Formulary Watch |

Pemoline removed from US market

In late October, FDA announced that pemoline will no longer be available in the United States because the risks of liver toxicity associated with the drug's use outweigh the benefits of the therapy.

Excessive reliance on class effect could negatively impact geriatric care

Too much reliance on class effect could undermine the medical care of geriatric patients, according to an article published in the Journal of the American Geriatric Society. In turn, the clinical community should work to ensure that sufficient choices remain to prescribe wisely for elderly patients, authors Mark H. Beers, MD, and Richard G. Stefanacci, DO, stated.

Acetaminophen, NSAIDs elevate hypertension risk in women

Acetaminophen at doses of more than 500 mg/d and nonsteroidal anti-inflammatory drugs (NSAIDs) at doses of more than 400 mg/d increase the risk of incident hypertension in younger and older women, according to cohort studies published in Hypertension.

FDA actions in brief

FDA extended the Prescription Drug User Fee Act action date to January 7, 2006, for lenalidomide (Revlimid, Celgene). The drug is intended to treat patients with transfusion-dependent anemia resulting from low- or intermediate-1-risk myelodysplastic syndromes associated with a deletion 5q cytogenetic abnormality.

First-time generic approvals

Amlodipine tablets 2.5, 5, and 10 mg (equiv to Norvasc tablets).

Pipeline Preview

Muraglitazar (Pargluva, Bristol-Myers Squibb, Merck) for the treatment of type 2 diabetes.

Kaletra

This tablet formulation of lopinavir and ritonavir provides several advantages over the capsule formulation.

Humira

This recombinant IgG1 monoclonal antibody exerts its therapeutic effect through inhibition of human tumor necrosis factor (TNF).

Arranon

The prodrug of a cytotoxic deoxyguanosine analogue, nelarabine inhibits DNA synthesis and leads to cell death.

A year of novel pharmacologic agents in review

In each issue, Formulary's "Focus on" article reviews a newly approved or investigational drug of interest to pharmacy and therapeutics committee members. Because so many readers have told the editors of Formulary that they reference this column frequently when making formulary decisions for their hospitals, health systems, or managed care organizations, the editors have compiled this review of all the "Focus on" articles published so far in 2005, along with updates on the status of each agent.

Pre-meal inhaled insulin lowers HbA1c levels more effective than rosiglitazone

Inhaled insulin (Exubera, Pfizer/Sanofi-Aventis) could be an effective therapy and alternative to rosiglitazone (Avandia, GlaxoSmithKline) for individuals who are early into the course of type 2 diabetes, according to a study published in Diabetes Care.

PREAMI trial

The ACE inhibitor perindopril significantly reduced left ventricular remodeling in a well-treated population of older patients with acute myocardial infarction (MI) and preserved ejection fraction, said Roberto Ferrari, MD, PhD, lead investigator of the Perindopril Remodeling in Elderly with Acute Myocardial Infarction (PREAMI).

Drug Watch: Prophylactic vaccines in late-stage development for the prevention of selected infectious diseases (October 2005) (PDF)

Review of prophylactic vaccines in late-stage development for the prevention of selected infectious diseases (October 2005).

Dr Lester M. Crawford resigns post as head of FDA; DTC advertising continues to draw regulatory attention

FEDERAL AND STATE GOVERNMENT ACTIONS AND THEIR IMPACT ON DRUG DECISION-MAKERS

A pharmacotherapeutic review of treatment options for infertility in women

The growing trend for women to wait later in life before having their first child has placed many women at a higher risk for difficult conception. There are numerous classes of medications available to assist women who have been diagnosed with infertility.Agents that are used in the treatment of infertility include: clomiphene citrate, aromatase inhibitors, gonadotropins, chorionic gonadotropins, gonadotropin-releasing hormone, gonadotropin-releasing hormone agonists, gonadotropin-releasing hormone antagonists, follitropins, and other miscellaneous agents. Medications chosen for a patient will vary depending on the identified cause of the infertility. Additionally, economic factors will play a role. It is important for healthcare professionals to be aware of treatment options and have a basic understanding of the role these medications play in the treatment of infertility. (Formulary. 2005;40:329–341.)

