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P T. 2011;36(3): 124-126, 138, 165-166

New Drugs/Drug News/New Medical Devices March 2011


Makena Reduces Risk of Preterm Birth

Hydroxyprogesterone caproate injection (Makena, Baxter) is now approved to reduce the risk of preterm delivery before 37 weeks of gestation in pregnant women with a history of at least one spontaneous preterm birth. This medication is not intended for women with a multiple pregnancy or other risk factors for preterm birth.

Granted an accelerated approval, Makena is given once weekly by injection into the hip by a health care provider. Treatment should begin at 16 weeks of gestation but no later than 21 weeks.

In a clinical trial, adverse effects included injection-site pain, swelling, or itching; hives; nausea; and diarrhea. Serious adverse reactions were rare. Pulmonary embolism and an infection at the injection site were also reported.

Hydroxyprogesterone caproate was originally approved under the trade name of Delalutin in 1956 for use in pregnant women. In 2000, however, Bristol-Myers Squibb, the original manufacturer, requested the drug’s withdrawal from the market for reasons unrelated to safety.

Source: FDA, February 4, 2011

Corifact, an Orphan Drug, In Factor XIII Deficiency

The FDA has approved Corifact (CSL Behring), the first product intended to prevent bleeding in people with congenital Factor XIII deficiency, a rare genetic defect. Factor XIII circulates in the blood and promotes normal clotting. Without treatment, a deficiency may lead to soft-tissue bruising, mucosal bleeding, and fatal intracranial bleeding. Newborns with this deficiency may have umbilical cord bleeding. The approval was based on results of a clinical study of 14 people.

Corifact is made from the pooled plasma of healthy donors. Patients receiving Corifact may develop antibodies against Factor XIII that may make the product ineffective.

Source: FDA, February 17, 2011


Once-Daily Gralise (Gabapentin) for Pain

Depomed has announced the FDA’s approval of gabapentin tablets (Gralise, DM-1796) for the once-daily treatment of postherpetic neuralgia (PHN), the pain that follows the healing of the rash associated with shingles. Gralise was approved as an orphan drug on the basis of two phase 3, placebo-controlled trials.

Gralise should be titrated over a two-week period to a dose of 1,800 mg once daily, taken with the evening meal. The tablets swell in gastric fluid and gradually release gabapentin. Gralise is not interchangeable with other gabapentin products because of differing pharmacokinetic profiles that affect the frequency of administration. Gabapentin should be withdrawn gradually, over a minimum of one week.

The safety and effectiveness of Gralise have not been studied in patients with epilepsy. Antiepileptic drugs, including gabapentin (the active ingredient in Gralise), may increase the risk of suicidal thoughts or behaviors in patients taking these medications for any indication.

Licensed to Abbott in the U.S., Canada, and Mexico, Gralise is expected to be available as 300-mg and 600-mg tablets.

Sources: Depomed, Globe Newswire, January 28, 2011


A Rare Form of Stroke Affects Veins

An uncommon form of stroke that involves the veins instead of the arteries occurs more often than thought, according to the American Heart Association and the American Stroke Association.

Cerebral venous thrombosis (CVT) is caused by a clot in the dural venous sinuses, veins that drain blood from the brain toward the heart. CVT is most common in women who are pregnant or who are taking oral contraceptives and in people 45 years of age and younger.

The incidence of CVT among pregnant women and those who have recently given birth ranges from one in 2,500 to one in 10,000. The risk is greatest during the third trimester of pregnancy and in the first four weeks after delivery. Up to 73% of CVT cases occur immediately after childbirth. Women who have had a CVT have a low risk of complications during future pregnancies.

If CVT is suspected, tests should be conducted to determine whether patients have an inherited or acquired factor in the blood that raises the risk of clotting. Patients should also be screened for conditions that increase the risk of CVT (e.g., use of oral contraceptives, inflammatory disease, and infection). If CVT is confirmed, anticoagulation (e.g., IV heparin) should be initiated and continued, lasting from three to 12 months to a lifetime.

Sources: Bloomberg News, Health Day News, Stroke, February 3, 2011

Are Some Biologics Safer Than Others?

Biologic agents that reduce inflammation have varying degrees of safety. Although the effectiveness of these medications is now well established, some of the drugs may have rare but serious side effects related to their immune-suppressing activities, including an increased risk of infection, cancer, congestive heart failure, and reactivation of tuberculosis (TB).

