Revised: 14 May 2013
Publications
Media Releases for 2004
| 21 Dec 2004 | Arthritis Drug Caution Advised by Ministry |
| 7 Dec 2004 | UK Antidepressant Report Reinforces NZ Actions |
| 21 Oct 2004 | New Advice on Prescribing Anti-Depressants |
| 1 Oct 2004 | Ministry Supports Recall of Arthritis and Pain Relief Drug |
| 5 Apr 2004 | Ibuprofen to be available from supermarkets |
| 24 Mar 2004 | Review of prescribing SSRI antidepressants to young people |
21 December 2004
Arthritis Drug Caution Advised by Ministry
An expert committee reviewing the safety of a group of arthritis drugs called COX-2 inhibitors has reinforced UK advice cautioning against their routine use where safe and effective alternatives are available.
The Medicines Adverse Reactions Committee is advising patients who are using Celebrex, Arcoxia, Mobic and Bextra they should talk with their health care provider about alternatives if they have concerns.
The Medicines Adverse Reactions Committee (MARC) has discussed a rapid literature review of the risk of use of COX-2 inhibitor medicine causing increased risk of cardiovascular events (heart attacks and/or stroke).
The MARC concluded that the increased risk of heart attack found for rofecoxib (Vioxx) may also occur to some degree for all of the other members of the COX-2 group of anti-inflammatory agents. The MARC conclusion is supported by the subsequent report from the United States National Institute of Health that it had stopped one of two long-term (3 years) studies of celecoxib (Celebrex) in the prevention of colon polyps due to an increased risk of cardiovascular events. The increase in cardiovascular risk was similar in size to the 1.96 times increased risk found after 18 months treatment in the Vioxx study of colon polyp prevention that lead to Vioxx being removed from the market in October of this year.
The Adenoma Prevention with Celebrex study (APC) that has been stopped found that patients taking celecoxib at doses of 200mg twice a day and 400mg twice a day have an increased risk of developing a cardiovascular event compared to patients on placebo of 2.5 and 3.4 times respectively. While the average duration of treatment in the APC study was 33 months when it was stopped, the available data does not indicate when the increased cardiovascular risk first becomes apparent. A parallel study of celecoxib using 400mg once per day as a preventative agent for colon polyps for a similar period of time has not shown increased risk.
In October 2004 the Ministry of Health (Medsafe) asked the manufacturers of COX-2 medicines to supply it with all the data they hold on the cardiovascular safety of these medicines. Like other medicines regulators around the world, Medsafe is in the process of reviewing the massive volumes of data supplied by the manufacturers to determine if use of a COX-2 medicine increases the risk of a patient developing a cardiovascular event. This analysis is unlikely to be completed before March 2005.
In the interim the MARC indicated it broadly supports the guidance issued by the United Kingdom "National Institute of Clinical Excellence" (NICE), which was distributed to all GPs by the New Zealand Best Practice Advocacy Centre in October of this year.
The MARC key messages are:
- COX-2 agents are not recommended for routine use in patients with rheumatoid arthritis (RA) or osteoarthritis (OA) except in circumstances where the patient is at "high risk " of developing a serious gastrointestinal adverse effect from other standard non-steroidal anti-inflammatory agents;
- COX-2 agents should not be routinely prescribed to patients at high risk of cardiovascular events (absolute risk of event >15-20% over 5 years) as there remains uncertainty about the safety of these agents when used in this group of patients;
- Prescribing COX-2 agents to patients already taking aspirin cannot be justified on current evidence.
- The increased benefit associated with use of COX-2 agents in patients at high risk of serious gastrointestinal adverse effects (estimated as between a 4 and 8 times reduction in serious events), may outweigh the increased risk of cardiovascular events in patients at high risk of myocardial infarction.
- A signal is emerging that use of some COX-2 agents as painkillers after major surgery may be associated with an increased risk of cardiovascular events. The MARC therefore advises that until the full evaluation of all the safety data is complete COX-2 agents should not be routinely used for post-operatively pain relief.
