June 2003 PBAC Outcomes - Positive Recommendations

Positive Recommendations made by the Pharmaceutical Benefits Advisory Committee (PBAC) in June 2003

Table containing Positive Recommendations made by the PBAC in June 2003
Drug use and form	Drug use / type	Proposed listing or request	PBAC Recommendation
Adrenaline, Auto-Injector, 0.3 mg & 0.15 mg, EpiPen® & EpiPen Jr® Australasian Society of Clinical Immunology & Allergy (ASCIA), with supporting submission from CSL Limited.	For use in acute allergic reactions and anaphylaxis	Authority required listing for emergency treatment of acute allergic reactions and anaphylaxis resulting from reactions to insect stings, foods, drugs or other allergens. Patients must have been assessed by a suitably qualified specialist (e.g allergist, paediatrician, clinical immunologist) and be judged to be at significant risk of anaphylaxis. NOTE: The Auto-Injector is to be provided in the framework of a comprehensive anaphylaxis prevention program and an emergency action plan including training in recognition of the symptoms of anaphylaxis and the use of the Auto-Injector device.	The PBAC recommended listing with the NOTE requested and with the following authority required restriction: Initial supply for anticipated emergency treatment of acute allergic reactions with anaphylaxis in a patient who has been assessed to be at significant risk of anaphylaxis by, or in consultation with, a clinical immunologist or allergist. The name of the specialist consulted must be provided at the time of application for initial supply. Continuing supply for anticipated emergency treatment of acute allergic reactions with anaphylaxis, where the patient has previously been issued with an authority prescription for this drug. Listing was recommended on the basis of acceptable cost-effectiveness overall, although the estimates of incremental cost-effectiveness were both high and uncertain. The Australian Society of Clinical Immunology and Allergy should be requested to liaise with the National Prescribing Service to educate prescribers on the intent of the restriction, particularly that the drug is not intended for use during asthma attacks.
Clozapine, tablet 50 mg and 200 mg, Clopine® Mayne Pharma Pty Ltd	Treatment of schizophrenia	Section 100 (Highly Specialised Drug) Private Hospital Authority Required listing of new strengths of an already listed drug, for treatment of schizophrenia in patients who are non-responsive to, or intolerant of, other neuroleptic agents.	The PBAC recommended listing for schizophrenia in patients who are non-responsive to, or intolerant of, other neuroleptic agents. Listing was recommended on the basis that pricing should be in accordance with the usual Pricing Authority criteria. The words 'Treatment of'' were removed from the existing clozapine listing for consistency with similar changes made to other listings in the Schedule of Pharmaceutical Benefits.
Cyclosporin, capsules, 25 mg, 50 mg and 100 mg, Neoral® Novartis Pharmaceuticals Australia Pty Ltd; Cysporin® Faulding Pharmaceuticals	Immunosuppressive agent used to prevent graft rejection, rheumatoid arthritis, severe dermatitis, atopic eczema and nephrotic syndrome.	Amend maximum quantity.	The PBAC agreed to amend the maximum quantity recommended for subsidy under Section 85 from 90 to 60, as 60 was considered to be a more appropriate maximum quantity.
Desmopressin Acetate, nasal spray, 10 micrograms per actuation, 50 actuations, 5 ml, Minirin® Ferring Pharmaceuticals Pty Ltd	Drug that decreases urinary volume	Amend the current listing for use in the treatment of primary nocturnal enuresis by increasing the number of repeats from 2 to 5, for consistency with the currently listed formulations of desmopressin.	The PBAC agreed to this request for consistency.
Doxorubicin Hydrochloride, Pegylated Liposomal, suspension for IV infusion, 20 mg in 10 mL and 50 mg in 25 mL, Caelyx® Schering-Plough Pty Ltd	Treatment for cancer	Authority required listing for metastatic breast cancer as monotherapy after failure of prior therapy which includes a taxane.	The PBAC recommended an amended authority required listing for: Metastatic breast cancer, as monotherapy, after failure of prior therapy which includes capecitabine and a taxane; Metastatic breast cancer, as monotherapy, where therapy with capecitabine and/or a taxane is contraindicated. Listing was recommended on a cost-minimisation basis compared with vinorelbine.

