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Medicines Safety Update Volume 7 Number 1, February 2016

2 February 2016

Medicines Safety Update is the medicines safety bulletin of the Therapeutic Goods Administration (TGA).

Mycophenolate mofetil - new contraindications relating to pregnancy and breastfeeding

Health professionals are advised that new contraindications relating to pregnancy and breastfeeding have been added to the Product Information for mycophenolate mofetil due to its mutagenic and teratogenic potential.

Mycophenolate mofetil is the 2-morpholinoethyl ester of mycophenolic acid that is used as an immunosuppressant. It is indicated for the prophylaxis of solid organ rejection in adults receiving allogeneic organ transplants and in paediatric patients (aged 2-18 years) receiving allogeneic renal transplants.

This medicine is now contraindicated in the following situations:

  • during pregnancy
  • in women of childbearing potential who are not using two reliable forms of contraception (including at least one highly effective method)
  • in women who are breastfeeding.

All patients of reproductive potential must be made aware of the increased risk of pregnancy loss and congenital malformations and be counselled regarding pregnancy prevention and planning.

For female patients of child bearing potential, they should use two reliable forms of contraception (including at least one highly effective method) before beginning treatment with mycophenolate mofetil, during treatment and for six weeks after discontinuation of therapy.

Sexually active men who are taking mycophenolate mofetil, including those who have had a vasectomy, should be advised to use condoms during treatment and for at least 90 days after ending treatment. Female partners of such men should also use a highly effective contraceptive during this time.

Use during breastfeeding has been contraindicated as a precaution because studies in rats have shown that mycophenolate mofetil can be excreted in milk. It is not known whether this medicine is excreted in human milk.

Post-market reports

Congenital malformations, including multiple malformations, have been reported in 23-27% of live births of children of patients exposed to mycophenolate mofetil in combination with other immunosuppressants during pregnancy.

The risk of malformations in live births for the overall population is estimated to be approximately 2%. Meanwhile, the risk for solid organ transplant patients treated with immunosupressants other than mycophenolate mofetil is approximately 4-5%.

Cases of spontaneous abortion, mainly in the first trimester, have also been reported in patients exposed to mycophenolate mofetil. The risk is estimated to be 45-49%, compared to a reported rate of 12-33% in solid organ transplant patients treated with other immunosuppressants.

Information for health professionals

If you are considering using mycophenolate mofetil in a patient of reproductive potential, either female and male, advise them of the increased risk of spontaneous abortion and congenital malformations associated with this medicine. Educate them regarding pregnancy prevention and planning.

Before starting treatment, female patients of childbearing potential must have two negative serum or urine pregnancy tests with a sensitivity of at least 25 mIU/mL.

The second test should be performed 8-10 days after the first one and immediately before starting treatment. Repeat pregnancy tests should be performed during routine follow-up visits. Results of all tests should be discussed with the patient.

Patients should be instructed to contact you immediately should they become pregnant.

Further information about this issue is available in the Product Information for mycophenolate mofetil.

Varenicline - risks of psychiatric symptoms and potential interaction with alcohol

Health professionals are advised that the Product Information and Consumer Medicine Information for varenicline have been recently updated to make information about psychiatric symptoms more prominent.

Varenicline is a partial agonist at alpha-4 beta-2 neuronal nicotinic acetylcholine receptors. It is indicated as an aid to smoking cessation in adults over the age of 18 years.

Information regarding reports of psychiatric symptoms associated with varenicline treatment was previously included in the medicine's Product Information (PI) and Consumer Medicine Information (CMI). However, the update strengthens the advice to health professionals and consumers regarding these potential adverse events.

Health professionals should discuss the benefits and risks with patients before prescribing varenicline.

The TGA also strongly encourages dispensing pharmacists to provide patients the CMI, or counsel them regarding the relevant information contained in that document.

The purpose of this update is to:

  • increase awareness that serious psychiatric symptoms have been reported in patients taking varenicline
  • stress the importance of advising patients and their families to stop treatment with varenicline and immediately contact a health professional if these symptoms are experienced or observed.

This information is now bolded in the Precautions section of the PI, under the heading 'Psychiatric Symptoms'.

The Precautions, Interactions With Other Medicines and Adverse Effects sections of the PI have also been updated regarding the need to advise patients that consuming alcohol may increase the risk of psychiatric symptoms.

Please note that there are a number of other factors that can also contribute to psychiatric symptoms being reported in relation to treatment with varenicline, including the effects of nicotine withdrawal, existing psychiatric conditions and use of some other medicines.

