IN THIS ARTICLE, you'll learn about nine new drugs, including:

Unless otherwise specified, the information in the following summaries applies to adults, not children. Consult the package insert for information about each drug's safety during pregnancy and breast-feeding. Also consult the package insert, a pharmacist, or a comprehensive drug reference for more details on precautions, drug interactions, and adverse reactions * for all these drugs.

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The first direct renin inhibitor

The renin-angiotensin-aldosterone system (RAAS) is important in regulating blood pressure (BP). Renin, secreted by the kidney, triggers the formation of inactive angiotensin I, which is converted into angiotensin II, a potent vasoconstrictor that can increase BP but also inhibits renin release, creating a negative feedback loop. Many of the drugs used to combat hypertension have focused on inhibiting angiotensin-converting enzyme (ACE) or angiotensin II receptors.

Aliskiren hemifumarate (Tekturna, Novartis), the first antihypertensive drug that's a direct renin inhibitor, decreases plasma renin activity (PRA) and inhibits the conversion of angiotensinogen to angiotensin I. This reduction in PRA isn't dose-related and doesn't correlate with BP reductions; researchers aren't sure yet if the new drug has any clinical advantage when compared with ACE inhibitors and angiotensin II receptor blockers.

Aliskiren is indicated to treat hypertension and may be used alone or in combination with other antihypertensive drugs. The new drug's use with maximum doses of ACE inhibitors hasn't been adequately studied, and BP reductions in African-American patients were smaller than those in Asian and white patients. In combination with hydrochlorothiazide or valsartan, aliskiren produced greater reductions in BP than when given alone.

Precautions: (1) Concurrent use with atorvastatin or ketoconazole may increase aliskiren concentrations. (2) Concurrent use with furosemide may decrease furosemide concentrations. (3) Use aliskiren cautiously in patients with preexisting renal impairment who are taking other drugs that act on the RAAS because of the risk of increased serum creatinine and blood urea nitrogen concentrations. (4) Use cautiously in patients at risk for hypotension, such as patients taking diuretics, patients on a low-salt diet, and patients receiving renal dialysis.

Adverse reactions: diarrhea, cough, rash

Supplied as: film-coated oral tablets containing 150 mg and 300 mg of aliskiren base

Dosage: 150 mg/day in a consistent pattern with regard to meals. If the patient's BP isn't adequately controlled, the daily dosage may be increased to 300 mg. In studies, dosages above 300 mg/day failed to provide a clear benefit and increased the incidence of diarrhea.

Nursing considerations: (1) Tell women to stop taking aliskiren as soon as possible if they become pregnant. (2) Tell the patient to stop taking aliskiren and contact her health care provider immediately if she develops swelling of the face, extremities, lips, tongue, glottis, or larynx. (3) Because of an increased risk of hyperkalemia, monitor serum electrolytes and renal function in a patient with diabetes who's also taking an ACE inhibitor. (4) Aliskiren may increase creatine kinase and serum uric acid concentrations. Patients also taking hydrochlorothiazide may experience additive increases in uric acid concentrations. (5) Tell the patient not to take aliskiren with a high-fat meal. Because food can affect the absorption of aliskiren, she should take it in a consistent relationship with a meal (for example, before breakfast each day).

A new weapon against metastatic breast cancer

An estimated 180,000 new cases of breast cancer are diagnosed each year in the United States. Many women with metastatic breast cancer have tumors that overexpress the human epidermal growth factor receptor 2 (HER2) protein, which is associated with more aggressive disease. As many as 10,000 women die each year of metastatic HER2-positive breast cancer.

Trastuzumab, the first monoclonal antibody that selectively binds to HER2, was marketed in 1998 and was an important advance in the treatment of breast cancer. But some patients with HER2-positive breast cancers don't benefit from this drug or stop responding to it over time.

