chemical structure of granisetron
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Granisetron

Granisetron is a serotonin 5-HT3 receptor antagonist used to treat nausea and vomiting following chemotherapy. Its main affect is to reduce the activity of the vagus nerve, which is a nerve that activates the vomiting center in the medulla oblongata. It does not have much effect on vomiting due to motion sickness. This drug does not have any effect on dopamine receptors or muscarinic receptors. more...

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Granisetron was invented by chemists working at the British drug company Beecham around 1988 and is expected to go generic in 2007/2008. It is produced by Roche Laboratories under the trade name Kytril®. The drug was approved in the United Kingdom in 1991 and in United States in 1994 by the FDA.

Granisetron breaks down slowly, staying in the body for a long time. One dose usually lasts 4 to 9 hours and is usually administered once or twice daily. This drug is removed from the body by the liver and kidneys.

Clinical Uses

  • Chemotherapy-induced nausea and vomiting
    • 5-HT3 receptor antagonists are the primary drugs used to treat and prevent chemotherapy-induced nausea and vomiting. Many times they are given intravenously about 30 minutes before beginning therapy.
  • Post-operative and post-radiation nausea and vomiting
  • Is a possible therapy for nausea and vomiting due to acute or chronic medical illness or acute gastroenteritis
  • Treatment of Cyclic vomiting syndrome although there are no formal trials to confirm efficacy.

Adverse Effects

Granisetron is a well-tolerated drug with few side effects. Headache, dizziness, and constipations are the most commonly reported side effects associated with its use. There have been no significant drug interactions reported with this drug's use. It is broken down by the liver's cytochrome P450 system and it has little effect on the metabolism of other drugs broken down by this system.

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new DRUGS04: PART III
From Nursing, 9/1/04 by Hussar, Daniel A

IN THIS ARTICLE, you'll learn about 10 new drugs, including:

* omalizumab, the first monoclonal antibody for severe allergy-related asthma

* aprepitant and palonosetron HCl, antiemetic drugs indicated for delayed nausea and vomiting related to chemotherapy

* alfuzosin HCl, an alpha-blocker for treating benign prostatic hyperplasia that's less likely to cause hypotension.

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.

Drug for psoriasis

Efalizumab

Immunosuppressive treatment for moderate to severe plaque psoriasis

Efalizumab (Raptiva; Genentech, Xoma) is an immunosuppressive recombinant monoclonal antibody indicated to treat patients with chronic moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. This drug joins alefacept (see "New Drugs04, Part I," in the February issue of Nursing2004) as the first biologic therapies marketed for psoriasis. Biologic therapies stimulate or restore the immune systems ability to fight disease.

Alefacept and efalizumab may help a patient who hasn't responded to other psoriasis treatments. If she doesn't respond well to one of the new drugs, she may respond to the other.

Unlike alefacept, which is administered intramuscularly, efalizumab is given subcutaneously (S.C.). The patient can more easily learn to self-administer it, giving it an advantage over alefacept.

Precautions: (1) Contraindicated in patients with chronic infections or a history of recurrent infection. Discontinue the drug if the patient develops a serious infection. (2) Use with caution in patients with a history of cancer and those at high risk for cancer. Discontinue efalizumab if the patient develops cancer during treatment. (3) Don't use concomitantly with other immunosuppressive drugs or phototherapy. (4) Don't administer acellular, live, or liveattenuated vaccines during efalizumab treatment. (5) Discontinue treatment if the patient experiences a hypersensitivity reaction.

Adverse reactions: headache, chills, fever, nausea, myalgia, thrombocytopenia, hypersensitivity reactions, worsening of psoriasis

Supplied as: single-use vials of 150 mg of the drug as a lyophilized powder, designed to deliver 125 mg of efalizumab in 1.25 ml

Dosage: 0.7 mg/kg, followed by weekly doses of 1 mg/kg, with a maximum single dose of 200 mg

