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.

SUMMARY CMI

Rifadin® Oral

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about taking this medicine, speak to your doctor or pharmacist.

1. Why am I taking Rifadin?

Rifadin contains the active ingredient rifampicin. Rifadin is an antibiotic taken with other medicines to treat tuberculosis and is taken to treat leprosy. It is also taken to prevent meningococcal disease and infections caused by Haemophilus Influenza Type B. For more information, see Section 1. Why am I taking Rifadin? in the full CMI.

2. What should I know before I take Rifadin?

Do not take Rifadin if you have ever had an allergic reaction to Rifadin or any of the ingredients listed at the end of the CMI.

Do not take Rifadin if you have jaundice.

Do not take Rifadin if you are taking saquinavir or ritonavir. These are medicines used to treat AIDS and HIV.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding or planning to breastfeed.

For more information, see Section 2. What should I know before I take Rifadin? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Rifadin and affect how it works.

A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I take Rifadin?

Follow the instructions provided when Rifadin was prescribed, including the number of days it should be taken.

More instructions can be found in Section 4. How do I take Rifadin? in the full CMI.

5. What should I know while taking Rifadin?

Things you should do
  • Remind any doctor, dentist, surgeon, or pharmacist you visit that you are taking Rifadin.
  • You should see your doctor monthly for a check-up.
  • Continue taking Rifadin exactly as prescribed by your doctor.
  • If you have a blood or urine test, tell your doctor you are taking Rifadin.
  • If you are about to be started on a new medicine, including oral contraceptives, tell your doctor you are taking Rifadin.
Things you should not do
  • Do not stop taking this medicine because you feel better.
Driving or using machines
  • Be careful before you drive or use any machines or tools until you know how Rifadin affects you.
Looking after your medicine
  • Store below 25°C.
  • Store Rifadin in a cool dry place away from moisture, heat or sunlight.

For more information, see Section 5. What should I know while taking Rifadin? in the full CMI.

6. Are there any side effects?

Serious side effects include allergic reactions, interstitial lung disease (including pneumonitis), severe bleeding or bruising, severe diarrhoea, severe stomach cramps, worsening of tuberculosis symptoms typically associated with exaggerated inflammatory symptoms including fever, swollen lymph nodes, breathlessness, cough and other symptoms such as headache, loss of appetite and weight loss. Stop using Rifadin and immediately contact a doctor if you experience any of the following symptoms such as nausea or vomiting, fever, feeling tired, loss of appetite, dark-colored urine, light-colored faeces, yellowing of the skin or white part of the eyes, itching, rash or upper stomach pain. These symptoms may be signs of liver injury.

For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.



FULL CMI

Rifadin® Oral (rif-ar-din)

Active ingredient: rifampicin (rif-am-pee-cin)


Consumer Medicine Information (CMI)

This leaflet provides important information about taking Rifadin. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about taking Rifadin.

Where to find information in this leaflet:

1. Why am I using Rifadin?
2. What should I know before I take Rifadin?
3. What if I am taking other medicines?
4. How do I take Rifadin?
5. What should I know while taking Rifadin?
6. Are there any side effects?
7. Product details

1. Why am I taking Rifadin?

Rifadin contains the active ingredient rifampicin. Rifadin is an antibiotic which kills certain types of bacteria that can cause serious infections.

Rifadin is taken with other medicines to treat tuberculosis and is taken to treat leprosy. Rifadin is also taken to prevent the following diseases:

  • Meningococcal disease that can cause meningitis.
  • Infections caused by the bacteria, Haemophilus Influenzae Type B. Despite the name, it is not related to influenza (‘the flu’). Symptoms of this infection can include meningitis, pneumonia, or conjunctivitis.