A Cochrane review was based on data from 163 studies of nine biologics used to treat arthritis and other conditions. Adverse events and TB reactivation were more likely among patients taking biologics than among controls. When compared with each other, adalimumab (Humira, Abbott) and infliximab (Remicade, Centocor) were associated with more adverse events, whereas abatacept (Orencia, Bristol-Myers Squibb) and anakinra (Kineret, Biovitrum Ab) were linked to fewer serious adverse events. Taking certolizumab pegol (Cimzia, UCB) was more likely to result in a serious infection compared with several other biologics.

The researchers say the results should be treated cautiously and emphasize that these are not head-to-head trials. Some adverse events were so rare that it was difficult to determine whether they were related to the drugs. Biologics did not seem to increase the likelihood of congestive heart failure or cancer compared with placebo, but there were few total cases. Even though the studies did show that a few more patients who were taking biologics had TB, the total number of patients was low.

Source: Cochrane Database Syst Rev, February 16, 2011

Flu Vaccine And Febrile Seizures

Seizures related to fever have been reported to be on the rise following vaccination with Fluzone influenza vaccine, made by Sanofi-Aventis. The seizures have usually affected children younger than two years of age. The FDA said that 42 cases of febrile seizures had been reported as of December 13, 2010, in children receiving trivalent inactivated influenza vaccine. Fluzone is the only influenza vaccine recommended for the 2010–2011 flu season in infants and children six to 23 months of age.

No increase in febrile seizures in those older than two years of age has been observed following vaccination with Fluzone or with MedImmune’s live attenuated influenza vaccine (FluMist nasal spray). In the reported cases, all children recovered and no lasting effects have been seen. Recommendations for the use of the vaccine in children have not changed.

Febrile seizures may occur with childhood illnesses that can cause fever, such as ear infections, colds, influenza, and other viral infections. These reactions sometimes occur after vaccination. Approximately 4% of young children have at least one febrile seizure in their lifetime, usually between six months and five years of age. The peak age is between 14 and 18 months.

Source: FDA, January 20, 2011


Recall: 70,000 Invega Syringes

Johnson & Johnson has recalled about 70,000 syringes of an injectable formulation of Invega after discovering cracks in the syringes, which could lead to infections or reduced efficacy in users. The recall affects products sold in the U.S., Australia, Canada, and South Korea.

The syringes contain 234-mg dosages of Invega Sustenna, an injectable formulation that can be given monthly to treat schizophrenia (the tablet formulation can be taken daily). The syringes were distributed beginning in March 2010. Other dosage strengths are not being recalled.

Some of the prefilled syringes had a hidden crack in the syringe barrel. The cracks could have been caused by stress during the label-application procedure. The cracks have the potential to compromise the sterility of the syringe contents and to cause injection-site or systemic infections. Leakage of the drug through the crack may result in a lower-than-intended therapeutic dose.

Sources: The Wall Street Journal, Associated Press, February 15 and 16, 2011

Heart Failure Device Favors Women

Women who receive a combination pacemaker/defibrillator device have shown a 70% reduction in heart failure compared with a 35% decline in men. The finding was unexpected. This appears to be the first heart treatment that has been more effective in women than in men.

The MADIT–CRT study (Multicenter Automatic Defibrillator Implantation Trial–Cardiac Resynchronization Therapy) was sponsored by Boston Scientific.

An earlier study, published in 2009, had indicated that patients fared better with combined cardiac resynchronization therapy plus a defibrillator than with a defibrillator alone. Women also benefited more from resynchronization therapy than men. In the newer study, there were dramatic reductions in heart failure and death from any cause. Men achieved a good result, but women fared better.

In women, heart failure was more often caused by a viral infection; in men, it was more often caused by blocked arteries. Women are more likely to experience left bundle branch block, a pattern of disorganized electrical impulses that respond well to a pacemaker. Women tend to have smaller hearts than men, and the device works better in smaller hearts.

The device was originally approved to treat severe heart failure, but last September, the FDA extended the approval to cover mild heart failure.

Sources: J Am Coll Cardiol, Reuters, February 7, 2011

U.S. Sues Cardiac Device Maker

The federal government has filed a civil suit against Boston Scientific Corporation and related Guidant entities under the False Claims Act for selling cardiac devices (Ventak Prizm 2 and Renewal 1 and 2) that the company is alleged to have known were defective. Guidant corrected the defect in this line of devices but continued to sell its remaining stock of defective devices.

Guidant is alleged to have known as early as 2002 and 2003 that the devices contained a potentially life-threatening defect and to have hidden problems from patients, physicians, and the FDA. In February 2010, Guidant pleaded guilty to misleading the FDA about the problems.