Nursing considerations: (1) Reconstitute efalizumab with 1.3 ml of sterile water for injection (supplied with the kit) for a concentration of 125 mg/1.25 ml. (2) Swirl the vial gently while reconstituting the drug. Don't shake the vial or the solution may foam. (3) Give the drug immediately after reconstitution or store it at room temperature and use it within 8 hours. (4) Store vials of the unreconstituted drug in their cartons to protect them from light and keep them in the refrigerator. (5) Teach the patient and her caregivers how to prepare, inject, and store the drug. Show them how to rotate injection sites among the thighs, abdomen, buttocks, and upper arms. (6) Monitor her platelet counts monthly when therapy begins and every 3 months throughout treatment. (7) Tell her that she may not experience significant therapeutic benefits until she's been taking the drug for at least 6 weeks. (8) Tell her to seek immediate medical attention if she experiences easy bleeding from the gums, bruising, or petechiae.

Drug for asthma

Omalizumab

First biologic for severe allergy-triggered asthma

About 17 million Americans have asthma, and 60% of them have asthma with an allergic component (for example, allergy to animal dander or dust mites). Omalizumab (Xolair; Genentech, Novartis) is the first biologic therapy approved to treat allergy-related asthma.

A recombinant humanized monoclonal antibody, omalizumab selectively binds to immunoglobulin E (IgE), preventing it from binding to receptors on the mast cells and basophils involved in the allergic response. Given S.C., omalizumab is indicated for adults and children over age 12 with moderate to severe persistent asthma triggered by a perennial aeroallergen whose symptoms aren't adequately controlled with inhaled corticosteroids.

Because of its cost (about 510,000 per year), omalizumab is being supplied through a restricted distribution program.

Precaution: This drug isn't indicated for acute asthma exacerbations and shouldn't be used to treat acute bronchospasm or status asthmaticus.

Adverse reactions: injectionsite reaction, viral injections, upper respiratory tract infection, sinusitis, headache, pharyngitis; rarely, anaphylaxis, malignancies

Supplied as: single-use vials of lyophilized powder containing 202.5 mg of omalizumab

Dosage: 150 to 375 mg given S.C. every 2 or 4 weeks, depending on serum IgE concentration and body weight. See the package insert for dosage recommendations based on these parameters.

Nursing considerations: (1) Reconstitute the drug with 1.4 ml of sterile water for injection, for a concentration of 150 mg in 1.2 ml. (2) During reconstitution, keep the vial upright and swirl it for 1 minute to evenly wet the powder, then swirl the vial for 5 to 10 seconds every 5 minutes until the powder dissolves. (This may take more than 20 minutes.) Don't shake the vial.

(3) Administer the dose within 4 hours if the vial is stored at room temperature or within 8 hours if the vial is stored in a refrigerator. (4) Omalizumab solution is slightly viscous and may take 5 to 10 seconds to administer. (5) Divide doses of more than 150 mg between injection sites and don't inject more than 150 mg into any one site. (6) Discard any unused drug. (7) Teach the patient to take other asthma medications as prescribed. Warn him not to reduce the dose of or stop taking any asthma medication (especially a systemic or inhaled corticosteroid) except as instructed by his prescriber.

Antiemetic drugs

Aprepitant, Palonosetron HCl

Two new treatments for delayed nausea and vomiting associated with chemotherapy

Nausea and vomiting, common adverse reactions to chemotherapy, may be acute or delayed (24 hours or longer after chemotherapy). Cisplatin and doxorubicin are commonly used antineoplastic drugs associated with delayed emesis. If nausea and vomiting aren't prevented or controlled, patients may experience anticipatory nausea and vomiting before subsequent doses of chemotherapy. Some patients become so ill that they refuse to continue cancer therapy.

Aprepitant and palonosetron are the first drugs approved to prevent delayed nausea and vomiting associated with cancer chemotherapy. Palonosetron is indicated for patients treated with moderately emetogenic chemotherapy; aprepitant is indicated for highly emetogenic chemotherapy, including high-dose cisplatin. Both drugs also prevent acute nausea associated with chemotherapy.

