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  1. Hussar, Daniel A. PhD

Article Content

THIS ARTICLE REVIEWS 16 drugs recently approved by the FDA, including:


> two new drugs approved for idiopathic pulmonary fibrosis.


> the only first-line oral medication for Gaucher disease type 1.


> nine antineoplastic drugs.


Unless otherwise specified, the information in the following summaries applies to adults, not children. Consult a pharmacist or the package insert for information on drug safety during pregnancy and breastfeeding. Consult a pharmacist, the package insert, or a current and comprehensive drug reference for more details on precautions, drug interactions, and adverse reactions for all these drugs.



Drug Facts and Comparisons. St. Louis, MO: Facts and Comparisons, Inc.; 2015.


Nursing2015 Drug Handbook. Philadelphia, PA: Lippincott Williams & Wilkins; 2015.


Physician's Desk Reference. 69th ed. Montvale, NJ: Medical Economics; 2015.




Keeping patients on their feet

Neurogenic orthostatic hypotension (NOH) is a major manifestation of many disorders associated with chronic autonomic failure such as Parkinson disease.1 Signs and symptoms of NOH, which typically include dizziness, lightheadedness, blurred vision, fatigue, and syncope when an individual stands, may severely limit routine daily activities that require standing or walking. To date, treatment options for NOH have been limited.


Droxidopa (Northera, Lundbeck) is a synthetic amino acid prodrug of norepinephrine that's metabolized to norepinephrine by dopa-decarboxylase. The new drug is thought to exert its pharmacologic effects through norepinephrine, which increases BP by inducing peripheral arterial and venous vasoconstriction.


Droxidopa is indicated for the treatment of orthostatic dizziness, lightheadedness, or the "feeling that you are about to black out" in adults with symptomatic NOH caused by primary autonomic failure (Parkinson disease, multiple system atrophy, and pure autonomic failure), dopamine beta-hydroxylase deficiency, and nondiabetic autonomic neuropathy.2 Its effectiveness was demonstrated over a 2-week period in which patients reported a decrease in symptoms such as dizziness and feeling faint. However, the duration of the improvement in patient symptoms hasn't been demonstrated for a period longer than 2 weeks, so the continued effectiveness of the drug should be assessed periodically. The FDA has approved droxidopa under the provisions of its accelerated approval program that provides access to promising drugs while the company conducts postapproval clinical studies to demonstrate long-term improvement in patient symptoms.


The most important concern with use of droxidopa is the potential for supine hypertension and the increased risk of cardiovascular events such as stroke. The risk of supine hypertension is increased by the concurrent use of other medications that increase BP. This risk is the subject of a boxed warning in the labeling.


Precautions: (1) Monitor supine BP before and during treatment and more frequently when the dosage is increased. Reduce the risk of supine hypertension by elevating the head of the bed and measure BP with the patient in this position. If supine hypertension can't be managed by elevating the head of the bed, the dosage of droxidopa should be reduced or treatment discontinued. (2) Droxidopa may exacerbate existing ischemic heart disease, dysrhythmias, and heart failure, and the potential for these complications should be carefully considered before initiating treatment. (3) Infrequently, postmarketing reports have identified a symptom complex including hyperpyrexia and confusion that resembles neuroleptic malignant syndrome. Closely monitor patients for this possibility when the dosage of droxidopa is changed or when concomitant levodopa is reduced abruptly or discontinued, especially if the patient is receiving a neuroleptic agent. (4) The formulation of droxidopa contains FD&C Yellow No. 5 dye (tartrazine), which may cause allergic-type reactions in susceptible individuals. Tartrazine sensitivity is often experienced by patients who also have aspirin hypersensitivity. (5) Concurrent use of carbidopa, a peripheral dopa-decarboxylase inhibitor used in combination with levodopa to treat Parkinson disease, may increase the patient's exposure to droxidopa, although the clinical significance is unclear.


Adverse reactions: headache, dizziness, nausea, hypertension, fatigue


Supplied as: 100 mg, 200 mg, and 300 mg capsules


Dosage: 100 mg three times a day, upon arising in the morning, at midday, and in the late afternoon at least 3 hours before bedtime (to reduce the potential for supine hypertension during sleep). The dosage should be titrated to symptomatic response in increments of 100 mg three times daily every 24 to 48 hours up to a maximum dosage of 600 mg three times a day.