Lapatinib (Tykerb, GlaxoSmithKline) has been effective in some patients who no longer benefit from trastuzumab therapy. Trastuzumab is a large protein molecule that targets the part of the HER2 protein on the outside of the cell; lapatinib is a small molecule that enters the cell and blocks the function of HER2 and other proteins. The two drugs don't appear to promote cross-resistance. Lapatinib also has an additive effect when used in combination with capecitabine.

Lapatinib is indicated in combination with capecitabine for patients with advanced or metastatic breast cancer whose tumors overexpress HER2 and who've had previous therapy including an anthracycline such as doxorubicin, a taxane such as docetaxel, and trastuzumab.

Whether the regimen containing lapatinib prolongs survival hasn't been determined. However, the approval of the new drug represents significant progress in extending the treatment options for breast cancers refractory to previous therapies.

Lapatinib also is being evaluated in regimens for the first-line treatment of breast cancer and in the treatment of head and neck cancer. However, these aren't labeled indications for the drug yet.

Lapatinib is supplied through a restricted distribution program from specialty pharmacies.

Precautions: (1) May reduce left ventricular ejection fraction (LVEF), usually within the first 9 weeks of treatment. Evaluate the patient's LVEF before and during treatment. (2) May prolong the QT interval, so use cautiously in patients with congenital long QT syndrome, in those taking antiarrhythmics or other medications that prolong the QT interval, and in patients who've received cumulative high-dose anthracycline therapy. (3) Lapatinib is extensively metabolized, primarily via the CYP 3A4 and CYP 3A5 pathways. The drug's concentration and activity may be increased by the concurrent use of a strong CYP 3A4 inhibitor such as clarithromycin, itraconazole, or ritonavir, as well as grapefruit products, and decreased by the concurrent use of a strong CYP 3A4 inducer such as carbamazepine, dexamethasone, phenobarbital, rifampin, or St. John's wort. Avoid concomitant use of these agents with lapatinib if possible.

Adverse reactions: diarrhea; nausea; vomiting; rash; palmar-plantar erythrodysesthesia (hand-foot syndrome) characterized by redness, numbness, tingling, swelling, and discomfort of the hands and feet

Supplied as: 250-mg tablets

Dosage: 1,250 mg (five tablets) once a day on days 1 to 21 in combination with capecitabine (2,000 mg/m²/day administered orally in two doses about 12 hours apart) on days 1 to 14. This cycle is repeated every 21 days. See the prescribing information for special dosing considerations.

Nursing considerations: (1) Tell the patient to take lapatinib at least 1 hour before or 1 hour after a meal and not to divide the daily dose. She should take doses of capecitabine with food or within 30 minutes after food. (2) Tell her to call her health care provider if she experiences shortness of breath, palpitations, or fatigue, which may indicate reduced LVEF. If she has a significant reduction in LVEF, lapatinib treatment should be discontinued until LVEF recovers and she's asymptomatic. (3) Correct hypokalemia and hypomagnesemia before starting lapatinib therapy, to decrease the likelihood of QT prolongation and its complications. (4) Administer an antidiarrheal agent promptly if diarrhea occurs. Severe diarrhea that causes dehydration and electrolyte depletion may require fluid and electrolyte replacement and an interruption of lapatinib therapy. (5) Tell women of childbearing potential not to become pregnant while being treated with this drug.

Part of a quadruple regimen against H. pylori

Helicobacter pylori, a primary cause of gastric and duodenal ulcers, is found in the stomach lining or duodenum in about two-thirds of the world's population. Most people with H. pylori have no symptoms. For those who develop ulcers and related symptoms, acid suppression therapy with antacids, histamine₂-receptor antagonists, and proton pump inhibitors is usually effective, but the recurrence rate is high. Regimens that combine an acid-suppressing drug and antibiotics targeting H. pylori are highly effective and associated with a low ulcer recurrence rate.

The most widely used combination regimens are omeprazole, amoxicillin, and clarithromycin (OAC) and lansoprazole, amoxicillin, and clarithromycin (available as PrevPac). However, resistance to clarithromycin is increasing.