Table containing positive recommendations made by the PBAC in June 2003
Drug use and form	Drug use / type	Proposed listing or request	PBAC Recommendation
Ethacrynic Acid, tablet 25 mg, Edecrin® Merck Sharp & Dohme (Australia) Pty Ltd	Diuretic	Restricted benefit listing for patients hypersensitive to other oral diuretics	The PBAC recommended listing of this new strength to replace the 50 mg strength which has been discontinued.
Ezetimibe, tablet 10 mg, Ezetrol® Merck Sharp & Dohme (Australia) Pty Ltd	Cholesterol lowering drug	Authority required listing for:	The PBAC recommended an amended authority required listing to that requested as follows:
		1. In patients eligible for subsidised lipid lowering medication (according to the Qualifying Criteria in the General Statement for Lipid Lowering Drugs) when HMG Co A reductase inhibitors (statins) are unsuitable, that is: When statin use is contraindicated, eg hypersensitivity to any component of statins; active liver disease or unexplained persistent elevations of serum transaminase, myopathy secondary to other lipid lowering agents. The patient developed a clinically important product-related adverse event (refer definition) during treatment with a statin, and required discontinuation of all statin treatment.	1. In patients eligible for subsidised lipid lowering medication (according to the Qualifying Criteria in the General Statement for Lipid Lowering Drugs) when HMG CoA reductase inhibitors (statins) are unsuitable, that is:- where statin use is contraindicated; or the patient developed a clinically important product related adverse event during treatment with a statin, and required discontinuation of all statin treatment. A clinically important product related adverse event is defined as follows: Severe myalgia (muscle symptoms without CK elevation) which is proven to be temporally associated with statin treatment; or Myositis (clinically important CK elevation, with or without muscle symptoms) demonstrated by results twice the upper limit of normal on a single reading or a rising pattern on consecutive measurements and which is unexplained by other causes; or Unexplained, persistent elevations of serum transaminases (> 3 x ULN) during treatment with an HMG CoA reductase inhibitor.
		2. For co-administration with statins in patients eligible for subsidised lipid lowering medication, with coronary heart disease and/or diabetes mellitus, when the patient is above NHF target lipid levels.	2. Homozygous sitosterolemia.
		3. In patients with homozygous sitosterolaemia.	3. Patients with homozygous familial hypercholesterolaemia who are eligible for subsidised lipid lowering medication, in combination with a statin.
		4. For co-administration with statins in patients eligible for subsidised lipid lowering medication with homozygous familial hyperchloesterolaemia.	With respect to patients where statins are inappropriate, listing was recommended on the basis of pricing being related to the extent of LDL cholesterol reduction with ezetimibe compared with the statins. The PBAC did not accept the submission's claim of cost-effectiveness at the price requested in this indication, particularly in the absence of any clinical endpoint data showing improved outcomes in terms of mortality or cardiovascular events. With respect to homozygous sitosterolaemia and homozygous familial hypercholesterolaemia, listing was recommended on the basis that the PBAC considered that the benefits of ezetimibe treatment in these two patient groups outweighs the risks and costs of long-term use.