Nursing considerations: (1) Assess patients for allergies, especially to tartrazine and aspirin, before treatment begins. (2) Monitor BP before and during treatment. (3) Teach patients about the risk of supine hypertension and teach them to rest and sleep in an upper-body elevated position. Teach them how to monitor their BP and manage BP elevations. (4) Tell patients that they can take droxidopa with or without food, but they should take doses the same way each time. (5) If patients miss a dose, instruct them to take the next scheduled dose. Warn them not to double a dose. (6) Inform patients about the risk of interactions with other drugs that increase BP and with certain drugs prescribed for Parkinson disease. Tell them to check with the healthcare provider before taking other drugs, including over-the-counter products.



1. Metzler M, Duerr S, Granata R, Krismer F, Robertson D, Wenning GK. Neurogenic orthostatic hypotension: pathophysiology, evaluation, and management. J Neurol. 2013;260(9):2212-2219. [Context Link]


2. Prescribing information. Northera (droxidopa) capsules, for oral use. [Context Link]




Aiming to delay disease progression

Over 120,000 Americans have idiopathic pulmonary fibrosis (IPF), an irreversible disease caused by progressive scarring (fibrosis) of the lower respiratory tract.1,21,2 Patients experience shortness of breath, cough, and difficulty in participating in physical activities. Most patients die within 5 years of diagnosis. Treatment has included supplemental oxygen, pulmonary rehabilitation, palliative care, and lung transplant.2


Pirfenidone (Esbriet, InterMune) is one of two drugs approved by the FDA late last year to treat patients with IPF. A pyridone derivative, it's thought to act by interfering with the production of transforming growth factor-beta-stimulated collagen synthesis and tumor necrosis factor-alpha. Its effectiveness was evaluated in three placebo-controlled trials in which the decline in forced vital capacity (FVC) was significantly reduced in patients treated with pirfenidone compared with those receiving placebo. However, no significant difference in all-cause mortality between the drug and placebo groups was found.3


Precautions: (1) Photosensitivity reactions were reported by 9% of those treated with pirfenidone in the clinical studies, so patients should avoid sun exposure, sunlamps, and other drugs causing photosensitivity. (2) Some patients have experienced elevated liver enzymes. Determine baseline serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin levels before initiating therapy and monitor them monthly for the first 6 months of therapy and at least every 3 months thereafter. (3) Use caution in patients with impaired hepatic or renal function. Pirfenidone is primarily metabolized via the CYP1A2 pathway, and approximately 80% of a dose is excreted in the urine as the 5-carboxy metabolite. The new drug isn't recommended for patients with end-stage renal disease requiring dialysis. (4) The systemic exposure and action of pirfenidone may be increased by the concurrent use of a strong CYP1A2 inhibitor such as fluvoxamine or a moderate CYP1A2 inhibitor such as ciprofloxacin. Use of a strong CYP1A2 inhibitor should be discontinued before initiating treatment with pirfenidone, if possible, or the dosage of pirfenidone should be reduced. (5) Smoking is an inducer of the CYP1A2 metabolic pathway; the exposure of pirfenidone in smokers was significantly lower compared to nonsmokers.


Adverse reactions: nausea, rash, upper respiratory tract infection, fatigue, diarrhea, abdominal pain, headache, dyspepsia, dizziness, vomiting, anorexia, gastroesophageal reflux disease, sinusitis, insomnia, weight loss, arthralgia


Supplied as: 267 mg capsules


Dosage: One capsule (267 mg) three times a day on days 1 through 7, two capsules three times a day on days 8 through 14, and three capsules three times a day on days 15 and onward; this is both the maintenance dosage and the maximum recommended dosage. Consult the product insert for dosage adjustments in patients taking a strong or moderate CYP1A2 inhibitor and in those who experience adverse reactions.


Nursing considerations: (1) To minimize adverse reactions, tell patients to take doses with food and at the same times each day. (2) Instruct patients to minimize or avoid exposure to sunlight, including sunlamps, use a sun block with an SPF of at least 50, wear protective clothing, and avoid other medications that cause photosensitivity. (3) Advise smokers to discontinue smoking before treatment begins and to avoid smoking during treatment.



