Sunday, 4 March 2012

efavirenz


ef-a-VYE-renz


Commonly used brand name(s)

In the U.S.


  • Sustiva

Available Dosage Forms:


  • Capsule

  • Tablet

Therapeutic Class: Antiretroviral Agent


Pharmacologic Class: Non-Nucleoside Reverse Transcriptase Inhibitor


Uses For efavirenz


Efavirenz is used in combination with other medicines for the treatment of the infection caused by the human immunodeficiency virus (HIV). HIV is the virus that causes acquired immune deficiency syndrome (AIDS).


Efavirenz will not cure or prevent HIV infection or AIDS; however, it helps keep HIV from reproducing and appears to slow down the destruction of the immune system. This may help delay the development of problems that usually result from AIDS or HIV disease. Efavirenz will not keep you from spreading HIV to other people. People who receive efavirenz may continue to have some of the problems usually related to AIDS or HIV disease.


efavirenz is available only with your doctor's prescription.


Before Using efavirenz


In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For efavirenz, the following should be considered:


Allergies


Tell your doctor if you have ever had any unusual or allergic reaction to efavirenz or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.


Pediatric


Appropriate studies have not been performed on the relationship of age to the effects of efavirenz in children younger than 3 years of age or those who weigh less than 13 kilograms (kg). Safety and efficacy have not been established.


Geriatric


Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of efavirenz in the elderly. However, elderly patients are more likely to have age-related kidney, liver, or heart problems, which may require caution and an adjustment in the dose for patients receiving efavirenz.


Pregnancy








Pregnancy CategoryExplanation
All TrimestersDStudies in pregnant women have demonstrated a risk to the fetus. However, the benefits of therapy in a life threatening situation or a serious disease, may outweigh the potential risk.

Breast Feeding


There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.


Interactions with Medicines


Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking efavirenz, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.


Using efavirenz with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.


  • Astemizole

  • Bepridil

  • Cisapride

  • Dihydroergotamine

  • Ergoloid Mesylates

  • Ergonovine

  • Ergotamine

  • Methylergonovine

  • Methysergide

  • Midazolam

  • Pimozide

  • St John's Wort

  • Triazolam

Using efavirenz with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.


  • Amprenavir

  • Bexarotene

  • Boceprevir

  • Cyclosporine

  • Dexamethasone

  • Etravirine

  • Everolimus

  • Fosamprenavir

  • Itraconazole

  • Maraviroc

  • Nevirapine

  • Posaconazole

  • Rifabutin

  • Rifampin

  • Rifapentine

  • Rilpivirine

  • Sirolimus

  • Tacrolimus

  • Tolvaptan

  • Voriconazole

Using efavirenz with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.


  • Atazanavir

  • Atorvastatin

  • Bupropion

  • Carbamazepine

  • Caspofungin

  • Clarithromycin

  • Darunavir

  • Desogestrel

  • Dienogest

  • Diltiazem

  • Drospirenone

  • Estradiol Cypionate

  • Estradiol Valerate

  • Ethinyl Estradiol

  • Ethynodiol Diacetate

  • Etonogestrel

  • Indinavir

  • Ketoconazole

  • Levonorgestrel

  • Lopinavir

  • Medroxyprogesterone Acetate

  • Mestranol

  • Methadone

  • Norelgestromin

  • Norethindrone

  • Norgestimate

  • Norgestrel

  • Pravastatin

  • Proguanil

  • Ritonavir

  • Saquinavir

  • Sertraline

  • Simvastatin

  • Telaprevir

Interactions with Food/Tobacco/Alcohol


Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.


Other Medical Problems


The presence of other medical problems may affect the use of efavirenz. Make sure you tell your doctor if you have any other medical problems, especially:


  • Alcohol or drug abuse, history of or

  • Mental illness, history of—May increase the chance of having serious psychiatric side effects.

  • Hepatitis B or

  • Hepatitis C or

  • Liver disease—Use with caution. Efavirenz may cause side effects to become worse.