The updated PI includes information from clinical trials and observational studies, which found similar incidence rates of suicidal thoughts and/or behaviour, as well as other common psychiatric symptoms, in patients treated with varenicline and those treated with placebo or alternative treatments.

Please report all suspected adverse events relating to treatment with varenicline, especially those involving psychiatric symptoms and/or interaction with alcohol.

The TGA will continue to monitor this issue.

Adverse event information

The Database of Adverse Event Notifications (DAEN) for medicines, including vaccines, contains information from reports of adverse events that the TGA has received. The TGA uses adverse event reports to identify when a safety issue may be present. While the DAEN does not contain all known information associated with the reports and cannot be used to determine if the benefits of taking the medicine outweigh the risks for individual patients, it can be a useful resource for health professionals and researchers.

Baclofen active pharmaceutical ingredient potential contamination

The TGA is aware of potential contamination of the active pharmaceutical ingredient baclofen, manufactured by Taizhou Xinyou Pharmaceutical & Chemical Co located in Taizhou City, Zhejiang Province, China. Baclofen manufactured by this company has not been used in any baclofen-containing products currently on the Australian Register of Therapeutic Goods and the TGA advises that it should not be used to compound sterile injectable medicines.

The active pharmaceutical ingredient (API) baclofen, a skeletal muscle relaxant, is used in central nervous system depressants. It is most commonly used to treat spasticity and a number of products that are included on the Australian Register of Therapeutic Goods (ARTG) contain this API.

TGA investigations have found that none of the products included on the ARTG contain the baclofen API manufactured by Taizhou Xinyou Pharmaceutical & Chemical Co. However, it has been used by some Australian compounders.

There is a risk that baclofen API manufactured by Taizhou Xinyou Pharmaceutical & Chemical Co could be contaminated with particulates. There is also a risk that it could be contaminated with endotoxin or microorganisms. Because of these risks, it could pose serious safety risks, especially if administered directly into the spinal column.

The TGA advises that baclofen API manufactured by Taizhou Xinyou Pharmaceutical & Chemical Co should not be used to compound sterile injectable medicines.

The TGA is continuing to investigate this issue and is liaising with Australian pharmacy organisations and State and Territory health departments to disseminate relevant information as it becomes available.

What to report? You don't need to be certain, just suspicious!

The TGA encourages the reporting of all suspected adverse reactions to medicines, including vaccines, over-the-counter medicines, herbal, traditional or alternative remedies.

We particularly request reports of:

  • all suspected reactions to new medicines
  • all suspected medicines interactions
  • suspected reactions causing death, admission to hospital or prolongation of hospitalisation, increased investigations or treatment, or birth defects.

Reports may be submitted:

For more information about reporting, visit or contact the TGA's Pharmacovigilance and Special Access Branch on 1800 044 114.


Medicines Safety Update is aimed at health professionals. It is intended to provide practical information to health professionals on medicine safety, including emerging safety issues. The information in Medicines Safety Update is necessarily general and is not intended to be a substitute for a health professional's judgment in each case, taking into account the individual circumstances of their patients. Reasonable care has been taken to ensure that the information is accurate and complete at the time of publication. The Australian Government gives no warranty that the information in this document is accurate or complete, and shall not be liable for any loss whatsoever due to negligence or otherwise arising from the use of or reliance on this document.

© Commonwealth of Australia 2016

This work is copyright. You may reproduce the whole or part of this work in unaltered form for your own personal use or, if you are part of an organisation, for internal use within your organisation, but only if you or your organisation do not use the reproduction for any commercial purpose and retain this copyright notice and all disclaimer notices as part of that reproduction. Apart from rights to use as permitted by the Copyright Act 1968 or allowed by this copyright notice, all other rights are reserved and you are not allowed to reproduce the whole or any part of this work in any way (electronic or otherwise) without first being given specific written permission from the Commonwealth to do so. Requests and inquiries concerning reproduction and rights are to be sent to the TGA Copyright Officer, Therapeutic Goods Administration, PO Box 100, Woden ACT 2606 or emailed to .

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For correspondence or further information about Medicines Safety Update, contact the TGA's Pharmacovigilance and Special Access Branch at or 1800 044 114.

Medicines Safety Update is written by staff from the Pharmacovigilance and Special Access Branch.

Editor: Dr Jane Cook

Deputy Editor: Mr Michael Pittman

TGA Acting Principal Medical Adviser: Dr Tony Gill

Contributors include: Dr Bronwen Harvey and Dr Pamela Whalan