Aprepitant

Aprepitant (Emend, Merck) is a substance P/neurokinin-1 receptor antagonist with a unique mechanism of action against chemotherapy-induced nausea and vomiting. This drug is given in combination with a serotonin subtype 3 (5-HT^sub 3^) receptor antagonist (such as ondansetron, granisetron, or dolasetron) and a corticosteroid such as dexamethasone. Compared with ondansetron and dexamethasone together, this regimen plus aprepitant was significantly better at reducing acute, delayed, and overall nausea and vomiting in clinical trials.

Precautions: (1) Contraindicated in patients taking pimozide. (2) Use with caution in patients taking other drugs metabolized via the CYP 3A4 metabolic pathway, including certain antineoplastic drugs. See the package insert for more information on potential drug interactions and dosage adjustments. (3) Not recommended for chronic continuous use to prevent nausea and vomiting. (4) Not indicated to treat nausea and vomiting. (5) Aprepitant may reduce the effectiveness of oral contraceptives. (6) Aprepitant may increase the metabolism and thereby reduce the action of warfarin and phenytoin.

Adverse reactions: asthenia, hiccups, diarrhea, fatigue

Supplied as: 80-mg and 125mg capsules

Dosage: 125 mg l hour before chemotherapy, followed by 80 mg once a day in the morning on days two and three following chemotherapy. Each dose is given with a 5-HT^sub 3^ receptor antagonist and a corticosteroid.

Nursing considerations: (1) Advise a patient using oral contraceptives to use alternative or additional methods of contraception when taking aprepitant. (2) Closely monitor the international normalized ratio of a patient on warfarin during the 2 weeks after aprepitant therapy starts. (3) Dosage adjustments aren't necessary in patients with renal insufficiency, patients undergoing hemodialysis, or patients with mild to moderate hepatic insufficiency.

Palonosetron HCl

Palonosetron HCl (Aloxi, MGI Pharma) is the fourth 5-HT^sub 3^ receptor antagonist to be marketed, joining ondansetron, granisetron, and dolasetron. This drug has a longer halflife and longer duration of action than its predecessors. Given intravenously (I.V), palonosetron is indicated to prevent acute nausea and vomiting associated with moderately and highly emetogenic chemotherapy. It's also indicated to prevent delayed nausea and vomiting associated with moderately emetogenic chemotherapy.

Palonosetron and aprepitant haven't been directly compared in clinical studies. Because their mechanisms of action are different, however, the two new drugs plus a corticosteroid could be used in the same regimen.

Precautions: Use with caution in patients who have or may develop prolonged cardiac conduction intervals, particularly the QT interval. This includes patients with hypokalemia or hypomagnesemia, those taking diuretics with a potential for inducing electrolyte abnormalities, those with congenital long QT syndrome, those taking antiarrhythmic drugs that prolong the QT interval, and those receiving cumulative high-dose anthracycline therapy.

Adverse reactions: headache, constipation, hypersensitivity reactions, prolongation of the QT interval

Supplied as: single-use vials of 0.25 mg of palonosetron

Dosage: 0.25 mg given I.V over 30 seconds, administered 30 minutes before the start of chemotherapy

Nursing considerations: (1) Don't mix palonosetron with other drugs in the I.V line. (2) Flush the I.V line with 0.9% sodium chloride solution before and after administering the drug. (3) Giving more than one palonosetron dose within 7 days isn't recommended. (4) Patients with hepatic or renal impairment don't need dosage adjustments.

Drug for BPH

Alfuzosin HCI

Convenient dosing, less effect on blood pressure

Most men over age 50 experience enlargement of the prostate gland (benign prostatic hyperplasia [BPH]), which is characterized by urinary hesitancy, incomplete bladder emptying, incontinence, or nocturia.

Two classes of medications have been used to treat BPH. Steroid 5-alpha-reductase inhibitors such as dutasteride and finasteride reduce prostate size and relieve symptoms, but they don't provide maximum clinical benefit for several months. Alpha^sub 1^adrenergic receptor blockers may provide prompt relief of BPH symptoms, but don't reduce prostate size. These drugs also have an antihypertensive effect.

