IN THIS ARTICLE, you'll learn about 14 recently marketed new drugs, including:

ustekinumab, which has a unique mechanism of action and is more effective than other drugs for the treatment of moderate-to-severe plaque psoriasis.

dronedarone HCl. Pharmacologically similar to amiodarone, it's specifically approved to prevent cardiovascular hospitalization (but not mortality) in select patients with persistent atrial fibrillation or flutter.

prasugrel HCl, which is indicated to reduce the rate of thrombotic cardiovascular events in patients with acute coronary syndromes treated with percutaneous coronary intervention.

abobotulinumtoxinA, a botulinum toxin approved to treat cervical dystonia and facial wrinkles.

Patients with acute coronary syndromes undergoing percutaneous coronary intervention (PCI) face the risk of platelet aggregation and thrombus formation at the procedure site, which can lead to acute myocardial infarction (MI), stroke, and death. Prasugrel HCl (Effient, Daiichi Sankyo; Lilly) is a new oral antiplatelet drug indicated to reduce the rate of thrombotic cardiovascular events (including stent thrombosis) in patients with acute coronary syndromes treated with PCI. These include patients with unstable angina or non-ST-segment elevation MI and patients with ST-segment elevation MI when managed with primary or delayed PCI. These indications are more limited than those for clopidogrel, a similar antiplatelet drug widely prescribed to reduce the risk of thrombosis following PCI, as well as in those who are to be managed medically or with coronary artery bypass graft (CABG) surgery. Prasugrel is most effective when combined with an aspirin regimen.

In studies comparing prasugrel with clopidogrel, the results are unclear. In one study, a prasugrel/aspirin regimen was more effective at preventing stent stenosis, MI, and death than a clopidogrel/aspirin regimen, but it was also more likely to cause bleeding. Some experts suspect that if prasugrel were given at lower dosages than those studied, the risks and benefits of the two drugs would be similar.

The labeling for prasugrel includes a black box warning about the bleeding risk, and it shouldn't be given to patients with active pathologic bleeding or a history of transient ischemic attack or stroke. However, if bleeding occurs during prasugrel therapy, it should be managed without stopping the drug, if possible, because discontinuation may increase the risk of cardiovascular events. Because prasugrel inhibits platelet activation and aggregation for the lifetime of platelets, withholding doses won't help manage bleeding.

A proton pump inhibitor may be prescribed to minimize gastrointestinal (GI) adverse reactions. Although omeprazole and esomeprazole may reduce the action of clopidogrel, they're not likely to affect the action of prasugrel.

Precautions: (1) Contraindicated in patients with active bleeding, as from peptic ulcers or intracranial hemorrhage. (2) Treatment shouldn't be initiated in patients with a history of transient ischemic attack or stroke. (3) Contraindicated in patients who may require urgent CABG surgery because of the bleeding risk. (4) Prasugrel should be discontinued at least 7 days before any surgery, if possible. (5) Use caution in patients with these risk factors for bleeding: body weight less than 60 kg, propensity to bleed (for example, because of recent trauma), concomitant use of other drugs that increase bleeding risk (such as warfarin, heparin, and nonsteroidal anti-inflammatory drugs), and advanced age. Prasugrel isn't recommended for patients over age 75 unless benefits clearly outweigh the risks. If prescribed for patients weighing less than 60 kg, a dosage reduction may be indicated.

Adverse reactions:bleeding, hypertension,hypercholesterolemia/hyperlipidemia, headache, back pain, dyspnea, nausea

Supplied as: 5-mg and 10-mg tablets

Dosage: loading dose of 60 mg followed by a maintenance dosage of 10 mg once a day. Patients should also be treated concomitantly with aspirin (75 to 325 mg/day).

Nursing considerations: (1) Prasugrel may be taken without regard to food. (2) Instruct patients to take it exactly as prescribed. (3) Tell patients that the drug will cause them to bruise and bleed more easily. Instruct them to watch for and report signs and symptoms of bleeding, such as dark tarry stools, nosebleeds, or bloody urine. (4) Ask patients to list all prescription drugs, over-the-counter products, and dietary supplements that they take (or plan to take) so the healthcare provider knows about other medications that might increase bleeding risk. Explain that taking aspirin and many other common remedies can increase their bleeding risk. (5) Warn patients not to discontinue the drug without first discussing it with the healthcare provider. (6) Tell patients to inform all healthcare providers and dentists that they're taking prasugrel before any invasive procedure is performed. (7) Instruct patients to get prompt medical attention if they experience any of the following signs and symptoms that can't otherwise be explained: fever, weakness, extreme skin paleness, purple skin patches, yellowing of the skin or eyes, or neurologic changes.

ANTIARRHYTHMIC DRUG

Dronedarone HCl

Helping patients stay out of the hospital

Structurally and pharmacologically similar to amiodarone, dronedarone HCl (Multaq, Sanofi-Aventis) is indicated to reduce the risk of cardiovascular hospitalization in patients with paroxysmal or persistent atrial fibrillation (AF) or atrial flutter (AFL), with a recent episode of AF/AFL and associated cardiovascular risk factors, who are in sinus rhythm or who will be cardioverted. The FDA specifically approved this drug to reduce the risk of cardiovascular hospitalization, but not cardiovascular mortality. One study that included patients with severe heart failure was terminated because mortality in the dronedarone group was twice that of the placebo group (8% versus 4%). In another study comparing it to amiodarone, dronedarone was less effective in reducing recurrences of AF but was better tolerated by patients.

A black box in the labeling warns against giving dronedarone to patients with moderate-to-severe heart failure (see Precautions below). If heart failure develops or worsens during therapy, dronedarone therapy should be suspended or discontinued.

Dronedarone also causes a moderate prolongation of the QT interval and may increase the risk of ventricular dysrhythmias.