1. Coalition for pulmonary fibrosis. Facts about idiopathic pulmonary fibrosis. [Context Link]


2. Raghu G, Mikacenic C. Pathogenesis of idiopathic pulmonary fibrosis. UpToDate. 2015. [Context Link]


3. Prescribing information. Esbriet (pirfenidone) capsules, for oral use. [Context Link]



Slowing the decline in FVC

Nintedanib (Ofev, Boehringer Ingelheim) inhibits multiple receptor tyrosine kinases (such as vascular endothelial growth factor receptor) that have been implicated in IPF pathogenesis. In addition, it inhibits certain nonreceptor tyrosine kinases, although whether this action contributes to efficacy in the treatment of IPF isn't known. Approved for the treatment of patients with IPF, nintedanib was evaluated for effectiveness in three placebo-controlled trials in which the decline in FVC was significantly reduced in patients treated with the new drug compared with those receiving placebo. However, as with pirfenidone, no statistically significant difference in all-cause mortality between the drug and placebo groups was found.1


Precautions: (1) Because most patients experience diarrhea, this response should be treated when it first develops with adequate hydration and antidiarrheal medication such as loperamide. (2) Use nintedanib with caution in patients who've have had recent abdominal surgery. Gastrointestinal (GI) adverse reactions have included GI perforation. (3) Use caution in patients at higher risk of cardiovascular events, including those with coronary artery disease. Some patients treated with nintedanib have experienced myocardial infarction and other arterial thromboembolic events. (4) Use the new drug in patients with a known risk of bleeding (for example, patients on anticoagulant therapy) only if the anticipated benefit outweighs the risk. Some patients treated with nintedanib in the clinical studies experienced bleeding. (5) In clinical studies, 14% of patients experienced elevated liver enzymes. Determine baseline serum ALT, AST, and bilirubin values before initiating therapy and monitor them monthly for the first 3 months of therapy and at least every 3 months thereafter. (6) Not recommended for use in patients with moderate or severe hepatic impairment. Nintedanib's main route of elimination is fecal/biliary excretion and the drug's safety hasn't been established for these patients. (7) Because nintedanib may cause fetal harm if it's administered during pregnancy, it's classified in Pregnancy Category D. The drug and/or its metabolites is also likely excreted in human milk. (8) The action of nintedanib may be increased by a P-gp and CYP3A4 inhibitor such as erythromycin, and concurrent use should be closely monitored. Conversely, its action may be reduced by a P-gp and CYP3A4 inducer such as rifampin, carbamazepine, phenytoin, or St. John's wort, and concurrent use should be avoided.


Adverse reactions: diarrhea, nausea, abdominal pain, vomiting, liver enzyme elevation, headache, hypertension, decreased appetite, weight loss


Supplied as: 100 mg and 150 mg capsules


Dosage: 150 mg twice a day with food, approximately 12 hours apart. Consult the prescribing information for recommended modifications for patients who experience adverse reactions.


Nursing considerations: (1) Instruct patients to take each dose with food and to swallow capsules whole with a liquid, without chewing or crushing them. (2) Advise smokers not to smoke during treatment because this can reduce the drug's effectiveness. (3) Tell women of childbearing potential to use effective contraception during treatment and for at least 3 months after treatment ends. (4) Warn breastfeeding women that the drug may be excreted in breast milk. They should discuss whether to stop breastfeeding or discontinue the drug with their healthcare provider. (5) Patients who miss a dose should take the next dose at the scheduled time. Warn them not to double a dose or take more than 300 mg in 1 day.



1. Prescribing information Ofev (nintedanib) capsules, for oral use. [Context Link]



Eliglustat tartrate

Long-term therapy for certain adults with type 1 Gaucher disease

A rare genetic disorder, Gaucher disease is caused by a deficiency of the lysosomal enzyme glucocerebrosidase (also known as glucosylceramidase or acid beta-glucosidase), which catalyzes the conversion of the sphingolipid glucocerebroside into glucose and ceramide. A deficiency of the enzyme results in the accumulation of glucosylceramide primarily in the lysosomal compartment of macrophages, giving rise to "Gaucher cells." These cells accumulate in the liver, spleen, and bone marrow, resulting in hepatosplenomegaly, as well as skeletal disease, anemia, and thrombocytopenia. Type 1 Gaucher disease, which most commonly affects people of Ashkenazi (eastern and central European) Jewish descent, is the most common type.1


Eliglustat tartrate (Cerdelga, Genzyme) is indicated for the long-term treatment of adult patients with Gaucher disease type 1 who are CYP2D6 extensive metabolizers (EMs), intermediate metabolizers (IMs), or poor metabolizers (PMs) as determined by an FDA-cleared test.2 Like miglustat, a previously approved oral drug for type 1 Gaucher disease, eliglustat is a glucosylceramide synthase inhibitor that acts as a substrate reduction therapy. However, the new drug is the only first-line oral treatment for certain patients with Gaucher disease.