Patients already taking COX-2 agents should discuss the continuing use of these medications with their GP, or specialist, the next time their prescription is due. Prescribers should discuss with their patients the available alternatives to the COX-2 agents and review the risks and benefits of these alternatives compared with the emerging clinical concerns about the COX-2 agents, before deciding on the best course of treatment for that individual. If the patient and prescriber decide that continued use of a COX-2 agent is appropriate, use of the lowest effective dose is prudent practice.
If patients are taking COX-2 agents on a regular basis and are concerned about their use of these medicines, they should discuss the risk and benefits of continued treatment with their healthcare provider. A number of alternative anti-inflammatory agents for the treatment of osteoarthritis and rheumatoid arthritis are available in New Zealand. Unlike the COX-2 agents, many of these agents are funded by PHARMAC.
| COX-2 agents available in NZ include: | |||
|---|---|---|---|
| Ingredient | Brand | Ingredient | Brand |
| celecoxib | Celebrex | etoricoxib | Arcoxia |
| valdecoxib | Bextra | parecoxib | Dynastat inj (parecoxib) |
| meloxicam | Mobic | ||
| Standard anti-inflammatory agents: | |||
| Ingredient | Brand | Ingredient | Brand |
| diclofenac - | Apo-Diclofenac | ketoprofen | Orudis |
| Apo-Diclo SR | Oruvail 100 | ||
| Voltaren D |
Oruvail 200 | ||
| ibuprofen | I-Profen | naproxen | Naxen |
| Brufen | Naprosyn SR 750 | ||
| Brufen Retard |
Synflex | ||
| sulindac | Daclin | tenoxicam | Tilcotil |
| Clinoril |
|||
| tiaprofenic acid | Surgam | piroxicam | Piram D |
| Surgam SA | |||
7 December 2004
UK Antidepressant Report Reinforces NZ Actions
A long awaited United Kingdom report into the safety of some antidepressants has recommended changes to UK prescribing and monitoring of the drugs - largely in line with the updated advice issued in New Zealand by Medsafe two months ago (October).
The report from the UK Committee on Safety of Medicines Expert Working Group On SSRIs (Selective Serotonin Reuptake Inhibitors) has confirmed that the benefits of treating depression in adults with these medicines outweigh the potential risks. However it recommends that when the medicines are prescribed there should be "careful and frequent patient monitoring by healthcare professionals", particularly in the early stages of treatment, during dose changes or where symptoms worsen.
SSRIs are antidepressant medicines given for the treatment of major depression disorders. They are one of three classes of medicines used for the treatment of depression. The other two classes are called tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs).
Ministry of Health spokesperson Dr Stewart Jessamine says the report's key findings and its recommendations for changes to the prescribing and consumer information is consistent with prescribing and packaging advice issued by Medsafe in October. Medsafe directed drug companies to change prescribing and consumer information for all antidepressants, and issued warnings about the need to monitor children and adults using antidepressants.
For adolescents or children with depression the UK report confirms the earlier recommendations against all SSRIs being used apart from fluoxetine (Prozac) where there is some evidence of overall benefit. However the report warns that this drug too, like other SSRIs, is likely to be linked with a small increased risk of self harm or suicidal thoughts. The UK report reiterates that while there is no clear evidence of an increased risk of self harm and suicidal thoughts in young adults aged 18 and over, careful monitoring is recommended. It says patients in this age group are at increased risk of suicidal thinking and action than other age groups with depression.
The UK report recommends tighter restrictions on one particular SSRI called Efexor (venlafaxine) because of the increased risk of heart damage in overdose. The UK restrictions include limiting prescribing of venlafaxine to specialists (rather than GPs), not using venlafaxine in individuals with heart disease and checking patients heart rhythm by electrocardiogram prior to beginning treatment.
Dr Jessamine says venlafaxine is available in New Zealand and funded by Pharmac as a third line treatment for depression and is usually prescribed by specialists. Prescribing information accompanying the drug already includes information that heart problems and heart rhythm disturbances can occur when taking this medication at high doses or in overdose.