Precautions: (1) Contraindicated in patients with New York Heart Association (NYHA) Class IV heart failure or NYHA Class II-III heart failure with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic. (2) Contraindicated in patients with second- or third-degree atrioventricular block or sick sinus syndrome (unless used with a functioning pacemaker). (3) Contraindicated in patients with bradycardia of less than 50 beats/minute. (4) Contraindicated in patients with a QTc interval of 500 ms or more, or a PR interval of more than 280 ms. (5) Dronedarone shouldn't be used with any other drugs or herbal products that prolong the QT interval, such as moxifloxacin, thioridazine, and Class I or Class III antiarrhythmics. (6) Contraindicated in pregnant or nursing women. Dronedarone is classified in Pregnancy Category X. (7) Maintain normal serum potassium and magnesium concentrations; depletion of these electrolytes may increase the risk of dysrhythmias. (8) Dronedarone increases digoxin exposure by 2.5-fold. If the two drugs must be used together, the digoxin dose should be reduced by one-half. (9) Dronedarone interacts with many other drugs, grapefruit juice, and herbal products (particularly St. John's wort). See the drug information insert for a complete listing and specific precautions.

Adverse reactions:diarrhea,asthenia, nausea, vomiting, abdominal pain, dermatologic effects (rash, pruritus), bradycardia

Supplied as: 400-mg tablets

Dosage: 400 mg with the morning meal and 400 mg with the evening meal

Nursing considerations: (1) Instruct patients to take each dose with food, which increases the drug's bioavailability. (2) Warn women of childbearing potential not to become pregnant while taking the drug and to use effective contraception. (3) Tell patients to avoid grapefruit juice, which may increase the drug's effects, and St. John's wort, which may diminish the drug's effects. Because dronedarone interacts with many drugs and other substances, teach patients to check with the healthcare provider before using any over-the-counter or herbal products. (4) Monitor for serum electrolyte imbalances and treat as ordered. (5) If patients miss a dose, they should wait and take the next dose as scheduled. Warn them not to take a double dose or try to make up a missed dose.

ANTIDIABETIC DRUG

Saxagliptin HCl

Second in its class to be marketed in the United States

Incretins are naturally occurring hormones that increase insulin secretion in the presence of elevated serum glucose concentrations (as occurs after meals). Saxagliptin HCl (Onglyza, Bristol-Myers Squibb; AstraZeneca) joins sitagliptin in a new class of oral drugs that increase the action of incretins. Saxagliptin is indicated for use as monotherapy or in combination regimens as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. The new drug hasn't been directly compared with sitagliptin in clinical studies, but the reduction of hemoglobin A1C attained with the recommended dosages of each is similar. Both drugs are generally well tolerated.

Saxagliptin isn't effective for treating patients with type 1 diabetes or diabetic ketoacidosis. It hasn't been studied in combination with insulin.

Precautions: (1) Monitor patients for acute pancreatitis, a rare but serious adverse reaction that has been reported with sitagliptin. (2) Monitor patients for hypoglycemia when using saxagliptin in combination with a drug known to cause hypoglycemia, such as a sulfonylurea; a lower dose of the latter drug may be indicated. (3) Reduce the dosage of saxagliptin when used concurrently with a strong inhibitor of the CYP3A4 metabolic pathway, such as ketoconazole, clarithromycin, and ritonavir. Consult the product insert for details on possible drug interactions. (4) Dosage should be reduced in patients with moderate or severe renal impairment. (5) A warning about infrequent but serious hypersensitivity reactions (anaphylaxis, Stevens-Johnson syndrome) is included in the labeling for sitagliptin, but this isn't currently in the labeling for saxagliptin. However, hypersensitivity-related events (such as urticaria and facial edema) were reported more commonly in patients taking saxagliptin than in those taking placebo.

Adverse reactions: upper respiratory tract infection, urinary tract infection, headache, peripheral edema when used in combination with a thiazolidinedione, hypersensitivity reaction (urticaria, facial edema)

Supplied as: 2.5-mg and 5-mg film-coated tablets

Dosage: 5 mg once a day

Nursing considerations: (1) Assess renal function before beginning saxagliptin therapy and periodically throughout therapy. (2) Tell patients that saxagliptin may be taken without regard to food. (3) Teach patients taking saxagliptin with a sulfonylurea how to recognize and respond to signs and symptoms of hypoglycemia. (4) As ordered, reduce the dosage to 2.5 mg/day in patients also taking a strong CYP3A4 inhibitor and in patients with moderate or severe renal impairment or end-stage renal disease. Because saxagliptin is removed by hemodialysis, administer it following hemodialysis. (5) If patients miss a dose, tell them to take it as soon as they remember, unless it's almost time for the next dose. In that case, they should take the next dose at the scheduled time, not a double dose, unless otherwise instructed by the healthcare provider. Advise them to call the healthcare provider if they have any questions about a missed dose.

DRUG FOR PSORIASIS

Ustekinumab

Help for patients with moderate or severe plaque psoriasis

A human monoclonal antibody, ustekinumab (Stelara, Centocor Ortho Biotech) is the first medication to selectively bind to interleukin (IL)-12 and IL-23. These naturally occurring proteins contribute to the psoriatic inflammatory process by activating natural killer cells and T cells. By preventing these proteins from binding with their natural receptors, the new drug decreases the autoimmune inflammatory response characteristic of psoriasis.

Although mild forms of psoriasis may respond to conservative treatment with topical medications, moderate to severe forms often require phototherapy or systemic therapy with tumor necrosis factor (TNF) inhibitors such as etanercept and adalimumab or other immunosuppressive medications. Ustekinumab is indicated for adults with moderate-to-severe plaque psoriasis who are candidates for phototherapy or systemic therapy.

Ustekinumab is given subcutaneously by a healthcare provider; in contrast, etanercept and most other medications given subcutaneously to treat psoriasis can be self-administered by patients. However, ustekinumab has a longer duration of action and is given every 12 weeks during maintenance treatment; etanercept is usually administered weekly and adalimumab every 2 weeks.

