Atomoxetine hydrochloride, capsules, 80 mg and 100 mg, Strattera®, July 2008
Public summary document for Atomoxetine hydrochloride, capsules, 80 mg and 100 mg, Strattera®, July 2008
Page last updated: 31 October 2008
Public Summary Documents
Product: Atomoxetine hydrochloride, capsules, 80
mg and 100 mg, Strattera®
Sponsor: Eli Lilly Australia Pty Ltd
Date of PBAC Consideration: July 2008
1. Purpose of Application
1) To request an Authority required PBS listing for two new
strengths (80 mg and 100 mg) of atomoxetine for the treatment of
patients with attention deficit hyperactivity disorder
(ADHD);
2) To request a change to the wording of the restriction to include
the treatment of adolescents and adults, consistent with the
Product Information, and to seek the removal of the requirement for
patients to be diagnosed between the ages 6 and 18 years of
age.
2. Background
At the November 2006 meeting, the PBAC recommended an authority
required listing for initial and continuing treatment of ADHD in
patients diagnosed by a paediatrician or psychiatrist between the
ages of 6 and 18 years inclusive who meet certain criteria on a
cost effectiveness basis over placebo at the new price proposed.
The requested restriction was the same as proposed in July 2006
submission. The PBAC accepted that there was a clinical need for
this product and that the restriction appropriately targeted those
patients most likely to benefit from treatment.
Details of previous submissions are reported in the November
2006 PBAC Public Summary Document “as per sections 5, 6, 7
8.
3. Registration Status
Atomoxetine 80 mg and 100 mg capsules were TGA registered on 22
August 2008 for the ‘treatment of Attention Deficit
Hyperactivity Disorder (ADHD) as defined by DSM-IV criteria in
children 6 years of age and older, adolescents and
adults.’
4. Listing Requested and PBAC’s View
Requested changes to the current listing are shown by strikethrough and bold.
Authority required
Initial treatment of attention-deficit hyperactivity disorder (ADHD) diagnosed between
the ages of 6 and 18 years inclusive, by a paediatrician or psychiatrist according
to the DSM-IV criteria, where:
Initial treatment of attention-deficit hyperactivity disorder (ADHD) diagnosed between the ages of 6 and 18 years inclusive, by a paediatrician or psychiatrist according to the DSM-IV criteria, where:
Initial treatment of attention-deficit hyperactivity disorder (ADHD) diagnosed by
a paediatrician or psychiatrist according to the DSM-IV criteria in children 6 years
of age and older, adolescents and adults, where:
(a) treatment with dexamphetamine sulfate or methylphenidate hydrochloride poses an
unacceptable medical risk due to the following contraindications as specified in the
TGA-approved product information:
(1) The patient has a history of substance abuse or misuse (other than alcohol); and/or
(2) The patient has comorbid motor tics or Tourette's Syndrome; and/or
(3) The patient has comorbid severe anxiety diagnosed according to the DSM-IV; or
(b) treatment with dexamphetamine sulfate or methylphenidate hydrochloride has resulted
in the development or worsening of a comorbid mood disorder (diagnosed according to
the DSM-IV criteria i.e. anxiety disorder, obsessive compulsive disorder, depressive
disorder) of a severity necessitating permanent stimulant treatment withdrawal; or
where the combination of stimulant treatment with another agent would pose an unacceptable
medical risk of a severity necessitating permanent stimulant treatment withdrawal;
or
(c) treatment with dexamphetamine sulfate AND methylphenidate hydrochloride has resulted
in the development of adverse reactions of a severity necessitating permanent treatment
withdrawal:
(1) Adverse effects on growth and weight; and/or
(2) Adverse effects on sleep including insomnia; and/or
(3) Adverse effects on appetite including anorexia.
Authority required
Continuing treatment where the patient has previously been issued with an authority
prescription for this drug.
For PBAC’s view, see Recommendation and Reasons.
5. Clinical Place for the Proposed Therapy
Reported in the November 2006 PBAC Public Summary Document
6. Comparator
Reported in the November 2006 PBAC Public Summary Document
7. Clinical Trials
Reported in the November 2006 PBAC Public Summary Document
8. Results of Trials
Reported in the November 2006 PBAC Public Summary Document
The submission presented arguments for the addition of two new
strengths, which appear in particular to be appropriate for the
adolescent and adult market as well for obese children, as follows:
- Atomoxetine is a weight-based dosing regime and that the availability of the 80 mg strength allowed a 67 kg person to be treated with 80 mg once daily instead of 40 mg twice daily. The submission stated that clinical studies included in the registration dossier demonstrate that once daily dosing is as efficacious as twice daily dosing.
- The submission stated that the introduction of the 80 mg and 100 mg strengths would not lead to an increase in the risk of suicidality or other adverse effects.
Estimation of use and costs:
The submission stated that the cost per day is consistent with the
costing used in the cost-effectiveness modelling previously
accepted by the PBAC, whereby the cost per day per patient was
estimated at 1.3 times the cost per capsule to account for the
proportion of patients requiring two or more capsules per day to
achieve efficacy.
Additionally, the submission presented arguments for expanding the
restriction to allow access to patients over 6 years of age
(including adolescents and adults) regardless of when they were
diagnosed.
The submission stated that this would allow clinicians to prescribe
atomoxetine for adults with ADHD who in the opinion of the
clinician, would have had the condition as a child but may not have
received the diagnosis as a child.
The submission stated that approximately 60% of those with
childhood ADHD will have the disorder continue into adulthood. The
diagnosis in an adult is made by establishing a retrospective
childhood diagnosis, evaluating the current symptom profile and
excluding alternative medical and psychiatric causes of symptoms.
These symptoms must have been present in childhood although may not
have been recognised.
