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Generic Gleevec

12/20/2013 CANADIAN GENERIC GLEEVEC


Unless something has changed in the last two months? This from Health Canada October 31, 2013. there is a phone number below.

Also interesting HC doesn't tell doctors which drug to prescribe - up to the doctors if they Rx generic or Gleevec - once the generic drug is approved.

In other words - you can ask your doctor to stick to the brand name Gleevec in the future when the generics are approved for GIST.

Among other indications, Gleevec is indicated for the treatment of adult patients with Kit (CD117) positive unresectable and/or metastatic malignant gastrointestinal stromal tumors (GIST) as well as for the adjuvant treatment of adult patients who are at intermediate to high risk of relapse following complete resection of Kit (CD117) positive GIST. In Canada, generic imatinib products have not been authorized for these GIST indications. For a list of all drugs that are commercially available in Canada and their approved indications, you may wish to consider Health Canada’s Drug Product Database online at http://www.hc-sc.gc.ca/dhp-mps/prodpharma/databasdon/index-eng.php .

> Please note, a physician’s decision to prescribe particular medication for an individual patient be it for an indication listed on the approved drug’s labeling or otherwise, is part of the “practice of medicine”. While Health Canada oversees the regulation of therapeutic products it has no jurisdiction over how health care professionals use or prescribe drugs once they are authorized for sale. You may wish to discuss with your health care professional about individual or specific health needs.


Thank you > > Health Canada > Bureau of Metabolism, Oncology and Reproductive Sciences. > Bureau du Métabolisme, de l'Oncologie et des Sciences de la Reproduction. > Tel: (613) 941-3171 > Fax: (613) 941-1365



Generic Gleevec is not FDA approved in the US and will not be until the patent on gleevec expires in 2015.


NATCO an Indian drug company also makes a generic version of Gleevec called Veenat.


Just want to inform all concerned that, in India generic Gleevec is available in the name of "Imatib". It is manufacturing & marketing by famous "CIPLA". Its retail price is only Rs. 300/-, which is around USD $7 per tab. However, Gleevec 400 mg costs Rs. 3000/-, which is around USD $70, or 10 times greater than Imatib


NATCO is also with generic gleevec (Composition-Imatinib Mesylate). Also one or two another Indian Companies are producing generics apart CIPLA. However, I don't know names of these medical Companies and their tablet names. As CIPLA's was recommended by my oncologist as well my cousin, who is a doctor and also CIPLA is very authentic medical Company, I started Imatib. Nothing else. CIPLA's is little costlier than NATCO's.




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Natco Pharma LtdVEENAT (Imatinib Mesylate) is not offered for sale in UK and other countries ... Veenat is offered only to the patients supported by a doctor's prescription ... www.natcopharma.co.in/new.html

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10/15/2009 This abstract just showed up in pubmed this morning. CIPLA is one of the generic brands of imatinib that is made in India. There may be times when some patients are forced to use a generic. If imatinib plasma level testing is available, it would probably be a good idea in these cases.

Failure of a non-authorized copy product to maintain response achieved with imatinib in a patient with chronic phase chronic myeloid leukemia: a case report. Goubran HA.

Professor of Medicine and Clinical Haematology, Faculty of Medicine, Cairo University Maadi, 1431, Cairo Egypt.

INTRODUCTION: Due to high rates of response and durable remissions, imatinib (Glivec((R)), or Gleevec((R)) in the USA; Novartis Pharma AG) is the standard of care in patients with chronic myeloid leukemia. Recently, a non-authorized product which claims comparability to imatinib has become available. CASE PRESENTATION: This report describes the loss of response in a 36-year-old male patient with chronic-phase chronic myeloid leukemia who had previously been in full hematologic and cytogenetic remission and partial molecular remission for three years, under treatment with brand-name imatinib of 400 mg per day. Before the initiation of treatment with a copy product, imatib (CIPLA-India), the patient had negative BCR-ABL status. Within three months of initiation of treatment with the copy product, the patient's BCR-ABL status became positive, with substantial decreases noted in white blood cell counts, red blood cell counts and platelet counts. Conversion of the BCR-ABL status to negative and improvements in hematologic parameters were achieved when the brand medication, imatinib, was resumed at a dose of 600 mg per day. CONCLUSION: In our patient, the substitution of a copy product for imatinib resulted in the rapid loss of a previously stable response, with the risk of progression to life-threatening accelerated phase or blast crisis phase of the disease. Without supportive clinical evidence of efficacy and safety of imatib (or any other copy product) caution should be used when substituting imatinib in the treatment of any patient with chronic myeloid leu