Risks and adverse reactions associated with ustekinumab are similar to those of the TNF inhibitors. Of greatest concern is the potential for serious infection. Patients with a clinically important active infection shouldn't be started on ustekinumab therapy. If a serious infection develops during therapy, treatment should be suspended until the infection is treated and resolves.

Precautions: (1) Should not be used in patients with active tuberculosis (TB). Patients with latent TB should receive antitubercular treatment before beginning ustekinumab therapy. (2) Patients shouldn't receive live vaccines during ustekinumab therapy. (3) Patients shouldn't receive bacillus Calmette-Guerin vaccinations during therapy, or for 1 year before initiating treatment or for 1 year following discontinuation of treatment because of a possible risk for disseminated infection. (4) Ustekinumab may increase the risk of malignancies, but the safety of its use in patients with a known or history of malignancy hasn't been evaluated. (5) In clinical trials, one patient developed reversible posterior leukoencephalopathy syndrome (RPLS), a potentially fatal neurologic disorder characterized by headache, confusion, vision disturbances, and seizures. Ustekinumab was discontinued, and the patient fully recovered with appropriate therapy.

Adverse reactions:nasopharyngitis, headache, upper respiratory tract infection, fatigue

Supplied as: single-use vials or prefilled syringes containing 45 mg (in 0.5 mL) or 90 mg (in 1 mL) of the drug

Dosage:For patients weighing 100 kg or less: 45 mg initially and in 4 weeks, then 45 mg every 12 weeks. For patients weighing more than 100 kg: 90 mg initially and in 4 weeks, followed by 90 mg every 12 weeks.

Nursing considerations: (1) Keep the drug refrigerated and in its original carton to protect it from light. Don't shake it. Discard any unused drug, as it contains no preservative. (2) Make sure patients have been tested for TB before beginning ustekinumab therapy. (3) Assess patients' vaccination status. Patients should have all recommended vaccinations before starting therapy. (4) Teach patients to avoid vaccinations during treatment unless approved by the healthcare provider. (5) Teach patients to recognize and report any signs or symptoms of infection, such as fever, chills, cough, or burning on urination. (6) Teach patients to immediately report signs and symptoms suggesting RPLS, such as headache, vision problems, confusion, or seizures. Therapy should be discontinued if these occur. (7) Make sure patients understand the need for follow-up visits with the healthcare provider throughout treatment.

DRUG FOR ALLERGIC CONJUNCTIVITIS

Bepotastine besilate

Aid for itchy eyes

The most common type of ocular allergy, allergic conjunctivitis, is characterized by pruritus, erythema, burning, tearing, and lid edema. Drugs used in ophthalmic formulations to treat this condition include antihistamines, antihistamine/mast cell stabilizers, corticosteroids, and the nonsteroidal anti-inflammatory drug ketorolac.

Bepotastine besilate (Bepreve, Ista) is a topically active, direct H1-receptor antagonist and an inhibitor of histamine release from mast cells. Its properties and use are similar to those for the dual-acting antihistamine/mast cell stabilizers (azelastine, epinastine, ketotifen, and olopatadine). It's indicated to treat ocular pruritus associated with allergic conjunctivitis. It hasn't been directly compared with other antihistamines and/or mast cell stabilizers, and no data suggest that it's more effective than these previously marketed medications.

Precaution: Bepotastine isn't indicated to treat contact lens-related eye irritation.

Adverse reactions: mild taste, eye irritation, headache, nasopharyngitis

Supplied as: ophthalmic solution containing the drug in a 1.5% concentration

Dosage: one drop in the affected eye or eyes twice a day

Nursing considerations: (1) Teach patients how to properly instill eye drops. Tell them not to touch the dropper tip to the eye or any other surface to avoid contaminating the medication. (2) Warn patients to remove contact lenses before instilling drops and to leave them out for at least 10 minutes afterward. The drug may be absorbed by soft contact lenses. (3) Tell patients not to wear a contact lens if the eye is red, and to consult their eye-care professional if signs and symptoms persist or worsen.

ANTIPSYCHOTIC DRUGS

Asenapine Iloperidone

Joining the already large class of atypical antipsychotic drugs, asenapine (Saphris, Schering-Plough) and iloperidone (Fanapt, Novartis) have both been approved for acute treatment of schizophrenia in adults. Asenapine has also been approved for acute treatment of manic or mixed episodes associated with bipolar I disorder in adults. It's thought that the efficacy of both drugs is mediated through a combination of antagonist activity at dopamine type 2 and serotonin type 2 receptors.

Most of the warnings and precautions associated with the use of asenapine and iloperidone are similar to those for other atypical antipsychotic drugs. The labeling for all these drugs includes a boxed warning regarding increased mortality in older adult patients with dementia-related psychosis, as well as the statement that these drugs aren't approved for the treatment of patients with dementia-related psychosis. Other shared warnings and precautions include the potential for cerebrovascular adverse reactions including stroke in older adults with dementia-related psychosis, neuroleptic malignant syndrome, tardive dyskinesia, hyperglycemia/diabetes mellitus, weight gain, orthostatic hypotension/syncope, hyperprolactinemia, seizures, cognitive and motor impairment, dysphagia, problems associated with body temperature regulation, and leukopenia, neutropenia, and agranulocytosis.

The possibility of suicide is inherent in psychiatric illness. For patient safety, these drugs should be prescribed in the smallest quantities consistent with good patient management to reduce the possibility of overdosage.

The labeling for both asenapine and iloperidone (as well as for selected other atypical antipsychotic drugs such as paliperidone and ziprasidone) includes a warning regarding prolongation of the QT interval and the risk of cardiac dysrhythmias. Use of these drugs should be avoided in patients with congenital long QT syndromes, hypokalemia and/or hypomagnesemia, or a history or cardiac dysrhythmias, as well as in patients being treated with other medications that are known to cause QT prolongation including Class IA or Class III antiarrhythmics, antipsychotic agents such as chlorpromazine, thioridazine, and ziprasidone, and antimicrobials such as moxifloxacin. See the product labeling for a complete listing.