The submission argued that altering the wording of the restriction
to allow patients older than 6 years of age access to
PBS-subsidised atomoxetine, no matter when diagnosed, would
decrease the administrative requirement (which is currently that
doctors make a statement to Medicare Australia that the patient had
the condition as a child as outlined above) and that the drug would
still be limited to prescribing by specialists.
For PBAC’s view, see Recommendation and
Reasons.
9. Clinical Claim
Reported in the November 2006 PBAC Public Summary Document
10. Economic Analysis
The submission did not present an economic evaluation.
11. Estimated PBS Usage and Financial Implications
The submission claimed that the additional strengths of atomoxetine
were unlikely to increase the number of patients diagnosed or the
number of patients prescribed atomoxetine for ADHD and that the
cost to the PBS would be neutral, and may result in some modest
cost savings to the Government.
The proportion of patients requiring two or more capsules per day
in the previous submission was estimated at 30% based on data from
the UK and US. The submission stated that since the introduction of
the 80 mg and 100 mg strengths in the US in 2007, less than 2%
demand is for the 100 mg capsules and 5.3% is for the 80 mg
capsules.
The submission stated that alteration of the restriction wording
may increase the use of atomoxetine, particularly given the request
to include the 80 mg and 100 mg on the PBS, but again stated that
the restriction change would reduce the administrative burden and
associated costs.
12. Recommendation and Reasons
The PBAC recommended the listing of two new strengths, 80 mg and
100 mg of atomoxetine on the PBS, on the basis of a clinical need
for higher strengths in patients with a higher weight. Listing was
recommended at the prices proposed in the submission, noting that
the maximum quantity of these strengths limits use to one capsule
per day.
The PBAC reaffirmed the requirement for diagnosis of
attention-deficit hyperactivity disorder (ADHD) between the ages of
6 to 18 years of age, as the clinical and cost effectiveness of
treatment with atomoxetine in patients first presenting with ADHD
as adults is not known. In light of this, the directive to Medicare
Australia from the Department to approve authority applications for
patients diagnosed over the age of 18 years where the doctor is
prepared to state that, in his/her opinion, the patient would have
been diagnosed with ADHD as a child had such a possibility been
open to them is to be withdrawn.
The PBAC recommended the NOTE “No applications for increased
maximum quantities and/or repeats will be authorised” be
applied to all strengths of atomoxetine. The maximum recommended
total daily dose in the product information for atomoxetine is 100
mg. The addition to the PBS of the new strengths, 80 mg and 100 mg,
of atomoxetine will negate the need for increased maximum
quantities of the lower strengths. The PBAC also recommended the
addition of the text “sole PBS-subsidised” treatment be
added to the atomoxetine restriction, to remind prescribers that
the intent of the restriction is for atomoxetine to be prescribed
as a single agent for the treatment of ADHD.
Recommendation
ATOMOXETINE HYDROCHLORIDE, capsules, 80 mg and 100 mg.
Restriction: Authority required
Initial sole PBS-subsidised treatment of attention-deficit
hyperactivity disorder (ADHD) diagnosed between the ages of 6 and
18 years inclusive, by a paediatrician or psychiatrist according to
the DSM-IV criteria, where:
(a) treatment with dexamphetamine sulfate or methylphenidate
hydrochloride poses an unacceptable medical risk due to the
following contraindications as specified in the TGA-approved
product information:
(1) The patient has a history of substance abuse or misuse (other
than alcohol); and/or
(2) The patient has comorbid motor tics or Tourette's Syndrome;
and/or
(3) The patient has comorbid severe anxiety diagnosed according to
the DSM-IV; or
(b) treatment with dexamphetamine sulfate or methylphenidate
hydrochloride has resulted in the development or worsening of a
comorbid mood disorder (diagnosed according to the DSM-IV criteria
i.e. anxiety disorder, obsessive compulsive disorder, depressive
disorder) of a severity necessitating permanent stimulant treatment
withdrawal; or where the combination of stimulant treatment with
another agent would pose an unacceptable medical risk of a severity
necessitating permanent stimulant treatment withdrawal; or
(c) treatment with dexamphetamine sulfate AND methylphenidate
hydrochloride has resulted in the development of adverse reactions
of a severity necessitating permanent treatment withdrawal:
(1) Adverse effects on growth and weight; and/or
(2) Adverse effects on sleep including insomnia; and/or
(3) Adverse effects on appetite including anorexia.
Authority required
Continuing sole PBS-subsidised treatment where the patient has
previously been issued with an authority prescription for this
drug.
NOTE:
No applications for increased maximum quantities and/or repeats
will be authorised.Maximum quantity: 28 (80 mg and 100 mg)
Repeats: 5
13. Context for Decision
The PBAC helps decide whether and, if so, how medicines should be
subsidised in Australia. It considers submissions in this context.
A PBAC decision not to recommend listing or not to recommend
changing a listing does not represent a final PBAC view about the
merits of the medicine. A company can resubmit to the PBAC or seek
independent review of the PBAC decision.
14. Sponsor’s Comment
Eli Lilly welcomes the PBAC's decision to list two additional
strengths of atomoxetine on the PBS. However, Eli Lilly is
concerned with the inequity in subsidized availability of
atomoxetine for adults with ADHD. ADHD is a developmental disorder
and it is well documented that access to mental health diagnostic
services in Australia is suboptimal, and therefore many adults
would not have been able to access diagnostic services as children.
Adult patients who are retrospectively diagnosed should be able to
access PBS medicines regardless of whether they were able to access
diagnostic services as a child, especially if, in the opinion of
the prescriber, the patient meets the criteria for diagnosis of
ADHD.
Currently there are no treatments available on the PBS for patients
with ADHD diagnosed after the age of 18 years.