Bismuth subcitrate potassium, also known as biskalcitrate, is a soluble, complex bismuth salt of citric acid that has been approved for use in a combination formulation (Pylera, Axcan) with metronidazole and tetracycline. The product, combined with omeprazole, is indicated to treat H. pylori infection and duodenal ulcer disease (active or a history of disease within 5 years). The quadruple regimen is at least as effective as the OAC regimen, with eradication rates of 88% and 83%, respectively, in one study. The quadruple regimen has also been effective in some patients in whom clarithromycin-containing regimens haven't worked.

Because the Pylera regimen is administered four times a day, it's less convenient than the OAC regimen, which is administered twice a day. However, the recommended 10-day duration of treatment with Pylera is shorter than the 14-day course of treatment recommended for some other regimens.

Precautions: (1) Because bismuth absorbs X-rays, the new product may interfere with X-ray diagnostic tests of the gastrointestinal tract. (2) Take appropriate precautions when using the new product in combination with other drugs; for example, photosensitivity reactions are a risk with tetracycline, and patients should avoid alcohol if taking metronidazole. See the package insert for more details.

Adverse reactions: stool abnormality (black stool attributable to bismuth), diarrhea, abdominal pain, dyspepsia, nausea, headache, taste perversion, neurotoxicity

Supplied as: capsules containing 125 mg of tetracycline in an inner capsule and a blend of 140 mg of bismuth subcitrate potassium and 125 mg of metronidazole in the outer area of the larger capsule

Dosage: three capsules four times a day after meals and at bedtime for 10 days. The patient also should take 20 mg of omeprazole separately, twice a day after the morning and evening meals for 10 days.

Nursing considerations: (1) Tell the patient to swallow the capsules whole with a full glass of water. (2) Tell him that bismuth may darken his tongue and stool, but this is temporary and harmless.

First patch for Parkinson's disease

The first transdermal (patch) system approved for the treatment of Parkinson's disease, rotigotine (Neupro, Schwarz Pharma) is similar to pramipexole (Mirapex) and ropinirole (Requip). Like those two drugs, rotigotine is a nonergoline dopamine agonist that appears to act primarily to stimulate dopamine (D2) receptors in the brain. However, rotigotine is applied once a day, a more convenient regimen than pramipexole and ropinirole, which are taken orally three times a day.

Rotigotine is indicated to treat early-stage idiopathic Parkinson's disease, a progressive disorder characterized by tremors, rigidity, bradykinesia, and posture instability. Rotigotine's effectiveness was demonstrated in placebo-controlled studies in patients who weren't receiving concomitant levodopa therapy. In those studies, the new drug reduced the severity of signs and symptoms associated with activities of daily living and motor function.

Although rotigotine hasn't been directly compared with pramipexole or ropinirole, the patch formulation may overcome the peaks and valleys in drug concentrations that occur with orally administered anti-Parkinson's drugs. Because of its gradual release from the patch, rotigotine may vary less in serum concentration and have a more consistent effect.

Some patients taking other anti-Parkinson's drugs have experienced symptoms resembling neuroleptic malignant syndrome when those drugs were abruptly discontinued or the dosage was rapidly reduced. Whether rotigotine can cause this complication isn't known.

Rotigotine is being studied for the treatment of advanced Parkinson's disease in conjunction with levodopa and for restless legs syndrome, but these aren't labeled indications.

Precautions: (1) Some patients have fallen asleep suddenly (sleep attacks) while engaged in normal activities such as driving, talking, or eating. (2) The action of rotigotine may be reduced by the concurrent use of a dopamine antagonist such as an antipsychotic drug or metoclopramide. (3) The sodium metabisulfite in the patch may cause allergic reactions, including anaphylactic or asthmatic reactions in susceptible people. (4) Because the backing layer contains aluminum, the patch should be removed before the patient has magnetic resonance imaging or electrical cardioversion to avoid skin burns.