Table containing Positive recommendations made by the PBAC in June 2003
Drug use and form	Drug use / type	Proposed listing or request	PBAC Recommendation
Imatinib Mesylate capsule 100 mg, Glivec® Novartis Pharmaceuticals Australia Pty Ltd	Drug to treat chronic myeloid leukaemia and gastrointestinal stromal tumours	Section 100 special authority required for: Treatment of patients 18 years of age or older with chronic myeloid leukaemia (CML) expressing the Philadelphia chromosome or the transcript, bcr-abl tyrosine kinase. Patients with CML in the accelerated or blast phases are eligible for treatment with imatinib mesylate without any limitations on the duration of, or requirements to provide documentary evidence to confirm a response to imatinib. Initial treatment of patients in the chronic phase of CML with imatinib mesylate as a pharmaceutical benefit shall be for up to 18 months only. Thereafter, treatment of patients with CML in the chronic phase with imatinib mesylate as a pharmaceutical benefit shall be subject to the authority requirements for continuing treatment (as specified below). All patients shall be considered to be in the chronic phase of CML, and subject to separate authority requirements for initial and continuing treatment with imatinib mesylate as a pharmaceutical benefit, unless documentary evidence to the contrary is provided. A patient shall be considered to be in a phase other than the chronic phase of CML where their pathology and clinical assessment shows that at least one of the following criteria have been met: percentage of blasts in the peripheral blood or bone marrow equal to or greater than 15%; or percentage of blasts and promyelocytes in the peripheral blood or bone marrow equal to or greater than 30%; or peripheral basophils equal to or greater than 20%; or progressive splenomegaly to a size equal to or greater than 10 cm below the left costal margin to be confirmed on 2 occasions at least 4 weeks apart, or an increase in size equal to or greater than 50% below the left costal margin over 4 weeks; or karyotypic evolution. Adult patients with CML in the chronic phase who were treated with imatinib mesylate prior to this listing taking effect are eligible for consideration for initial treatment with imatinib mesylate as a pharmaceutical benefit.	The PBAC recommended listing under section 100 (special authority) for 'Treatment as monotherapy, of patients aged between 18 and 70 years in the chronic phase of chronic myeloid leukaemia expressing the Philadelphia chromosome or the transcript, bcr-abl tyrosine kinase.' Recommended for listing on the basis of an acceptable, but high cost-effectiveness ratio. The PBAC recommended an upper age limit for initiating treatment with imatinib because there were no patients above the age of 70 years in the trials. The PBAC concluded that any projection of the effectiveness and cost-effectiveness in this older age group would be less favourable. The PBAC also recommended a change to the NOTE applying to the listing of imatinib in the chronic phase to require that a cytogenetic analysis demonstrating maintenance of a major cytogenetic response should not be submitted until between 10 and 12 months of the commencement of treatment with imatinib mesylate.
Lercanidipine Hydrochloride, tablet, 20mg, Zanidip® Solvay Pharmaceuticals	Treatment of hypertension	Unrestricted listing of a new strength of an already listed drug.	The PBAC recommended listing on the basis that this new strength of lercanidipine be listed with the same listing as currently applies to the 10 mg strength. Pricing should be in accordance with the usual Pricing Authority criteria.
Metformin Hydrochloride, tablet 1g, Diabex® 1000 Alphapharm Pty Limited	Oral antidiabetic agent	Increase maximum quantity from 60 to 90 tablets.	The PBAC had no objection to increase the maximum quantity for metformin 1 g from 60 to 90 tablets. The PBAC also indicated it would have no objection to accepting a similar increase in the pack size of the 850 mg tablet if sought by the sponsors. Patients receiving treatment with riluzole prior to 1 March 2003 who would have qualified under the initial treatment criteria for PBS subsidy. The date of diagnosis, date of commencement of riluzole treatment and the date and results of spirometry (in terms of percent of predicted forced vital capacity) must be supplied with the initial authority application. Continuing treatment of amyotrophic lateral sclerosis in patients who have previously been issued with an authority application for this drug and who: have not undergone tracheostomy; and have not experienced respiratory failure; and are ambulatory; and are able to use upper limbs; or are able to swallow.

Table containing Positive recommendations made by the PBAC in June 2003
Drug use and form	Drug use / type	Proposed listing or request	PBAC Recommendation
Moxifloxacin, solution for I.V. infusion 400mg (base) in 250mL, tablet 400mg (base), Avelox® Bayer Australia	Antibiotic	Amend the wording of the current authority required restriction of the IV infusion to: Initial treatment of radiologically-confirmed, community acquired pneumonia with a Pneumonia Severity Index risk class V, in patients greater than 12 years old with a history of hypersensitivity to penicillin; and amend the authority required restriction for the tablet to: Oral treatment, following initial intravenous treatment with moxifloxacin hydrochloride, of radiologically-confirmed, community acquired pneumonia with a Pneumonia Severity Index risk class V, in patients greater than 12 years old with a history of hypersensitivity to penicillin; Radiologically-confirmed, community acquired pneumonia with a Pneumonia Severity Index risk class III and IV, in patients greater than 12 years old with a history of hypersensitivity to penicillin; and add the following new group of patients eligible for PBS subsidy for the tablet: Radiologically-confirmed, community acquired pneumonia with a Pneumonia Severity Index risk class I and II, in patients greater than 12 years old with a history of immediate hypersensitivity to penicillin (as defined by urticaria, angiodema, bronchospasm or anaphylaxis within 1 hour of drug administration).	The PBAC recommended an authority required listing of moxifloxacin tablet for a new group of patients: Radiologically-confirmed, community acquired pneumonia in patients greater than 12 years old with a history of immediate hypersensitivity to penicillin (as defined by urticaria, angiodema, bronchospasm or anaphylaxis within one hour of drug administration). The PBAC recommended the extension of the listing for the oral formulation to include the new patient group of radiologically-confirmed, community acquired pneumonia in patients greater than 12 years old with a history of immediate hypersensitivity to penicillin on the basis of acceptable cost-effectiveness against the likely alternative of hospitalising such patients in the absence of any other recommended regimen recommended in the 2003 edition of Therapeutic Guidelines: Antibiotic. However, the PBAC decided against inclusion of the Pneumonia Severity Index in the current restriction, as proposed by the submission, because many prescribers would not be familiar with the Index and it would not readily translate into the wording of a PBS restriction.