2. What should I know before I take Rifadin?

Warnings

Do not take Rifadin if:

  • you are allergic to rifampicin or other similar antibiotics such as rifabutin or rifaximin.
  • you are allergic to any of the ingredients listed at the end of this leaflet.
Always check the ingredients to make sure you can use this medicine.
  • you are taking saquinavir/ritonavir. These medicines are used to treat acquired immune deficiency syndrome (AIDS) and human immunodeficiency virus (HIV) infections.
  • you have jaundice (yellowing of the eyes and skin)
  • you are breastfeeding or planning to breastfeed
  • you have previously taken any rifampicin containing medicinal product and had liver problems. If you are unsure talk to your doctor. Inflammation of the liver has been reported in patients taking Rifadin with symptoms developing within a few days to a few months following the start of treatment. Stop using Rifadin and contact a doctor if you have symptoms of liver problems (see section 6. Are there any side effects?)

Check with your doctor if you:

  • have any other medical conditions
  • have any problems with your liver including liver disease
  • have a problem with bleeding or a tendency to bruise easily
  • have diabetes
  • are taking other antibiotics
  • wear soft contact lenses. 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.
  • are taking any medicines for any other condition
  • are taking oral contraceptives. You should change to an alternative method of birth control.
  • have any allergies to any other medicines or any other substances, such as foods, preservatives or dyes
  • have a history of lung inflammation (interstitial lung disease/pneumonitis)
  • experience reappearance or worsening of symptoms of tuberculosis (see section 6. Are there any side effects?)
  • develop a rash or experience any symptoms of thrombotic microangiopathy during your treatment (see section 6. Are there any side effects?)

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Rifadin should not be used while breastfeeding. Rifadin passes into breast milk and there is a possibility your baby may be affected.

3. What if I am taking other medicines?

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

Some medicines may interfere with Rifadin and affect how it works.

Rifadin should not be taken with the following medicines:

  • the combination of saquinavir and ritonavir, antiviral agents used to treat acquired immune deficiency syndrome (AIDS) and human immunodeficiency virus (HIV) infections.
  • If you are taking dapsone (an antibiotic) with rifampicin, it may cause methemoglobinemia (decrease in oxygen in your blood caused by changes in red blood cells).
  • If you are taking paracetamol and rifampicin, it can increase the risk of liver damage.
  • halothane, a general anaesthetic (a sleep inducing medicine)
  • medicines used to treat Hepatitis C (antiviral agents), such as daclatasvir, simeprevir, sofosbuvir and telaprevir
  • Cephalosporin antibiotics, such as cefazolin used to treat infection
  • oral contraceptives

Rifadin and some medicines may interfere with each other and affect how they work, such as:

  • antacids
  • atovaquone
  • isoniazid
  • p-aminosalicylic acid (PAS)
  • medicines for the treatment or prevention of breast cancer
  • medicines used to treat thyroid deficiency
  • medicines for nocturnal cramps
  • medicines for breathing difficulties
  • medicines to treat diabetes
  • medicines to treat nausea or vomiting

Heart or blood-related

  • medicines that thin the blood, such as clopidogrel
  • medicines to lower cholesterol
  • medicines for treating heart problems
  • medicines for treating high blood pressure, such as enalapril

Infections or immune system-related

  • medicines to treat bacterial or fungal infections, such as antibiotics or ketoconazole
  • medicines to treat tuberculosis or leprosy
  • medicines for treating human immunodeficiency virus (HIV)
  • medicines to treat malaria
  • medicines to treat inflammatory conditions
  • medicines used to keep the body from rejecting transplanted organs

Mental health, brain or pain-related

  • medicines to treat mental illnesses, such as anxiety or depression
  • medicines used to control or prevent seizures
  • medicines that can cause sedation
  • medicines for pain

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Rifadin.

4. How do I take Rifadin?

How much to take

  • Follow the instructions provided when Rifadin was prescribed, including the number of days it should be taken.
  • Swallow Rifadin capsules whole with a glass of water.
  • If you need to take an antacid, take it at least 1 hour after your dose of Rifadin.

When to take Rifadin

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

If you forget to take Rifadin

Rifadin should be taken regularly at the same time each day. If you miss your dose at the usual time, take the dose as soon as you remember, and then resume taking Rifadin as directed.

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 you missed.