  • Hypersensitivity reactions (e.g., Stevens-Johnson syndrome, erythema multiforme, toxic skin eruptions), history of—Should not be used in patients with this condition.

  • Seizures, history of—Use with caution. May increase chances of convulsions occurring.

Proper Use of efavirenz


Take efavirenz exactly as directed by your doctor. Do not take it more often, and do not take it for a longer time than your doctor ordered. Also, do not change the dose or stop taking efavirenz without checking first with your doctor. When your supply of efavirenz is running low, contact your doctor or pharmacist ahead of time. Do not allow yourself to run out of efavirenz.


efavirenz comes with a patient information insert. Read and follow the instructions in the insert carefully. Ask your doctor if you have any questions.


Keep taking efavirenz for the full time of treatment even if you begin to feel better. It is also important that you continue taking all other medicines for HIV infection your doctor has instructed you to take. Efavirenz will not work if it is taken alone. It must be taken with other HIV medicines.


efavirenz works best when there is a constant amount in the blood. To help keep blood levels constant, do not miss any doses. Also, it is best to take the doses at evenly spaced times during the day. For example, if you or your child are taking one dose per day, try to take it at the same time each day. If you need help planning the best times to take your medicine, check with your doctor.


Efavirenz should be taken on an empty stomach because the amount of efavirenz absorbed into the body may be increased when taken with food, which might increase the chance of side effects.


Swallow the tablets whole with water. Do not break, crush, or chew it.


Take efavirenz at bedtime, especially during the first 2 to 4 weeks, to lessen central nervous system (CNS) side effects that may occur with efavirenz. These effects usually lessen after you have been taking efavirenz for awhile.


Dosing


The dose of efavirenz will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of efavirenz. If your dose is different, do not change it unless your doctor tells you to do so.


The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.


  • For oral dosage forms (capsules or tablets):
    • For treatment of HIV infection:
      • Adults—600 milligrams (mg) once a day, taken with other medicines.

      • Children 3 years of age and older (by weight)—
        • 10 to 15 kilograms (22 to 33 pounds) of body weight: 200 mg once a day, taken with other medicines.

        • 15 to 20 kilograms (33 to 44 pounds) of body weight: 250 mg once a day, taken with other medicines.

        • 20 to 25 kilograms (44 to 55 pounds) of body weight: 300 mg once a day, taken with other medicines.

        • 25 to 32.5 kilograms (55 to 71.5 pounds) of body weight: 350 mg once a day, taken with other medicines.

        • 32.5 to 40 kilograms (71.5 to 88 pounds) of body weight: 400 mg once a day, taken with other medicines.

        • 40 kilograms (88 pounds) of body weight or over: 600 mg once a day, taken with other medicines.


      • Children up to 3 years of age—Use and dose must be determined by your doctor.



Missed Dose


If you miss a dose of efavirenz, take it as soon as possible. However, if it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not double doses.


Storage


Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.


Keep out of the reach of children.


Do not keep outdated medicine or medicine no longer needed.


Ask your healthcare professional how you should dispose of any medicine you do not use.


Precautions While Using efavirenz


It is very important that your doctor check the progress of you or your child at regular visits, to make sure efavirenz is working properly. Blood tests may be needed to check for unwanted effects.


Using efavirenz while you are pregnant can harm your unborn baby. Use an effective form of birth control to keep from getting pregnant. You should not become pregnant while you are taking efavirenz and for 12 weeks after stopping it. If you think you have become pregnant while using the medicine, tell your doctor right away. Your doctor may want you to join a pregnancy registry for patients taking an anti-HIV medicine.


Do not use efavirenz if you or your child are also using Atripla®, bepridil (Vascor®), cisapride (Propulsid®), ergot medicines (e.g., dihydroergotamine, ergonovine, ergotamine, methylergonovine, Bellergal-S®, Cafergot®, DHE 45®, Ergostat®, Sansert®, or Wigraine®), midazolam (Versed®), pimozide (Orap®), triazolam (Halcion®), or voriconazole (Vfend®).


Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal (e.g., St. John's wort) or vitamin supplements.


efavirenz may cause some people to become dizzy, lightheaded, drowsy, or less alert than they are normally. Even if taken at bedtime, it may cause some people to feel drowsy or less alert on arising. Make sure you know how you react to efavirenz before you drive, use machines, or do anything else that could be dangerous if you are not alert.


Check with your doctor before taking efavirenz with alcohol or other medicines that affect the central nervous system (CNS). The use of alcohol or other medicines that affect the CNS with efavirenz may worsen the side effects of efavirenz, such as dizziness, poor concentration, drowsiness, unusual dreams, and trouble with sleeping. Some examples of medicines that affect the CNS are antihistamines or medicine for allergies or colds; sedatives, tranquilizers, or sleeping medicine; medicine for depression; medicine for anxiety; prescription pain medicine or narcotics; medicine for attention deficit and hyperactivity disorder; medicine for seizures or barbiturates; muscle relaxants; or anesthetics, including some dental anesthetics.


efavirenz may increase your risk of having serious mental or behavioral problems. Tell your doctor if you or your child develop any mood changes, strange thoughts, or any unusual behavior while you are using efavirenz.


Liver problems may occur while you are using efavirenz. Stop using efavirenz and check with your doctor right away if you or your child are having more than one of these symptoms: abdominal pain or tenderness; clay-colored stools; dark urine; a fever; a headache; itching; loss of appetite; nausea and vomiting; skin rash; swelling of the feet or lower legs; unusual tiredness or weakness; or yellow eyes or skin.


efavirenz may increase the level of cholesterol and fats in your blood. If this condition occurs, your doctor may give you a medicine to lower the cholesterol and fats. Talk to your doctor if you have concerns.


When you or your child start taking HIV medicines, your immune system may get stronger. If or your child you have certain infections, such as pneumonia or tuberculosis, you may notice new symptoms when your body tries to fight them. If this occurs, be sure to tell your doctor right away.


Efavirenz may cause you or your child to have excess body fat. Tell your doctor if you or your child notice changes in your body shape, such as an increased amount of fat in the upper back and neck, or around the chest and stomach area. You might also lose fat from the legs, arms, and face.


efavirenz will not keep you from giving HIV to your partner during sex. Make sure you understand this and practice safe sex, even if your partner also has HIV, by using a latex condom or other barrier method. efavirenz will also not keep you from giving HIV to other people if they are exposed to your blood. Do not re-use or share needles with anyone.


Birth control pills may not work as well while you are using efavirenz. Use an additional form of birth control along with your pills while you are taking efavirenz and for 12 weeks after stopping it to keep from getting pregnant. Other forms of birth control include condoms, diaphragms, or contraceptive foams or jellies.


Stop using efavirenz and check with your doctor right away if you or your child develop a skin rash; blistering, peeling, or loosening of the skin; red skin lesions; sores or ulcers on the skin; or fever or chills while you or your child are using efavirenz.


Tell the doctor in charge that you or your child are taking efavirenz before you have any medical tests. The results of some tests may be affected by efavirenz.


efavirenz Side Effects


Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.


Check with your doctor immediately if any of the following side effects occur:


More common
  • Depression

  • skin rash or itching

Less common
  • Blood in the urine

  • difficult or painful urination

  • pain in the lower back or side

Rare
  • Abdominal or stomach pain

  • blistering

  • changes in vision

  • clumsiness or unsteadiness

  • confusion

  • convulsions (seizures)

  • cough

  • dark urine

  • delusions

  • double vision

  • fainting

  • fast or pounding heartbeat

  • fever or chills

  • headache (severe and throbbing)

  • hives

  • inappropriate behavior

  • loss of appetite

  • mood or mental changes (severe)