Sources:,, January 27, 2011

Lap-Band Weight-Loss Surgery An Option for More Patients

The FDA has approved Allergan’s Lap-Band weight-loss device for patients with a body mass index (BMI) as low as 30 if they have at least one weight-related medical condition (e.g., diabetes or hypertension). The surgery had initially been reserved for those with a BMI of 40.

The Lap-Band, used to shrink the size of the stomach to reduce food intake, is an inflatable ring that is surgically implanted around the upper portion of the stomach. When the surgical wounds have healed, saline solution is injected into the ring to expand it, limiting the amount of food that can be consumed.

Potential risks include those associated with the initial surgery itself, slippage of the ring after it is inflated, leakage of saline fluid, and erosion of the plastic.

According to Allergan, more than 65% of patients were no longer obese after one year, and many showed improvements in cholesterol levels, diabetes, hypertension, and quality of life.

Source: The Los Angeles Times, February 16, 2011

Test Aids Kidney Recipients

The QMS Everolimus Immunoassay (Thermo Fisher Scientific) has been approved to manage potential organ rejection in kidney transplant patients by maintaining appropriate everolimus levels.

Everolimus (Zortress, Novartis) was approved in April 2010 for use in adult kidney recipients at low-to-moderate immunologic risk. Recipients are routinely given immunosuppressants such as a regimen containing everolimus, cyclosporine, basiliximab (Simulect, Novartis), and corticosteroids.

Some immunosuppressants are associated with toxic effects that can injure transplanted kidneys. Balancing levels of immunosuppressants is critical because transplant patients must take these drugs for the rest of their lives.

Source: FDA, February 11, 2011

Stabilizer Prevents External Hemorrhoids in Childbirth

Plexus Biomedical, Inc., has been granted a new classification and approval from the FDA to market the first device shown to help prevent external hemorrhoids during vaginal childbirth. Hemorrhoids associated with vaginal delivery are a frequent complication of child-birth, affecting from 750,000 to 1 million women in the U.S. each year.

The Hem-Avert Perianal Stabilizer supports the patient’s perianal region during labor and delivery. The device is easily applied and is used externally.

In a clinical study, none of the women who had been randomly chosen to use the device during labor and delivery developed hemorrhoids, whereas 25% of controls who delivered without the device developed hemorrhoids as a direct result of vaginal delivery. This finding is consistent with the incidence of hemorrhoids reported in the medical literature.

Source: Plexus, February 23, 2011


Marvin M. Goldenberg, PhD, RPh, MS

Name: Varian Proton Therapy System

Manufacturer: Varian Medical Systems, Palo Alto, Calif.

Approval Date: January 10, 2011

Purpose: The Varian system provides a form of radiation to treat lesions and tumors. Precise intensity-modulated proton therapy is delivered via pencil-beam scanning technology.

Description: Proton therapy, an advanced form of radiotherapy, uses high-energy particles (protons) instead of x-rays (photons) to deliver the dose to a target volume. Protons destroy tumors but stop at specified depths within the anatomy, reducing exposure of healthy tissue. Scanning beam technology enables physicians to control the shape of the dose distribution inside the patient’s body. Irradiation from multiple angles is combined to improve control of dose distributions.

Benefit: Normal tissue is spared, and time is saved; there is no need to manually insert separate shaping accessories for each beam angle in order to match the beam to the shape of the tumor. The device is effective for cancers that are difficult to treat with conventional radio-therapy, offering improved cost efficiency and providing high-quality care.


Name: Formula Balloon-Expandable Renal Stent System

Manufacturer: Cook, Inc., Bloomington, Ind.

Approval Date: January 14, 2011

Purpose: The system is used to reopen narrowed areas of the renal arteries.

Description: The device consists of two components, the stent and the delivery system. The stent is an implant constructed of stainless steel tubing, laser-cut into a mesh shape. It is mounted onto a long, thin, tube-like device, the delivery catheter. The stent system is inserted after balloon angioplasty, a method that is less invasive than surgery.

The stent is threaded up to the renal artery through a catheter and is inserted in either the groin or the arm. A wire is inserted into the vessel in the arm or groin and advanced to the blocked renal vessel. The stent on the delivery catheter is advanced over the wire to the blocked area. The stent is released from the delivery catheter and opens over the blockage by inflating a balloon underneath the stent on the delivery device.

Benefit: The stent is useful in opening blockages in patients with reduced blood flow to the renal arteries after unsuccessful balloon angioplasty of a single occluded lesion.

Caution: The device is not intended for patients who have bleeding problems; who cannot take anticoagulants; who have blockages that cannot be expanded appropriately; and who have an occlusion near or close to short-lasting clots.


Name: Trek and Mini-Trek Balloon Dilatation Catheter System

Manufacturer: Abbott, Abbott Park, Ill.