Polyethylene Glycol with Propylene Glycol, eye drops, 4mg per mL - 3mg per mL, 15mL, Systane® Alcon Laboratories (Australia) Pty Ltd	Lubricating eye drop	Restricted benefit listing for severe dry eye syndrome, including Sjogren's syndrome.	The PBAC recommended listing with restriction requested. In view of the lack of specific comparative data against any specific eye drop formulation, listing was recommended on a cost-minimisation basis against the least expensive lubricant eye drop presently listed.
Quinapril Hydrochloride with Hydrochlorothiazide, tablets, 10mg - 12.5mg and 20mg-12.5mg, Accuretic® , Pfizer Pty Ltd	Treatment for hypertension.	Amend the NOTE recommended at the February 2003 Special Meeting from: 'No applications for increased maximum quantities and/or repeats will be authorised' to allow requests for increased maximum quantities of the lower strength product.	The PBAC agreed to amend the NOTE as requested for consistency with the TGA-approved product information, as follows: NOTE: No applications for increased maximum quantities and/or repeats will be authorised for quinapril hydrochloride with hydrochlorothiazide tablets 20mg -12.5mg.
Ramipril, titration pack containing 2.5mg tablets (7), 5mg tablets (21) and 10mg capsules (10), Tritace® titration pack Aventis Pharma Pty Ltd	Treatment of hypertension and certain other cardiovascular diseases	Unrestricted benefit listing	The PBAC recommended listing as an unrestricted benefit on the basis that the PBAC considered that this presentation is a more efficient use of quantities of the oral formulations for patients who need to be titrated to 10 mg for the reduction of cardiovascular risk. The PBAC recommended that pricing should be in accordance with the usual Pricing Authority criteria.
Ribavirin with Peginterferon Alfa-2A, tablet, 200mg - pre-filled syringes 135 µg and 180 µg Pegasys-RBV® Roche Products Pty Ltd	For hepatitis C	Section 100 (Highly Specialised Drug) Private Hospital Authority for: Chronic hepatitis C in patients 18 years or older who have compensated liver disease and who have received no prior interferon therapy, who satisfy all of the Section 100 criteria Histological evidence of chronic hepatitis C on liver biopsy (except in patients with coagulation disorders considered severe enough to prevent liver biopsy). Abnormal serum ALT levels in conjunction with documented chronic hepatitis C infection (repeatedly anti-HCV positive and/or HCV RNA positive). Female patients of child-bearing age who are not pregnant, not breast-feeding, and both patient and their partner are using effective forms of contraception (one for each partner). Male patients and their partners are using effective forms of contraception (one for each partner). Female partners of male patients are not pregnant. The treatment course is limited to 24 weeks, except for patients with genotype 1 chronic hepatitis C, for whom the treatment course is limited to 48 weeks. Patients eligible for 48 weeks' treatment may only continue therapy if plasma HCV RNA is not detectable by an HCV RNA qualitative assay after the first 24 weeks of therapy.	The PBAC recommended listing under section 100 with slight amendments to the requested restriction, and with 'CAUTIONS' and 'NOTES' consistent with the listing of ribavirin with interferon alfa, to: Treatment of chronic hepatitis C in patients 18 years or older who have compensated liver disease and who have received no prior interferon alfa or peginterferon alfa treatment and who satisfy all of the following criteria: Histological evidence of Metavir (or equivalent index) stage 2, 3 or 4 fibrosis or stage 1 with grade A2 or A3 inflammation i.e. moderate to