Consumer medicine information

Mycobutin Capsules

Rifabutin

BRAND INFORMATION

Brand name

Mycobutin

Active ingredient

Rifabutin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Mycobutin Capsules.

What is in this leaflet

Please read this leaflet carefully before taking Mycobutin. This leaflet answers some common questions about Mycobutin. It does not contain all the available information and 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 Mycobutin against the expected benefits it will have for you.

Ask your doctor if you have any concerns about taking this medicine.

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

What Mycobutin is used for

Mycobutin contains the active ingredient, rifabutin. It is an antibiotic, an agent used to kill certain types of germs, known as mycobacteria.

Mycobutin is used in combination with other medicines to treat mycobacterial infections e.g. tuberculosis (TB) or Mycobacteria avium-intracellulare complex (MAC). It may also be used to prevent infections in patients with HIV disease.

Your doctor, however, may prescribe Mycobutin for another purpose. Ask your doctor if you have any questions about why Mycobutin has been prescribed for you.

Mycobutin can only be obtained on prescription from a doctor.

Before taking Mycobutin

Some information is provided below. However, always talk to your doctor if you have concerns or questions about your treatment.

When you must not take it

Do not take Mycobutin and talk to your doctor or pharmacist if:

  • you are allergic to rifabutin or other rifamycin antibiotics (e.g. rifampicin)
  • you are allergic to any of the other ingredients listed at the end of this leaflet
  • the packaging is torn or shows signs of tampering

Do not take Mycobutin capsules after the expiry date printed on the pack has passed.

Do not give Mycobutin to children.

Before you take Mycobutin

You should tell your doctor if you:

  • have or have had problems with your liver or kidneys
  • are or may become pregnant during the time in which you are taking Mycobutin.
  • are breastfeeding or intend to breast-feed

Your doctor may need to adjust your dose or your treatment in these situations.

When taking Mycobutin, your urine (and possibly skin or body secretions) may become a red-orange colour. Contact lenses, especially soft contact lenses, may be permanently stained.

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

In particular, tell your doctor if you are taking:

  • treatments for HIV, e.g. saquinavir, indinavir, ritonavir, amprenavir, fosamprenavir, lopinavir, , nevirapine
  • other antibiotics, e.g. clarithromycin, erythromycin, chloramphenicol, trimethoprim, atovaquone
  • anti-fungal treatments, e.g. fluconazole, itraconazole, ketoconazole, posaconazole, voriconazole
  • oral contraceptives
  • oestrogens, e.g. in hormone replacement therapy (HRT)
  • heart medicines
  • medicines taken orally for diabetes
  • epilepsy medicines, e.g. phenytoin
  • sedatives, sleeping pills or medicines to treat anxiety
  • corticosteroids (used to treat inflammatory diseases, such as skin disorders, asthma or rheumatoid arthritis, or as replacement therapy in adrenal disorders)
  • tacrolimus (used to prevent organ transplant rejection)
  • methadone or other opiates, such as morphine (used for severe pain or to treat drug dependence)
  • cisapride (used to treat heartburn or stomach ulcers)
  • warfarin (used after a heart attack or to treat blood clotting disorders)

Ask your doctor or other health care professional if you are not sure about this list of medicines.

It is very important that your doctor knows all the medicines you are taking. The dose of Mycobutin or the other medicine may need to be adjusted.

How to take Mycobutin

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the box, ask your doctor or pharmacist for help.

Mycobutin capsules should be swallowed whole once a day. They may be taken at any time and need not be taken with food.

How much to take

The dose of Mycobutin depends on the infection for which you are being treated and the other medicines you are taking. The usual dose of Mycobutin will be 2 to 4 capsules per day (1-2 capsules per day for newly diagnosed pulmonary tuberculosis patients), but this may not always apply. Your doctor will decide your dose.

How long to take it

Continue taking Mycobutin until your doctor tells you to stop. You will usually need to take Mycobutin for a number of months.

