Janssen Identifies Trace Amounts of TBA in 5
Batches of PREZISTA (darunavir) in the EU and Canada
The Company is Working With Regulatory Authorities|
High Wycombe, UK - 11 May 2011 - Janssen-Cilag International N.V. today announced the company is working with regulatory authorities in five countries to address trace amounts of TBA (2,4,6 tribromoanisole) identified in five batches of the HIV/AIDS medicine PREZISTA® (darunavir). The countries affected include the United Kingdom, Ireland, Germany, Austria and Canada.
Janssen initiated discussions with regulatory authorities after receiving four consumer reports of an uncharacteristic ("musty, mouldy") odour. The company's investigation determined that the odour is likely caused by trace amounts of TBA. As discussions with regulatory authorities in each of the five countries continue, the company is committed to recalling and replacing any affected bottles of product remaining in the marketplace - estimated to be fewer than 2,000 in countries where recalls have been initiated.
Company discussions with the European Medicines Agency resulted in agreement on a Class II recall at the wholesale and retail (pharmacy) level. Discussions with regulatory authorities in Canada are underway to determine the appropriate course of action. The Company does not anticipate a product shortage resulting from the company's actions to recall and replace affected product.
Patients should not stop taking their medication. Anyone experiencing an uncharacteristic odour associated with PREZISTA®400mg or 600mg Tablets - or anyone with questions about the company's actions to recall and replace - should contact the company at 0800 032 3013 (freephone).
It should be noted that in the UK PREZISTA® 400mg is only affected. PREZISTA® 75mg, 150mg and 300mg are not subject to this action.
TBA is a byproduct of a chemical preservative sometimes applied to wood often used in the construction of pallets on which products are transported and stored. While not considered to be toxic, TBA can generate an offensive odour and a very small number of patients have reported temporary gastrointestinal symptoms. As it relates to PREZISTA®, there have been no reported serious adverse events caused by the presence of TBA.
In January 2010, Janssen instituted a number of actions to reduce the potential of TBA contamination, including requiring suppliers to verify that they do not use pallets made from chemically-treated wood. An internal investigation is underway with suppliers to evaluate all potential sources of TBA. In addition, Janssen is working with peer companies to better understand how and where TBA is entering and impacting the supply chains and what it can do to further mitigate this exposure.
About PREZISTA® (darunavir)
PREZISTA Indication: Adults
PREZISTA, co-administered with ritonavir and with other antiretroviral agents, is indicated for the treatment of HIV-1 infection.
This indication is based on analyses of plasma HIV-1 RNA levels and CD4+ cell counts from two controlled, Phase 3 trials of 48 weeks duration in antiretroviral treatment-naïve and treatment-experienced patients, and two controlled, Phase 2 trials of 96 weeks duration in clinically advanced, treatment-experienced adult patients.
In treatment-experienced adult patients, the following points should be considered when initiating therapy with PREZISTA/ritonavir:
· Treatment history and, when available, genotypic or phenotypic testing, should guide the use of PREZISTA/ritonavir.
· The use of other active agents with PREZISTA/ritonavir is associated with a greater likelihood of treatment response.
Important Safety Information
PREZISTA does not cure HIV-1 infection or AIDS, and does not prevent passing HIV-1 to others.
· Coadministration of PREZISTA/ritonavir is contraindicated with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events (e.g., alfuzosin, dihydroergotamine, ergonovine, ergotamine, methylergonovine, cisapride, pimozide, oral midazolam, triazolam, lovastatin, or simvastatin)
· Coadministration of PREZISTA/ritonavir is also contraindicated with rifampin and products containing St. John's wort(Hypericum perforatum) because this may cause significant decrease in plasma concentration of darunavir, resulting in loss of therapeutic effect and development of resistance
· Coadministration is not recommended with indinavir, lopinavir/ritonavir, saquinavir, pravastatin, salmeterol, and colchicine in patients with hepatic or renal impairment.
· Caution should be used when prescribing agents such as sildenafil, vardenafil, tadalafil, or other substrates, inhibitors, or inducers of CYP3A in patients receiving PREZISTA/ritonavir.
· This list of potential drug interactions is not complete.