He says Medsafe, the Ministry's regulation and safety arm, will be seeking further information from the UK on venlafaxine as well as undertaking a literature review before referring the issues to its Medicines Adverse Reactions Committee to consider whether tighter restrictions should also apply in New Zealand. The issue will be considered by the committee in the new year.
Dr Jessamine says regulatory authorities around the world are consistently taking a more precautionary approach in their advice with respect to antidepressants.
Background
SSRIs are antidepressant medicines given for the treatment of major depression disorders. SSRIs are on of three classes of medicines used for the treatment of depression. The other two classes are called tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs).
The SSRI medicines available in New Zealand are:
- Citalopram (brand names: Cipramil, Celapram)
- Escitalopram (brand name: Lexapro, Cipralex)
- Fluoxetine (brand names: Fluox, Prozac, Apo-fluoxetine, Lovan, Plinzene, Flexetor, Fluohexal)
- Fluvoxamine (brand name: Luvox) - not marketed
- Paroxetine (brand name: Aropax)
- Sertraline (brand name: Zoloft)
- Venlafaxine (brand name: Efexor)
TCAs currently available in New Zealand are:
- Amitriptyline (brand name: Amitrip)
- Clomipramine (brand name: Anafranil, Apo-clomipramine, Clopress)
- Desipramine (brand name: Pertofran)
- Doxepin (brand name: Anten)
- Dothiepin (brand name: Dopress)
- Imipramine (brand name: Tofranil)
- Maprotiline (brand name: Ludiomil)
- Mianserin (brand name: Tolvon)
- Noritriptyline (brand name: Norpress)
- Trimipramine (brand name: Tripress, Surmontil)
Other antidepressants available in New Zealand are:
- Mirtazapine (brand name: Remeron)
- Moclobemide (brand name: Aurorix, Apo-moclobemide)
- Reboxetine (brand name: Edronax)
- Tranylcypromine (brand name: Parnate)
- In New Zealand, none of the SSRIs have ever been licensed for use
in those aged less than 18 years (however, it is recognised that off-label
use occurs in this age group). All NZ data sheets (information provided
for medicine prescribers) for all SSRIs currently state that "Safety
and effectiveness in children has not been established". All but fluoxetine
and sertraline go further to state that "use is not recommended in children".
Data sheets are available on the Medsafe web site
www.medsafe.govt.nz.
- In June 2003, the UK Committee on Safety of Medicines issued a letter
to UK prescribers advising against the use of paroxetine as therapy
for children and adolescents with depressive illness. This advice was
based on new data from GlaxoSmithKline (GSK)-sponsored clinical trials
of Aropax in paediatric patients. At this time, the New Zealand data
sheet for paroxetine (Aropax) was updated to advise that clinical trials
do not support the use of paroxetine in the treatment of children with
major depressive disorder (MDD). In addition, GlaxoSmithKline issued
a related Dear Doctor letter to New Zealand prescribers.
- In June 2003, Medsafe and the Medicines Adverse Reactions Committee
(MARC; an expert advisory committee to the Minister of Health) reviewed
the 'Technical document summaries - Summary of clinical safety data'
for paroxetine provided to Medsafe by GSK. The Committee agreed that
the data were not of sufficient quality to justify any additional regulatory
action (beyond that already taken by GSK) regarding the use of paroxetine
at that time. The decision was made to keep a watching brief on this
issue.
- In August 2003, Wyeth updated the New Zealand data sheet for venlafaxine
(Efexor) to advise against prescribing venlafaxine as therapy for children
and adolescents with depressive illness. This was based on data from
paediatric trials, which showed increased reports of suicide-related
adverse events in paediatric patients receiving venlafaxine treatment
for MDD. In addition, Wyeth issued a related Dear Doctor letter to New
Zealand prescribers.