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

If you take too much Rifadin

If you think that you have taken too much Rifadin, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26 in Australia), or (by calling 0800 764 766 in New Zealand), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should do this even if there are no signs of discomfort or poisoning.

  • If you take too much Rifadin you may experience nausea, vomiting, stomach pain, itching, headache, tiredness, dizziness, swelling, fast or uneven heartbeat or other problems with heartbeating.

5. What should I know while taking Rifadin?

Things you should do

  • You should see your doctor monthly for a check-up. Your doctor may order blood tests from time-to-time to check your progress or check for any side effects.
  • Continue taking Rifadin exactly as prescribed by your doctor.
  • If you have a blood test or urine test, tell your doctor you are taking Rifadin. Rifadin may affect the results of some blood and urine tests.
  • If you are about to be started on a new medicine, including oral contraceptives, tell your doctor that you are taking Rifadin.
  • If you are using oral contraception you should change to alternative methods of birth control.

Call your doctor straight away if you:

  • develop new or sudden worsening of shortness of breath, possibly with a dry cough or fever that is not responding to antibiotic treatment
These could be symptoms of lung inflammation (interstitial lung disease/pneumonitis) and can lead to serious breathing problems due to collection of fluid in the lungs and interfere with normal breathing which can lead to life threatening conditions.
  • become or intend to become pregnant
  • are breastfeeding or intend to breastfeed
  • are about to start taking any new medicine

Remind any doctor, surgeon, dentist or pharmacist you visit that you are using Rifadin.

Things you should not do

  • Do not stop taking this medicine because you feel better. If you do not complete the full treatment your infection may not completely clear or may return.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Rifadin affects you.

Rifadin may cause dizziness, drowsiness or other undesirable effects in some people.

Looking after your medicine

  • Store below 25°C

Follow the instructions in the carton on how to take care of your medicine properly.

Store Rifadin in a cool dry place away from moisture, heat or sunlight; for example:

  • do not store it in the bathroom or near a sink, or
  • do not store it in the car or on window sills.

Keep it where young children cannot reach it.

Getting rid of any unwanted medicine

If you no longer need to take this medicine or it is out of date, take it to any pharmacy for safe disposal.

Do not take this medicine after the expiry date.

6. Are there any side effects?

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

Less serious side effects

Less serious side effectsWhat to do
Central nervous system-related:
  • drowsiness
  • fatigue
  • difficulty in concentrating
  • confusion
  • mental problems
General:
  • problems with your period
  • 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.
Skin or eye-related:
  • yellow discolouration of skin or eyes
  • conjunctivitis
  • problems with your eyesight
Thrush-related:
  • white, furry, sore tongue and mouth. These are signs of oral thrush.
  • sore and itchy vagina with or without discharge. These are signs of vaginal thrush.
Muscle or nerve-related:
  • poor coordination
  • muscle weakness
  • pain in the fingers or toes
  • numbness
Stomach or gut-related:
  • heartburn
  • loss of appetite
  • nausea
  • vomiting
  • upset stomach
  • gut discomfort
  • wind
  • cramps
  • diarrhoea. Do not take any diarrhoea medicine without first checking with your doctor.
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
Liver-related:
  • nausea or vomiting, fever, feeling tired, loss of appetite, darkcolored urine, light-colored faeces, yellowing of the skin or white part of the eyes, itching, rash or upper stomach pain.
Stop using Rifadin and immediately contact a doctor if you experience any of these symptoms. These symptoms may be signs of liver injury.
Skin-related:
  • severe red and/or itchy skin, blisters or pimples, bleeding, peeling or bruising of the skin
Blood and lymph related:
  • blood in the urine or any other urination disturbances
  • severe bleeding or bruising more easily than normal
  • blood clots in small blood vessels (thrombotic microangiopathy). Symptoms may include increased bruising, bleeding, fever, extreme weakness, headache, dizziness or light-headedness. Your doctor may find changes in your blood and the function of your kidneys.
General:
  • itching, weakness, loss of appetite, nausea, vomiting, stomach or gut pain, yellowing of the eyes or skin or dark urine
  • worsening of tuberculosis symptoms which are typically associated with exaggerated inflammatory symptoms (reported between 2 weeks and as late as 18 months after the initiation of anti-tuberculosis treatment). These symptoms include fever, swollen lymph nodes, breathlessness and cough. Other symptoms include headache and gut symptoms such as loss of appetite and weight loss.
  • fever, chills, headache or dizziness
  • bone pain.
  • new or sudden worsening of shortness of breath, possibly with a cough or fever (interstitial lung disease/pneumonitis)
Liver-related:
  • inflammation of the liver as shown by yellowing of the skin and white part of eyes. This may be associated with an increase in liver enzymes as shown through a blood test.
Allergy-related:
  • swelling of the face, lips, tongue or throat which may cause difficulty in breathing or swallowing
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these serious side effects.
Stomach or gut-related:
  • severe stomach cramps or gut cramps
  • watery and severe diarrhoea, which may also be bloody. Do not take any diarrhoea medicine without first checking with your doctor.
  • fever, in combination with one or both above.
Tell your doctor immediately if you notice any of these serious side effects, particularly if they occur several weeks after stopping treatment with Rifadin.
These are rare but serious side effects. You may have a rare serious condition affecting your bowel, which may need urgent medical attention.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may occur in some people.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects as follows:

Australia: Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems.

New Zealand: nzphvc.otago.ac.nz/reporting

By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

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

What Rifadin capsules contains

Active ingredient
(main ingredient)
150 mg or 300 mg of rifampicin per capsule
Other ingredients
(inactive ingredients)
  • maize starch
  • magnesium stearate

The capsule shell also contains:

  • titanium dioxide
  • erythrosine
  • indigo carmine
  • gelatin
Potential allergenssulfur dioxide

What Rifadin syrup contains

Active ingredient
(main ingredient)
100 mg of rifampicin per 5 mL of syrup
Other ingredients
(inactive ingredients)
  • agar
  • sucrose
  • methyl hydroxybenzoate
  • propyl hydroxybenzoate
  • potassium sorbate
  • saccharin
  • sodium metabisulfite
  • polysorbate 80
  • Raspberry Aroma 15 D 90
  • diethanolamine
  • purified water
Potential allergens
  • methyl hydroxybenzoate
  • propyl hydroxybenzoate
  • potassium sorbate
  • sodium metabisulfite
  • saccharin

Do not take this medicine if you are allergic to any of these ingredients.

Diabetics should note that Rifadin syrup contains 2 g of sugar per 5 mL of syrup.

Rifadin preparations do not contain azo dyes.

What Rifadin looks like

Rifadin 150 mg capsules have a blue cap and red body each marked “R-150”. They come in packs of 100 capsules (Aust R 233442).

Rifadin 300 mg capsules are opaque red and marked “R-300”. They come in packs of 100 capsules (Aust R 233443).

Rifadin 100 mg per 5 mL syrup is a red liquid supplied in 60 mL bottles (Aust R 10113).

Who distributes Rifadin

Rifadin is supplied in Australia by:

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

Rifadin is supplied in New Zealand by:

sanofi-aventis new zealand limited
56 Cawley Street
Ellerslie
Auckland

® Registered Trademark

This leaflet was prepared in February 2022.

rifadin-ccdsv17-cmiv15-17feb22

Published by MIMS April 2022

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.
Rifadin IV infusion contains 600 mg rifampicin per vial.

Excipients with known effect.

Capsules.

Contain sulfites.

Syrup.