Do not stop taking Mycobutin unless your doctor tells you to, even if you feel better. If you do not complete the full course prescribed by your doctor, all of the germs causing your infection may not be killed. These germs may continue to grow and multiply so that your infection may not clear completely or it may return.

If you forget to take it

If it is almost time for your next dose, skip the dose you missed and take your next dose when you are meant to. Otherwise, take it as soon as you remember, and then go back to taking Mycobutin as you would normally.

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

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

If you take too much (overdose)

Immediately telephone your doctor or pharmacist or Poisons Information Centre (telephone 13 11 26), or go to Accident and Emergency at your nearest hospital if you think that you or anyone else may have taken too much Mycobutin.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention. Keep telephone numbers for these places handy.

An excessive dose may lead to severe side effects. You should inform your doctor as soon as possible.

While taking Mycobutin

Things you must do

Keep all appointments with your doctor and always discuss any problems you may be experiencing during your course of treatment with him/her.

Mycobutin may affect the liver or reduce the body's ability to make red or white blood cells or platelets. Regular blood tests may be required.

As part of your treatment, you may be given other medicines including other antibiotics. It is important to keep taking these medicines as well as Mycobutin unless you are told otherwise by your doctor or pharmacist.

Tell your doctor immediately if you become pregnant while you are taking Mycobutin.

If you get severe diarrhoea, tell your doctor or pharmacist immediately. Do this even if it occurs several weeks after Mycobutin has been stopped. Diarrhoea may mean you have a serious condition affecting your bowel.

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

Mycobutin has been prescribed for you by your doctor. Do not give it to anyone else, even if they seem to have the same condition as you.

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

Things you must not do

Whilst you are taking Mycobutin, do not start taking any other medicines, prescription or not, without first telling your doctor or pharmacist.

Things to be careful of

Oral contraceptives may be affected by Mycobutin. Discuss with your doctor about using a different means of birth control during treatment with Mycobutin.

Contact lenses may be permanently stained. Therefore, it is better not to wear contact lenses, particularly soft contact lenses, during a treatment course of Mycobutin.

Side effects

Mycobutin, like all other medicines, may cause unwanted side effects. These are usually mild and disappear when you have completed the course.

Tell your doctor or pharmacist as soon as possible if you do not feel well after taking Mycobutin. You may need medical treatment if you get certain side effects.

Mycobutin is generally given together with other medications, so it is not always easy to identify which medicine may be causing the side effects that you may experience.

Common side effects reported are:

  • nausea or vomiting
  • jaundice (yellowing of the skin)
  • pain in joints and muscles
  • skin rash
  • fever

Less common side effects are:

  • allergic reactions causing problems with breathing, or shock
  • skin discolouration

Mycobutin, particularly when used with some other medicines, has been associated with mild to severe inner eye inflammation (uveitis). Tell your doctor as soon as possible if you get red sore eyes after taking Mycobutin.

Mycobutin can also cause changes in the levels of certain chemicals in your blood and can also increase or decrease the levels of red or white cells or platelets in your blood.

Tell your doctor if you have signs of anaemia (tiredness or pale complexion) or unexpected bleeding or bruising.

Tell your doctor immediately or go to the nearest hospital if you experience diarrhoea during your treatment with Mycobutin.

Other side effects not listed above may happen in some people.

Tell your doctor as soon as possible if you experience any side effects, including any effects not listed above.

After taking Mycobutin

Tell your doctor immediately if you notice watery and severe diarrhoea which may be bloody, particularly if they occur several weeks after stopping Mycobutin. These are rare but serious side effects. You may need urgent medical attention. Mycobutin can cause certain bacteria (that are normally harmless and present in the bowel) to multiply

Storage

Keep your capsules in their original packaging, including outer carton, until it is time to take them. If you take the medicine out of the pack, it may not keep well.

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

Do not store Mycobutin or any other medicines in a bathroom or near a sink.

Do not leave it in the car or on window sills. Heat and dampness can destroy some medicines.

Keep Mycobutin where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor tells you to stop taking Mycobutin or the medicine has passed its expiry date, ask your pharmacist what to do with any that is left over.