Approval Date: January 31, 2011

Purpose: The balloon dilatation catherer system is used in angioplasty to open narrowed coronary arteries. These catheters open up lesions before a stent is placed. Patient outcomes are usually improved when the stent is expanded in the vessel.

Description: The device is available in two catheter designs. The Mini-Trek (1.5–2 mm in diameter) is used to access small vessels. The Trek is available in more than 70 sizes, in various diameters(1.2–5 mm), and in various lengths (6–30 mm).

Benefit: The Trek system enables physicians to treat a broad range of patients with tortuous anatomy and complex lesions in narrow vessels. It can take many attempts to find the right catheter that is flexible enough to travel through blood vessels and streamlined enough to push through calcified lesions. The device allows easy, accurate placement of the balloon to restore blood flow rapidly.



Sublingual Immunotherapy Relieves Allergies

Immunotherapy given as sublingual (SL) tablets or drops is a safe and effective way to treat allergies caused by pollen and dust mites, according to Cochrane researchers. The approach may be an alternative to immunotherapy injections in children.

Common therapies include antihistamines and nasal corticosteroids. If these prove unsuccessful, doctors may recommend immunotherapy. Desensitization involves exposing patients to increasing doses of an allergen. Traditionally, immunotherapy is performed with injections, but the allergens are now also available as SL formulations.

Although a 2003 Cochrane review had suggested that SL immunotherapy was effective, those findings were based on a small number of trials. The researchers were able to add more studies to their current review, including trials of pollen and dust mites and one trial of cat allergens. SL immunotherapy significantly reduced symptoms of allergic rhinitis and lessened the need for medication compared with placebo. Few serious adverse effects were reported.

Source: Cochrane Database Syst Rev 2010, December 8, 2010

Two Drugs Look Promising For Hepatitis C Infection

Two investigational agents—telaprevir and boceprevir—may have the potential to treat hepatitis C virus (HCV) infection. About two-thirds of hepatitis C patients are thought to be baby-boomers who have been harboring the infection for years. HCV can take two or three decades for the damage to become manifest.

Current two-drug treatments cure only about 40% of patients with the most common variety of the virus, and these agents cause adverse effects. Major studies are now showing that adding a new drug—either telaprevir (Vertex) or boceprevir (Merck)—may be able to boost these cure rates to as high as 75%. They allow some patients to reduce treatment time in half (to six months), lessening the duration of adverse effects. If approved, these drugs would be the first to directly target HCV.

Although HCV infection is often thought to result from the injection of illegal drugs, the virus could have originated from a blood transfusion before 1992, when testing of the blood supply began.

Approximately 3.2 million Americans, and 170 million people worldwide, have chronic HCV infection. In the U.S., the number of new infections has decreased, but the disease’s toll is rising. HCV is a leading cause of the need for liver transplantation.

Telaprevir and boceprevir block an enzyme (protease) needed for the virus to reproduce. These drugs must be taken with ribavirin tablets (e.g., Copegus, Rebetol) and interferon injections, which appear to boost the immune system.

From 67% to 75% of patients receiving treatment, including either boceprevir or telaprevir, respectively, showed no signs of HCV six months after their last dose. Only 25% of African-Americans were helped by standard therapy, but adding one of the new drugs more than doubled their cure rates.

Adverse effects may include flu-like symptoms. Telaprevir may produce a severe rash, and boceprevir may cause anemia.

It is not known how much these drugs will add to the price of treatment, which already can cost $30,000, but the cost would be less expensive than a liver transplant.

Source: Associated Press, January 18, 2011

Can a Protein-Like Molecule Improve Memory?

Researchers may have found a method that seems to decrease forgetting in rats. Scientists from Mount Sinai School of Medicine in New York have shown that a molecule that occurs naturally in the human brain during memory formation appeared to enhance the strength and duration of some types of memories in rats.

Insulin growth factor II (IGF-II) is a protein-like molecule that has a role in cell growth and development and tissue repair. When this substance was blocked from the brain, the rats did not recall what they had learned. Yet declarative memory, the ability to remember places and facts, improved. This form of memory is affected in patients with Alzheimer’s disease and other forms of dementia, and researchers have sought ways to improve or preserve it.

Because IGF-II can cross the blood–brain barrier, it might be able to be administered through the bloodstream or as a vapor intranasally rather than as an injection into the brain. IGF-II already exists in the body and is therefore unlikely to be toxic. It also may be able to build connections between nerve cells in the brain to form new long-term memories.

