings and Precautions for Use).
Headache, drowsiness, fatigue, menstrual disturbances (in women receiving long-term antituberculosis therapy with regimens containing rifampicin), post-partum haemorrhage, fetal maternal haemorrhage, ataxia, dizziness, inability to concentrate, mental confusion, visual disturbances, muscular weakness, fever, pains in the extremities and generalised numbness have also been noted. Psychoses have been rarely reported.
Encountered occasionally have been flushing, pruritus, urticarial rash, allergic dermatitis, pemphigus, pemphigoid, acneform lesions, sore mouth, sore tongue and exudative conjunctivitis. Rarely, hepatitis or a shock-like syndrome with hepatic involvement and abnormal liver function tests (e.g. elevations in serum bilirubin, bromsulfophthalein, alkaline phosphatase, serum transaminases) have also been observed. Elevations in blood bilirubin, aspartate aminotransferase and alanine aminotransferase have been commonly reported. An increase in blood creatinine and hepatic enzymes have also been reported. Cholestasis has also been reported.
Hypersensitivity reactions have been reported. Erythema multiforme, including Stevens-Johnson syndrome, toxic epidermal necrolysis, Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome, acute generalised exanthematous pustulosis (AGEP), and vasculitis have been reported rarely.
Rifampicin can cause certain bodily fluids such as sputum, urine, sweat and tears to become red orange, yellow or brown in colour (see Section 4.4 Special Warnings and Precautions for Use). Tooth discolouration (which may be permanent) has also been reported.
Thrombocytopenia with or without purpura may occur, usually associated with intermittent therapy, but is reversible if the drug is discontinued as soon as purpura occurs. Cerebral haemorrhage and fatalities have been reported when rifampicin administration has been continued or resumed after the appearance of purpura. Eosinophilia, leucopenia, oedema, muscle weakness and myopathy have been reported to occur in a small percentage of patients treated with rifampicin. Agranulocytosis has been reported very rarely. Disseminated intravascular coagulation has been rarely reported. Vitamin K dependent coagulation disorders and bleeding have been reported. Porphyria has been reported.
Elevations in BUN and serum uric acid have occurred. Rarely, haemolysis, haemoglobinuria, haematuria, renal insufficiency or acute kidney injury have been reported and are generally considered to be hypersensitivity reactions. These have usually occurred during intermittent therapy or when treatment was resumed following intentional or accidental interruption of a daily dosage regimen and were reversible when rifampicin was discontinued and appropriate therapy instituted.
Rare reports of adrenal insufficiency have been observed in patients with compromised adrenal function.
Reactions usually occurring with intermittent dosage regimens and most probably of immunological origin include the following:
"Flu-like syndrome" consisting of episodes of fever, chills, headache, dizziness and bone pain appearing most commonly during the third to the sixth month of therapy. The frequency of the syndrome varies but may occur in up to 50% of patients given once weekly regimens with a dose of rifampicin of 25 mg/kg or more. These symptoms may be a prelude to more serious complications such as renal hypersensitivity reactions. It is preferable in such cases to change to daily medication.
Shortness of breath/ dyspnoea and wheezing.
Anaphylaxis/ anaphylactic reaction.
Decrease in blood pressure, and shock.
Haemolytic anaemia.
Acute kidney injury, usually due to renal tubular necrosis or tubulointerstitial nephritis, but cortical necrosis has been reported.
During the treatment of leprosy with Rifadin, a lepromatous reaction may occur. Mild reactions do not require cessation of Rifadin therapy; in other cases corticosteroid therapy may be required and withdrawal of rifampicin considered.

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 (Australia) or https://nzphvc.otago.ac.nz/reporting/ (New Zealand).

4.9 Overdose

Symptoms.

Nausea, vomiting, abdominal pain, pruritus, headache and increasing lethargy will probably occur within a short time after acute ingestion; actual unconsciousness may occur with severe hepatic involvement. Transient increases in liver enzymes and/or bilirubin may occur. Brownish-red or orange discolouration of the skin, urine, sweat, saliva, tears and faeces is proportional to amount ingested. Facial or periorbital oedema has also been reported in paediatric patients. Hypotension, sinus tachycardia, ventricular arrhythmias, seizures and cardiac arrest were reported in some fatal cases.
Liver enlargement, possibly with tenderness, can develop within a few hours after severe overdosage, and jaundice may develop rapidly. Hepatic involvement may be more marked in patients with prior impairment of hepatic function. Other physical findings remain essentially normal. Direct and total bilirubin levels may increase rapidly with severe overdosage; hepatic enzyme levels may be affected, especially with prior impairment of hepatic function. A direct effect upon the haematopoietic system, electrolyte levels or acid base balance is unlikely.
Although it has not been observed in humans, animal studies suggest a possible neurodepressant action associated with very high doses of rifampicin. Where overdoses of other drugs, including such potentially hepatotoxic substances as isoniazid, pyrazinamide or ethionamide, have occurred simultaneously, the signs and symptoms of acute poisoning may be aggravated and/or modified.
The minimum acute lethal or toxic dose is not well established. However, nonfatal acute overdoses in adults have been reported with doses ranging from 9 to 12 g of rifampicin. Fatal acute overdoses in adults have been reported with doses ranging from 14 to 60 g. Alcohol or a history of alcohol abuse was involved in some of the fatal and nonfatal reports. Nonfatal overdoses in paediatric patients aged 1 to 4 years old of 100 mg/kg for one to two doses have been reported.

Treatment.