Product Description

What Mycobutin looks like

Mycobutin capsules are opaque and red-brown in colour with the words "Pharmacia & Upjohn" and "Mycobutin" printed on them in white ink. They are supplied in blister packs of 30 capsules

Identification

Mycobutin can be identified by an Australian Register Number which is found on the carton:
AUST R 55038.

Ingredients

Each capsule contains 150 mg rifabutin as the active ingredient. Other ingredients (mainly as filling agents) are:

  • microcrystalline cellulose
  • sodium lauryl sulfate
  • magnesium stearate
  • silicon dioxide
  • gelatin

The colorants in the capsule are

  • red iron oxide
  • titanium dioxide

White printing ink is used on the capsules.

Supplier

Pfizer Australia Pty Ltd
Sydney NSW
Toll Free Number: 1800 675 229
www.pfizer.com.au

This leaflet was revised in October 2019.

© Pfizer Australia Pty Ltd

Published by MIMS December 2019

BRAND INFORMATION

Brand name

Mycobutin

Active ingredient

Rifabutin

Schedule

S4

 

1 Name of Medicine

Rifabutin.

6.7 Physicochemical Properties

Chemical name: (12E,22E,24Z)- (9S,14S,15R,16S,17R,18R,19R,20S,21S)- 3,5,9,10-tetrahydro-6,18,20- trihydroxy-1'-isobutyl-14-methoxy- 7,9,15,17,19,21,25-heptamethyl- 5,10,26-trioxospiro[9,4- (epoxypentadeca [1,11,13] trienimino)- 2H-furo[2',3':7,8] naphtho[1,2-d]imidazole- 2,4-piperidine]-16-yl acetate.
The empirical formula is C46H62N4O11.

Chemical structure.

The structural formula is as follows:

CAS number.

72559-06-9.

2 Qualitative and Quantitative Composition

Mycobutin (rifabutin) is a wide spectrum, semi-synthetic ansamycin antibiotic particularly active on acid-fast bacilli, including atypical and multidrug-resistant mycobacteria.
Each Mycobutin capsule for oral administration contains 150 mg of rifabutin.

3 Pharmaceutical Form

The hard gelatin capsules are opaque and red-brown in colour with the words "Pharmacia & Upjohn" and "Mycobutin" imprinted on the capsule in white ink.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Rifabutin has activity in vitro against laboratory strains and clinical isolates of M. tuberculosis. To date, in vitro studies have shown that from one-third to half of M. tuberculosis strains resistant to rifampicin are susceptible to rifabutin, indicating that cross resistance between the two antibiotics is incomplete.
The in vivo activity of rifabutin on experimental infections caused by M. tuberculosis is about 3 to 10 times greater than that of rifampicin, in agreement with the in vitro findings.
Rifabutin has been shown to be active against nontuberculous (atypical) mycobacteria including M. avium-intracellulare complex (MAC) in vitro, as well as in vivo, on experimental infections caused by these pathogens in mice with induced immunodeficiency.
In vitro susceptibility testing methods and diagnostic procedures used for determining minimum inhibitory concentration (MIC) values against MAC organisms and other mycobacterial species have not been standardised.

Clinical trials.

No data available.

5.2 Pharmacokinetic Properties

In humans, rifabutin maximum plasma concentrations are reached around 2-4 hours after oral administration. The pharmacokinetics of rifabutin is linear after single dosing of 300, 450 and 600 mg to healthy volunteers. With these doses, Cmax is in the range of 0.4-0.7 microgram/mL. Although systemic levels of rifabutin following multiple dosing decreased by 38%, its terminal half-life remained unchanged.
Rifabutin, due to its high lipophilicity, demonstrates a high propensity for distribution and intracellular tissue uptake. It is widely distributed in various animal organs with the exception of the brain. In particular, in human lung tissue the concentrations measured up to 24 hours after dosing are about 5-10 times higher than the plasma levels. Substantially higher intracellular tissue levels than those seen in plasma have been observed in both rat and man.
About 85% of the drug is bound to plasma proteins. Binding does not appear to be influenced by renal or hepatic dysfunction.
Renal and biliary clearance of unchanged drug each contribute approximately 5% to CLs/F. About 30% of the dose is excreted in the faeces. Rifabutin and its metabolites are eliminated mainly by the urinary route. The t1/2β of Mycobutin in humans is approximately 35-40 hours.
The bioavailability of rifabutin from the capsule dosage form, relative to a solution, was 85% in healthy adult volunteers. High fat meals slow the rate without influencing the extent of absorption from the capsule.