  • muscle cramps or pain

  • nausea or vomiting

  • nerve pain

  • open sores

  • pain, tenderness, bluish color, or swelling of the leg or foot

  • rapid weight gain

  • seeing, hearing, or feeling things that are not there

  • sense of constant movement of self or surroundings

  • sores, ulcers, or white spots in the mouth or on the lips

  • speech disorder

  • swelling or tenderness in the upper abdominal or stomach area

  • swelling of the hands, arms, feet, or legs

  • thoughts of suicide or attempts at suicide

  • tightness in the chest

  • tingling, burning, numbness, or pain in the hands, arms, feet, or legs

  • tingling, burning, or prickling sensations

  • tremor

  • troubled breathing

  • unusual tiredness

  • weight loss

  • wheezing

  • yellow eyes or skin

Incidence not known
  • Actions that are out of control

  • attack, assault, or force

  • continuing vomiting

  • delusions of persecution, mistrust, suspiciousness, or combativeness

  • difficult or labored breathing

  • early appearance of redness or swelling of the skin

  • general feeling of tiredness or weakness

  • irritability

  • late appearance of rash with or without weeping blisters that become crusted, especially in sun-exposed areas of the skin, may extend to unexposed areas

  • light-colored stools

  • nervousness

  • shortness of breath

  • talking, feeling, and acting with excitement

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:


More common
  • Diarrhea

  • dizziness

  • drowsiness

  • headache

  • increased sweating

  • poor concentration

  • trouble with sleeping

Less common or rare
  • Abnormally decreased sensitivity, particularly to touch

  • agitation or anxiety

  • belching

  • change in sense of taste or smell

  • dry mouth

  • excessive gas

  • false sense of well-being

  • flaking and falling off of the skin

  • flushing

  • general feeling of discomfort

  • heartburn

  • indigestion

  • joint pain

  • lack of feeling or emotion

  • loss of hair

  • loss of memory

  • loss of sense of reality

  • mood changes

  • pain

  • painful, red, hot, or irritated hair follicles

  • ringing in the ears

  • stomach discomfort

  • unusual dreams

  • weakness

Incidence not known
  • Difficulty having a bowel movement (stool)

  • discoloration of the fingernails or toenails

  • dizziness or lightheadedness

  • feeling of constant movement of self or surroundings

  • increased amount of fat in the upper back and neck, or around the chest and stomach area

  • lose fat from the legs, arms, and face

  • sensation of spinning

  • swelling of the breasts or breast soreness in both females and males

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.


Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

See also: efavirenz side effects (in more detail)



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More efavirenz resources


  • Efavirenz Side Effects (in more detail)
  • Efavirenz Dosage
  • Efavirenz Use in Pregnancy & Breastfeeding
  • Efavirenz Drug Interactions
  • Efavirenz Support Group
  • 2 Reviews for Efavirenz - Add your own review/rating


  • Efavirenz Professional Patient Advice (Wolters Kluwer)

  • Efavirenz Monograph (AHFS DI)

  • Efavirenz MedFacts Consumer Leaflet (Wolters Kluwer)

  • Sustiva Prescribing Information (FDA)

  • Sustiva Consumer Overview



Compare efavirenz with other medications


  • HIV Infection
  • Nonoccupational Exposure
  • Occupational Exposure

Thursday, 1 March 2012

Iressa


Generic Name: Gefitinib
Class: Antineoplastic Agents
VA Class: AN900
Chemical Name: N-(3-chloro-4-fluorophenyl)-7-methoxy-6-[3-(4-morpholin)propoxy]-4-quinazolamine
Molecular Formula: C22H24ClFN4O3
CAS Number: 184475-35-2

Introduction

Antineoplastic agent; synthetic anilinoquinazoline.1 2 3 4


Uses for Iressa


Non-small Cell Lung Cancer (NSCLC)


Monotherapy for continued treatment of locally advanced or metastatic NSCLC after failure of both platinum-based and docetaxel regimens due to disease progression or unacceptable toxicity in patients who are benefiting or have benefited from gefitinib.1


No survival benefit demonstrated.1 Therefore, consider other agents that have been shown to prolong survival (e.g., erlotinib, docetaxel) for management of advanced NSCLC in patients who have received 1 or 2 previous chemotherapy regimens and have refractory disease or unacceptable toxicity.1 12


Use of gefitinib currently is limited to patients already receiving and benefiting from the drug or who are enrolled in a clinical trial.11 12 13 (See Restricted Distribution Program under Dosage and Administration.)


