FDA Notifications
BMS issues letter about omeprazole
Bristol-Meyers Squibb has issued a "Dear Healthcare Provider" letter regarding important new pharmacokinetic data concerning the coadministration of atazanavir (Reyataz) and ritonavir (Norvir) with omeprazole (Prilosec).
Omeprazole is a proton-pump inhibitor (PPI) for the treatment of acid-related diseases that works by suppressing gastric acid secretion.
The following observations were made from a randomized, open-label, multiple-dose drug interaction study:
- A 76% reduction in atazanavir area under the concentration-time curve (AUC) and a 78% reduction in atazanavir trough plasma concentration (Cmin) were observed when atazanavir/ ritonavir 300/100 mg was coadministered with omeprazole 40 mg.
Based on the study results, the recommendations are:
- Do not coadminister atazanavir or atazanavir/ ritonavir with omeprazole due to the reduction in atazanavir exposure levels. This recommendation is consistent with the current atazanavir U.S. package insert.
- It is not known whether the over-the-counter dose of omeprazole (20 mg once daily) would produce similar results; therefore, coadministration is not recommended.
- Increasing the atazanavir/ritonavir dose to 400/100 mg in combination with omeprazole did not result in atazanavir exposures comparable to those observed with a regimen of atazanavir/ritonavir 300/100 mg without omeprazole.
- Simultaneous administration of 8 ounces of cola given in an effort to decrease (acidify) gastric pH did not appear to affect this reduction.
Investigations regarding the potential drug interaction between atazanavir sulfate and H2 Receptor antagonists (another type of gastric medication) when coadministered are ongoing. Until data are available, clinicians should note the following statements from the atazanavir (Reyataz) package insert: "Reduced plasma concentrations of atazanavir are expected if H2 Receptor antagonists are administered with Reyataz (atazanavir sulfate). This may result in loss of therapeutic effect and development of resistance. To lessen the effect of H2 Receptor antagonists on atazanavir exposure, it is recommended that an H2 Receptor antagonist and Reyataz be administered as far apart as possible, preferably 12 hours apart."
To view the complete letter, go to www.adobe.com/products/acrobat/readstep2.html.
Copackaged drug regimen approved for PEPFAR
The FDA announced the tentative approval of a copackaged antiretroviral drug regimen, consisting of lamivudine/zidovudine fixed dose combination tablets and nevirapine tablets for the treatment of HIV-1 infection in adults. It is manufactured by Aspen Pharmacare of South Africa.
A tentative approval means the FDA has concluded a drug product has met all of the required quality, safety, and efficacy standards, even though it may not yet be marketed in the United States due to existing patents and/or exclusivity. It does, however, make the product eligible for use under the President’s Emergency Plan for AIDS Relief (PEPFAR) program.
The copackaged drug products are a complete antiretroviral drug regimen that have met the FDA’s quality, safety, and efficacy standards and will be available for potential procurement by PEPFAR for use in South Africa and developing nations. It is the first tentative approval of a product to treat HIV/AIDS under the new expedited FDA review process for PEPFAR, and the first tentative approval of an HIV drug regimen manufactured by a non-U.S.-based generic pharmaceutical company.
Aspen’s lamivudine/zidovudine fixed-dose combination tablets are a version of the FDA-approved Combivir tablets manufactured by GlaxoSmithKline, and the nevirapine tablets are a version of Viramune tablets manufactured by Boehringer-Ingelheim.
The new copackaged product consists of both lamivudine/zidovudine fixed-dose tablets and nevirapine tablets, one of each tablet to be taken twice daily, after the initial two-week initiation phase of this nevirapine regimen.
FDA issues final guidance on nucleic acid tests
The FDA has issued final guidance on the Use of Nucleic Acid Tests on Pooled and Individual Samples from Donors of Whole Blood and Blood Components (including Source Plasma and Source Leukocytes) to Adequately and Appropriately Reduce the Risk of Transmission of HIV-1 and HCV.
FDA’s blood-testing rules require establishments that collect blood and blood components (e.g., whole blood and blood components, including source plasma and source leukocytes) to test each donation of human blood or blood component intended for use in preparing a blood product for evidence of infection due to specific communicable disease agents. The purpose is to reduce the risk of transfusion-transmitted transmission of communicable disease.
The purpose of the guidance is to inform blood collecting and processing establishments that:
1. The FDA has licensed nucleic acid tests (NAT) as tests to screen blood donors for HIV-1 ribonucleic acid (RNA), and HCV RNA.
2. These licensed tests can detect evidence of infection at a significantly earlier stage than is possible under previously approved tests using antibody or antigen detection technology; including the HIV-1 p24 antigen test.
