Larry D. Sasich

Safety of sildenafil citrate

Sir—In your editorial on sildenafil citrate (Viagra), you state that “Public information to consumers and health professionals covers safety adequately, if not to the total satisfaction of consumer groups such as the US Public Citizen”. Although this editorial involved an internet search, we point out information that is not in the FDA-approved label for the drug but in our petition for stronger warnings filed with the FDA on Aug 20, 1998, and available on our web site (www.citizen.org/hrg), as follows. “[We] demand that the FDA immediately convene a meeting on Viagra of its cardiovascular advisory committee—a committee which was completely bypassed during the dangerously-rushed six months between the submission of the new drug application for Viagra to the FDA and its approval . . . An ongoing joint task force of the American College of Cardiology and the American Heart Association (ACC/AHA) . . . has just issued an interim report which expresses concerns about the risks of the drug to new categories of patients with cardiovascular disease. . . . the ACC/AHA said that: The cardiovascular effects of Viagra may be potentially hazardous for patients with certain medical profiles, and clinicians need to exercise caution when advising the following patients who are considering taking Viagra: Patients with active coronary ischemia [decreased blood flow to the heart] who are not on nitrates; Patients with congestive heart failure and borderline low blood pressure and borderline low volume status; Patients on a complicated multidrug, anti-hypertensive program; and Patients on drugs (erythromycin cimetidine) or who have conditions (eg, liver or renal disease) that can prolong the half-life of Viagra.” Summarising these concerns, none of which (other than the above drug interactions) are reflected in the current labelling for Viagra, Dr Adolph M Hutter Jr, co-chair of the expert committee that developed the statement, said: “It can be dangerous for some patients to take Viagra, even if they are not on nitrates. Their medical condition or their medications can alter the effect that Viagra might have on their bodies, which might lead to an excessive drop in blood pressure”. In addition to the ACC/AHA suggestions for new warnings with which we agree, there is no information in the current label that addresses the findings of severe periarteritis that occurred in both rats and dogs, even though the (FDA) pharmacology reviewer stated that this was the most important toxicological finding and seems closely related to the inhibition of the phosphodiesterase type 5 enzyme which is located in vascular smooth muscle. The “special attention and warnings” referred to in your editorial for patients with a history of heart disease are not included in the official labelling for the drug but should be included, otherwise public information does not cover safety adequately.

The US FDAs withdrawal of the breast cancer indication for Avastin (bevacizumab).

On November 18, 2011, the US Food and Drug Administration (US FDA) announced that breast cancer indication for Avastin (bevacizumab) had been withdrawn after concluding that the drug has not been shown to be safe and effective for the treatment of breast cancer. The specific indication that was withdrawn was for the use of bevacizumab in metastatic breast cancer, with paclitaxel for the treatment of patients who have not received chemotherapy for metastatic HER2-negative breast cancer. The US FDAs decision has been met with emotion and confusion among the public and health professionals. The purpose of this article is to review the regulatory history of bevacizumab for breast cancer and to examine the scientific evidence that led to the approval and subsequent withdrawal of this indication. Bevacizumab also provides the opportunity to illustrate the value of free publicly available US FDA reviews that may contain rigorously reviewed unpublished data and analyses and to contrast the decisions made in the US and Europe about bevacizumab and breast cancer.

The usefulness and scientific accuracy of private sector Arabic language patient drug information leaflets

BACKGROUND Inadequate access to useful scientifically accurate patient information is a major cause of the inappropriate use of drugs resulting in serious personal injury and related costs to the health care system. The definition of useful scientifically accurate patient information for prescription drugs was accepted by the US Secretary of the Department of Health and Human Services in 1996 as that derived from or consistent with the US FDA approved professional product label for a drug. Previous quality content studies found that English language patient drug information leaflets distributed by US pharmacies failed to meet minimum criteria defining useful and scientifically accurate information. METHOD AND FINDINGS Evaluation forms containing the explicit elements that define useful scientifically accurate information for three drugs with known serious adverse drug reactions were created based on the current US FDA approved professional product labels. The Arabic language patient drug information leaflets for celecoxib, paroxetine, and lamotrigine were obtained locally and evaluated using a methodology similar to that used in previous quality content patient drug information studies in the US. The Arabic leaflets failed to meet the definition of useful scientifically accurate information. The celecoxib leaflet contained 30% of the required information and the paroxetine and lamotrigine leaflets contained 24% and 20%, respectively. There are several limitations to this study. The Arabic leaflets from only one commercial North American vendor were evaluated and the evaluation included a limited number of drugs. A larger study is necessary to be able to generalize these results. CONCLUSIONS The study results are consistent with those of previous quality content studies of commercially available English patient drug information leaflets. The results have important implications for patients as access to a reliable source of drug information may prevent harm or limit the suffering from serious adverse drug reactions.

DIONYSOS study comparing dronedarone with amiodarone

In their clinical review of the management of atrial fibrillation, Lafuente-Lafuente and colleagues mention the anticipated release of results comparing dronedarone with amiodarone.1 The results of the DIONYSOS study of the efficacy and safety of dronedarone v amiodarone for the maintenance of sinus rhythm in patients with atrial fibrillation were made publicly …

Clinical trial transparency.

In a CMAJ news article,[1][1] Goldacre overlooks the estimated 30% to 50% of clinical trials that are submitted to the US Food and Drug Administration (FDA) in support of new drug approvals. These trials remain unpublished and have been available on the agency’s website free of charge since 1998.[

Paroxetine and Study 329: what we already knew and when.

The re-analysis of Study 329 using the Restoring Invisible and Abandoned Trials (RIAT) protocol missed crucial aspects of patient drug safety.1 2 3 The fact that paroxetine had not been shown to be safe and effective in paediatric patients was made publicly available on the Food and Drug Administration website in 1998,4 three years before the publication …

Drug approval packages and briefing documents are already freely available

Goldacre lists four levels of clinical trial transparency, three of which are priorities for the AllTrials campaign.1 The first three of these priorities have been freely available for years for drugs approved or discussed by advisory committees in the US, yet these documents are rarely used. These documents are prepared by scientists from the US Food and …