Alfuzosin HCl (Uroxatml, Sanofi-Synthelabo) is the fourth alpha-blocker approved to treat BPH, joining doxazosin, terazosin, and tamsulosin. Like tamsulosin, alfuzosin is more selective for alpha,-adrenergic receptors in the lower urinary tract than other drugs in its class. Although alfuzosin is less selective than tamsulosin, both drugs have a less pronounced effect on blood pressure than the other alphablockers and neither is labeled to treat hypertension.

Studies suggest that patients may get the greatest benefit from combination therapy with an alpha-blocker and dutasteride or finasteride.

Precautions: (1) Don't give alfuzosin with another alphablocker. (2) Contraindicated in patients with moderate to severe hepatic impairment. (3) Contraindicated for concurrent use with potent CYP 3A4 metabolic pathway inhibitors (such as clarithromycin, itraconazole, and protease inhibitors). Use cautiously in patients taking moderate CYP 3A4 inhibitors, such as diltiazem. See the package insert for details. (4) Use cautiously in patients taking antihypertensive medications. (5) Don't give concurrently with vardenafil (Levitra) or tadalafil (Cialis) because the combination may reduce blood pressure excessively. Alphablockers and sildenafil (Viagra) may be used together cautiously with appropriate dosage adjustments and precautions; see package insert for details. (6) Use with caution in patients with a history of QT prolongation and those taking drugs known to prolong the QT interval. (7) Use cautiously in patients with severe renal insufficiency because clearance may be reduced.

Adverse reactions: dizziness, headache, postural hypotension, syncope, fatigue, prolongation of the QT interval

Supplied as: 10-mg extendedrelease tablets

Dosage: 10 mg once a day

Nursing considerations: (1) Because alfuzosin may cause postural hypotension and dizziness, warn the patient not to drive, operate machinery, or perform other hazardous tasks after the first dose or after a dosage increase until he determines how the drug affects him. (2) If he's also taking sildenafil, warn him not to take more than 25 mg within 4 hours of taking alfuzosin. (3) Teach him to take each dose of alfuzosin after the same meal every day and tell him not to crush or chew the extended-release tablets.

Drug for peritoneal dialysis

Icodextrin

More fluid removal for long-dwell exchanges

A treatment for end-stage renal disease, peritoneal dialysis (PD) removes extra fluid and waste from the blood by filtering it through the peritoneal membrane. Dialysis solution used for PD is instilled into the peritoneal cavity through a flexible catheter. After a prescribed dwell time, the solution is drained and new solution instilled. Patients who perform PD at home typically perform four to six exchanges a day, including one long dwell (usually overnight).

Solutions used for PD contain glucose (dextrose) as the osmotic agent that drives fluid removal. During long dwell times with dextrose solutions, more dialysis fluid may be absorbed into the bloodstream than is removed by dialysis. This could pose problems because the patient's kidneys have little or no ability to remove excess fluid from the bloodstream.

Icodextrin (Extraneal, Baxter) is a starch-derived, water-soluble glucose polymer that works as a colloid osmotic agent when included in PD solutions. Given once a day in the long (8- to 16hour) dwell, icodextrin removes more fluid than dextrose solutions and also clears more creatinine and urea nitrogen. Like dextrose PD solutions, icodextrin contains electrolytes and lactate to maintain normal electrolyte acid-base levels.

Icodextrin is contraindicated in patients allergic to cornstarch or icodextrin and in patients with a glycogen storage disease. Use icodextrin with caution in patients who've had abdominal surgery within the past 30 days or who have conditions that compromise the integrity of the abdominal wall, abdominal surface, or intraabdominal cavity. This solution may not be appropriate for patients with hypercalcemia, particularly those on low-calcium PD solutions.

Adverse reactions reported with the use of icodextrin include rash, peritonitis, upper respiratory infection, and hypertension.

The solution is supplied in 1.5-, 2-, or 2.5-liter bags. Each 100 ml of icodextrin PD solution contains 7.5 grams of icodextrin.

Monitor the patient's volume status, body weight, nutritional status, and electrolyte levels. Also closely monitor blood glucose levels in patients with diabetes. Patients using insulin may need to adjust their insulin dosage. Measure blood glucose levels with a glucosespecific method (monitor and test strips) to avoid interference from maltose released from icodextrin.