5.3 Preclinical Safety Data

Genotoxicity.

Rifabutin was not mutagenic in a standard series of assays for gene mutations and chromosomal damage.

Carcinogenicity.

Long-term carcinogenicity studies were conducted with rifabutin in mice and rats. Rifabutin was not carcinogenic in mice at oral doses up to 180 mg/kg/day, giving rise to rifabutin plasma levels of 2.6 microgram/mL and 1.8 microgram/mL in female and male mice, respectively. Rifabutin was not carcinogenic in rats at oral doses up to 60 mg/kg/day, giving rise to rifabutin plasma levels of 9.2 microgram/mL and 7.1 microgram/mL in male and female rats, respectively. Serum levels in humans after dosing with 600 mg rifabutin were in the order of microgram/mL.

4 Clinical Particulars

4.1 Therapeutic Indications

Mycobutin is indicated for:
the prophylaxis of M. avium-intracellulare complex (MAC) infections in patients with advanced HIV infection (CD4 counts lower than 200/microlitre);
the treatment of infections caused by MAC and other atypical mycobacteria, including in immunocompromised patients;
the treatment of chronic multidrug resistant pulmonary tuberculosis in the presence of rifampicin resistant, rifabutin sensitive M. tuberculosis strains;
the treatment of newly diagnosed pulmonary tuberculosis in the presence of rifampicin resistant, rifabutin sensitive M. tuberculosis strains.
In accordance with the commonly accepted criteria for the treatment of mycobacterial infections, Mycobutin should always be given in combination with other antimycobacterial drugs not belonging to the family of rifamycins.

4.3 Contraindications

Mycobutin is contraindicated in patients with a history of hypersensitivity to rifabutin or other rifamycins (e.g. rifampicin).
Due to insufficient clinical experience in children, Mycobutin should not be used in these patients.
Concomitant use of ritonavir and rifabutin is contraindicated.

4.4 Special Warnings and Precautions for Use

Mycobutin may impart a red-orange colour to the urine and possibly to skin and body secretions. Contact lenses, especially the soft variety, may be permanently stained.
In accordance with the commonly accepted criteria for the treatment of mycobacterial infections, Mycobutin should always be given in combination with other antimycobacterial drugs not belonging to the family of rifamycins.
It is recommended that white blood cell and platelet counts and liver enzymes be monitored periodically during treatment because Mycobutin may be associated with neutropenia and more rarely thrombocytopenia.
Rifamycins have been associated with drug induced hepatic breakdown of vitamin K in pregnant women and their offspring (see Section 4.6 Fertility, Pregnancy and Lactation, Use in pregnancy).
Protease inhibitors act as substrates or inhibitors of the CYP450 3A4 enzyme and have significant drug interactions with rifabutin. As a result, before concomitant use of these drugs, an overall assessment of the patient and their medication should be made (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
Clostridium difficile associated diarrhoea (CDAD) has been reported with use of nearly all antibacterial agents, including rifabutin, and may range in severity from mild diarrhoea to fatal colitis. Treatment with antibacterial agents alters the normal flora of the colon leading to overgrowth of C. difficile.
C. difficile produces toxins A and B which contribute to the development of CDAD. Hypertoxin producing strains of C. difficile cause increased morbidity and mortality, as these infections can be refractory to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhoea following antibiotic use. Careful medical history is necessary since CDAD has been reported to occur over two months after the administration of antibacterial agents.

Uveitis.