The following discussion centers on individual considerations for each of the new drugs.

Asenapine

Sublingual medication for schizophrenia and certain bipolar episodes

Dissolving in seconds following sublingual administration, asenapine has properties most similar to those of quetiapine and olanzapine. Although the labeled indications are the acute treatment of schizophrenia and bipolar disorder, it's generally recommended that treatment be continued beyond the acute response in patients who respond well to the medication. The long-term risks and benefits for individual patients should be periodically reevaluated.

Precautions: (1) Observe the warnings and precautions identified above for atypical antipsychotics. (2) Avoid the use of asenapine in patients taking other medications known to prolong the QT interval and in those who have other risk factors for QT prolongation. (3) Not recommended for patients with severe hepatic impairment. (4) Because of the risk of sedation, dizziness, and hypotension, use cautiously with other central nervous system (CNS)-active drugs and antihypertensive medications. (5) Use cautiously with fluvoxamine and paroxetine; consult the product labeling for recommended dosage adjustments.

Adverse reactions: In patients with schizophrenia: somnolence, akathisia, oral hypoesthesia. In patients with bipolar disorder:somnolence, dizziness, extrapyramidal signs and symptoms including akathisia, weight gain.

Supplied as: 5-mg and 10-mg sublingual tablets

Dosage: In patients with schizophrenia: 5 mg twice a day. In patients with bipolar disorder: 10 mg twice a day; may be reduced to 5 mg twice a day if patient experiences adverse reactions.

Nursing considerations: (1) Instruct patients to put the tablet under the tongue and let it dissolve completely. Tell them not to chew, crush, or swallow the tablet. (2) Instruct patients to wait at least 10 minutes after drug administration to eat or drink. Eating or drinking immediately after drug administration significantly reduces the drug's bioavailability. (3) Warn patients of the risk of orthostatic hypotension and advise them to rise slowly from a seated or recumbent position. (4) Monitor patients for signs and symptoms of hyperglycemia (polydipsia, polyuria, weakness), a possible adverse reaction to antipsychotic drugs in general. (5) Instruct patients to avoid alcoholic drinks while taking asenapine because of the risk of adverse CNS reactions.

Iloperidone

Second-line oral treatment for schizophrenia

Although approved for acute treatment of schizophrenia in adults, iloperidone is considered a second-line treatment because of its ability to prolong the QT interval and the need to titrate the dosage slowly. The labeling advises prescribers to use other drugs first and to "consider the need to titrate iloperidone slowly to avoid orthostatic hypotension." Although slow titration may reduce adverse reactions, it may also delay the drug's effectiveness compared with other antipsychotic medications that don't require titration. This is a significant disadvantage for iloperidone.

Following oral administration, iloperidone is rapidly absorbed and reaches peak plasma concentrations in 2 to 4 hours.

Precautions: (1) Observe the warnings and precautions identified above for atypical antipsychotics. (2) Avoid the use of iloperidone in patients taking other medications known to prolong the QT interval and in those who have other risk factors for QT prolongation. (3) To reduce the risk of dizziness, orthostatic hypotension, and syncope, titrate the dosage over 7 days to the target maintenance dosage. (4) Reduce the dosage of iloperidone by one-half in patients also taking a strong CYP3A4 inhibitor, such as clarithromycin or ketoconazole, or CYP2D6 inhibitor such as fluoxetine or paroxetine. Consult the product insert for detailed dosage adjustment information. (5) Because of the risk of sedation, dizziness, and hypotension, use cautiously with other CNS-active drugs and antihypertensive medications.

Adverse reactions: dizziness, somnolence, tachycardia, dry mouth, weight gain, nasal congestion, fatigue, orthostatic hypotension, syncope, priapism, hyperglycemia

Supplied as: 1-mg, 2-mg, 4-mg, 6-mg, 8-mg, 10-mg, and 12-mg tablets

Dosage: initially, 1 mg twice a day with daily adjustments made to 2 mg twice a day, 4 mg twice a day, 6 mg twice a day, 8 mg twice a day, 10 mg twice a day, and 12 mg twice a day on days 2, 3, 4, 5, 6, and 7, respectively. Target maintenance range: 6 to 12 mg twice a day. Maximum recommended dosage: 12 mg twice a day.

Nursing considerations: (1) Iloperidone may be taken without regard to food. (2) Monitor patients for signs and symptoms of hyperglycemia such as polydipsia, polyuria, and weakness. (3) Warn patients about the risk of dizziness and orthostatic hypotension, and instruct them to rise slowly from a seated or recumbent position. (4) Tell patients to avoid alcoholic beverages while taking iloperidone.

ANTIBIOTIC

Telavancin HCl

A synthetic derivative of vancomycin

Classified as a lipoglycopeptide antibiotic, telavancin HCl (Vibativ, Astellas; Theravance) acts by inhibiting bacterial cell wall synthesis and also by binding to the bacterial membrane, disrupting membrane function. It's a synthetic derivative of vancomycin and has proven generally similar to vancomycin in effectiveness in clinical trials, although clinical cure rates for telavancin were lower in patients age 65 and older and in patients with a creatinine clearance of 50 mL/minute or less. Telavancin has a longer duration of action than vancomycin and is administered once every 24 hours.

Administered I.V., telavancin is indicated to treat adults with complicated skin and skin structure infections caused by susceptible isolates of certain Gram-positive bacteria, including methicillin-susceptible and -resistant isolates of Staphylococcus aureus, and vancomycin-susceptible isolates of Enterococcus faecalis. It's unlikely to be effective against enterococci or staphylococci that are resistant to vancomycin.