- In December 2003, the UK Committee on Safety of Medicines (CSM)
issued a letter to UK health professionals informing them that a CSM
Expert Working Group had completed a review of the safety and efficacy
of SSRIs in the treatment of paediatric MDD. On the basis of this review
of the available clinical trial data, the CSM advised prescribers that
paroxetine, citalopram, escitalopram, sertraline, and venlafaxine are
contraindicated (meaning should not be used) in paediatric MDD. The
balance of risks and benefits of fluoxetine in these patients was deemed
to be favourable. A copy of this letter, which also provides general
prescribing advice, can be found at
http://www.mca.gov.uk/aboutagency/regframework/csm/csmhome.htm
- In March 2004, the Medicines Adverse Reactions Committee decided
there was not enough information to warrant changing the existing advice
about the prescribing of SSRIs to people under the age of 18. There
was a commitment to place a high priority on reviewing the safety of
SSRIs as more data became available.
- In September 2004, two FDA advisory committees discussed an analysis
of paediatric suicidality information based on new data and concluded
that there is some increased risk of suicidal thoughts and behaviours
associated with all SSRIs studied. The MARC is in broad agreement with
this conclusion but notes that there is no clinical trial evidence to
associate SSRIs with risk of completed suicide in any age group.
- In September 2004, the MARC recommended that datasheets for Tricyclic
Antidepressants currently approved for use in treating MDD in children
and adolescents be updated to say these medicines are not recommended
for use in patients under 18 years of age unless upon the advice of
an appropriate specialist (and contraindicated in children under 13
years of age). In addition, the MARC have recommended updates to all
antidepressant medicine datasheets (including SSRIs, TCAs, and MAOIs)
to provide advice on monitoring for clinical worsening and warn of possible
increased suicide risk with all antidepressant treatments. The minutes
of the 22 September 2004 MARC meeting are available on the Medsafe web
site: www.medsafe.govt.nz/Profs/adverse/Minutes119.htm
- The key findings of the 6 December 2004 report from the UK Committee
on Safety of Medicines (http://www.mhra.gov.uk)
Expert Working Group On SSRIs are available in a letter sent to UK health
professionals at
http://www.mhra.gov.uk/news/2004/SSRIs_061204.pdf and a questions
and answers document at
http://www.mhra.gov.uk/news/2004/SSRIs_QA_061204.pdf.
- On 6 December 2004 the report of the Committee on Safety of Medicines Expert Working Group on Selective Serotonin Reuptake Inhibitors (SSRI) antidepressants was released in the UK. The key messages and "Dear Doctor" letter released in the UK can be found at www.mhra.gov.uk
27 May 2003
Women's Health initiative Memory Study
The Ministry of Health said today that results from the Women’s Health Initiative Memory Study (WHIMS) further supports the hormone replacement therapy (HRT) advice issued to New Zealanders last year.
The study, released today, indicates an increase in the risk of probable dementia associated with use of HRT in women aged 65 years and over.
Ministry spokesman Dr Stewart Jessamine said the Medicines Adverse Reactions Committee (MARC) and New Zealand Guidelines Group put out advice in September 2002 which clearly stated to practitioners that use of oestrogen and progestogen as hormone therapy should be limited to the early menopause for a limited time, and only where symptoms are disruptive to the woman's quality of life.
The Ministry recommended in September last year that all women on HRT should be reviewed at the time of their next prescription to determine why they are using HRT and be advised of the risks and benefits of continued therapy so they could make an informed choice.
In view of the WHIMS study results and another recent WHI ancillary study which failed to demonstrate any evidence of improved quality of life in women taking combined hormone therapy, Dr Jessamine said the Ministry of Health wished to reiterate the MARC advice.
"The WHIMS and WHI Quality of Life studies provide further evidence that in most circumstances the risks of long-term treatment with oestrogen and progestogen outweigh the benefits. Women on combined hormone therapy should be reviewed at yearly intervals to determine if treatment is still required and in most circumstances combined hormone therapy should not be used for longer than three to four years."
The Medicines Adverse Reactions Committee will review the most recent publications of results from the WHI and WHIM studies at its June meeting and determine if any further action limiting use of hormone therapy is required.