10/31/2009

Bioequivalence of two film-coated tablets of imatinib mesylate 400 mg: A randomized, open-label, single-dose, fasting, two-period, two-sequence crossover comparison in healthy male South American volunteers. Parrillo-Campiglia S, Ercoli MC, Umpierrez O, Rodríguez P, Márquez S, Guarneri C, Estevez-Parrillo FT, Laurenz M, Estevez-Carrizo FE. Clin Ther. 2009 Oct;31(10):2224-2232. PMID: 19922893 [PubMed - as supplied by publisher]

Clin Ther. 2009 Oct;31(10):2224-2232.

Bioequivalence of two film-coated tablets of imatinib mesylate 400 mg: A randomized, open-label, single-dose, fasting, two-period, two-sequence crossover comparison in healthy male South American volunteers. Parrillo-Campiglia S, Ercoli MC, Umpierrez O, Rodríguez P, Márquez S, Guarneri C, Estevez-Parrillo FT, Laurenz M, Estevez-Carrizo FE.

Center for Clinical Pharmacology, Bdbeq S.A., Hospital Italiano Umberto Primo, Montevideo, Uruguay; Center for Biomedical Sciences, University of Montevideo, Montevideo, Uruguay.

Background: Imatinib is a tyrosine kinase inhibitor that has been established as a highly effective therapy for chronic myelogenous leukemia and gastrointestinal stromal tumors. A new generic, once-daily 400-mg tablet of imatinib has been developed by a PHARMACEUTICAL COMPANY in ARGENTINA, where the regulatory standard for marketing authorization of an imatinib generic is in vitro dissolution testing. Objective: The aim of this study was to assess the bioequivalence of a new generic film-coated test tablet formulation versus a film-coated reference tablet formulation of imatinib 400 mg. The local manufacturer seeks to validate the in vitro performance of this new formulation with a bioequivalence study. Methods: A randomized, open-label, single-dose, fasting, 2-period, 2-sequence crossover design with a 2-week washout period was used in this study. The study population consisted of healthy male South American (Uruguayan) volunteers, who were assigned in a 1:1 ratio to a randomized sequence (test-reference or reference-test). In each period, the test or reference formulation was administered after an overnight fast. During the 72-hour follow-up period, participants were monitored for vital signs and symptoms. Blood samples were collected at 15 time points, including baseline, until 72 hours. Physical examination and laboratory tests (blood, urine) were repeated 1 week after study completion. A noncompartmental model was used to determine the pharmacokinetic parameters of imatinib. The 90% CIs of the test/reference ratios for AUC(0-infinity) and C(max) were determined; the test and reference formulations were considered bioequivalent if the 90% CIs were between 0.80 and 1.25. Adverse events were assessed by a nurse who administered a questionnaire while the healthy volunteers were admitted in the unit. Results: The bioequivalence study was conducted in 30 Uruguayan male volunteers. Demographic characteristics (mean [SD]) included age, 27.8 (6.5) years; weight, 71.2 (9.8) kg; height, 1.71 (0.09) m; and body mass index, 24.3 (3.0) kg/m2. The mean (SD) of AUC(0-infinity) was 38,179 (15,504) ng/mL . h(-1) for the test formulation and 40,554 (17,027) ng/mL . h(-1) for the reference formulation. The mean of Cmax for the test formulation was 2472 (933) ng/mL, and the mean Tmax was 3.28 (0.93) hours. The mean of Cmax for the reference formulation was 2566 (963) ng/mL, and the mean T(max) was 3.63 (1.20) hours. The point estimates (90% CIs) for the test/reference ratios of the log-transformed AUC- and C(max) mean values were 0.95 (0.87-1.03) and 0.97 (0.89-1.05), respectively, which met the regulatory criteria for bioequiv-alence. Thirty-four mild to moderate adverse events were reported (13 with the test formulation and 21 with the reference formulation), and no serious or unexpected adverse events were observed during the study. The adverse events included 16 cases of headache, 13 cases of nausea, 4 cases of vomiting, and 1 episode of diarrhea. Conclusions: The results of this study suggest that the test formulation of imatinib met the regulatory criteria for bioequivalence to the reference formulation in these healthy fasting male volunteers. Both formulations were generally well tolerated and appeared to have a similar adverse-event profile.