The labeling for the drug includes a boxed warning about possible risks to fetal development. Women of childbearing potential should have a serum pregnancy test before using the drug. If the benefits outweigh the risks for a pregnant woman, she should be enrolled in a pregnancy registry for the drug by calling 1-888-658-4228.

Precautions: (1) Avoid using in pregnant patients unless the benefit clearly outweighs the risk of adverse fetal development outcomes. (2) Telavancin may prolong the QT interval. Use caution when using it with other drugs with a similar potential, such as certain antiarrhythmic drugs and ziprasidone. (3) Avoid using telavancin in patients with congenital long QT syndromes, known prolongation of the QT interval, uncompensated heart failure, or severe left ventricular hypertrophy. (4) Assess renal function before beginning therapy, during therapy (at 48- to 72-hour intervals, as indicated), and after therapy ends. Lower dosages as directed in patients with impaired renal function.

Adverse reactions:taste disturbance, nausea, vomiting, foamy urine

Supplied as: single-use vials containing the equivalent of 250 mg and 750 mg of telavancin base (to be reconstituted and diluted before administration)

Dosage: 10 mg/kg, administered I.V. over 60 minutes every 24 hours for 7 to 14 days. In patients whose creatinine clearance is between 30 and 50 mL/minute: 7.5 mg/kg every 24 hours. In patients whose creatinine clearance is between 10 and 29 mL/minute: 10 mg/kg every 48 hours.

Nursing considerations: (1) Store vials in the refrigerator. (2) Reconstitute vial contents with 15 mL or 45 mL (depending on vial amount) of 5% dextrose injection, sterile water for injection, or 0.9% sodium chloride injection to a drug concentration of 15 mg/mL. Dilute the reconstituted solution before infusion as directed. See the product insert for complete instructions. (3) Reconstitution usually occurs in less than 2 minutes but can take up to 20 minutes. The solution should be clear, with no visible particles. (4) Following reconstitution, administer the drug within 4 hours when stored at room temperature, or within 72 hours when refrigerated. (5) Monitor renal function values during therapy. (6) Maintain the ordered infusion rate. Infusing telavancin too rapidly may cause infusion-related reactions such as "red man syndrome," which is characterized by flushing of the upper body, urticaria, pruritus, and rash. (7) Collect specimens for coagulation tests as close as possible to a patient's next dose, because telavancin may interfere with certain coagulation test results. (8) Instruct women of childbearing potential to use reliable contraception while on telavancin therapy. (9) Monitoring serum concentrations of telavancin (typically done with vancomycin) isn't considered necessary.

ANTIEPILEPTIC DRUG

Vigabatrin

Beware the risk of vision loss

Vigabatrin (Sabril, Lundbeck) is the first drug approved to treat infants and young children (age 1 month to 2 years) with infantile spasms for whom potential benefits outweigh the risk of permanent vision loss, which is the subject of a boxed warning in the labeling. Infantile spasms usually appear in the first year of life and consist of a sudden bending forward of the body accompanied by stiffening of the arms and legs. They often occur in clusters of up to 100 spasms, and infants may experience dozens of clusters and several hundred spasms a day.

Vigabatrin is also approved as adjunctive therapy to treat adults with refractory complex partial seizures who've responded inadequately to several alternative treatments and for whom benefits outweigh the risk of vision loss. Because many other antiepileptic drugs (AEDs) are available, vigabatrin isn't a first-line drug for partial seizures.

Bilateral concentric visual field constriction ranging from mild to severe occurs in 30% or more of patients taking vigabatrin. Progressive loss of peripheral vision may lead to tunnel vision and disability. In some patients, the drug may also damage the central retina, decreasing visual acuity. The onset of vision loss is unpredictable and can occur at any point in therapy.

Vigabatrin is available only through a restricted distribution program (1-888-45-SHARE). Only prescribers and pharmacies registered in the program may prescribe and dispense vigabatrin for patients who meet criteria for the drug and are enrolled in the program.

Precautions: (1) Vision should be assessed at baseline (no later than 4 weeks after starting vigabatrin) by an ophthalmic professional with expertise in visual field interpretation and the ability to perform dilated indirect ophthalmoscopy of the retina. Vision should then be assessed at least every 3 months during therapy, and 3 to 6 months following discontinuation of therapy. (2) Monitor adult patients for suicidal ideation and behavior, depression, or mood changes, risks associated with AEDs. (3) The drug decreases alanine transaminase and aspartate transaminase in most patients, which may preclude the use of these markers in detecting early hepatic injury. (4) Vigabatrin may reduce the plasma concentration of phenytoin by about 20% and increase the peak serum concentration of clonazepam by 30%.

Adverse reactions: In patients with infantile spasms:somnolence, bronchitis, vision loss, ear infection, acute otitis media. In adults with complex partial seizures:headache, somnolence, fatigue, dizziness, vision loss, convulsion, nasopharyngitis, weight gain, upper respiratory tract infection, visual field defect, nystagmus, blurred vision, diplopia, depression

Supplied as: a powder for oral solution in packets containing 500 mg of the drug (for treatment of infantile spasms); 500-mg tablets (for adults with refractory complex partial seizures)

Dosage: For infants: 50 mg/kg/day in two divided doses. The dosage can be titrated in 25 to 50 mg/kg/day increments every 3 days, to a maximum of 150 mg/kg/day. For adults: initially, 500 mg twice a day; the total daily dose may be increased in 500-mg increments at weekly intervals to the target maintenance dosage of 1,500 mg twice a day.

Botulinum toxins are neuromuscular blocking agents that, when injected into muscle, inhibit the release of the neurotransmitter acetylcholine from peripheral cholinergic nerve endings. Interruption of cholinergic transmission results in a localized reduction of muscle activity that gradually reverses over time.