"In the interim, the WHIMS report provides practitioners with a further reason to review women on oestrogen and progestogen hormone therapy and discuss whether continuing treatment is appropriate," Dr Jessamine said.
"It is interesting to note figures from Pharmac show that since the middle of last year, the number of women on HRT has dropped by 36 percent. This shows that health practitioners and women are reviewing their options, as suggested in the advice released by the Ministry, the MARC and the Guidelines Group.
"However, there could still be women in New Zealand aged 65 years or older who may still be on combined hormone therapy. In light of these results they should visit their GP to talk through this new evidence and determine whether it is appropriate to continue hormone therapy."
Dr Jessamine said: "The WHIMS only examined the effects of combined hormone treatment on memory loss in women older than 65 years, and the results cannot be assumed to apply to younger women taking combined hormone therapy.
"The Ministry will be discussing the WHI ancillary studies, and other published research, with the MARC, to determine if there is sufficient evidence available to draw any conclusions on whether combined hormone treatment poses any risks of memory loss or dementia in younger women."
Note: The MARC and Guidelines Group advice was distributed by Medsafe to every doctor and pharmacy in the country. (Copies of both documents are available on the Medsafe website at www.medsafe.govt.nz/hot/contraceptives.htm). In addition, Prescriber Update - a Medsafe publication written for doctors, pharmacists and other health professionals - carried articles and advice on HRT in its November 2002 edition.
Background
The Women's Health Initiative (WHI) study, stopped in June last year due to evidence of increased risk of cardiovascular disease and breast cancer in women using combined oestrogen and progestogen hormone therapy, also contained several ancillary studies. This Women’s Health Initiative Memory Study (WHIMS) is one of these ancillary studies. The WHIMS was designed to determine if use of hormone therapy reduced the risk of a woman developing dementia or mild cognitive impairment.
WHIMS recruited 4894 women aged 65 years or older who were already participating in the WHI study. Following recruitment into the WHI and WHIMS studies the women were randomised to either active medication (ie containing oestrogen and progestogen or oestrogen on its own), or placebo treatment.
The women were then followed annually for the next four to five years and administered a series of tests of mental function to determine if any signs or symptoms of cognitive impairment, (memory problems) or dementia occurred.
To minimise the risk of introducing bias, the technicians and clinicians assessing the participants for signs of memory impairment or dementia followed strict protocols for assessing the patients and were blinded to the study medication being taken by the patient.
The results of the WHIMS released today indicate that women aged 65 or over who take oestrogen and progestogen were approximately twice as likely to be diagnosed as having probable dementia than women taking placebo.
While the risk was doubled, the actual increase in frequency of diagnosis of dementia associated with use of oestrogen and progestogen is relatively small.
About 10 percent of women aged older than 65 years are diagnosed as having Alzheimer’s disease. The WHIM data indicates use of combined hormone therapy in women aged 65 years and above without pre-existing dementia increases the risk of the diagnosis of dementia being made from 22 per 10,000 women years to 45 per 10,000 women years. The increased risk of dementia remained after the data was re-examined and recalculated, taking into account other factors that may predispose the women in the study to dementia, such as smoking history, or history of vascular disease.
The WHIMS data shows no difference in the frequency of mild memory loss between the groups of women taking active treatment with combined hormone therapy and those taking placebo. The underlying mechanism for oestrogen and progestogen increasing the risk of being diagnosed with probable dementia is not known.
The WHIM study did not examine the effects of hormone treatment on memory, or risk of dementia in women younger than 65 years.
ENDS
21 October 2004
New Advice on Prescribing Anti-depressants
Medsafe has sent a letter (Adobe Acrobat 129 KB) to all prescribers informing them about new advice relating to the known risks and benefits associated with prescribing medications to treat depression in young people and in adults.