Intensive supportive and symptomatic measures should be instituted. Since nausea and vomiting are likely present, activated charcoal slurry instilled into the stomach following evacuation of gastric contents could help absorb any remaining drug in the gastrointestinal tract. Antiemetic medication may be required to control severe nausea/ vomiting.
Active diuresis (with measured intake and output) will help promote excretion of the drug. Bile drainage may be indicated in the presence of serious impairment of hepatic function lasting more than 24 to 48 hours; under these circumstances, extracorporeal haemodialysis may be required. In patients with previously adequate hepatic function, reversal of liver enlargement and impaired hepatic excretory function probably will be noted within 72 hours, with rapid return toward normal thereafter.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia) or the National Poisons Centre on 0800 POISON or 0800 764 766 (New Zealand).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Antimycobacterials, antibiotic. ATC code: J04AB02.

Mechanism of action.

Rifampicin is particularly active against rapidly growing extracellular organisms but it also has bactericidal activity intracellularly and against slow and intermittently growing Mycobacterium tuberculosis. Rifampicin inhibits DNA dependent RNA polymerase activity in susceptible cells. Specifically, it interacts with bacterial RNA polymerase, but does not inhibit the mammalian enzyme. Cross resistance to rifampicin has only been shown with other rifamycins.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

Absorption.

Rifampicin is readily absorbed from the stomach and the duodenum. Peak serum concentrations of the order of 7 microgram/mL (range 6 to 32 microgram/mL) occur about 2 to 4 hours after an oral dose of 600 mg on an empty stomach.
Absorption of rifampicin is reduced when the drug is ingested with food.

Distribution.

Rifampicin is widely distributed throughout the body. It is present in effective concentrations in many organs and body fluids, including cerebrospinal fluid. Rifampicin is about 80% protein bound. Most of the unbound fraction is not ionised and, therefore, diffuses freely in tissues.
Rifampicin crosses the placenta and serum levels in the foetus equal 15 to 96% of the maternal levels. It also appears in breast milk.

Metabolism.

In normal subjects the biological half-life of rifampicin in serum averages about 3 hours after a 600 mg dose.

Excretion.

After absorption, rifampicin is rapidly eliminated in the bile and an enterohepatic circulation ensues. During this process rifampicin undergoes progressive deacetylation so that nearly all the drug in the bile is in this form in about 6 hours. This metabolite retains essentially complete antibacterial activity. Intestinal reabsorption is reduced by deacetylation and elimination is facilitated. Up to 30% of a dose is excreted in the urine, with about half of this being unchanged drug.

5.3 Preclinical Safety Data

Genotoxicity.

No data available.

Carcinogenicity.

There are no known human data on the long-term potential for carcinogenicity. A few cases of accelerated growth of lung carcinoma have been reported in man, but a causal relationship with the drug has not been established.
Rifampicin was associated with an increased incidence of liver tumours in the females of one strain of mice at doses from 2 to 10 times the recommended human therapeutic doses administered for 60 weeks. In another strain of mice and in rats, no increase of tumours was found. All these studies were carried out during most of the animals' life span.
Rifampicin has been reported to possess immunosuppressive potential in rabbits, mice, rats, guinea pigs, human lymphocytes in vitro and humans.
There are no known human data on the long-term potential for mutagenicity. There was no evidence of mutagenicity in bacteria, Drosophila melanogaster or mice. An increase in chromatid breaks was noted when whole-blood cell cultures were treated with rifampicin. Increased frequency of chromosomal aberrations was observed in vitro in lymphocytes obtained from patients treated with combinations of rifampicin, isoniazid and pyrazinamide, and combinations of streptomycin, rifampicin, isoniazid and pyrazinamide.

6 Pharmaceutical Particulars

6.1 List of Excipients

Excipients present in the capsules are maize starch, magnesium stearate, titanium dioxide, erythrosine, indigo carmine and gelatin.
Excipients present in the injection are sodium formaldehyde sulfoxylate and sodium hydroxide, the diluent is water for injections.
Excipients present in the syrup are agar, sucrose, methyl hydroxybenzoate, propyl hydroxybenzoate, potassium sorbate, saccharin, sodium metabisulfite, polysorbate 80, raspberry aroma 15 D 90, diethanolamine and purified water.

6.2 Incompatibilities

Physical incompatibility (precipitate) was observed with undiluted (5 mg/mL) and diluted (1 mg/mL in normal saline) diltiazem hydrochloride and rifampicin (6 mg/mL in normal saline) during simulated Y-site administration.

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.

In-use shelf life for intravenous infusion.

For instructions on reconstitution or dilution of Rifadin IV before administration (see Section 4.2 Dose and Method of Administration).
After reconstitution with the solvent, the solution is stable for up to 30 hours.
Dilutions in glucose 5% for injections are stable for up to 8 hours at room temperature and should be prepared and used within this time. Precipitation of rifampicin from the infusion solution may occur beyond this time.
Rifadin IV infusion is compatible with normal saline for up to 6 hours.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

Capsules 150 mg, 300 mg: packed in PVC/PVDC-Alu-PVDC blister strips in packs of 100.
Syrup 100 mg/5 mL: 60 mL - amber glass bottles.
IV infusion 600 mg; with 10 mL sterile water for injection solvent - glass vials.

6.6 Special Precautions for Disposal

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

6.7 Physicochemical Properties

Rifampicin is a semisynthetic antibiotic derivative of rifamycin B. Specifically, rifampicin is the hydrazone, 3-(4-methylpiperazinyliminomethyl) rifamycin SV. It is only slightly soluble in water and is rather unstable to light and moisture.

Chemical structure.


C43H58N4O12.

CAS number.

13292-46-1.

7 Medicine Schedule (Poisons Standard)

S4 Prescription Only Medicine.

Summary Table of Changes