AbobotulinumtoxinA (Dysport, Ipsen) joins two previously marketed botulinum toxins: botulinum toxin type A (Botox, now designated as onabotulinumtoxinA) and botulinum toxin type B (Myobloc, now designated as rimabotulinumtoxinB). AbobotulinumtoxinA hasn't been directly compared to the other two toxins in clinical studies.

Like its predecessors, abobotulinumtoxinA is indicated for adult patients with cervical dystonia (also called spasmodic torticollis), which is characterized by involuntary contractions of neck muscles, causing abnormal head position and neck pain. Reduced mobility, diminished self-esteem, social isolation, and occupational disability can severely compromise the patient's quality of life. The new drug can be given to both toxin-naive and previously treated patients.

AbobotulinumtoxinA is also approved for an esthetic/cosmetic purpose: temporary improvement of moderate-to-severe glabellar lines (such as crow's feet and frown lines) associated with procerus and corrugator muscle activity in adults younger than age 65.

The abobotulinumtoxinA formulation contains human albumin, which carries a remote risk of transmission of viral diseases and a theoretical risk of transmission of Creutzfeldt-Jakob disease (CJD). However, no transmissions of viruses or CJD have ever been reported for albumin.

Precautions: (1) The potential for remote spread of the toxin's effect from the area of injection is the subject of a boxed warning in the labeling. Swallowing and breathing difficulties can be life-threatening. Use caution in patients with underlying conditions (such as myasthenia gravis and amyotrophic lateral sclerosis) that predispose them to this adverse reaction. (2) Concurrent use with an aminoglycoside, muscle relaxant, or other drug that interferes with neuromuscular transmission may result in an increased response. (3) Use caution in patients being treated for glabellar lines who have surgical alterations to facial anatomy, excessive weakness or atrophy in target muscles, marked facial asymmetry, inflammation at the injection site, ptosis, deep dermal scarring, thick sebaceous skin, or the inability to substantially lessen glabellar lines by physically spreading them apart. The drug is less likely to be effective; raising the dosage would increase the risk of adverse reactions without a corresponding increase in effectiveness. (4) Use caution if used concurrently with medications having anticholinergic activity because of potentially excessive systemic anticholinergic effects, such as blurred vision. (5) Don't administer to patients who are allergic to milk products, because the drug formulation may contain trace amounts of cow-milk protein.

Adverse reactions:In patients treated for cervical dystonia: muscular weakness, dysphagia, dry mouth, injection-site discomfort or pain, fatigue, headache, musculoskeletal pain, eye symptoms, dysphonia

Supplied as: single-use vials containing 300 units and 500 units of drug in a lyophilized form. Store vials in the refrigerator.

Dosage: For cervical dystonia: 500 units administered I.M. as a divided dose among affected muscles. The peak effect occurs between 2 and 4 weeks. Re-treatment upon return of symptoms shouldn't occur in intervals of less than 12 weeks. The dosage may be titrated in 250-unit steps between 250 and 1,000 units, depending on patient response. For glabellar lines: 50 units divided in five equal aliquots of 10 units each injected into affected muscles. Re-treatment should occur no more frequently than every 3 months.

Nursing considerations: (1) Assess the patient for allergies, particularly to milk products, before treatment begins. (2) Reconstitute a vial containing 500 units with 1 mL of 0.9% sodium chloride injection without preservative to provide a solution of 500 units/mL. (3) Reconstitute a vial containing 300 units with 0.6 mL of 0.9% sodium chloride injection without preservative to provide a solution of 250 units/0.5 mL. (4) Vials containing 300 units of the drug should be used to treat glabellar lines. Consult the product labeling for more information regarding reconstitution and administration. (5) Gently swirl the vial to dissolve the medication. (6) Obtain a 23- or 25-gauge needle for drug administration. (7) If the solution isn't administered immediately, store it in a refrigerator and use within 4 hours. (8) Monitor patients for adverse reactions. (9) Warn patients that toxic effects have been reported hours to weeks after injection, and to seek emergency treatment if they experience any difficulty swallowing, speaking, or breathing.

ANTINEOPLASTIC DRUGS

Pazopanib HCl

Another option for advanced renal cell carcinoma

The most common type of kidney cancer, renal cell carcinoma, is curable by surgical removal of the kidney if detected in time. However, if surgery isn't appropriate or the cancer has metastasized, the prognosis is poor.

Administered orally, pazopanib HCl (Votrient, GlaxoSmithKline) is the latest drug to be marketed to treat advanced renal cell carcinoma. It's classified as a multi-tyrosine kinase inhibitor of vascular endothelial growth factor receptors as well as other growth factor receptors.

In a placebo-controlled trial, progression-free survival for patients taking pazopanib averaged 9.2 months, compared with 4.2 months for patients in the control group. It hasn't been directly compared in clinical studies to other drugs used to treat advanced renal cell carcinoma such as sunitinib and sorafenib, which have similar properties.

A serious risk of pazopanib is hepatoxicity, the subject of a boxed warning in its labeling.

Precautions: (1) Obtain liver function tests before treatment starts, at least once every 4 weeks for at least the first 4 months of treatment (or as clinically indicated), and periodically thereafter. Based on changes in liver function tests, treatment should be reduced, interrupted, or discontinued. (2) Pazopanib may prolong the QT interval. Use cautiously in patients with a history of QT interval prolongation or other risk factors, such as concurrent use of other drugs that may prolong the QT interval. (3) Some patients taking pazopanib have experienced fatal hemorrhage. The drug shouldn't be used in patients with a history of hemoptysis, cerebral hemorrhage, or clinically significant GI hemorrhage in the last 6 months. (4) Unusual but serious adverse reactions include arterial thrombotic events, GI perforation or fistula, hypertension, hypothyroidism, and proteinuria. Consult the product insert for details. (5) Because pazopanib may impair wound healing, it should be discontinued at least 7 days before scheduled surgery. (6) Avoid concurrent use with a strong CYP3A4 inhibitor such as clarithromycin, ketoconazole, and ritonavir, as well as with grapefruit juice. If one of these medications must be used, a reduction in the pazopanib dosage is recommended. (7) Avoid concurrent use of a strong CYP3A4 inducer such as rifampin, because these drugs reduce the concentration and activity of pazopanib. If chronic use of a strong CYP3A4 inducer is unavoidable, pazopanib shouldn't be prescribed. Consult the product insert for more information and precautions related to potential drug interactions.