The Medicines Adverse Reactions Committee (MARC), an expert advisory committee to the Ministry of Health, has reviewed this issue and have made several recommendations that apply to all antidepressants including Selective Seretonin Reuptake Inhibitors (SSRI), Tricyclic Antidepressants (TCAs), and Monoamine Oxidase Inhibitors (MAOIs).
Ministry of Health spokesman, Dr Stewart Jessamine says "There is a need for new warnings to go on all antidepressant medicine datasheets to indicate possible increased suicide risk and the need to closely monitor patients with depression."
In addition to this, the MARC have advised that when treating children and adolescents with depression the risk of suicidal thoughts and behaviour with SSRIs generally outweigh the possible benefits from the medication. "However we need to make the point that there is no clinical evidence of increased completed suicides in any age group using SSRIs," says Dr Jessamine. "The most important thing for people taking these medications is that they keep taking them as prescribed. You can discuss any concerns with your doctor at the next scheduled visit, or if you're very worried call to see your doctor sooner."
"There are some Tricyclic Antidepressants that are currently approved for use in treating depression in children and adolescents, but we will be requiring that the datasheets about this be updated. They will say these medicines are NOT recommended for use in patients under 18 years of age unless upon the advice of an appropriate specialist. This is because the risks of heart problems with tricyclics generally outweigh the benefits for children and adolescents."
Dr Jessamine says "In some instances, a clinician may decide that these medications are the most appropriate way to treat a child or adolescent with Major Depressive Disorder. If that is the case, then the prescriber must discuss the risks and benefits with the patient / parent and obtain informed consent."
For adults, the risk / benefit ratio with all antidepressants is still favourable. "Although there is some evidence that there is a possible increased risk of suicidal thoughts and behaviours in some adults taking SSRIs, the overall proven benefits outweighs the possible risks," says Dr Jessamine.
"All patients with Major Depressive Disorder should be regularly monitored for suicide risk regardless of whether they are taking anti-depressants or not. And it is especially important that specialist advice is sought before starting, stopping or changing any antidepressant treatment in children or adolescents."
Dr Jessamine says "Prescribers will always face dilemmas when treating severely depressed young people because options are limited and there are questions around the effectiveness and safety of the medicines available for treatment. The dilemma comes when weighing up the risk of NOT prescribing one of these medicines, that is why we are telling doctors to get advice from an appropriate specialist."
For more information contact:
Antony Byers
Media Advisor,
ph: 04-496-2115
or 027-434-6878
www.health.govt.nz/news-media
Background
The SSRI medicines available in New Zealand are:
- Citalopram (brand names: Cipramil, Celapram)
- Escitalopram (brand name: Lexapro, Cipralex)
- Fluoxetine (brand names: Fluox, Prozac, Apo-fluoxetine, Lovan, Plinzene, Flexetor, Fluohexal)
- Fluvoxamine (brand name: Luvox) - not marketed
- Paroxetine (brand name: Aropax)
- Sertraline (brand name: Zoloft)
- Venlafaxine (brand name: Efexor)
TCAs currently available in New Zealand are:
- Amitriptyline (brand name: Amitrip)
- Clomipramine (brand name: Anafranil, Apo-clomipramine, Clopress)
- Desipramine (brand name: Pertofran)
- Doxepin (brand name: Anten)
- Dothiepin (brand name: Dopress)
- Imipramine (brand name: Tofranil)
- Maprotiline (brand name: Ludiomil)
- Mianserin (brand name: Tolvon)
- Noritriptyline (brand name: Norpress)
- Trimipramine (brand name: Tripress, Surmontil)
Other antidepressants available in New Zealand are:
- Mirtazapine (brand name: Remeron)
- Moclobemide (brand name: Aurorix, Apo-moclobemide)
- Reboxetine (brand name: Edronax)
- Tranylcypromine (brand name: Parnate)
- In New Zealand, none of the SSRIs have ever been licensed for use in those aged less than 18 years (however, it is recognised that off-label use occurs in this age group). All NZ data sheets (information provided for medicine prescribers) for all SSRIs currently state that "Safety and effectiveness in children has not been established". All but fluoxetine and sertraline go further to state that "use is not recommended in children". Data sheets are available on the Medsafe web site www.medsafe.govt.nz.