Adverse reactions: nausea; somnolence; dizziness; headache; vomiting; application-site reactions including erythema, edema, and pruritus; insomnia; hallucinations; symptomatic hypotension and syncope; elevation of heart rate and BP; weight gain and fluid retention; and compulsive behaviors, such as the urge to gamble, increased sexual urges, and repeating meaningless actions

Supplied as: transdermal patches that deliver about 2 mg, 4 mg, or 6 mg of rotigotine over 24 hours.

Dosage: initially, 2 mg/24 hours, increased weekly by 2 mg/24 hours to the maximum dosage of 6 mg/24 hours, based on patient response and tolerance

Nursing considerations: (1) Before initiating therapy, assess the patient for previous reactions to sulfites. Sensitivity to sulfites is more common in patients with asthma. (2) Teach the patient to apply the patch to clean, dry, unbroken, healthy skin on the abdomen, thigh, hip, flank, shoulder, or upper arm. He should press the patch firmly in place for 20 to 30 seconds. Tell him not to apply it to skin folds, under a waistband, or on areas that could be rubbed by tight clothing. (3) Warn him about sleep attacks and tell him not to drive or engage in other potentially hazardous activity until he learns how the drug affects him. Also tell him not to take other sedating medications or drink alcohol while using the patch. (4) Teach him to apply the patch at about the same time every day and rotate the application site daily. Instruct him not to apply creams, lotions, or other topical products on the patch application site and tell him not to use the same site more than once every 14 days. (5) Remind him to avoid dislodging the patch while showering, bathing, or during physical activity. Also warn him not to expose the patch to sources of direct heat, such as heating pads, electric blankets, heat lamps, saunas, hot tubs, and prolonged direct sunlight. (6) Show him how to remove and dispose of the patch by folding it over so that it sticks to itself. (7) Tell the patient not to discontinue therapy abruptly. (8) If the patch causes a skin rash or irritation, tell the patient to avoid direct sunlight on the area until the skin heals and not to apply a patch to the irritated area.

New oral treatment for a life-threatening disorder

Pulmonary arterial hypertension (PAH) is a rare, life-threatening condition involving restricted blood flow to the lungs caused by constriction of smooth muscle in the pulmonary vascular system. Signs and symptoms include shortness of breath, fatigue, chest pain, dizziness, and fainting. Over time, the overloaded right ventricle is damaged, leading to heart failure. Without treatment, patients may die within 3 years.

An estimated 100,000 Americans have PAH. The disorder may be primary (not associated with other clinical disorders) or secondary (developing as a complication of conditions such as scleroderma and lupus or mixed connective tissue disorders or the use of appetite suppressants).

Ambrisentan (Letairis, Gilead Sciences) is an endothelin receptor antagonist similar to bosentan (Tracleer), one of various drugs that have been approved for PAH. Like that drug, ambrisentan is given orally. However, the new drug has a longer duration of action and is given only once a day; bosentan is given twice a day.

Ambrisentan exhibits a high selectivity for certain peptide hormone receptor subtypes called ET_A receptors, which help mediate vascular smooth muscle function. This drug appears to have greater selectivity for these receptors than bosentan, but the clinical implications are unclear. Ambrisentan and bosentan haven't been directly compared in clinical trials.

A designated orphan drug, ambrisentan is indicated for the treatment of PAH (World Health Organization Group 1) in patients with class II or III symptoms to improve exercise capacity and delay clinical worsening. This indication is similar to that for bosentan, although indications for bosentan also include patients in class IV, who have severe symptoms even at rest.

In studies, ambrisentan provided a significant improvement in the 6-minute walk distance, typically after 4 weeks of treatment. The drug also significantly delayed time to clinical worsening. In a 1-year follow-up, 95% of patients in two key studies were still alive.

Results of an uncontrolled study of patients with PAH who'd discontinued bosentan or an investigational endothelin receptor antagonist because of aminotransferase elevations suggest that ambrisentan may be an appropriate option in patients who've experienced asymptomatic aminotransferase elevations while using bosentan.