When Mycobutin is given in association with clarithromycin, the dosage of Mycobutin should be reduced to 300 mg (see Section 4.8 Adverse Effects (Undesirable Effects), Uveitis/corneal deposits).
Because of the possibility of occurrence of uveitis, patients should be carefully monitored when Mycobutin is given in combination with clarithromycin (or other macrolides) and/or fluconazole (and related compounds).
If uveitis occurs, the patient should be referred to an ophthalmologist. If considered necessary, Mycobutin treatment should be discontinued and appropriate treatment given (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions; Section 4.8 Adverse Effects (Undesirable Effects)).

Malabsorption.

Gastric pH alteration due to progressing HIV disease has been linked with malabsorption of some drugs used in HIV positive patients (e.g. rifampin, isoniazid). Drug serum concentration data from AIDS patients with varying disease severity (based on CD4+ counts) suggest that rifabutin absorption is not influenced by progressing HIV disease.

Use in hepatic impairment.

Mycobutin should be used with caution in cases of liver insufficiency. For patients with severe liver insufficiency a dose reduction should be considered. Mild hepatic impairment does not require a dose modification.

Use in renal impairment.

Mild to moderate renal impairment does not require any dosage adjustment. Severe renal impairment (creatinine clearance below 30 mL/minute) requires a dosage reduction of 50%.

Use in the elderly.

No data available.

Paediatric use.

Due to insufficient clinical experience in children, Mycobutin should not be used in these patients.

Effects on laboratory tests.

No data available.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Although structurally similar to rifampicin, rifabutin appears to induce enzymes of the P450 system to a lesser extent.
Therefore, as rifabutin has been shown to induce the enzymes of the cytochrome P450 3A subfamily, treatment may affect the pharmacokinetic behaviour of drugs metabolised by the enzymes belonging to that subfamily (as is seen with rifampicin).
Rifabutin accelerates the metabolism of fluconazole, methadone, oral contraceptives and phenytoin.
Rifabutin decreases the concentration of atovaquone, benzodiazepines, opiate analgesics, sulfamethoxazole, tacrolimus and trimethoprim.
Rifabutin accelerates the metabolism and may decrease plasma concentrations of astemizole, calcium channel blockers, cisapride, clarithromycin, corticosteroids, cyclosporin, erythromycin, indinavir, itraconazole, ketoconazole, lidocaine, lovastatin, midazolam, nevirapine, oestrogens, quinidine, ritonavir, saquinavir, terfenadine, theophylline, triazolam, warfarin and zidovudine.
Upward adjustment of the dosage of some of the drugs listed above may be required when administered with Mycobutin keeping in mind that some of the interactions show wide interindividual variability. The drugs normally subject to this include dapsone, narcotic analgesics (including methadone), anticoagulants, corticosteroids, cardiac glycoside preparations (although not digitalis), quinidine, oral hypoglycaemic agents and oral contraceptives. It is important to note that during Mycobutin therapy oral contraception may not be adequate and patients should be advised to use other forms of contraception.
There are insufficient data to assess whether dose adjustments are necessary when nevirapine and rifabutin are coadministered. Concomitant use of these drugs should be carefully monitored and the combination only used if clearly indicated.
When rifabutin is used concomitantly with clarithromycin, a decreased dose of rifabutin is recommended due to the increase in plasma concentrations of rifabutin.
Other macrolide antibiotics may also inhibit metabolism of rifabutin.
When administered with indinavir, the dosage of rifabutin should be reduced by half.
Protease inhibitors act as substrates or inhibitors of CYP450 3A4 mediated metabolism. Therefore, due to significant drug-drug interactions between protease inhibitors and rifabutin, their concomitant use should be based on the overall assessment of the patient and a patient specific drug profile.
Other drugs such as ketoconazole, barbiturates, benzodiazepines, verapamil, β-blocking drugs, disopyramide, mexiletine, chloramphenicol and anticonvulsants, may also require consideration for potential dose adjustment during concomitant therapy, based on the known effects of rifampicin.
In contrast, no significant interactions may be expected with ethambutol, pyrazinamide, theophylline, sulfonamides and zalcitabine (DDC).
Although pharmacokinetic data have shown that Mycobutin, when given in combination with zidovudine, reduces the plasma levels of the latter, a large controlled clinical study has shown that these changes are of no clinical relevance.
Clinical studies have shown that Mycobutin does not affect the pharmacokinetics of didanosine (DDI), isoniazid (for the latter, see Section 4.8 Adverse Effects (Undesirable Effects), Blood and lymphatic system) and fluconazole. Fluconazole however increases rifabutin plasma levels. Zidovudine and DDI were shown not to affect the pharmacokinetics of rifabutin.
In addition, some drugs increase the concentration of rifabutin and these include the following. Ciprofloxacin, clarithromycin, enoxacin, erythromycin, fluconazole, indinavir, itraconazole, ketoconazole, ritonavir and saquinavir.
Major interactions in this category leading to a significant increase in side effects occur with clarithromycin, fluconazole, indinavir, ritonavir and, in particular, saquinavir.
Table 1 summarises the results and magnitude of the various drug interactions with rifabutin. The clinical relevance of these interactions and subsequent dose modifications should be judged in light of the population studied, severity of the disease, patient's drug profile and the likely impact on the risk/benefit ratio.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Studies in rats at oral doses of rifabutin at 160 mg/kg/day have shown impairment of spermatogenesis and effects on the gonads without any significant effect on the numbers of live offspring.
(Category C)
Reproduction studies have been carried out in rats and rabbits given rifabutin at oral dose levels up to 200 and 80 mg/kg/day, respectively. Teratogenicity was not observed in either species. In rats, at an oral dose of 40 mg/kg/day, rifabutin caused an increase in skeletal variants. In rabbits, at an oral dose of 80 mg/kg/day, rifabutin caused maternotoxicity and an increase in fetal skeletal anomalies. There are no adequate and well controlled studies in pregnant women.
Because animal reproduction studies are not always predictive of human response, rifabutin should be used in pregnant women only if the potential benefit justifies the potential risk to the fetus.
During the late stages of pregnancy, rifampicin has been associated with serious vitamin K deficiency in mother and neonate, resulting in haemorrhagic disturbances. Mycobutin has not been studied in pregnancy. This should be borne in mind if, in exceptional cases, the physician considers the benefit of treatment outweighs the risk, and wishes to treat a pregnant woman with Mycobutin.
It is not known whether rifabutin is excreted in human breast milk. Because many drugs are excreted in human milk and the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