The effectiveness of eliglustat was demonstrated in a placebo-controlled study in which the primary endpoint was the percentage change in spleen volume. Compared with placebo, treatment with eliglustat resulted in a greater reduction in spleen volume, and also greater improvement in liver volume, hemoglobin concentrations, and platelet counts.


In a second study, eliglustat was compared with imiglucerase in patients who were previously treated and stabilized with imiglucerase or other enzyme replacement therapy. Imiglucerase has been the standard of treatment for type 1 Gaucher disease for approximately 20 years. Treatment with the new drug resulted in similar stabilization of hemoglobin concentration, platelet count, and spleen and liver volume as achieved with imiglucerase. This demonstrated eliglustat to be noninferior to imiglucerase.


Precautions: (1) Not recommended in patients with preexisting cardiac disease (such as heart failure, bradycardia, and ventricular dysrhythmias) and long QT syndrome, or in combination with Class IA antiarrhythmic drugs (such as quinidine and procainamide) and Class III antiarrhythmic drugs (such as amiodarone and sotalol). Eliglustat may increase PR and QT intervals and prolong QRS duration, particularly at higher concentrations. (2) Not recommended for patients with moderate to severe renal impairment or any degree of hepatic impairment because the drug hasn't been studied in these patients. (3) Because eliglustat is a CYP2D6 substrate, its activity will be influenced by the patient's CYP2D6 metabolizer status and the concurrent use of a CYP2D6 inhibitor or inducer. An FDA-cleared test for determining CYP2D6 genotype should be used to determine a patient's CYP2D6 metabolizer status. Patients who are CYP2D6 ultra-rapid metabolizers may not attain a sufficient concentration of eliglustat to achieve a therapeutic effect. A specific dosage recommendation isn't provided for patients whose CYP2D6 genotype can't be determined (indeterminate metabolizers). (4) Eliglustat is contraindicated in patients who are CYP2D6 EMs and IMs and taking certain drugs affecting CYP2D6 metabolism. Consult the prescribing information for full precautions about drug interactions and recommended treatment adjustments for these patients. (5) Concurrent use with a strong CYP3A inducer such as carbamazepine, rifampin, and St. John's wort may significantly reduce the action of eliglustat and isn't recommended. Consult the prescribing information for recommendations for patients who are also being treated with a CYP3A inhibitor.


Adverse reactions: fatigue, headache, nausea, diarrhea, back pain, pain in extremities, upper abdominal pain


Supplied as: 84 mg capsules


Dosage: 84 mg twice a day in patients who are CYP2D6 EMs or IMs, and 84 mg once a day in patients who are CYP2D6 PMs.


Nursing considerations: (1) Tell patients to swallow capsules whole with water. Warn them not to open, crush, dissolve, or chew the capsules. (2) Patients may take doses without regard to food, but instruct them to avoid grapefruit products because they inhibit the CYP3A pathway. (3) If patients miss a dose, they should skip it and take the next scheduled dose. Warn them not to take a double dose.



1. U.S. National Library of Medicine. Genetics Home Reference. Gaucher disease. 2014. [Context Link]


2. Prescribing information. Cerdelga (eliglustat) capsules, for oral use. [Context Link]



Elosulfase alfa

First drug approved for a rare pediatric disorder

Mucopolysaccharidoses comprise a group of rare genetic lysosomal storage disorders caused by the deficiency of specific lysosomal enzymes required for the catabolism of glycosaminoglycans (GAGs). Mucopolysaccharidosis Type IVA (MPS IVA, also called Morquio A syndrome) is an autosomal recessive lysosomal storage disease characterized by the absence or marked reduction in N-acetylgalactosamine-6-sulfatase activity. The deficiency of this enzyme results in the accumulation of certain GAG substrates in the lysosomal compartment of cells leading to widespread cellular, tissue, and organ dysfunction. Disease onset occurs during childhood. The most common manifestations are problems with bone development, growth, pulmonary function, and mobility. Some patients experience vision and hearing loss.1 Death often occurs in the second or third decade of life in patients with severe forms of the disease. Approximately 800 patients have been diagnosed with MPS IVA in the United States.2


Elosulfase alfa (Vimizim, BioMarin) is a purified human enzyme produced by recombinant DNA technology.3 Human N-acetylgalactosamine-6-sulfatase is a hydrolytic lysosomal GAG-specific enzyme that's taken up into lysosomes and increases the catabolism of GAGs. Administered by I.V. infusion, it's indicated for patients with MPS IVA. It's the first drug to be approved for treating patients with this disease.