In the study, when rats were placed in a two-compartment cage where they received a mild shock of the foot at one end, they quickly learned to avoid that area. Some rats then received an injection of IGF-II in the hippocampus. After several weeks, rats that had received IGF-II showed greater avoidance of the location than rats that had received a control injection of another growth factor or saline solution.

IGF-II did not appear to improve memory in the amygdala, which stores memories of emotional reactions.

The researchers plan to administer IGF-II to the entire body to see whether it can produce the same memory-boosting effects as direct injection into brain regions.

Sources: Nature, January 26, 2011; The Wall Street Journal, January 27, 2011

Salamander Extract Helps Normalize Breast Cancer Cells

Using salamander oocyte extract, scientists at the University of Nottingham have coaxed breast cancer cells back into normal cells. The breast cancer cells were epigenetically reprogrammed to activate a tumor-suppressing response that halted cancer progression.

The oocyte was taken from the axolotl salamander (Ambystoma mexicanum) to activate the tumor-suppressing genes via chromatin remodeling. Using this technique, the researchers reprogrammed the breast cancer cells within six hours, in contrast to several weeks observed with previous methods.

Although the African clawed frog, Xenopus laevis, has been widely studied, the axolotl is thought to have more molecular components in common with mammals and resembles a human system more closely. Axolotls can regenerate lost appendages and other vital organs, and their embryos are relatively large, allowing scientists to work with them easily.

In chromatin remodeling, the chromatin complexes—which are formed by tightly wound DNA, effectively silencing the genes contained with that genome region—are unwound to allow genes to be expressed within those complexes. To test the stability of the reprogrammed cells, the researchers injected the reprogrammed cells into the mice.

Over the course of three months, the reprogrammed cells showed no signs of aggressive tumor-like behavior, and the mice exhibited almost normal cellular growth rates.

It is possible that axolotl oocyte extract could become a basic epigenetic reprogramming tool and that these optimized molecules could become a breast cancer treatment in the future.

Sources: Molec Cancer, January 13, 2011;, February 9, 2011

Interleukin-15 Might Be A Factor in Celiac Disease

People who have high levels of interleukin-15 (IL-15) may have the tendency to develop celiac disease. This condition is caused by an abnormal immune response to gluten, a protein found in grains such as wheat, rye, barley and in foods such as cereal, pasta, and beer.

Celiac disease occurs in about 1% of the population and can lead to anemia, poor bone health, fatigue, and weight loss.

In a new study, blocking IL-15 in mice helped reverse the disease. Vitamin A and retinoic acid, a by-product of vitamin A and used in Retin-A and Roche’s former drug Accutane as acne treatments, may exacerbate the problem and trigger an inflammatory response. The research team suggests that an imbalance of compounds like IL-15, which regulate the immune system, could be an underlying cause of food allergies.

Aware that many people with celiac disease have high levels of IL-15 in the intestines, the team first recreated the disease in mice. When they increased levels of this compound in mice, early symptoms of celiac disease developed.

Adding retinoic acid to the mix only made the symptoms worse, causing inflammation and tissue damage. However, when they blocked IL-15, the sick mice were once again able to tolerate gluten.

Although it is not clear why IL-15 is dysregulated, having mice that develop the disease will allow the team to study potential treatments. Drugs that inhibit IL-15 are also being studied in patients with rheumatoid arthritis.

Sources: Nature, Reuters, February 9, 2011

A Potential Double Benefit: Ro 48-8071 for Breast Cancer And Cholesterolemia

A new drug product holds promise for being able to eradicate breast cancer cells as well as helping to reduce cholesterol levels.

Dr. Salman Hyder and his research team at the University of Missouri in Columbia has discovered a small molecule, Ro 48-8071. Initially developed for controlling cholesterol synthesis, it also destroys human breast cancer cells. This activity was discovered as the research team was investigating PRIMA-1, a drug that targets a common mutated gene in human breast cancer cells.

During the study, Dr. Xiaoquin Zou compared the chemistry of PRIMA-1 binding to thousands of proteins using a software program she developed called MDock. She and the researchers found that PRIMA-1 showed excellent binding properties to a protein called oxidosqualene cyclase (OSC), which is involved in producing cholesterol.

This discovery led the group to investigate whether known OSC inhibitors, such as Ro 48-8071, which can stop cholesterol production, also killed breast cancer cells.

The team suggested the possibility that one mechanism used by PRIMA-1 to kill cancer cells might include shutting down cholesterol synthesis. It is known that Ro 48-8071 does stop cholesterol synthesis and has been proven to be as effective in destroying cancer cells as PRIMA-1 without harming other normal breast cells.

Many studies must still be completed, including testing on humans.

Source: J Molec Graphics Modelling, February 22, 2011