NAT is a nucleic acid amplification technology that includes polymer chain reaction, or PCR, to detect certain viral components. NAT enables the earliest and most sensitive detection of disease-causing human viruses in blood and plasma donations. A recently infected person would have virus particles in the bloodstream.
Although the blood or plasma could be infectious, the infection may not be detected using current antibody tests because the person may not yet have developed antibodies. This time frame before measurable antibody production is called the "window period." Over time, the person would make enough antibodies for the antibody test to be effective. However, because NAT can detect RNA or DNA from a very small number of virus particles, it can reduce the window period by detecting the infection earlier.
This guidance combines and finalizes the NAT draft guidance [www.fda.gov/ohrms/dockets/98fr/01d-0584_gdl0001.pdf dated December 2001, 67 FR 4719 (Jan. 31, 2002)] and the draft guidance Use of Nucleic Acid Tests on Pooled and Individual Samples from Donors of Whole Blood and Blood Components for Transfusion to Adequately and Appropriately Reduce the Risk of Transmission of HIV-1 and HCV [www.fda.gov/ohrms/dockets/98fr/040902c.pdf dated March 2002, 67 FR 17077 (April 9, 2002)].
The complete final guidance document can be found at www.fda.gov/cber/gdlns/hivhcvnatbld.htm. t
Consumers warned about unapproved test kits
The FDA is warning consumers not to use unapproved home-use diagnostic test kits that have been marketed nationwide via the Internet by Globus Media of Montreal, Canada. In fact, no home-use test kits intended for diagnosing HIV, syphilis, and dengue fever are approved for sale in the United States.
The use of these products could result in false results (though there is no confirmed evidence of false positives) that could lead to significant adverse health consequences.
The illegal kits are labeled as:
- Rapid HIV Test Kit
- Rapid Syphilis Test Kit
- One Step Cassette Style Cocaine Test
- One Step Cassette Style Marijuana (THC) Test
- One Step Cassette Style Amphetamine Test
- Rapid Dengue Fever Test
- One Step Midstream Style HCG Urine (Home)
- Pregnancy Test
The FDA has not approved or evaluated the performance of any of Globus Media’s products. As a result, consumers cannot know with any degree of certainty that test results are correct. For example, a person testing positive for HIV or the AIDS virus using one of these tests may not be infected with HIV, or worse, someone infected with HIV may test negative and not seek medical treatment, or spread the virus to others.
The tests were sold through web sites and distributed throughout the United States, usually by overnight delivery services.
They have been made available for sale on several web sites, including www.htkit.com and www.hstkits.com.
The kits usually are contained in a paper envelope with instructions inside the packaging. The envelope, instructions, and packaging may not accurately identify the manufacturer, packer, or distributor. The name of the kit appears on the instructions.
Consumers who have these products should not use them. Anyone who has used one of these test kits should be retested using valid test methods.
The FDA has issued an import alert which alerts FDA field personnel to the possible importation of these devices, provides guidance as to their detention and refusal of admission into the United States and also advises U.S. Customs officials about these products.
Other unapproved tests also may be available through the Internet. You can find a list of FDA approved/licensed tests for HIV and hepatitis at www.fda.gov/cber/products.testkits.htm.
Roche issues drug interaction warning
Roche Laboratories Inc. has issued a "Dear Health Care Provider" letter to communicate an important drug interaction warning for saquinavir/ritonavir, used as part of combination therapy for treatment of HIV infection. It reads:
"Drug-induced hepatitis with marked trans-aminase elevations has been observed in healthy volunteers receiving rifampin — 600 mg once daily in combination with ritonavir 100 mg/ saquinavir 1000 mg twice daily (ritonavir boosted saquinavir)."
As a result of high incidence of hepatotoxicity in a Phase I, randomized, open-label, multiple-dose clinical pharmacology study in healthy volunteers, Roche now advises prescribers that: "Rifampin SHOULD NOT be administered to patients also receiving saquinavir/ritonavir (ritonavir boosted saquinavir) as part of combination antiretroviral therapy (ART) for HIV infection." Rifampin is known as Rifampicin outside of the United States.
Roche is collaborating closely with the FDA on this issue, and appropriate changes to the package insert will be made as soon as possible.
Health care professionals are encouraged to report any unexpected events associated with the use of saquinavir/ritonavir directly to Roche Laboratories at (800) 526-6367 or to the FDA MedWatch program by phone at (800) FDA-1088, by fax at (800) FDA-0178, or by mail to MED WATCH, 5600 Fishers Lane, Rockville, MD 20852-9787.
BMS issues letter about omeprazole, Copackaged drug regimen approved for PEPFAR, FDA issues final guidance on nucleic acid tests, Consumers warned about unapproved test kits, Roche issues drug interaction warning.Subscribe Now for Access
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