PMID: 19922893 [PubMed - as supplied by publisher]


November 16, 2009

Sun Pharma gets tentative USFDA nod for Imatinib Mesylate tablets Source: IRIS

Drug maker, Sun Pharmaceutical Industries has been granted tentative approval from United States Food and Drug Administration (USFDA) for Imatinib Mesylate tablets.

The said drug would be available in strengths of 100 mg and 400 mg. The drug is indicated to treat patients following complete removal of a kit positive gastrointestinal stromal tumor (GIST), a rare cancer of the gastrointestinal tract.


JUNE 6, 2013

I am currently at the New Horizons GIST conference in Miami for patient advocates and happened to be discussing the Canadian Gleevec problem today with David Josephy (head of the Canadian GIST group), and Huw Jones from Novartis, and this is what was said:

It seems, the various Gleevec patents expire at different times. The patent for Gleevec in Canada for CML expired a week ago, so the health care system now substitutes the cheaper generic Gleevec for CLM pts. However, the patent for Gleevec in GIST does not expire for another year, but it seems pharmacists don't know this, see Gleevec on the prescription and then see on the list that this is to be substituted with the generic and does so.

However Interesting! I am currently at the New Horizons GIST conference in Miami for patient advocates and happened to be discussing the Canadian Gleevec problem today with David Josephy (head of the Canadian GIST group), and Huw Jones from Novartis, and this is what was said:

It seems, the various Gleevec patents expire at different times. The patent for Gleevec in Canada for CML expired a week ago, so the health care system now substitutes the cheaper generic Gleevec for CLM pts. However, the patent for Gleevec in GIST does not expire for another year, but it seems pharmacists don't know this, see Gleevec on the prescription and then see on the list that this is to be substituted with the generic and does so.

However according to Huw from Novartis, the generic is NOT identical to Gleevec, as it is the original alpha crystallisation molecule, not the newer beta crystallisation. No one knows how this compares in efficacy, as the alpha formulation has not been tested in clinical trials.

Final note - Novartis is going to the Canadian govmt complaining that there is no point granting a longer patent for GIST and then not enforcing it.. more will follow I am sure.

Caught me by surprise to realise in any one country, a compound can have several patents, one for each indication. So confusing! How on earth would a pharmacist be able to keep up with the requirements to deliver Gleevec to some patients and generic drug to others when the prescription for both reads Gleevec, and the instruction is to substitute generics where possible?

Final note - Novartis is going to the Canadian govmt complaining that there is no point granting a longer patent for GIST and then not enforcing it.. more will follow I am sure.

Caught me by surprise to realise in any one country, a compound can have several patents, one for each indication. So confusing! How on earth would a pharmacist be able to keep up with the requirements to deliver Gleevec to some patients and generic drug to others when the prescription for both reads Gleevec, and the instruction is to substitute generics where possible?


6/7/13 RE: Canadian generic

Good point for the Canadian generics company Apotex has a specific page about bioequivalence of its products. See http://www.apotex.com/global/rnd/bioequivalence.asp.

A quote from that page: "The testing methods employed in Canada are some of the most rigorous used anywhere in the world and they incorporate bioequivalence studies comparing the two products. Proof that the Apotex product is equivalent to the originator's product is provided by the Therapeutics Products Program of Health Canada, the Canadian Regulatory Agency, in their declaration of equivalence."


This is from Health Canada's web site: http://www.hc-sc.gc.ca/hl-vs/iyh-vsv/med/med-gen-eng.php


"To prove that their products are safe and effective, generic drug manufacturers must demonstrate that the generic drug performs similarly to the brand name drug. The studies that compare the generic drug with the brand name drug are called "comparative bioavailability" studies. In these studies, the level of a medicinal ingredient in the blood of healthy human volunteers is measured. During the studies, each volunteer gets the brand name drug and the new generic drug. The generic drug must show that it delivers the same amount of medicinal ingredient at the same rate as the brand name drug."