Ambrisentan's potential for teratogenicity and liver damage are the subject of black-box warnings in the product labeling. It's available only through a restricted distribution program.

Precautions: (1) Classified in Pregnancy Category X, ambrisentan is contraindicated in pregnant women. (2) Ambrisentan isn't recommended in patients with elevated aminotransferases (greater than three times the upper normal limit) at baseline because this makes monitoring liver injury more difficult. Ambrisentan also isn't recommended for patients with moderate or severe hepatic impairment. (3) Ambrisentan concentrations may be increased by the concurrent use of strong CYP 3A4 inhibitors (such as clarithromycin and ketoconazole), strong CYP 2C19 inhibitors (such as omeprazole), and strong P-glycoprotein (P-gp) inhibitors (such as cyclosporine). (4) Ambrisentan's action may be decreased by the concurrent use of inducers of CYP 3A4, CYP 2C19, P-gp, and uridine 5'-diphosphate glucuronosyltransferases.

Adverse reactions: peripheral edema, headache, nasal congestion, palpitations, flushing

Supplied as: 5-mg and 10-mg film-coated tablets

Dosage: 5 mg once a day, increasing to 10 mg once a day if well tolerated

Nursing considerations: (1) Tell the patient not to split, crush, or chew the tablets. (2) Before starting treatment, make sure a female patient isn't pregnant. Instruct a woman of childbearing potential to use at least two reliable methods of contraception during therapy. (Women who have a Copper T 380A or LNg 20 intrauterine device need no additional contraception.) Pregnancy tests should be performed monthly. (3) Before starting treatment and monthly during treatment, obtain serum aminotransferase concentrations (and bilirubin if aminotransferase concentrations are elevated). (4) Discontinue treatment if aminotransferase elevations are accompanied by symptoms of liver injury (anorexia, nausea, vomiting, fever, malaise, fatigue, right upper quadrant abdominal discomfort, pruritus, jaundice) or increases in bilirubin greater than twice the upper limit of normal. (5) Like bosentan, ambrisentan may cause a transient decrease in hemoglobin concentration and hematocrit. Obtain a hemoglobin level before initiating treatment, at 1 month following initiation of treatment, and periodically thereafter.

New treatment for schizophrenia

Paliperidone (Invega, Janssen) is the major active metabolite of risperidone; both drugs are designated chemically as benzisoxazole derivatives, and both are classified as atypical antipsychotic drugs. They're thought to exhibit antipsychotic activity through a combination of central dopamine type 2 and serotonin type 2 antagonism. Like its parent compound, paliperidone also is an alpha-adrenergic receptor antagonist and a histamine₁-receptor antagonist.

Paliperidone is approved for both acute and maintenance treatment of schizophrenia. In a long-term efficacy study, paliperidone was shown to delay the time to relapse of symptoms.

Paliperidone hasn't been directly compared with risperidone in clinical studies, but it's unlikely to be more effective than its parent compound. Unlike risperidone, paliperidone isn't indicated as monotherapy or in combination regimens for the short-term treatment of acute manic or mixed episodes associated with bipolar I disorder, nor is it indicated for treating irritability associated with autistic disorder in children and adolescents ages 5 to 18.

Also unlike the labeling for risperidone, paliperidone's labeling notes that it may prolong the QT interval and increase the risk of cardiac dysrhythmias. A boxed warning states that older adults with dementia-related psychosis are at increased risk for death if they take paliperidone.