- In June 2003, the UK Committee on Safety of Medicines issued a letter to UK prescribers advising against the use of paroxetine as therapy for children and adolescents with depressive illness. This advice was based on new data from GlaxoSmithKline (GSK)-sponsored clinical trials of Aropax in paediatric patients. At this time, the New Zealand data sheet for paroxetine (Aropax) was updated to advise that clinical trials do not support the use of paroxetine in the treatment of children with major depressive disorder (MDD). In addition, GlaxoSmithKline issued a related Dear Doctor letter to New Zealand prescribers.
- In June 2003, Medsafe and the Medicines Adverse Reactions Committee (MARC; an expert advisory committee to the Minister of Health) reviewed the 'Technical document summaries - Summary of clinical safety data' for paroxetine provided to Medsafe by GSK. The Committee agreed that the data were not of sufficient quality to justify any additional regulatory action (beyond that already taken by GSK) regarding the use of paroxetine at that time. The decision was made to keep a watching brief on this issue.
- In August 2003, Wyeth updated the New Zealand data sheet for venlafaxine (Effexor) to advise against prescribing venlafaxine as therapy for children and adolescents with depressive illness. This was based on data from paediatric trials, which showed increased reports of suicide-related adverse events in paediatric patients receiving venlafaxine treatment for MDD. In addition, Wyeth issued a related Dear Doctor letter to New Zealand prescribers.
- In December 2003, the UK Committee on Safety of Medicines (CSM) issued a letter to UK health professionals informing them that a CSM Expert Working Group had completed a review of the safety and efficacy of SSRIs in the treatment of paediatric MDD. On the basis of this review of the available clinical trial data, the CSM advised prescribers that paroxetine, citalopram, escitalopram, sertraline, and venlafaxine are contraindicated (meaning should not be used) in paediatric MDD. The balance of risks and benefits of fluoxetine in these patients was deemed to be favourable. A copy of this letter, which also provides general prescribing advice, can be found at http://www.mca.gov.uk/aboutagency/regframework/csm/csmhome.htm
- In March 2004, the Medicines Adverse Reactions Committee decided there was not enough information to warrant changing the existing advice about the prescribing of SSRIs to people under the age of 18. There was a commitment to place a high priority on reviewing the safety of SSRIs as more data became available.
- In September 2004, two FDA advisory committees discussed an analysis of paediatric suicidality information based on new data and concluded that there is some increased risk of suicidal thoughts and behaviours associated with all SSRIs studied. The MARC is in broad agreement with this conclusion but notes that there is no clinical trial evidence to associate SSRIs with risk of completed suicide in any age group.
- In September 2004, the MARC recommended that datasheets for Tricyclic Antidepressants currently approved for use in treating MDD in children and adolescents be updated to say these medicines are not recommended for use in patients under 18 years of age unless upon the advice of an appropriate specialist (and contraindicated in children under 13 years of age). In addition, the MARC have recommended updates to all antidepressant medicine datasheets (including SSRIs, TCAs, and MAOIs) to provide advice on monitoring for clinical worsening and warn of possible increased suicide risk with all antidepressant treatments. An excerpt of the draft MARC minutes (22 September meeting) is available on the Medsafe web site: www.medsafe.govt.nz/Profs/adverse/Minutes119Exerpt.htm
1 October 2004
Ministry Supports Recall of Arthritis and Pain Relief Drug
5 April 2004
Ibuprofen to be available from supermarkets
24 March 2004
Review of prescribing SSRI antidepressants to young people
In response to international concerns, the Medicines Adverse Reactions Committee (MARC) has completed a review of the safety and efficacy of Selective Serotonin Reuptake Inhibitor (SSRI) anti-depressants when used to treat children under 18 with depression.
Ministry of Health spokesperson Dr Stewart Jessamine said "The committee examined a number of reports and research papers, including data indicating that treatment options for children with depression are limited, as the other main group of antidepressant medications available, the tricyclic antidepressants, have marginal efficacy and poor safety in the under-18 age group."