Adverse reactions:diarrhea, hypertension, hair color changes (depigmentation), nausea, vomiting, anorexia, fatigue, increased liver function test levels, increased serum glucose levels, increased serum total bilirubin, leukopenia, neutropenia, thrombocytopenia

Supplied as: 200-mg and 400-mg tablets

Dosage: 800 mg once a day at least 1 hour before or 2 hours after a meal. See the product insert for recommended dosage adjustments for patients with hepatic impairment and for those taking a strong CYP3A4 inhibitor.

Nursing considerations: (1) Tell patients to avoid grapefruit juice, which increases the concentration and activity of pazopanib. (2) Teach patients to swallow the tablet whole and to take it at least 1 hour before or 2 hours after a meal. Crushing the tablets or taking them with food significantly increases the drug's bioavailability, increasing the risk of adverse reactions. (3) If patients miss a dose, they should skip that dose if the next dose is scheduled in less than 12 hours. (4) Emphasize the importance of regular blood tests for liver function throughout therapy, as directed by the healthcare provider. (5) Tell women of childbearing potential to use reliable contraception to prevent pregnancy. Pazopanib is classified in Pregnancy Category D, meaning it can cause fetal harm. (6) Women who are nursing should discontinue nursing or not use the drug.

Ofatumumab

New treatment for refractory leukemia in adults

Chronic lymphocytic leukemia (CLL), a slowly progressing blood and bone marrow disease, is the most common form of leukemia in adults. Approximately 15,000 new cases are diagnosed in the United States each year, according to the FDA.

Ofatumumab (Arzerra, GlaxoSmithKline) is approved for the treatment of CLL refractory to fludarabine and alemtuzumab. A human monoclonal antibody, ofatumumab binds to the CD20 antigen, which is expressed on the surface of normal B lymphocytes and on malignant B cells in patients with CLL.

Ofatumumab is administered I.V. in a 12-dose course of treatment. In clinical trials, it caused infusion reactions in 44% of patients on the first day of treatment and in 29% on the second day. These reactions include bronchospasm, dyspnea, laryngeal edema, pulmonary edema, flushing, hypertension, hypotension, syncope, cardiac ischemia/infarction, back pain, abdominal pain, pyrexia, rash, urticaria, and angioedema. To reduce risks, patients must be premedicated with acetaminophen, an antihistamine, and a corticosteroid. Therapy should be interrupted for infusion reactions of any severity.

Most patients treated with ofatumumab experience neutropenia, and 42% of patients with normal neutrophil counts at the beginning of therapy experience this response at a grade 3 or 4 level of severity. Complete blood cell (CBC) counts and platelet counts should be monitored regularly during therapy, and more frequently in patients who develop grade 3 or grade 4 cytopenias. Patients being treated with ofatumumab must also be monitored for two rare but serious complications: progressive multifocal leukoencephalopathy (PML) and small bowel obstruction. Suspect PML in any patient with new or changing neurologic signs and symptoms.

Precautions: (1) Screen patients for hepatitis B virus (HBV) infection before initiating treatment, because of the potential for HBV reactivation. (2) Don't administer live virus vaccines to patients who've recently received ofatumumab.

Adverse reactions: infusion reactions, neutropenia, pneumonia, pyrexia, cough, diarrhea, anemia, fatigue, dyspnea, rash, upper respiratory tract infection, bronchitis, nausea

Supplied as: single-use vials containing 100 mg of the drug in a 5-mL volume. Store vials in the refrigerator.

Dosage: 12 doses administered via I.V. infusion in a multiweek course of treatment as specified in the product labeling

Nursing considerations: (1) Carriers of HBV should be closely monitored for clinical or lab signs of active HBV infection during treatment and for up to 12 months following the last infusion. (2) Before each dose of ofatumumab, premedicate the patient as ordered with acetaminophen 1,000 mg, an oral or I.V. antihistamine (cetirizine 10 mg or equivalent), and an I.V. corticosteroid (prednisolone 100 mg or equivalent). The dosage of the corticosteroid shouldn't be reduced for doses 1, 2, and 9, but may be reduced for the other doses based on the parameters in the product labeling. (3) Prepare the drug for administration in polyolefin bags containing 1,000 mL of 0.9% sodium chloride injection. Consult the product labeling for specific directions. (4) Mix the diluted solution by gentle inversion, not shaking. (5) Administer the diluted solution using an I.V. pump, an inline filter provided with the product, and a polyvinyl chloride administration set. (6) Flush the I.V. line with 0.9% sodium chloride injection before and after each dose. (7) Maintain the infusion rate directed in the product labeling; never give the drug as an I.V. bolus. (8) Store drug vials and diluted drug solutions in the refrigerator. Start the infusion within 12 hours of drug preparation. (9) Monitor CBC and platelet counts throughout therapy. (10) Because of the risk of PML, monitor for and report new onset or changes in preexisting neurologic signs and symptoms. (11) Warn the patient to check with the healthcare provider before getting any vaccinations.

Pralatrexate

First drug approved for peripheral T-cell lymphoma

Classified as a non-Hodgkin lymphoma, peripheral T-cell lymphoma (PTCL) occurs in almost 10,000 patients each year in the United States. Many drugs are used to treat it off-label, but pralatrexate (Folotyn, Allos) is the first drug labeled to treat this disease. Given I.V., it's specifically indicated to treat patients with relapsed or refractory PTCL. Its approval is based on the overall response rate in clinical studies, but clinical benefit such as an improvement in progression-free survival or overall survival hasn't yet been demonstrated.