Precautions: (1) Not approved for treatment of patients with dementia-related psychosis. (2) Because of the risk of suicide inherent in psychotic illnesses, the drug should be prescribed in the smallest effective quantities to reduce the possibility of overdose. (3) Avoid using paliperidone in patients with long QT syndrome or a history of cardiac dysrhythmias and in patients taking medications known to cause QT prolongation (such as procainamide, quinidine, amiodarone, sotalol, chlorpromazine, thioridazine, and moxifloxacin. (4) Because the inert components of the tablet are eliminated in the stool in the tablet shell, paliperidone shouldn't be used in patients with preexisting severe gastrointestinal tract narrowing, such as esophageal motility disorders, or inflammatory bowel disease. (5) A dopamine antagonist, paliperidone may reduce the action of levodopa and other dopamine agonists. (6) Paliperidone's alpha-adrenergic blocking activity may cause orthostatic hypotension, so use cautiously in patients also taking other drugs that may decrease BP, such as antihypertensive agents and other alpha-blockers such as tamsulosin. (7) Use cautiously in patients taking other medications with central nervous system (CNS) depressant activity because of the risk of excessive CNS depression. (8) Reduce the dosage for patients with moderate to severe renal impairment. Dosage adjustments aren't necessary in patients with mild or moderate hepatic impairment; paliperidone use hasn't been evaluated in patients with severe hepatic impairment.

Adverse reactions: tachycardia, headache, somnolence, weight gain, QT interval prolongation, akathisia, extrapyramidal disorders, neuroleptic malignant syndrome, hyperglycemia or diabetes, stroke, orthostatic hypotension/syncope, seizures, cognitive and motor impairment, dysphagia, priapism, thrombotic thrombocytopenic purpura, problems associated with disruption of body temperature regulation, galactorrhea, amenorrhea, gynecomastia, and impotence

Supplied as: 3-mg, 6-mg, and 9-mg extended-release tablets

Dosage: Initially, 6 mg once a day in the morning with liquid; may be increased in 3-mg increments (following intervals of over 5 days) to a maximum of 12 mg/day. For patients with moderate to severe renal impairment, the maximum recommended dosage is 3 mg/day.

Nursing considerations: (1) Warn the patient about the drug's potential for sedation and orthostatic hypotension. Tell him not to drink alcohol or take other sedating products while being treated with paliperidone and advise him to avoid activities requiring alertness until he determines how the drug affects him. (2) Because food may increase the bioavailability of paliperidone, tell him to take the drug consistently with or without food each day. (3) Tell him to swallow the tablet whole, without chewing, dividing, or crushing it. Also tell him not to be concerned if he sees the tablet shell in his stool. (4) Be aware that patients with psychotic illness are at risk for suicide.

First drug for a rare blood disorder

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder that can lead to disability and premature death. An estimated 5,000 Americans are affected, with the average age of onset in the early 30s.

Patients with PNH have a genetic mutation that leads to the development of abnormal red blood cells (RBCs) that are deficient in terminal complement inhibitors, making them vulnerable to destruction. Patients with PNH experience persistent hemolysis, leading to anemia, hemoglobinuria, fatigue, debilitating weakness, shortness of breath, gastrointestinal symptoms, blood clots, and increased risk of stroke and myocardial infarction. Treatment includes periodic blood transfusions and immunosuppressive therapy, but about 50% of patients die within 15 years of diagnosis.

Eculizumab (Soliris, Alexion), a designated orphan drug, is a recombinant humanized monoclonal antibody that prevents generation of terminal complement and inhibits terminal complement-mediated intravascular hemolysis. The first drug to be approved for treating PNH, it's administered via intravenous (I.V.) infusion. Although it doesn't cure PNH, eculizumab reduces the destruction of RBCs and related complications. In a placebo-controlled study of 87 patients, those treated with eculizumab needed significantly fewer blood transfusions and reported less fatigue and better quality of life.

Eculizumab is available through a restricted distribution system.

Precautions: (1) Because it inhibits the immune system, eculizumab increases the risk of infection, particularly meningococcal infections such as septicemia and meningitis caused by Neisseria meningitidis. This is the subject of a black-box warning in the drug's labeling. (2) Eculizumab is contraindicated in patients with unresolved serious N. meningitidis infection and in patients who aren't vaccinated against N. meningitidis. (3) Use cautiously in patients with any systemic infection.