Ranolazine: An update on the novel antianginal agent

Ranolazine (Ranexa, CV Therapeutics) is a partial fatty acid oxidase inhibitor that increases the amount of ATP produced from glucose and increases the ability of the myocardium to retain functionality despite a reduced oxygen supply. Ranolazine is under FDA review for the treatment of chronic stable angina (CSA). Ranolazine was first reviewed in the August 2003 issue of Formulary. Since the initial review of ranolazine by FDA, additional data have emerged that merit an update in this journal. Clinical trials have demonstrated the efficacy of ranolazine as both monotherapy and combination therapy in patients with CSA. Recently published clinical trials (MARISA and CARISA) have shown an improvement in symptom-limited exercise duration. The results of the ERICA trial demonstrated a reduction in weekly anginal attacks when ranolazine was added to maximum-dose amlodipine therapy. Headache and generalized weakness were the most commonly reported adverse events in clinical trials. Prolongation of the QT interval has raised concerns; however, a lack of development of ventricular tachyarrhythmias-specifically Torsade de Pointes-remains an important safety finding. (Formulary. 2005;40:323–328.)

Imagine Trial

Initiating therapy with the ACE inhibitor quinapril within the first 7 days after coronary artery bypass graft (CABG) surgery does not lead to better outcomes among patients already receiving optimal therapy, said Wiek H. van Gilst, MD, lead investigator of IMAGINE (Ischemia Management with Accupril Post Bypass Graft via Inhibition of Angiotensin Converting Enzyme).

PCI-Clarity trial

Early use of clopidogrel, started prior to rather than at the time of angioplasty, reduces the risk of death, MI, or stroke by nearly half, reported Marc S. Sabatine, MD, MPH, lead investigator of PCI-CLARITY (Clopidogrel as Adjunctive Reperfusion Therapy).

ASCOT-BLPA

An antihypertensive regimen of amlodipine with added perindopril significantly reduces all-cause mortality and most major adverse cardiovascular outcomes compared with a regimen of atenolol with the addition of a diuretic, according to the final results of ASCOT-BPLA (Anglo-Scandinavian Cardiac Outcomes Trial Blood Pressure Lowering Arm).

OASIS-5 trial

The factor Xa inhibitor fondaparinux prevents death, MI, and refractory ischemia at 9 days as well as the low-molecular-weight heparin enoxaparin in patients with acute coronary syndromes (ACS), while reducing the incidence of bleeding.

CIBIS III trial

A beta blocker first strategy appears to be as safe and effective as an ACE inhibitor first strategy for the treatment of older patients with heart failure, and may confer an early survival advantage.

PREAMI trial

The ACE inhibitor perindopril significantly reduced left ventricular remodeling in a well-treated population of older patients with acute myocardial infarction (MI) and preserved ejection fraction, said Roberto Ferrari, MD, PhD, lead investigator of the Perindopril Remodeling in Elderly with Acute Myocardial Infarction (PREAMI).

FDA actions in brief

FDA approved a new influenza vaccine (Fluarix, GlaxoSmith-Kline) for adults aged 18 years and older.

First-time generic approvals

Clonazepam orally disintegrating tablets 0.125, 0.25, 0.5, 1, and 2 mg (equiv to Klonopin rapidly disintegrating tablets).

Pipeline Preview

Nelarabine (Arranon, GlaxoSmithKline) injection for the treatment of T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma in pediatric and adult patients whose disease has not responded to or has relapsed following treatment with at least 2 chemotherapy regimens.

Ambien CR

This non-benzodiazepine hypnotic is delivered in 2 stages through the use of a bi-layered tablet.

Remicade

Infliximab, a chimeric monoclonal antibody, exerts its effect through inhibition of human tumor necrosis factor alpha (TNF alpha).

Celebrex

This NSAID is believed to exert its therapeutic effect through inhibition of prostaglandin synthesis, primarily via inhibition of cyclooxygenase-2 (COX-2). Celecoxib was approved on July 29, 2005, for the relief of the signs and symptoms of ankylosing spondylitis (AS).

Drug Watch: Agents in late-stage development for the treatment of epilepsy and migraine (September 2005) (PDF)

Review of agents in late-stage development for the treatment of epilepsy and migraine (September 2005).

Advisory committee recommends continued marketing of beta 2-agonists, black box warning for formoterol

FDA's Pulmonary-Allergy Drugs Advisory Committee voted unanimously that the long-acting beta 2-agonists salmeterol (Serevent and Advair, GlaxoSmithKline) and formoterol (Foradil, Novartis) should remain on the market despite concern over reports of asthma-related deaths associated with the use of salmeterol.