New Products for Pharmacists: Rx and generics (January 2013)

New generics

Greenstone LLC, the generic pharmaceutical subsidiary of Pfizer, has received FDA approval of its diclofenac/misoprostol tablets in dosage strengths of 50 and 75 mg. The company’s diclofenac sodium/misoprostol tablets product is the authorized generic of, and equivalent to Arthrotec. Greenstone also received FDA approval of its phenytoin tablets, USP in the dosage strength of 50 mg. Its phenytoin tablets product is the authorized generic of, and equivalent to Dilantin Infatabs. (http://greenstonellc.com)

New drugs

FDA has approved Fulyzaq (crofelemer, Salix Pharmaceuticals and Napo Pharmaceuticals Inc.) 125-mg delayed-release tablets, a botanical prescription drug for the treatment of the symptoms of diarrhea in HIV/AIDS patients taking antiretroviral therapy. Many HIV/AIDS patients experience diarrhea and discontinue or switch their antiretroviral therapies. Fulyzaq can be used by HIV/AIDS patients whose diarrhea is not caused by an infection from a virus, bacteria, or parasite, according to FDA. Fulyzaq is administered twice daily to manage watery diarrhea due to the loss of electrolytes and water in the gastrointestinal tract. The safety and efficacy of Fulyzaq were established in a clinical trial of 374 HIV-positive patients who were taking antiretroviral therapy and had prolonged diarrhea of a month or more. Approximately 18% of patients who took Fulyzaq experienced a clinical response compared with only 8% of placebo-treated patients. Common side effects of the botanical drug in the clinical trial were upper respiratory tract infection, bronchitis, cough, flatulence, and increased liver enzyme bilirubin. (www.salix.com)

Sirturo (bedaquiline, Janssen Therapeutics, a division of Janssen Products LP) was FDA-approved for the treatment of adults with multi-drug resistant pulmonary tuberculosis (TB) when other alternatives are not available.
Mycobacterium tuberculosis causes one of the world’s deadliest infections. For individuals who develop multi-drug resistant TB because M. tuberculosis becomes resistant to isoniazid and rifampin, Sirturo may be used but not without risks, according to Edward Cox, MD, MPH, director of the Office of Antimicrobial Products in the FDA’s Center for Drug Evaluation and Research. Sirturo’s label includes a Boxed Warning about the risk of QT prolongation, which could lead to an abnormal and potentially fatal heart rhythm. Nine patients who received the drug died compared to two patients receiving placebo during clinical trials. The manufacturer will distribute the drug through a single source and provide educational materials to ensure its appropriate use. It was approved following two phase 2 trials, demonstrating quicker resolution time compared to placebo for the patients’ sputum to be free of M. tuberculosis. Common side effects of Sirturo included nausea, joint pain, and headache. (www.janssentherapeutics.com)

FDA approved Eliquis (apixaban, Bristol-Myers Squibb), a factor Xa inhibitor anticoagulant, which is indicated to reduce the risk of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. In a clinical trial of more than 18,000 patients with atrial fibrillation not caused by cardiac valve disease, Eliquis was more effective than warfarin in the reduction of stroke. Patients who receive Eliquis  or other FDA-approved anticoagulants are at increased risk for bleeding,
including life-threatening and fatal bleeding. Eliquis must be dispensed with a patient Medication Guide, which includes instructions about its safe use. Healthcare professionals must counsel patients about the signs and symptoms of possible bleeding. The recommended dose is 5 mg orally twice daily. However, in patients with two of the following characteristics (aged 80 years and older, body weight ≤60 kg, or serum creatinine ≥1.5 mg/dL), reduce the dose to 2.5 mg orally twice daily. (www.bms.com)

Adasuve (loxapine, Alexza Pharmaceuticals) inhalation powder for oral inhalation use was FDA-approved for the acute treatment of agitation associated with schizophrenia or bipolar I disorder in adults. The Adasuve label includes a Boxed Warning alerting patients and healthcare providers about the risk of potentially lethal bronchospasm and increased mortality in the elderly with dementia-related psychosis. The typical antipsychotic must be administered as a single dose in a 24-hour period by a healthcare professional within an enrolled healthcare facility. Adasuve is available as a 10-mg unit in a single-use inhaler and only through a Risk Evaluation and Mitigation Strategy (REMS) program. The drug is contraindicated for patients with asthma or chronic obstructive pulmonary disease, or other lung disease associated with bronchospasm; for patients with acute respiratory signs and symptoms; and a known hypersensitivity to loxapine or amoxapine. The most common adverse reactions compared to placebo were dysgeusia, sedation, and throat irritation. (www.adasuve.com)