Adverse reactions: headache, nasopharyngitis, back pain, nausea, fatigue, hypersensitivity, or other infusion-related reactions

Supplied as: single-use vials containing 300 mg of the drug (30 mL of a 10-mg/mL solution)

Dosage: 600 mg every 7 days for the first 4 weeks, followed by 900 mg for the fifth dose 7 days later, then 900 mg every 14 days thereafter

Nursing considerations: (1) The drug must be diluted to a final admixture concentration of 5 mg/mL in a final admixed infusion volume of 120 mL for a 600-mg dose and 180 mL for a 900-mg dose. See the prescribing information for details. (2) Before administering a dose, let the admixture come to room temperature. Administer it as an I.V. infusion over 35 minutes, never I.V. bolus. Monitor the patient for at least 1 hour after completing an infusion for signs and symptoms of an infusion reaction. (3) If the patient hasn't had a meningococcal vaccination, make sure he's vaccinated at least 2 weeks before starting therapy and revaccinated according to current guidelines. Teach him that vaccination isn't always effective and monitor him for signs and symptoms of meningococcal infection. (4) Store vials in a refrigerator, protected from light. (5) During therapy, monitor serum lactate dehydrogenase (LDH) concentrations. These concentrations increase during hemolysis, so monitoring LDH can help you assess the patient's response to treatment and the potential for complications if treatment is discontinued. (6) Closely monitor the patient for at least 8 weeks after therapy stops. He may be at increased risk for serious hemolysis when treatment is discontinued.

Ointment with a new drug that tames impetigo

Impetigo is a highly contagious infection of the top layers of the skin, usually caused by Staphylococcus aureus or Streptococcus pyogenes. Most common in infants and children up to age 6, impetigo spreads easily in child care settings, schools, and other places where people are in close contact. When localized and involving limited areas of skin, impetigo is usually treated topically with mupirocin (Bactroban) ointment; more extensive lesions are usually treated with an oral antibiotic such as cephalexin.

Retapamulin (Altabax, GlaxoSmithKline), a semisynthetic derivative that inhibits bacterial protein synthesis, is the first of a new class of antibacterial drugs called pleuromutilins. It's active against S. aureus and S. pyogenes, and possibly other strains of staphylococci and streptococci that are resistant to other drugs, although this hasn't been evaluated in clinical studies. Cross-resistance with other classes of antibacterial drugs hasn't been reported.

Retapamulin is indicated for adults and children age 9 months and older. It can be applied on skin surface areas of 100 cm² or less in adults and up to 2% total body surface area in children to treat impetigo caused by S. aureus (methicillin-susceptible isolates only) or S. pyogenes. In a clinical study, retapamulin was 86% effective, compared with 52% for placebo. The drug hasn't been compared with mupirocin ointment.

Because retapamulin is applied twice a day for 5 days, patients may find it more convenient than mupirocin, which usually is applied three times a day for at least 8 days. However, unlike retapamulin, mupirocin is active against methicillin-resistant isolates of S. aureus. Also, mupirocin is available in other formulations (including a cream and nasal spray) for additional indications for which retapamulin hasn't been evaluated.

Precautions: (1) Not for systemic or mucosal use. (2) May cause microbial overgrowth.

Adverse reactions: application-site irritation, headache, pruritus, diarrhea, nasopharyngitis

Supplied as: 5-gram, 10-gram, and 15-gram tubes of ointment containing the drug in a 1% concentration (10 mg/gram)

Dosage: Apply a thin layer of ointment to the affected area twice a day for 5 days.

Nursing considerations: (1) Discontinue use of retapamulin if the patient experiences severe local irritation or sensitization. (2) Cover the treated area with a sterile bandage or gauze dressing to protect it and to avoid accidental transfer of ointment to the eyes or other areas. (3) Tell the patient (or her parents) to contact the health care provider if symptoms don't improve within 4 days of starting treatment.