4.8 Adverse Effects (Undesirable Effects)

The tolerability of Mycobutin in multiple drug regimens was assessed in long-term studies with daily dosages up to 600 mg in both immunocompetent and immunocompromised patients suffering from tuberculosis and nontuberculous mycobacteriosis.
Mycobutin was often given in these studies as part of a multidrug regimen, and it is not possible to define with certainty a drug-event relationship.
Treatment discontinuation was necessary in approximately 13% of patients with HIV infection and 5% of patients with tuberculosis in clinical trials, related to gastrointestinal symptoms, liver function test abnormalities and blood or lymphatic system disorders.
Adverse reactions identified through either clinical trials or postmarketing surveillance by system organ class (SOC) are listed below.
*Adverse reactions not observed in a clinical trial.
**Adverse reactions neither observed in the clinical trials nor in the spontaneous reporting for rifabutin and are mandated for the pharmacological class.

Blood and lymphatic system.

Pancytopenia, white blood cells disorder (including agranulocytosis*, leukopenia, lymphopenia*, granulocytopenia*, neutropenia*, white blood cell count decreased*, neutrophils count decreased*), thrombocytopenia, platelet count decreased* and anaemia (approximately 4-9%). The frequency and severity of haematological reactions may be increased by combined administration of isoniazid.

Immune system disorders.

Anaphylactic shock**, hypersensitivity*, bronchospasm*, rash, eosinophilia.

Eye disorders.

Uveitis*, corneal deposits*.

Gastrointestinal disorders.

