ONE NEW DRUG, TWO INDICATIONS
Treating depression and diabetic peripheral neuropathy.
The U.S. Food and Drug Administration recently approved a new selective serotonin and norepinephrine reuptake inhibitor, duloxetine (Cymbalta), for treatment of major depressive disorder and for diabetic peripheral neuropathy. Duloxetine is available in capsules that contain enteric coated pellets, designed to prevent its breakdown by stomach acid. Both its antidepressant and pain-inhibitory effects are related to the potentiation of serotonin and norepinephrine in the central nervous system. Although it's used to treat diabetic neuropathy, duloxetine doesn't correct nerve damage; in clinical trials, diabetic neuropathy was decreased in some patients as soon as one week after starting the therapy.
According to the manufacturer's prescribing information, duloxetine is contraindicated in patients taking a monoamine oxidase inhibitor (MAOI), as is true with all selective serotonin reuptake inhibitors (SSRIs), because the combination may cause serious, even fatal, reactions. Duloxetine should not be started until at least 14 days after stopping treatment with an MAOI. Conversely, MAOIs should not be started until at least five days after treatment with duloxetine is discontinued. Duloxetine is also contraindicated in patients who have uncontrolled narrow-angle glaucoma because it increases the risk of mydriasis.
Duloxetine increases the risk of elevated serum transaminase levels (up to three times the upper limit of the normal range in fewer than 1% of subjects in clinical trials). Caution must be used if the patient has liver disease, and use of the drug should be avoided in patients who abuse alcohol. Duloxetine is associated with small increases in blood pressure (an average of 2 mmHg systolic and 0.5 mmHg diastolic). Caution should be used in anyone with a history of mania. As with all SSRIs, duloxetine requires close monitoring for worsening depression and increased suicidal ideation or desires.
Duloxetine is metabolized by the hepatic isoenzymes cytochrome P-450 (CYP) 2D6 and CYP1A2. Drugs that inhibit these isoenzymes are likely to cause an increase in the serum levels of duloxetine, although no dosage adjustments have been recommended. Because duloxetine also moderately inhibits CYP2D6, other drugs coadministered with it that are also metabolized by this isoenzyme may show significant elevations in serum levels. If the other drug metabolized by CYP2D6 also has a narrow therapeutic index, coadministration of that drug with duloxetine must be done cautiously. Duloxetine is also highly protein bound; when it's coadministered with other highly protein-bound drugs it's likely to displace some of the other drug, producing elevated serum levels and increasing the risk of adverse effects.
The most common adverse effects of duloxetine are nausea, dry mouth, constipation, decreased appetite, fatigue, somnolence, and sweating. Adverse effects on sexuality are also possible, as they are with all drugs that alter the central nervous system. Men treated with duloxetine are more likely to have problems achieving orgasm than before treatment; this effect does not pertain to women.
Before a patient starts duloxetine therapy, the nurse should take a detailed drug history, assess the patient's liver function, and determine alcohol use. The nurse should also find out whether the patient is taking other drugs metabolized by CYP2D6 or CYP1A2. The lists of such drugs change and are extensive; a consultation with a pharmacist or use of a drug database may be warranted. The nurse will need to monitor liver enzymes, as well as blood pressure and weight, throughout therapy, and ask the patient about difficulties with sexual performance.
Eli Lilly and Company. Cymbalta [prescribing information]. 2004. http://pi.lilly.com/us/cymbaltapi.pdf; Eli Lilly and Company. FDA approves antidepressant Cymbalta for treatment of pain caused by diabetic peripheral neuropathy, which affects up to 5 million Americans [press release]. 2004. http://newsroom.lilly.com/news/Product/2004-09-07_cymbalta_fda_apprvl_dpn.html.
Use of duloxetine should be avoided in patients who abuse alcohol.
NEW DRUG APPROVED
A new rapid-acting insulin.
A new rapid-acting insulin is on the market: insulin glulisine (Apidra), a recombinant DNA insulin that can be administered subcutaneously or with an insulin pump. When administered subcutaneously it can be used alone or with neutral protamine Hagedorn (NPH) insulin. Insulin glulisine should not be mixed with any other type of insulin if administered by pump. Because of the rapid onset of insulin glulisine, it must be administered closer to the time of a meal than either regular or NPH insulin.
Insulin glulisine is given 15 minutes or less before the start of a meal or within 20 minutes after starting a meal. As with regular insulin, if combined with NPH insulin in a syringe, insulin glulisine should be drawn up first. This drug will also become available for use with a multi-dose pen delivery device.
U.S. Food and Drug Administration. Apidra. 2004. http://www.fda.gov/cder/consumerinfo/druginfo/apidra.htm.
New Warnings and Safety Concerns
Medications and adverse effects.
Zoledronic acid (Zometa Injection) and pamidronate disodium (Aredia Injection).
Precautions and adverse effects informaton has been revised. The two bisphosphonates, which are used to prevent bone resorption and the hypercalcemia of malignancy, are reportedly associated with osteonecrosis of the jaw in patients with cancer. Many affected patients were also receiving corticosteroids and chemotherapy, known to be risk factors in osteonecrosis. Furthermore, the majority of the patients who developed osteonecrosis while taking either of the bisphosphonates also underwent dental procedures, such as tooth extraction. Because these procedures appear to either heighten the risk of osteonecrosis of the jaw or exacerbate the condition, they should be avoided, if possible, during bisphosphonate treatment. Nurses should assess patients' dental health and secure for them appropriate preventive dentistry prior to initiating bisphosphonate treatment.
Levothyroxine (Levoxyl), a thyroid hormone replacement. Information on precautions, adverse reactions, and dosage and administration has been revised, following reports of gagging, choking, tablets being stuck in the throat, and dysphagia-incidents that appear to have been related to patients taking the drug without water. To prevent these adverse effects, nurses should instruct patients to take the medication with a full glass of water.
Infliximab (Remicade).
There is a new warning on the label of infliximab, a tumor necrosis factor (TNF) blocker used to treat both rheumatoid arthritis and Crohn disease, prompted by the incidence of malignancies. This warning is also expected to appear on labels of other TNF blockers. There was an increased incidence of lymphoma among patients receiving infliximab in clinical trials, one six times greater than would be expected in the general population. Other malignancies have also been noted, but incidences of these were found to be the same as in the general population. Although the role of TNF blockers in malignancy development has not been studied, great caution should be exercised if infliximab is being considered as therapy in patients with a history of malignancy or if therapy is continued after a patient develops such a growth.
Wyeth, manufacturer of pantoprazole sodium (Protonix IV), and the U.S. Food and Drug Administration have issued safety warnings concerning breakage of the drug's glass injection vials when used in combination with a spiked IV system adaptor. Wyeth has not studied the use of spiked IV systems in the administration of injectable pantoprazole, does not recommend it, and suggests that the manufacturer of such a system be contacted for advice or assistance regarding its use. If alternative methods of delivery are possible, the safest approach would be to avoid administering pantoprazole in vials using a spiked IV system adaptor.
U.S. Food and Drug Administration. 2004 safety alerts for drugs, biologics, medical devices, and dietary supplements. 2004. http://www.fda.gov/medwatch/safety/2004/safety04.htm.