Warnings & Precautions
· PREZISTA must be coadministered with ritonavir and food to achieve the desired antiviral effect. Failure to administer PREZISTA with ritonavir and food may result in a loss of efficacy of darunavir. Please refer to ritonavir prescribing information for additional information on precautionary measures
· Drug-induced hepatitis (e.g., acute hepatitis, cytolytic hepatitis) has been reported with PREZISTA/ritonavir. During the clinical development program (N=3063), hepatitis has been reported in 0.5% of patients receiving combination therapy with PREZISTA/ritonavir. Patients with preexisting liver dysfunction, including chronic active hepatitis B or C, have an increased risk for liver function abnormalities, including severe hepatic adverse events
Post-marketing cases of liver injury, including some fatalities, have been reported. A causal relationship with PREZISTA/ritonavir therapy has not been established
Appropriate laboratory testing should be conducted prior to initiating therapy with PREZISTA/ritonavir and patients should be monitored during treatment. Increased AST/ALT monitoring should be considered in patients with underlying chronic hepatitis, cirrhosis, or in patients who have pretreatment elevations of transaminases, especially during the first several months of PREZISTA/ritonavir treatment. Evidence of new or worsening liver dysfunction (including clinically significant elevation of liver enzymes and/or symptoms such as fatigue, anorexia, nausea, jaundice, dark urine, liver tenderness, hepatomegaly) in patients on PREZISTA/ritonavir should prompt consideration of interruption or discontinuation of treatment
· Severe Skin Reactions: Severe skin reactions (0.4%), accompanied by fever and/or elevations of transaminases in some cases, Stevens-Johnson Syndrome (<0.1%), and toxic epidermal necrolysis (post-marketing experience) have been reported in patients receiving PREZISTA/ritonavir. Discontinue PREZISTA/ritonavir immediately if signs or symptoms of severe skin reactions develop (including, but not limited to, severe rash or rash accompanied with fever, general malaise, fatigue, muscle or join aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia)
In clinical trials (N=3063), rash (all grades, generally mild to moderate, regardless of causality) occurred in 10.3% of patients receiving PREZISTA/ritonavir. Discontinuation due to rash was 0.5%
· Sulfa Allergy: PREZISTA should be used with caution in patients with known sulfonamide allergy
· Diabetes Mellitus/Hyperglycemia and Hemophilia: New-onset or exacerbations of preexisting diabetes mellitus, hyperglycemia, and increased bleeding in hemophiliacs have been reported in patients receiving protease inhibitors. Initiation or dose adjustments of insulin or oral hypoglycemic agents may be required. A causal relationship between protease inhibitors and these events has not been established
· Fat Redistribution: Redistribution and/or accumulation of body fat have been observed in patients receiving ARV therapy. The causal relationship, mechanism, and long-term consequences of these events have not been established
· Immune reconstitution syndrome has been reported in patients treated with ARV therapy
· Resistance/Cross Resistance: The potential for HIV-1 cross-resistance among protease inhibitors has not been fully explored in PREZISTA/ritonavir-treated patients
Use in Specific Populations
· Hepatic Impairment: PREZISTA/ritonavir is not recommended for use in patients with severe hepatic impairment. There are no pharmacokinetic or safety data available in patients with severe hepatic impairment
· Pregnancy: PREZISTA should be used during pregnancy only if the potential benefit justifies the potential risk. No adequate and well-controlled studies have been conducted in pregnant women
· In treatment-naïve adult patients, the most common adverse drug reactions (5%) reported of at least moderate intensity (≥Grade 2) in the PREZISTA/ritonavir arm through 96 weeks were diarrhea (8%), headache (6%), abdominal pain (5%), and rash (5%)
· In treatment-experienced adult patients, the most common adverse drug reactions (5%) reported of at least moderate intensity (≥Grade 2) in the PREZISTA/ritonavir arm through 96 weeks were diarrhea (14%), nausea (7%), rash (7%), abdominal pain (6%), and vomiting (5%)
This is not a complete list of all adverse drug reactions reported with the use of PREZISTA/ritonavir.
Full prescribing information is available at www.PREZISTA.com.
Pamela Van Houten
Business Unit Communication Leader, Virology, North America
Global Pharmaceuticals Communication & Public Affairs
Johnson & Johnson Pharmaceutical Services, LLC
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