Clostridium difficile colitis**, nausea, vomiting.

Hepatobiliary disorders.

Jaundice (approximately 8-12%), hepatic enzyme increased*.

Skin and subcutaneous tissue disorders.

Skin discolouration.

Musculoskeletal and connective tissue disorders.

Arthralgia, myalgia (approximately 3%).

General disorders and administration site condition.

Pyrexia (approximately 2-4%), rash (approximately 3-4%) and, rarely (< 1%), other hypersensitivity reactions such as eosinophilia, bronchospasm and shock might occur, as has been seen with other antibiotics.

Uveitis/corneal deposits.

Mild to severe, reversible uveitis has been reported. The risk is very low when Mycobutin is used at 300 mg as monotherapy in MAC prophylaxis but increases when Mycobutin is administered at higher doses in combination with clarithromycin for MAC treatment (see Section 4.4 Special Warnings and Precautions for Use). Corneal deposits have been reported during routine ophthalmologic surveillance of some HIV positive paediatric patients receiving Mycobutin as part of a multiple drug regimen for MAC prophylaxis. The deposits are tiny, almost transparent, asymptomatic peripheral and central corneal deposits, and do not impair vision.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

Dosage.

Mycobutin can be administered as a single, daily, oral dose at any time, independently of meals.
Caution should be applied when rifabutin is coadministered with any of the other drugs listed (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). Dosages of either drug may need to be adjusted on a case by case basis.

Adults.

Mycobutin as a single agent.

Prophylaxis of MAC infection in immunodepressed patients: 300 mg (2 capsules) daily.

Mycobutin in combination regimens.

In nontuberculous mycobacterial disease: 300 to 600 mg (2 to 4 capsules) daily for up to 6 months after negative cultures are obtained.
In chronic, multidrug resistant pulmonary tuberculosis: 300 to 450 mg (2 to 3 capsules) daily for up to 6 months after negative sputum cultures are obtained.
In newly diagnosed pulmonary tuberculosis: 150 to 300 mg (1 to 2 capsules) daily for 6 months.
When Mycobutin is given in association with clarithromycin, the dosage of Mycobutin should be reduced to 300 mg once daily.
When Mycobutin and indinavir are coadministered, the dosage of Mycobutin should be halved and the dosage of indinavir increased to 1,000 mg four times a day.

Children.

There are inadequate data to support the use of Mycobutin in children at the present time.

Elderly.

No specific recommendations for dosage alterations in the elderly are suggested.

4.7 Effects on Ability to Drive and Use Machines

There have been no reports of adverse effects of Mycobutin on the ability to drive and use machines.

4.9 Overdose

A specific toxic dose of rifabutin has not been established, although a syndrome of arthralgia/arthritis has been reported following daily monotherapy of 1 g or more. Other signs and symptoms of overdosage are likely to be similar to adverse effects from normal therapeutic doses.
There is no specific antidote. Treatment is symptomatic and supportive, including respiratory and cardiovascular function. Plasma rifabutin levels may confirm overdosage but are not clinically useful. Monitor complete blood count, liver enzyme levels and fluid-electrolyte status as indicated, and perform an ophthalmological examination if the patient exhibits ocular symptoms.
An aqueous slurry of activated charcoal may be administered after a potentially toxic ingestion, but it is most effective within one hour of ingestion. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via nasogastric tube once the airway is protected.
Rifabutin is approximately 85% protein bound, is extensively distributed into various tissues and is not primarily excreted via the urinary route, therefore, neither haemodialysis nor forced diuresis are expected to be of any benefit.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Microcrystalline cellulose, sodium lauryl sulfate, magnesium stearate, silicon dioxide, iron oxide red, titanium dioxide, Opacode monogramming ink S-1-7085 White, TekPrint SB-0007P White Ink, gelatin.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

Mycobutin is supplied as 150 mg capsules in:
PVC/Al blister packs of 30 (3 strips of 10 capsules);
Glass bottles of 30 - not marketed.

6.6 Special Precautions for Disposal

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

Summary Table of Changes