Precautions: (1) Before giving any dose of pralatrexate, the severity of mucositis shouldn't exceed grade 1, the platelet count should be at least 100,000/mm³ for the first dose and at least 50,000/mm³ for all subsequent doses, and the absolute neutrophil count should be at least 1,000/mm³. (2) During therapy, monitor CBC counts, including platelets, and severity of mucositis weekly. (3) Obtain serum chemistry test results, including hepatic and renal function tests, before the start of the first and fourth dose in each cycle of treatment. Dosage adjustment may be indicated if liver function tests are abnormal. (4) The drug hasn't been evaluated in patients with renal impairment. Use caution in patients with moderate-to-severe renal impairment. (5) The occurrence of severe adverse reactions may require a reduction in dosage, omission of a dose, or interruption of therapy. Consult the product labeling for recommendations. (6) Provide folic acid and vitamin B₁₂ supplementation before and during therapy as directed in the product labeling. (7) Advise women of childbearing potential to avoid becoming pregnant because the drug may cause fetal harm.

Adverse reactions: mucositis, thrombocytopenia, nausea, fatigue, anemia, constipation, pyrexia, edema, cough, epistaxis, vomiting, neutropenia

Supplied as: single-use vials containing the drug in a concentration of 20 mg/mL in volumes of 1 mL (20 mg) and 2 mL (40 mg). Store vials in the refrigerator.

Dosage: 30 mg/m² administered I.V. push over 3 to 5 minutes via the side port of a free-flowing 0.9% sodium chloride injection I.V. line once a week for 6 weeks in 7-week cycles until the disease worsens or unacceptable toxicity develops

Nursing considerations: (1) Don't dilute the drug before administration. (2) Tell women of childbearing potential to use reliable contraception to prevent pregnancy. Nursing mothers should discuss with the healthcare provider whether to discontinue nursing or not use the drug. (3) Teach patients about the need for folic acid and vitamin B₁₂ supplementation to reduce treatment-related mucositis and hematological toxicity.

DRUG FOR CAPS

Canakinumab

Treatment for a group of rare genetic disorders

Cryopyrin-associated periodic syndromes (CAPS) are a group of rare inherited chronic inflammatory diseases characterized, in part, by symptoms such as recurrent rash, fever/chills, joint pain, fatigue, and eye pain or redness. CAPS include three related disorders classified as autoinflammatory diseases: familial cold autoinflammatory syndrome (FCAS); Muckle-Wells syndrome (MWS); and neonatal-onset multisystem inflammatory disease (NOMID), the most severe form. The incidence of CAPS in the United States is approximately one in 1 million people.

Symptoms of FCAS are triggered by exposure to cooling temperatures. MWS is often associated with hearing loss and/or amyloidosis (an accumulation of amyloid protein in the kidneys and other organs). NOMID is characterized by major CNS complications.

Canakinumab (Ilaris, Novartis) joins rilonacept as the second drug to be approved to treat CAPS. It's indicated to treat CAPS in adults and children age 4 and older, including FCAS and MWS. Neither canakinumab nor rilonacept has been evaluated to a significant extent in patients with NOMID.

Most patients with CAPS have a genetic mutation that increases the activity of cryopyrin, a protein that regulates inflammation. Increased cryopyrin activity leads to an overproduction of IL-1 beta, resulting in an inflammatory response and signs and symptoms of CAPS. Administered subcutaneously, canakinumab neutralizes the activity of IL-1 beta by blocking its interaction with IL-1 receptors.

Because canakinumab may interfere with the immune response to infection, treatment shouldn't be initiated in patients with active infections. An increased risk of infection exists if the new drug is used concurrently with a TNF blocker, such as adalimumab or etanercept, or with the IL-1 blocker anakinra. Like other immunosuppressant drugs, canakinumab may also increase the risk of malignancies.

Like rilonacept, canakinumab is administered subcutaneously, but it's given only once every 8 weeks. In contrast, rilonacept is given once a week. Another advantage is that it's indicated for children age 4 and older; rilonacept is currently not approved for use in children under age 12.

Precautions: (1) Don't initiate treatment in patients with active infections. (2) Don't use concurrently with TNF blockers or another IL-1 blocker. (3) Don't administer live vaccines to patients taking canakinumab.

Adverse reactions:nasopharyngitis, diarrhea, influenza, rhinitis, headache, nausea, vertigo, injection-site reactions

Supplied as: single-use vials containing 180 mg of the drug in a lyophilized powder form. Store vials in the refrigerator.

Dosage:For patients weighing more than 40 kg: 150 mg every 8 weeks. For patients weighing 15 to 40 kg: 2 mg/kg every 8 weeks. Dosage may be increased to 3 mg/kg every 8 weeks in children with an inadequate response.

Nursing considerations: (1) Assess patients for active infection before starting treatment. If a patient subsequently develops a serious infection, treatment should stop. (2) Reconstitute vial contents with 1 mL of preservative-free sterile water for injection to provide a solution that contains 150 mg/mL. Slowly swirl the vial at a 45-degree angle for about 1 minute; then allow it to stand for 5 minutes. Then gently turn the vial upside down and back again 10 times and allow it to stand for about 15 minutes. (3) If the solution isn't administered within 60 minutes following reconstitution, store it in a refrigerator and give it within 4 hours. (4) Patients should receive all recommended vaccines before starting therapy with canakinumab.

SELECTED REFERENCES

Drug Facts and Comparisons. St. Louis, MO: Facts and Comparisons, Inc.; 2010.

Hussar DA. New Drugs (2005-2009) and Comparison Ratings, NDCR 2010 Edition. King of Prussia, Pa.: Moore Road Press; 2010.

Nursing2010 Drug Handbook. Ambler, PA: Lippincott Williams & Wilkins; 2010.

Physician's Desk Reference, 64th ed. Montvale, NJ: Medical Economics; 2010.