The effectiveness of elosulfase alfa was evaluated in a placebo-controlled study of 176 patients ranging from age 5 to 57. The primary endpoint was the change from baseline in the distance walked in 6 minutes (6-minute walk test) at Week 24. On average, the patients treated with elosulfase alfa walked 22.5 meters farther in 6 minutes compared with patients who received placebo. One of the other endpoints included changes from baseline in the rate of stair climbing in 3 minutes. However, no difference was found in the rate of stair climbing between patients in the two groups.


Many of the patients continued in an extension trial for an additional 48 weeks. Patients who continued to receive elosulfase alfa experienced no further improvement in walking ability.


Some patients have experienced hypersensitivity reactions to the drug, including anaphylaxis. This is the subject of a boxed warning in its labeling. These reactions have occurred as early as 30 minutes from the start of an infusion but as late as 6 days after infusion.


Elosulfase alfa is classified in Pregnancy Category C and there is a registry (1-800-983-4587) that collects data on pregnant women and breastfeeding mothers who are treated with the drug. The use of elosulfase alfa in children under age 5 hasn't been evaluated.


Precautions: (1) Due to the risk of hypersensitivity reactions, appropriate medical support should be readily available when the drug is administered and patients should be closely observed for an appropriate period following administration. An antihistamine, with or without an antipyretic, should be administered before the infusion. (2) Discontinue the infusion immediately if severe signs and symptoms of hypersensitivity occur. Less severe reactions may be managed by slowing the infusion or stopping it temporarily. (3) Monitor patients with acute respiratory illness especially closely; they may be at risk for serious acute exacerbation of their respiratory compromise due to hypersensitivity reactions.


Adverse reactions: pyrexia, vomiting, headache, nausea, abdominal pain, chills, fatigue

Table Recently appro... - Click to enlarge in new windowTable Recently approved antineoplastic drugs

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


Dosage: 2 mg/kg once a week, administered over a minimum range of 3.5 to 4.5 hours based on infusion volume


Nursing considerations: (1) As prescribed, administer an antihistamine, with or without an antipyretic, 30 to 60 minutes before starting the infusion. (2) The volume of the injection needed to provide the calculated dose from the vial(s) should be withdrawn and diluted with 0.9% sodium chloride injection to a final volume of 100 mL (for patients who weigh less than 25 kg [55 lb]) or 250 mL (for patients who weigh 25 kg or more). Gently rotate (don't shake) the I.V. bag to distribute the drug. (3) Administer the diluted solution using a low-protein binding infusion set equipped with a low-protein binding 0.2 micrometer in-line filter. Consult the prescribing information for more details about drug administration. (4) Closely monitor patients for signs and symptoms of a hypersensitivity reaction during and after the infusion; for example, cough, erythema, throat tightness, urticaria, flushing, rash, and nausea and vomiting. Teach patients (or their parents) to recognize signs and symptoms of a hypersensitivity reaction and to immediately seek emergency medical attention if they occur. (5) Store drug vials in the refrigerator.



1. U.S. National Library of Medicine. Genetics Home Reference. Mucopolysaccharidosis type IV. [Context Link]


2. FDA approves Vimizim to treat rare congenital enzyme disorder. FDA news release. July 14, 2014. [Context Link]


3. Prescribing information. Vimizim (elosulfase alfa) injection, for intravenous use. [Context Link]




Indicated as an adjunct to diet

Generalized lipodystrophy is a rare disorder characterized by a lack or loss of fat (adipose) tissue. Patients with congenital generalized lipodystrophy are born with little or no adipose tissue; those with acquired generalized lipodystrophy lose adipose tissue over time. The deficiency of adipose tissue leads to hypertriglyceridemia and ectopic deposition of fat in nonadipose tissues such as liver and muscle, contributing to metabolic abnormalities, including insulin resistance. Patients may experience severe insulin resistance at a young age and develop diabetes mellitus that's difficult to control and/or markedly elevated blood triglyceride concentrations that can result in pancreatitis.1


The hormone leptin is secreted by adipocytes. It's involved in the regulation of food intake and other hormones such as insulin, and plays a major role in energy metabolism. Leptin deficiency that results from the loss of adipose tissue contributes to excess caloric intake, which exacerbates the metabolic abnormalities.