12/20/13

Hello Everyone:

In November 2004, my husband was diagnosed with GIST and at that time he was given a prognosis of 3 weeks to 3 months to live. Fortunately after surgery to remove as many of the tumours in his GI tract as the surgeon could see, he started on 400 mg. of Gleevec and has taken this pill every day for the last nine years. He has managed the side effects that accompany this powerful drug, while still maintaining as many of his normal activities as possible. Two years ago, he had surgery for a new tumour (this time much smaller and only one) and since that time every cat scan has been clear. Gleevec has been provided to him at no charge from the BC Cancer Agency for which we are very grateful. He has consistently been told to “keep doing what you are you doing”. Last week, when he picked up his three month supply of Gleevec he was surprised to find it had been replaced with a bioequivalent drug called Teva Imatinib. We have done some research on the internet and below is what we have found so far. We are wondering if anyone else has experience with a generic imatinib? Our biggest concern is that GISTers are being treated the same as leukemia patients. Leukemia patients are able to have their blood tested to check for cancer markers - GIST patients cannot and the only way we will be able to tell if the disease has progressed is if they find tumours through a cat or pet scan. Also, there is no appeal process a patient can access to get back on Gleevec if they cannot tolerate the generic drug.

We are also assuming that everything we have researched on the internet is true - if anyone has more up to date information, we would very much appreciate hearing it.


OUR RESEARCH:

Here is what we have found out so far:

• The Gleevec pill WE currently take uses a beta formulation of imatinib mesylate.

The bioequivalent pill Teva Imatinib (generic drug) is an alpha crystal formulation of imatinib mesylate.

• The generic drug manufacturers are allowed to submit the same clinical trial data submitted by the branded product because the Canadian government does not require generic manufacturers to conduct clinical trials on their own product stating the original trials are sufficient to accept the bioequivalent drug.

Health Canada states (http://www.hc-sc.gc.ca/hl-vs/iyh-vsv/med/med-gen-eng.php) that "To prove that their products are safe and effective, generic drug manufacturers must demonstrate that the generic drug performs similarly to the brand name drug. The studies that compare the generic drug with the brand name drug are called "comparative bioavailability" studies. In these studies, the level of a medicinal ingredient in the blood of healthy human volunteers is measured. During the studies, each volunteer gets the brand name drug and the new generic drug. The generic drug must show that it delivers the same amount of medicinal ingredient at the same rate as the brand name drug." However, it is not required to show the efficacy of the drug.

There are currently no comparative studies providing information that the alpha and beta molecules are truly equivalent in clinical effects and side effects.

The generic drug uses different binding agents than Gleevec. Given that the biggest difficulty for a GIST patient on chemotherapy is managing the side-effects, this is a huge unknown for us.

• The cost of the generic drugs are generally 18 to 26% of the branded drug.

• One drug compound can have several patents, one for each indication.

• Gleevec is used for treating GIST and also Chronic Myelogenous Leukemia (CML) as well as other diseases.

Novartis, the manufacturer of Gleevec states the generic is NOT identical to Gleevec as it is the alpha crystallization molecule, not the newer beta crystallization molecule.

• No one knows how these compare in efficacy, as the alpha crystallization has not been tested in clinical trials.

• Various Gleevec patents expire at different times.

• The patent for Gleevec in Canada for CML expired in June 2013.

The patent for Gleevec in GIST does not expire for another year.

• There is a concern that pharmacists are not made aware of this – they see Gleevec on the prescription and then see on the list provided by the policy makers that Gleevec is to be substituted with a generic and they do so.

• And most importantly, the Teva formulation is not even indicated for GIST – see the product monograph at http://cmlsociety.org/wp-content/uploads/2013/10/TEVA-imatinib.pdf.


We understand the economics of the decision to switch to a generic drug if in fact it is truly of ‘equal value’ to the branded drug. Given the information above, we are not convinced that is true. We are feeling very stressed about the uncertainty of this situation and would very much appreciate any information or insight you can provide. Thank you in advance!


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GSI Disclaimer: http://www.gistsupport.org/disclaimer.php Information on GSI's website & listserv is NOT medical advice. Consult with licensed health professionals.






I think that people also need to be aware that there are differences in the "other" ingredients" in the different generics that people might be sensitive to. So one could have a reaction or side effect, that might come from what the drug is made up of, not just the "medicinal ingredient".