Blood concentrations of dialyzable drugs may be reduced by dialysis, so adjust dosages as needed.

Administer icodextrin PD solution over 10 to 20 minutes for the long dwell. For the patient's comfort, you may warm the solution to 98.6° F (37° C), but only with dry heat, such as a heating pad. Don't put the solution in water or a microwave oven.

Drug for Gaucher disease

Miglustat

A new, oral approach to a rare genetic disorder

Gaucher disease is an autosomal recessive lysosomal storage disorder affecting the liver, spleen, and bone marrow. It causes hepatosplenomegaly, anemia, thrombocytopenia, and skeletal complications, which may lead to frequent fractures. Signs and symptoms, which can become evident at any age, vary widely in severity and may worsen unpredictably. Standard care includes l.V enzyme replacement therapy. Although rare in the general population, Gaucher disease is the most common genetic disorder among Jews of eastern European (Ashkenazi) descent.

Miglustat (Zavesca, Actelion) inhibits the enzyme glucosylceramide synthase, which is involved in synthesizing most glycosphingolipids. This action reduces the burden on the deficient enzyme and is called substrate reduction therapy. The drug is indicated for patients with mild to moderate type 1 Gaucher disease for whom enzyme replacement therapy isn't an option; for example, because of an allergy or poor venous access. Administered orally, miglustat reduced liver and spleen volume and increased hemoglobin levels and platelet counts in studies.

Miglustat is available through a restricted distribution program from CuraScript specialty pharmacy.

Precautions: (1) Contraindicated in women who may become pregnant (Pregnancy Category X). (2) Use isn't recommended in patients with severe renal impairment. (3) Reduce the dosage for patients with mild to moderate renal impairment. see the package insert for details.

Adverse reactions: diarrhea, weight loss, tremor or exacerbation of existing tremor, peripheral neuropathy

Supplied as: 100-mg capsules

Dosage: 100 mg three times a day

Nursing considerations: (1) Treat diarrhea with an antidiarrheal medication and diet changes. Teach the patient to avoid highcarbohydrate foods. (2) Obtain a baseline neurologic exam before therapy and repeat evaluations every 6 months during treatment. Teach the patient to report any numbness, pain, or burning in the hands, arms, legs, or feet. (3) If the patient experiences hand tremors, inform him that this may clear up on its own after about 3 months of treatment. (4) Warn all patients of the drug's known ability to cause birth defects. Before seeking to conceive, male patients should discontinue treatment with miglustat and maintain reliable contraception for 3 months. (5) Tell the patient that he can take miglustat without regard to food.

Antineopalstic drugs

Bortezomib, Tositumomab and iodine-131 tositumomab

Bortezomib First new drug for multiple myeloma in a decade

Multiple myeloma is the second most common hematologie cancer, after nonHodgkins lymphoma, affecting about 45,000 Americans. At any given time, 25% of these patients are in the relapsed, refractory stage and don't respond to standard treatment.

Bortezomib (Vdcade, Millennium), a proteasome inhibitor, disrupts certain enzyme pathways involved in the growth and survival of cancer cells. This novel mechanism of action may help patients who've become refractory to other agents. Given I.V., the drug is indicated for use in patients with multiple myeloma whoVe received at least two previous therapies and have experienced disease progression since the last therapy.

Because of promising results in clinical trials, bortezomib was approved under the Food and Drug Administration's accelerated approval process; however, a clinical benefit such as prolonged survival hasn't yet been demonstrated. Bortezomib is also being evaluated as a first-line treatment for multiple myeloma and as a treatment for other cancers.

Precautions: (1) Use caution with other drugs that may cause peripheral neuropathy because the frequency and severity of peripheral neuropathy symptoms may increase. (2) Use caution with other drugs that may cause sedation and other central nervous system effects. (3) Bortezomib may interact with other drugs metabolized by cytochrome P450 enzymes. see the package insert for details about potential drug interactions.