Metreleptin (Myalept, Bristol-Myers Squibb) is a recombinant human leptin analog that binds to and activates leptin receptors. Administered by subcutaneous injection, it's indicated as an adjunct to diet as replacement therapy to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy.2


Metreleptin was evaluated in a study of 48 patients with generalized lipodystrophy who also had hypertriglyceridemia, diabetes, and/or elevated concentrations of fasting insulin. Patients experienced reductions in A1c, glucose, and triglycerides within 4 months of starting treatment. Patients in the study included children as young as 1 year. The use of metreleptin hasn't been evaluated in patients with complications of partial lipodystrophy, HIV-related lipodystrophy, or liver disease, including nonalcoholic steatohepatitis.


Because of serious risks associated with metreleptin, including severe infections, it's available only through the Myalept Risk Evaluation and Mitigation Strategy program in which prescribers must receive training and certification. Pharmacists must also be certified and can dispense the drug only after receiving the appropriate authorization form for each new prescription.


Metreleptin is classified in Pregnancy Category C. Women who become pregnant during treatment are encouraged to enroll in a program that monitors outcomes in pregnant women by calling 1-855-6MYALEPT.


Precautions: (1) Metreleptin is contraindicated for patients with general obesity not associated with congenital leptin deficiency. (2) Some patients have developed antimetreleptin antibodies with neutralizing activity. These could reduce the drug's effectiveness, inhibit endogenous leptin action, worsen metabolic control, and/or lead to severe infection. Patients who experience loss of efficacy or severe infection during treatment should be tested for antimetreleptin antibodies with neutralizing activity. (3) T-cell lymphoma has been experienced by some patients with acquired generalized lipodystrophy, whether treated or not treated with metreleptin. Prescribers should carefully weigh the benefits and risks associated with metreleptin in patients with significant hematologic abnormalities and/or acquired generalized lipodystrophy. (4) Other risks associated with the use of metreleptin include hypersensitivity reactions, exacerbation of autoimmune diseases, and hypoglycemia when used concomitantly with insulin or an insulin secretagogue such as a sulfonylurea. Blood glucose concentrations should be closely monitored in patients being treated concurrently with these agents; a large reduction in dosage of insulin or an insulin secretagogue may be indicated.


Adverse reactions: headache, hypoglycemia, weight loss, abdominal pain


Supplied as: a solid, lyophilized cake in a vial that contains 11.3 mg of the drug


Dosage: The recommended initial dosage in male patients weighing more than 40 kg (88.1 lb) is 2.5 mg via subcutaneous injection once a day, and in female patients weighing more than 40 kg, 5 mg once a day. The maximum daily dose in both male and female patients is 10 mg. In male and female patients weighing less than or equal to 40 kg, the recommended initial dosage is 0.06 mg/kg once a day. Consult the product labeling for additional information.


Nursing considerations: (1) Store vials in a refrigerator. (2) Reconstitute the drug with 2.2 mL of sterile Bacteriostatic Water for Injection (BWFI) or preservative-free Water for Injection (WFI) that provides a solution containing the drug in a 5 mg/mL concentration. (3) Preservative-free WFI is recommended to reconstitute the drug for neonates and infants. When reconstituted with BWFI, the product contains benzyl alcohol that has been associated with serious adverse reactions such as "gasping syndrome," particularly in neonates and low-birth-weight infants. Gasping syndrome is characterized by central nervous system depression, metabolic acidosis, gasping respirations, and high levels of benzyl alcohol and its metabolites in blood and urine.2 (4) After reviewing the Medication Guide with patients, teach them how to reconstitute metreleptin and administer it subcutaneously in the abdomen, thigh, or back of the upper arm once a day, at the same time every day. Tell them how to rotate injection sites and warn patients who also inject other medications to use a different site for each drug. (5) Inform patients that the drug can be administered without regard to meals.