FDA approved Varizig, a varicella zoster immune globulin (VZIG) preparation, manufactured by Cangene Corporation, for reducing the severity of varicella zoster virus (VZV) infections in high-risk individuals. It should be administered within four days after exposure. Varizig is the only FDA-
approved immune globulin for VZV after exposure that is available in the United States. The preparation had been approved as an orphan drug by FDA and received a priority review. Varizig is administered in two or more injections, depending on the weight of the recipient, according to FDA. It is
approved for immunocompromised children and adults, newborns, pregnant women, premature infants, children younger than 1 year old, and adult with no immunity to VZV. The most common adverse effects from Varizig were injection-site pain and headache. (www.cangene.com)

Another drug, which received priority review and is now FDA-approved, is Iclusig (ponatinib, ARIAD Pharmaceuticals). Iclusig is indicated for the treatment of adults with chronic myeloid leukemia (CML) and Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL), two rare blood and bone marrow diseases. The drug blocks certain proteins that promote the development of cancerous cells. Iclusig is taken once daily to treat patients with chronic, accelerated, and blast phases of CML and Ph+ ALL whose leukemia is resistant or intolerant to tyrosine kinase inhibitors (TKIs). Ponatinib targets CML cells that have a specific mutation, known as T315l, which makes these cells resistant to currently approved TKIs. Iclusig’s label includes a Boxed Warning that the drug can cause blood clots and liver toxicity. The most common side effects reported during clinical trials included hypertension, rash, abdominal pain, fatigue, headache, dry skin, constipation, fever, joint pain, and nausea. (www.ariad.com)

FDA approved Gattex (teduglutide for injection, NPS Pharmaceuticals) for the treatment of adults with short bowel syndrome (SBS) who require additional nutrition from intravenous feeding. Gattex, a recombinant analog of human glucagon-like peptide 2, is injected once daily to help improve the absorption of fluids and nutrients in the intestine. It is the third drug approved by FDA for this indication. The drug was approved with a REMS program, which included a communication plan and training for prescribers. Patients taking Gattex have a potential increased risk of developing cancer and polyps in the intestine, obstructions to the intestine, gallbladder disease, biliary track disease, and pancreatic disease. The FDA is requiring a postmarket study of SBS patients treated with the drug in a routine clinical setting to continue to evaluate the potential increased risk of developing colorectal cancer and other conditions. The most common side effects associated with Gattex in clinical trials were abdominal pain, injection site reactions, nausea, headaches, abdominal distension, and upper respiratory tract infection. Walgreens Infusion Services has recently  been selected as a provider of Gattex. (www.npsp.com/Gattex)

FDA approved Juxtapid (lomitapide, Aegerion Pharmaceuticals) as an orphan drug to reduce low-density lipoprotein (LDL) cholesterol, total cholesterol, apolipoprotein B, and non-high-density lipoprotein (non-HDL) cholesterol in patients with homozygous familial hypercholesterolemia (HoFH). It is an adjuctive treatment for use with a low-fat diet and other lipid-lowering treatments. This rare cholesterol disorder is inherited and causes abnormally high levels of circulative LDL cholesterol. In the United States, approximately one in 1 million individuals have the disease. Juxtapid’s safety and efficacy were evaluated in a clinical trial of 29 patients with the disorder. For those who could tolerate the treatment, LDL levels dropped by approximately one-half during the first 26 weeks of treatment. Juxtapid’s label includes a Boxed Warning about a serious risk of liver toxicity  because of its association with liver enzyme abnormalities and accumulation of fat in the liver. It also interacts with several other medications. Juxtapid was approved with a REMS program that includes
elements to ensure safe use, such as prescriber and pharmacy certification and documentation of safe-use conditions to accompany each new prescription. FDA has required three postmarketing studies for the drug. The most common adverse effects were diarrhea, nausea, vomiting, indigestion, and abdominal pain. (www.aegerion.com)

New indication

FDA has expanded the use of Tamiflu, (oseltamivir phosphate, Genentech/Roche) to children as young as 2 weeks old who have flu symptoms that have been present for 2 days or less. Tamiflu, an influenza neuraminidase inhibitor, was first approved in 1999, and can be used prophylactically in patients 1 year and older. It is available in capsule form and as an oral suspension. For individuals who cannot swallow pills, the oral suspension should be used. If the oral suspension is not available, the capsule can be opened and mixed with sweetened liquid for administration. However, if the appropriate strength is not available, a pharmacist can compound an emergency supply of suspension from Tamiflu 75-mg capsules, according to the package insert.

Tamiflu is contraindicated in individuals with a hypersensitivity to the drug. The most common side effects have been nausea and vomiting. (www.tamiflu.com)