Contains methyl hydroxybenzoate, propyl hydroxybenzoate, potassium sorbate, sodium metabisulfite and saccharin.
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.
Cases of drug-induced liver injury, including fatal cases (especially when used in combination with other anti-tuberculosis drugs), have been reported in patients treated with rifampicin with an onset of a few days to a few months following treatment initiation. Signs and symptoms include elevated serum hepatic enzymes, cholestatic jaundice, hepatitis, hepatotoxicity, hepatocellular injury, and mixed liver injury. Most patients recovered on discontinuation of rifampicin treatment; nevertheless, progression to acute liver failure requiring liver transplantation can occur. The mechanism of rifampicin-induced liver injury is not clearly elucidated, but data indicate either an immuno-allergic mechanism or direct toxicity of metabolic products. Patients should be instructed to contact their physician in case symptoms suggestive of liver injury occur. In such patients rifampicin should be discontinued and liver function should be assessed. Rifampicin should not be re-introduced in patients with an episode of hepatic injury during treatment with rifampicin for which no other cause of liver injury has been determined.

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.

Interstitial lung disease (ILD)/pneumonitis.

There have been reports of ILD or pneumonitis in patients receiving Rifadin for treatment of tuberculosis. ILD/pneumonitis is a potentially fatal disorder. Careful assessment of all patients with an acute onset and/or unexplained worsening of pulmonary symptoms (dyspnoea accompanied by dry cough) and fever should be performed to confirm the diagnosis of ILD/pneumonitis. If ILD/pneumonitis is diagnosed, Rifadin should be permanently discontinued in case of severe manifestations (respiratory failure and acute respiratory distress syndrome) and appropriate treatment initiated as necessary.

Paradoxical drug reaction.

After initial improvement of tuberculosis under therapy with Rifadin, the symptoms may worsen again. In affected patients, clinical or radiological deterioration of existing tuberculous lesions or the development of new lesions have been detected. Such reactions have been observed within the first few weeks or months of initiation of tuberculosis therapy.
The cause of this paradoxical reaction is still unclear, but an exaggerated immune reaction is suspected as a possible cause. When a paradoxical reaction is suspected, symptomatic therapy to suppress the exaggerated immune reaction should be initiated if necessary. Furthermore, continuation of the planned tuberculosis combination therapy is recommended.
Patients should be advised to seek medical advice immediately if their symptoms worsen. The symptoms that occur are usually specific to the affected tissues. Possible general symptoms include cough, fever, tiredness, breathlessness, headache, loss of appetite, weight loss or weakness (see Section 4.8 Adverse Effects (Undesirable Effects)).

Thrombotic microangiopathy.

Cases of thrombotic microangiopathy (TMA), manifested as thrombotic thrombocytopenic purpura (TTP) or haemolytic uremic syndrome (HUS), including fatal cases, have been reported with rifampicin use. If laboratory or clinical findings associated with TMA occur in a patient receiving rifampicin, treatment should be discontinued and thorough evaluation for TMA performed, including platelet levels, renal function, serum lactate dehydrogenase (LDH) and a blood film for schistocytes (erythrocyte fragmentation). ADAMTS13 activity and anti-ADAMTS13-antibody determination should be completed. If anti-ADAMTS13 antibody is elevated in conjunction with low ADAMTS13 activity, treatment with rifampicin should not be resumed and patients should be treated accordingly (consider plasma exchange).

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.
Concomitant use of paracetamol with rifampicin may increase the known risk of hepatotoxicity seen in relation to each drug.
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, toremifene), 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.
Rifampicin has also been shown to increase the clearance of dapsone and the production of the hydroxylamine metabolite of dapsone which could increase the risk of methemoglobinemia.
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, acneiform 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.
Drug-induced liver injury (including fatal cases especially when used in combination with other anti-tuberculosis drugs) has 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. Thrombotic microangiopathy including thrombotic thrombocytopenic purpura/haemolytic uremic syndrome have 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.
Paradoxical drug reaction: Recurrence or appearance of fresh symptoms, physical and radiological signs in a patient who had previously shown improvement with appropriate anti-tuberculosis treatment is called a paradoxical reaction, which is diagnosed after excluding poor compliance of the patient to treatment, drug resistance, side effects of antitubercular therapy, secondary bacterial/fungal infections.
Interstitial lung disease (including pneumonitis) has been reported.
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.

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.

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. Antitumor activity in vitro has also been shown with rifampicin.

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