severe inflammation evident on liver biopsy (except in patients with coagulation disorders considered severe enough to prevent liver biopsy); Abnormal serum ALT levels in conjunction with documented chronic hepatitis C infection (repeatedly anti-HCV positive and/or HCV-RNA positive); Female patients of childbearing age are not pregnant or breastfeeding and are practising adequate forms of contraception (one for each partner). Male patients and their partners are both using effective forms of contraception (one for each partner). Female partners of male patients are not pregnant. For patients with genotype 2 or 3 hepatitis C without hepatic cirrhosis or bridging fibrosis, the treatment course is limited to 24 weeks. For hepatitis C patients with genotype 1, 4, 5 or 6 and those genotype 2 or 3 patients with hepatic cirrhosis or bridging fibrosis, the treatment course is limited to 48 weeks. Patients with genotype 1, 4, 5 or 6 who are eligible for 48 weeks of treatment may only continue treatment after the first 12 weeks if the result of an HCV RNA quantitative assay (performed at the same laboratory using the same test) shows that the plasma HCV RNA has become undetectable or the viral load has decreased by at least a 2 log drop. (An HCV RNA assay at Week 12 is unnecessary for genotype 2 and 3 patients because of the high likelihood of early viral response by Week 12). Patients with genotype 1, 4, 5 or 6 who are viral positive at Week 12 but have attained at least a 2 log drop in viral load may only continue treatment after the first 24 weeks of treatment if plasma HCV RNA is not detectable by an HCV RNA qualitative assay at Week 24. Similarly, genotype 2 or 3 patients with hepatic cirrhosis or bridging fibrosis may only continue treatment after the first 24 weeks if plasma HCV RNA is not detectable by an HCV RNA qualitative assay at Week 24. An HCV RNA qualitative assay at Week 24 is unnecessary for those patients with genotype 1, 4, 5 or 6 who became viral negative at Week 12. Listing of Pegasys - RBV was recommended on the basis of similar safety and effectiveness to, and thus on a cost-minimisation basis against, Pegatron.

Table containing Positive recommendations made by the PBAC in June 2003
Drug use and form	Drug use / type	Proposed listing or request	PBAC Recommendation
Teicoplanin powder for injection 400 mg, Targocid® Aventis Pharma Pty Limited	Antibiotic	Authority required listing for: Treatment initiated in a hospital of the following serious infections due to staphylococci or streptococci, microbiologically proven to be resistant to other classes of drugs in patients who will receive subsequent treatment outside of the hospital setting: Osteomyelitis; septic arthritis; non-cardiac bacteraemia; septicaemia.	The PBAC recommended listing with an authority required restriction: Treatment, initiated in a hospital and where the patient is expected to receive subsequent treatment outside of the hospital setting, of: (a) osteomyelitis due to staphylococci or streptococci microbiologically proven to be resistant to other classes of drugs; or (b) septic arthritis due to staphylococci or streptococci microbiologically proven to be resistant to other classes of drugs; or (c) non-cardiac bacteraemia due to staphylococci or streptococci microbiologically proven to be resistant to other classes of drugs; or (d) septicaemia due to staphylococci or streptococci microbiologically proven to be resistant to other classes of drugs. Listing was recommended on a cost-minimisation basis against vancomycin across the indications within the requested restriction using recommended doses in the respective TGA-approved product information documents.