Adverse reactions: fatigue, malaise, weakness, nausea, diarrhea, decreased appetite, constipation, thrombocytopenia, peripheral neuropathy, pyrexia, vomiting, anemia, neutropenia

Supplied as: single-use vials containing 3.5 mg of the drug as a powder

Dosage: 1.3 mg/m^sup 2^ administered as an I.V bolus twice a week for 2 weeks, followed by a 10-day rest period

Nursing considerations: (1) Reconstitute the drug with 3.5 ml of 0.9% sodium chloride injection and administer it within 8 hours of reconstitution. (2) Monitor patients for symptoms of peripheral neuropathy or for worsening of preexisting peripheral neuropathy. See the package insert for details on dosage adjustments for patients who experience peripheral neuropathy. (3) Frequently monitor complete blood cell counts, including platelet counts. (4) Administer antiemetic or antidiarrheal medications as needed to manage adverse reactions. (5) Provide fluid and electrolyte replacement if needed to prevent dehydration. (6) Tell the patient that the drug may cause fatigue, malaise, and weakness. Warn him to avoid driving and other activities requiring alertness until he determines how treatment affects him. (7) Teach him to take precautions against postural hypotension, a particular risk for patients with a history of syncope, those who are dehydrated, and those taking antihypertensive medication.

Tositumomab and iodine-131 tositumomab

Second radioimmunotherapy regimen for non-Hodgkin's lymphoma

Immunotherapy has been used to treat non-Hodgkin's lymphoma since 1997, when rituximab, the first monoclonal antibody for cancer treatment, was approved. Recently, these drugs have been combined into regimens known as radioimmunotherapy, in which the monoclonal antibody delivers cytotoxic radiation directly to malignant cells. The Zevalin regimen (ibritumomab tiuxetan linked with yttrium-90) was marketed in 2002. Tositumomab and iodine-131 tositumomab (Bexxar, Corixa, GlaxoSmithKline), the second radioimmunotherapy regimen on the market, has properties similar to those of the Zevalin regimen.

Tositumomab is a murine monoclonal antibody that binds with an antigen on the surface of B cells and stimulates the immune system against cancer cells. When linked to iodine-131, it delivers two types of radiation to the body: beta radiation, which exerts cytotoxic effects, and gamma radiation, which is tracked via gamma camera scans to evaluate the distribution and clearance of radiation from the body. Iodine131 is rapidly eliminated from the body in the urine.

The Bexxar regimen is indicated for patients with certain types of nonHodgkin's lymphoma refractory to rituximab who've relapsed following chemotherapy. The regimen consists of two components-tositumomab and radioactive tositumomab-administered as two I.V infusions 7 to 14 days apart. The first (the dosimetric dose) is a small quantity of radioactive tositumomab administered to evaluate radiation clearance from the body. The therapeutic dose is based on the results.

Tositumomab is administered before the dosimetric and therapeutic doses to reduce the number of circulating B cells. This allows the largest possible amount of radioactive tositumomab to bind to lymphoma cells.

Precautions: (1) Contraindicated in patients with more than 25% lymphoma marrow involvement or , impaired bone marrow reserve. (2) Screen patients who've previously received murine proteins for human antimouse antibodies before starting therapy.

Adverse reactions: nausea, vomiting, abdominal pain, asthenia, prolonged and severe cytopenia, hypersensitivity reactions, secondary malignancies, pneumonia, pleural effusion, dehydration, hypothyroidism, infusion toxicity, diarrhea

Supplied as: two separate packages, one for the dosimetric dose and the other for the therapeutic dose. See the package insert for details on dosage and administration.

Dosage: See the package insert for details. Note: Only physicians trained in dose calculation and administration of the Bexxar regimen should administer this treatment.

Nursing considerations: (1) Take appropriate precautions to protect yourself, other health care professionals, family members, and others in close contact with the patient from the effects of gamma radiation. (2) Obtain complete blood cell counts before therapy and then at least weekly for up to 12 weeks. (3) Determine concentrations of thyroidstimulating hormone (TSH) before therapy begins and initiate use of a thyroid-blocking drug as ordered at least 24 hours before administration of the radioactive drug; the patient should continue receiving a thyroid blocker for 2 weeks after administration of the therapeutic dose. Teach him that his TSH concentrations should be monitored annually after treatment. (4) If ordered, administer acetaminophen and an antihistamine before therapy to minimize fever, chills, and other infusion reactions. (5) Because of the potential for toxic effects on both male and female gonads, tell all patients to use effective contraception methods during treatment and for 12 months afterward.