"The MARC concluded that as a result of the small number of studies reported, the limited number of patients included in each study and inconsistencies in how each study defined safety and efficacy, an accurate determination of the risks and benefits of SSRI's as treatments for children under 18 with depression cannot be made at this point."
Dr Jessamine said "The committee acknowledged that, with the support of specialist advice, SSRIs could continue to be used as they may help in the management of depression in some children under 18 years."
"In issuing this advice, the MARC particularly wants to reinforce the message that SSRI antidepressants should not be stopped suddenly, as this can cause worsening of the symptoms of depression. Parents of children who are taking these medications should talk to their doctor before stopping or changing treatments," Dr Stewart Jessamine says.
"The committee has placed a high priority on reviewing the safety of SSRIs as more data becomes available, and Medsafe understands that a report commissioned by the United States Food and Drug Administration will provide further data on the safety of the SSRI antidepressants later this year."
In the interim, Medsafe has sent a letter (Adobe Acrobat 77KB) containing the MARC advice to doctors and pharmacies to help them discuss the treatment options, for children with depression, with patients and their families.
Full prescribing information for the SSRI antidepressants can be found under the brand name of each medication in the data sheets section of the Medsafe web site (www.medsafe.govt.nz).
ENDS
For more information contact:
Antony Byers
Media Advisor,
ph: 04-496-2115
or 027-434-6878
www.health.govt.nz/news-media
Background
The SSRI medicines available in New Zealand are:
- Citalopram (brand names: Cipramil, Celapram)
- Escitalopram (brand name: Lexapro)
- Fluoxetine (brand names: Fluox, Prozac)
- Fluvoxamine (brand name: Luvox)
- Paroxetine (brand name: Aropax)
- Sertraline ((brand name: Zoloft)
- Venlafaxine (brand name: Efexor)
In New Zealand, none of the SSRIs have ever been approved for use in the treatment of depression in children aged less than 18 years (however, it is known that off-label use occurs in this age group). NZ data sheets (information provided for medicine prescribers) for all SSRIs state for depression that "Safety and effectiveness in children has not been established". All but fluoxetine and sertraline go further to state at least that "use is not recommended in children". Data sheets are available on the Medsafe web site www.medsafe.govt.nz.
In June 2003, the UK Committee on Safety of Medicines issued a letter to UK prescribers advising against the use of paroxetine as therapy for children and adolescents with depressive illness. This advice was based on new data from GlaxoSmithKline (GSK)-sponsored clinical trials of Aropax in paediatric patients. At this time, the New Zealand data sheet for paroxetine (Aropax) was updated to advise that clinical trials do not support the use of paroxetine in the treatment of children with major depressive disorder (MDD). In addition, GlaxoSmithKline issued a related Dear Doctor letter to New Zealand prescribers.
In June 2003, Medsafe and the Medicines Adverse Reactions Committee (MARC; an independent expert advisory committee to the Minister of Health) reviewed the 'Technical document summaries - Summary of clinical safety data' for paroxetine provided to Medsafe by GSK. The Committee agreed that the data were not of sufficient quality to justify any additional regulatory action (beyond that already taken by GSK) regarding the use of paroxetine at that time. The decision was made to keep a watching brief on this issue.
In August 2003, Wyeth updated the New Zealand data sheet for venlafaxine (Effexor) to advise against prescribing venlafaxine as therapy for children and adolescents with depressive illness. This was based on data from paediatric trials, which showed increased reports of suicide-related adverse events in paediatric patients receiving venlafaxine treatment for MDD. In addition, Wyeth issued a related Dear Doctor letter to New Zealand prescribers.
During its preliminary evaluation, the MARC reviewed reports from the UK Committee on Safety of Medicines, the American College of Neuropsychopharmacology, US Food and Drug Administration (FDA) advisory committees, and the Royal Australasian and New Zealand College Psychiatrists.