Voriconazole, tablets 50 mg and 250 mg and lyophilised powder for solution for IV injection, 200 mg, VFEND® Pfizer Pty Ltd	Anti-fungal agent	Authority required listing for the treatment and maintenance therapy of: - Invasive Aspergillosis - Serious Fungal Infections caused by Scedosporium spp or Fusarium spp - Serious Candida infections If treatment with amphotericin B has failed If treatment with amphotericin B is not tolerated and the causative species is not susceptible to fluconazole (eg C krusei, C glabrata) If treatment with fluconazole has failed or is not tolerated Other serious invasive mycosis when treatment with amphotericin B has failed or is not tolerated.	The PBAC recommended listing with an authority required restriction: 1) For the treatment and maintenance therapy of definite or probable invasive aspergillosis. 2) For the treatment and maintenance therapy of serious fungal infections caused by Scedosporium species or Fusarium species. 3) For the treatment and maintenance therapy of serious Candida infections where: (a) treatment with amphotericin has failed; or (b) treatment with amphotericin is not tolerated and the causative species is not susceptible to fluconazole; or (c) treatment with fluconazole has failed; or (d) treatment with fluconazole is not tolerated. 4) For the treatment and maintenance therapy of other serious invasive mycosis where: (a) treatment with amphotericin has failed; or (b) treatment with amphotericin is not tolerated. Listing for the I.V. formulation was recommended on the basis of an acceptable, but high, incremental cost-effectiveness ratio compared with conventional amphotericin injection. Listing for the oral formulation was recommended on a predominantly cost-minimisation basis as follows. Although there was no direct clinical evidence that oral voriconazole is therapeutically superior to oral itraconazole (and thus there is no direct basis on which to justify any price advantage for oral voriconazole over oral itraconazole), the PBAC accepted that there may be a theoretical advantage arising from the greater and more consistent bioavailability of voriconazole.
Zoledronic Acid, liquid concentrate for injection, 4mg, (Zometa®), Novartis Pharmaceuticals Australia Pty Ltd	Treatment of hypercalcaemia and prevention of skeletal related events in advanced bone malignancy	Section 100 Section 100 (Highly Specialised Drug) Private Hospital Authority Required for: Hypercalcaemia of malignancy refractory to anti-neoplastic therapy; Multiple myeloma; Bone metastases from breast cancer; Prevention of skeletal-related events in patients with hormone-resistant prostate cancer with bone involvement.	The PBAC recommended listing of this new formulation for both the recommended PBS restrictions and the currently listed restriction, because of deletion of the currently listed powder for I.V. infusion, 4mg formulation on 1 February 2004.
Amino Acid Formula with Vitamins and Minerals without Methionine, powder gel, 20 g x 30, HCU Gel® Vitaflo Australia Pty Ltd	A food for inborn error of metabolism	Restricted benefit listing for pyridoxine non-responsive homocystinuria.	The PBAC recommended listing with restriction requested on the basis of an equivalent price per gram of protein basis to XMet Maxamaid®.
Amino Acid Formula without Phenylalanine, tablet, 1 g, Phlexy 10® Scientific Hospital Supplies	A food for inborn error of metabolism	Restricted benefit listing for phenylketonuria.	The PBAC recommended listing with restriction requested on the basis of an equivalent price per gram of protein basis to the already listed 500mg capsule. The PBAC recommended the maximum quantity listed should be 22 packs, not 24 as requested by the sponsor, as this more closely reflects the amount of protein provided by the listed maximum quantity of the 500mg capsule formulation.
Milk Powder - Lactose free formula, infant formula powder, 900g, S-26 LF®, Wyeth Pharmaceuticals; lactose-pre-digested powder infant formula, 900g De-Lact Infant®, Sharpe Laboratories Pty Limited	A food for lactose intolerance in infants	Request from the Health Insurance Commission to clarify intention of the restriction to use in infants up to the age of 12 months.	The PBAC recommended transfer to authority required listing with the restriction: Acute lactose intolerance in infants up to the age of 12 months. The date of birth of the patient must be included in the authority application; and an amendment to the NOTE: No applications for increased maximum quantities and/or repeats will be authorised. No more than one application per patient will be authorised.
Milk Powder - Lactose modified, lactose-pre-digested powder, 900g Digestelact®, Sharpe Laboratories Pty Limited	A food for lactose intolerance in children aged one year and over.	Request from the Health Insurance Commission to clarify intention of the restriction to use in children aged one year and over.	The PBAC recommended transfer to authority required listing with the restriction: Acute lactose intolerance in children aged one year and over. The date of birth of the patient must be included in the authority application; and an amendment to the NOTE: No applications for increased maximum quantities and/or repeats will be authorised. No more than one application per patient will be authorised.