Antihyperlipidemic drug

Rosuvastatin calcium

A new statin joins the lineup.

Rosuvastatin calcium (Crestor, AstraZeneca) is the seventh statin to be marketed in the United States, joining atorvastatin, fluvastatin, lovastatin, pravastatin, and simvastatin. Another drug, cerivastatin, was withdrawn from the market in 2001 following reports of serious adverse reactions.

Statin drugs inhibit cholesterol synthesis, reducing plasma concentrations of lowdensity lipoprotein (LDL) cholesterol and total cholesterol. To a lesser extent, they also reduce the concentrations of apolipoprotein B and triglycerides and increase the concentration of high-density lipoprotein cholesterol.

In clinical studies, rosuvastatin, when used as an adjunct to diet, reduced LDL cholesterol significantly more than the same milligram doses of atorvastatin, pravastatin, and simvastatin and has been designated by some as a "superstatin." However, the differences probably are due to the differences in milligram potency among the agents.

Rosuvastatin also is indicated for patients with homozygous familial hypercholesterolemia as an adjunct to other lipid-lowering treatments or if other treatments aren't available.

Precautions: (1) Contraindicated in patients with active liver disease or unexplained persistent elevations of serum transaminases. (2) Use with caution in patients with a history of liver disease or substantial alcohol consumption. (3) Discontinue treatment if the patient has markedly elevated creatine kinase levels or if myopathy is suspected or diagnosed. (4) Temporarily withhold therapy if the patient has an acute, serious condition that suggests myopathy or that could predispose him to renal failure secondary to rhabdomyolysis (such as major surgery, sepsis, trauma, hypotension, or a severe metabolic, endocrine, or electrolyte disorder). (5) Not recommended as a first-line statin in patients of Asian ancestry because of the risk of elevated systemic bioavailability of the drug.

Adverse reactions: pharyngitis, headache, myalgia, myopathy, rhabdomyolysis, proteinuria, microscopic hematuria

Supplied as: 5-mg, 10-mg, 20-mg, and 40-mg tablets

Dosage: 10 mg once a day. See the package insert for additional dosing guidelines and adjustments.

Nursing considerations: (1) Avoid concurrent use of a statin with a fibrate or lipidlowering doses of niacin because of the risk of myopathy and rhabdomyolysis, unless the benefit of combined therapy outweighs the risks. (2) Monitor liver function tests before therapy, at 12 weeks after starting therapy or increasing the dosage, and semiannually thereafter. (3) Reduce the dosage or discontinue therapy as ordered if serum transaminase values are more than three times the upper limit of normal. (4) Tell the patient to contact his health care provider immediately if he experiences unexplained muscle pain, tenderness, or weakness, especially if he also has malaise and fever. (5) If the patient takes an antacid, tell him to take it at least 2 hours after taking a dose of rosuvastatin. (6) Teach the patient about diet and lifestyle changes that can help lower cholesterol. (7) If the patient is also taking warfarin, monitor his international normalized ratio value closely. (8) The health care provider may lower the dosage of rosuvastatin if the patient is also taking cyclosporine. (9) Rosuvastatin may be taken without regard to meals.

* Common adverse reactions are italicized throughout this article.

SELECTED REFERENCES

Drug Facts and Comparisons. St. Louis, Mo., Facts and Comparisons, Inc., 2004.

Nursing2004 Drug Handbook. Springhouse, Pa., Lippincott Williams & Wilkins, 2004.

Physicians' Desk Reference, 58th edition. Montvale, N.J., Medical Economics, 2004.

BY DANIEL A. HUSSAR, PHD

Remington Professor of Pharmacy

Philadelphia College of Pharmacy * University of the Sciences in Philadelphia, Pa.

Copyright Springhouse Corporation Sep 2004
Provided by ProQuest Information and Learning Company. All rights Reserved

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