Once-a-day medication for children as young as 6

Lisdexamfetamine dimesylate (Vyvanse, Shire) is indicated for treatment of attention-deficit hyperactivity disorder (ADHD) in children ages 6 to 12. Children with ADHD are abnormally hyperactive, inattentive, and impulsive; the cause of the disorder isn't fully understood. A prodrug of dextroamphetamine, lisdexamfetamine is rapidly absorbed and converted to dextroamphetamine after oral administration. A sympathomimetic amine with CNS stimulant activity, dextroamphetamine is thought to block the reuptake of norepinephrine and dopamine.

Lisdexamfetamine hasn't been studied in children under age 6, although some other amphetamine products are indicated for use in children as young as 3. Although not approved for use in adolescents and adults, the drug is being evaluated for older patients and is likely to be prescribed for adolescents and adults with ADHD.

The gradual conversion of lisdexamfetamine to dextroamphetamine means the new drug has a long duration of action and can be given once a day. Lisdexamfetamine is intended for use as part of a total treatment program for ADHD that may also include psychological, educational, and social measures.

Precautions: (1) Contraindicated in patients with advanced arteriosclerosis, symptomatic cardiovascular disease, and moderate to severe hypertension. Patients are at increased risk for sudden death if they have underlying serious heart problems or defects. (2) Contraindicated in patients with hyperthyroidism, glaucoma, a history of drug abuse, or in an agitated state. (3) Lisdexamfetamine increases the risk of serious psychiatric problems, such as hearing voices, becoming suspicious for no reason, and manic behavior, even in patients with no history of psychiatric problems. (4) Because of the risk of hypertensive crisis, concurrent use with a monoamine oxidase inhibitor (MAOI), or use within 14 days of taking an MAOI, is contraindicated. (5) Amphetamines may increase the action of other sympathomimetic agents, tricyclic antidepressants, meperidine, and propoxyphene. (6) Amphetamines may reduce the action of antihypertensive agents, adrenergic blockers, and the sedative action of sedating antihistamines such as diphenhydramine. (7) Amphetamine activity may be reduced by the concurrent use of haloperidol, lithium carbonate, chlorpromazine, and urinary acidifying agents. (8) Children treated with stimulant medications for an extended time may experience lesser increases in height and weight. (9) Lisdexamfetamine has the potential to lower the seizure threshold and exacerbate phonic tics and symptoms of Tourette's syndrome. (10) The drug is a Schedule II controlled substance because of its potential for dependence.

Adverse reactions: decreased appetite, insomnia, upper abdominal pain, irritability, vomiting, decreased weight, nausea, dizziness, dry mouth

Supplied as: 30-mg, 50-mg, and 70-mg capsules

Dosage: 30 mg once a day in the morning. May be increased at weekly intervals in increments of 20 mg/day to a maximum recommended dosage of 70 mg/day

Nursing considerations: (1) Teach the parents to have the patient swallow the capsules whole or dissolve the capsule's contents in a glass of water and have him drink it immediately. Lisdexamfetamine may be taken without regard to food, although a high-fat meal may increase the time needed to reach peak concentration. (2) Administer doses in the morning; afternoon doses may increase the possibility of insomnia.

(3) Tell the patient (or his parents) to seek medical attention if he experiences chest pain, unexplained syncope, or other cardiac symptoms. (4) Teach parents to monitor the patient for psychiatric adverse events such as auditory hallucinations, delusional thinking, or mania and to notify the health care provider if these occur. (5) Monitor a child's height and weight. If he isn't growing or gaining weight as expected, the prescriber may interrupt treatment. (6) Because lisdexamfetamine is a CNS stimulant, caution patients about engaging in potentially hazardous activities.

Drug Facts and Comparisons. Facts and Comparisons, Inc., 2008.

Nursing2008 Drug Handbook. Lippincott Williams & Wilkins, 2008.

Physicians' Desk Reference, 62nd edition. Medical Economics, 2008.

^*Common adverse reactions are italicized throughout this article. [Context Link]