Web site: November 2005
Prescriber Update 2005;26(2):21-22
Medsafe Pharmacovigilance Team
Update on COX-2 inhibitors
Leflunomide - watch for respiratory symptoms
Isotretinoin - contraception is critical
Reminder about obtaining patient consent
Miconazole oral gel interaction with warfarin
Update on Salamol inhalers
Medsafe has recently concluded the updating of the data sheets for the following COX-2 inhibitors: Arcoxia® (etoricoxib), Celebrex® (celecoxib), Dynastat® (parecoxib), Mobic® (meloxicam) and Prexige® (lumiracoxib). These changes were recommended by the Medicines Adverse Reactions Committee (MARC), and are intended to best manage the cardiovascular risks of the COX-2 inhibitors and to identify those select patients in whom appropriate use may be warranted. Key points for prescribers are:
Prescribers are additionally encouraged to continue reporting any suspect adverse reaction of clinical concern relating to the use of COX-2 inhibitors. These reports will assist Medsafe and MARC in the ongoing safety monitoring of these medicines.
Leflunomide (Arava®) is a disease-modifying anti-rheumatic agent indicated for the treatment of rheumatoid arthritis. It is often used in conjunction with methotrexate. The Centre for Adverse Reactions Monitoring (CARM) has received seven reports of pneumonitis occurring in patients taking leflunomide together with methotrexate. Clinical trial data indicate that pneumonitis can also occur with leflunomide alone. This disorder is characterised by dyspnoea, hypoxia and lung infiltrates. Initial symptoms in the CARM reports were various combinations of dyspnoea, cough, fever, lethargy, weight loss and influenza-like symptoms followed by rapid progression to acute respiratory compromise. Early recognition is important as pneumonitis can be life-threatening or lead to persistent disability. Patients should be informed about initial warning symptoms so that these can be investigated immediately and the suspect medicines discontinued.
Isotretinoin is highly teratogenic, which means that effective contraception is essential for all women of childbearing age (including those with a history of infertility) for whom isotretinoin is a treatment option. Women should be counselled about the risk of teratogenicity so they know it is critical that they not become pregnant while on isotretinoin. Prescribers must also exclude pregnancy prior to starting isotretinoin, and inform women to continue using contraception for one month after stopping isotretinoin.
Prescribers are reminded of their obligation to obtain informed consent from patients when making treatment decisions. This requirement forms part of the Code of Health and Disability Services Consumers' Rights 1996, which states that every consumer has the right to be fully informed of the risks and benefits of the proposed treatment. The Code also states that consumers have the right to receive the information they need to make an informed choice or give informed consent.
If a clinician is considering prescribing an unapproved medicine (i.e. a medicine that has not been assessed by Medsafe against regulatory standards for safety, efficacy and quality), the onus is on the prescriber to satisfy themself that the medicine is of appropriate safety, quality and efficacy before deciding to prescribe it.
Medsafe considers that, in order for clinicians to comply with the Code, during the consultation the patient should be advised about 1) the unapproved status of the medicine; and 2) the information that led the clinician to decide why that particular unapproved medicine is the most appropriate treatment for the patient. It is only after this information has been communicated that the patient's informed consent for treatment with an unapproved medicine is considered to have been obtained.
Prescribers are reminded of the potentially severe interaction between miconazole oral gel (Daktarin® oral gel) and warfarin. Clinically significant increases in the international normalised ratio (INR) of patients stabilised on warfarin have been reported following concomitant use of miconazole oral gel, due to systemic absorption. Warfarin patients who are given miconazole oral gel should be monitored for change in anticoagulant effect and the dose of warfarin adjusted, if necessary. As miconazole oral gel can be purchased without a prescription, both pharmacists and prescribers should inform patients taking warfarin of the potential for this interaction.
Testing of the Salamol® brand of salbutamol inhalers has shown that blockages can be prevented by washing the device once every week. Remove the metal canister and rinse the plastic mouthpiece under warm water for 30 seconds, shake to remove excess water then leave it to air dry (overnight if possible). Reassemble the inhaler device once dry. Patients may wish to keep a spare inhaler handy for use while the cleaned inhaler is drying.