1. Food and Drug Administration. FDA approves Myalept to treat rare metabolic disease. News release. February 25, 2014. [Context Link]


2. Prescribing information. Myalept (metreleptin) for injection for subcutaneous use. [Context Link]




Treatment for a tropical illness

Leishmaniasis is caused by the parasite Leishmania species that is transmitted to humans via bites of sand flies. The disease occurs primarily in people who live in the tropics and subtropics. Patients in the United States who experience the infection usually acquired it when they were living or traveling in a tropical country.1


The three main types of leishmaniasis are cutaneous, mucosal, and visceral. Treatment options are very limited. In the United States, the treatment of choice for patients with visceral leishmaniasis is liposomal amphotericin B. Cutaneous and mucosal leishmaniasis have been treated with amphotericin B or oral azole antifungal drugs.


Administered orally, miltefosine (Impavido, Knight) was approved by the FDA in 2014, although it was previously available in other countries. It's indicated for adults and adolescents age 12 and older and weighing at least 30 kg (66 lb) for the treatment of visceral leishmaniasis caused by Leishmania donovani, cutaneous leishmaniasis caused by Leishmania braziliensis, Leishmania guyanensis, and Leishmania panamensis, and mucosal leishmaniasis caused by Leishmania braziliensis.2 It's the first drug to be approved in the United States for treatment of cutaneous and mucosal leishmaniasis.


The effectiveness of miltefosine in the treatment of patients with visceral leishmaniasis was evaluated in a study in which it was compared with amphotericin B, which is administered I.V. An initial cure was achieved in 98% of the patients treated with each of the medications. When patients were evaluated again 6 months after treatment ended, the final cure rates were 94% and 97% for miltefosine and amphotericin B, respectively.


When miltefosine was evaluated in a placebo-controlled study in patients with cutaneous leishmaniasis, 66% of those treated with the new drug experienced a cure, compared with 30% of those receiving placebo. In a study in patients with mucosal leishmaniasis, 62% of the patients experienced a complete resolution of symptoms.


The efficacy of miltefosine against species of Leishmania other than those specifically studied in the clinical trials and identified in the labeled indications hasn't been evaluated. The clinical trial results and other experience in the treatment of leishmaniasis also suggest geographic variation in the clinical response to the drug by the same species of Leishmania.


Precautions: (1) Vomiting and diarrhea, which are common adverse reactions, may result in volume depletion. Encourage fluid intake and monitor renal function weekly during therapy and for 4 weeks after therapy ends. (2) Also monitor serum transaminases, bilirubin, and platelet counts during therapy. (3) Stevens-Johnson syndrome has been infrequently reported. Treatment should be discontinued if an exfoliative or bullous rash occurs during therapy. (4) Miltefosine is contraindicated in patients with Sjogren-Larsson syndrome, which is caused by a genetic defect in fatty aldehyde dehydrogenase activity; symptoms include congenital ichthyosis and intellectual disability.3 (5) Because miltefosine may cause fetal harm, it's contraindicated during pregnancy. Obtain a urine or serum pregnancy test before initiating treatment. Women of childbearing potential should use effective contraception during therapy and for 5 months after therapy ends. (6) Whether miltefosine is excreted in breast milk is unknown. Breastfeeding women should discuss whether to discontinue nursing or not use the drug with their healthcare provider. Women shouldn't breastfeed for 5 months following completion of miltefosine therapy.


Supplied as: 50 mg capsules


Dosage: 50 mg twice a day with breakfast and dinner in patients weighing 30 kg to 44 kg (66 to 97 lb), and 50 mg three times a day with breakfast, lunch, and dinner in patients weighing 45 kg or more. The recommended course of treatment is 28 consecutive days.


Adverse reactions: nausea, vomiting, anorexia, dizziness, abdominal pain, pruritus, somnolence, diarrhea, elevated serum transaminases and creatinine, thrombocytopenia


Nursing considerations: (1) Remind patients to take the drug with food as prescribed to reduce gastrointestinal adverse reactions. (2) Encourage patients to drink plenty of fluids if they experience vomiting and/or diarrhea. (3) Instruct women of childbearing potential to use effective contraception during therapy and for 5 months after therapy ends. Warn them that vomiting and diarrhea can reduce the absorption and effectiveness of oral contraceptives. If they experience these adverse reactions, they should use additional nonhormonal or alternative methods of contraception.



1. Food and Drug Administration. FDA approves Impavido to treat tropical disease leishmaniasis. News release. March 19, 2014. [Context Link]


2. Prescribing information. Impavido (miltefosine) capsules, for oral use. [Context Link]


3. Rizzo WB. Genetics of Sjogren-Larsson syndrome. Medscape. [Context Link]