No benefit from adding gefitinib to initial standard platinum-based chemotherapy in patients with NSCLC or as a component in combination chemotherapy in patients with advanced disease.1 3


Iressa Dosage and Administration


General



  • Consult specialized references for procedures for proper handling and disposal of antineoplastics.



Administration


Oral Administration


Administer orally once daily without regard to meals.1


For patients who have difficulty swallowing solids, prepare dispersion by placing tablet in a half glass of noncarbonated drinking water (do not use other liquids).1 Without crushing the tablet, stir water until tablet is dispersed (approximately 10 minutes).1 Drink liquid (containing dispersed tablet) immediately, then rinse glass with a half glass of water and drink remaining water.1 May also administer the aqueous dispersion through a nasogastric tube.1


Restricted Distribution Program


After September 15, 2005, available only through the Iressa Access Program.12 13 As part of this program, renewal prescriptions are dispensed through a mail order pharmacy for patients meeting specified criteria.13 Contact AstraZeneca at 800-601-8933 or consult the Iressa website () for additional information.13


Dosage


Adults


NSCLC

Oral

250 mg once daily.1 Higher dosages do not increase response and may increase toxicity.1


If used with potent CYP3A4 inducer, consider dosage adjustment.1 (See Interactions.)


Discontinue gefitinib if interstitial lung disease develops.1 (See Pulmonary Toxicity under Cautions.)


May interrupt therapy briefly (up to 14 days) if adverse dermatologic reactions or poorly tolerated diarrhea (sometimes with dehydration) occurs.1 Reinitiate at dosage of 250 mg once daily.1


Interrupt therapy if adverse ocular manifestations (e.g., pain, aberrant eyelash) develop; following resolution, make decision regarding reinitiation at dosage of 250 mg once daily.1


Special Populations


Hepatic Impairment


No dosage adjustments necessary in patients with moderate to severe hepatic impairment and liver metastases.1 9 (See Special Populations under Pharmacokinetics.)


Renal Impairment


No dosage adjustments necessary.1 9 (See Renal Impairment under Cautions.)


Cautions for Iressa


Contraindications



  • Known severe hypersensitivity to gefitinib or any ingredient in the formulation.1



Warnings/Precautions


Warnings


Pulmonary Toxicity

Interstitial lung disease, sometimes fatal, reported; described as interstitial pneumonia, pneumonitis, or alveolitis.1 7 Manifestations often include acute onset of dyspnea, sometimes associated with cough or low-grade fever, usually becoming severe within a short time and requiring hospitalization.1 8


Risk of increased mortality in patients with concurrent idiopathic pulmonary fibrosis whose condition worsens while receiving gefitinib.1


If acute onset or worsening of pulmonary symptoms (dyspnea, cough, fever) occurs, interrupt therapy, promptly evaluate patient, and institute appropriate therapy.1 If diagnosis of interstitial lung disease is confirmed, discontinue gefitinib and provide appropriate treatment.1


Fetal/Neonatal Morbidity and Mortality

May cause fetal harm; neonatal mortality soon after parturition, reduction in number of offspring born alive, and reduced fetal weight demonstrated in animals.1


Avoid pregnancy during therapy; if pregnancy occurs, apprise of potential fetal hazard or risk of pregnancy loss.1


Sensitivity Reactions


Hypersensitivity Reactions

Allergic reactions, including angioedema and urticaria, reported.1


Major Toxicities


GI Effects

Diarrhea, nausea, vomiting, anorexia, and weight loss reported.1


Dermatologic Effects

Rash, acne, and dry skin reported.1 Toxic epidermal necrolysis and erythema multiforme reported rarely.1


Ocular Effects

Ocular pain and corneal erosion or ulcer, sometimes in association with aberrant eyelash growth, reported.1 Corneal membrane sloughing, ocular ischemia, or ocular hemorrhage reported rarely.1


Other Adverse Effects

Hemorrhage (e.g., epistaxis, hematuria) reported.1 Pancreatitis reported rarely.1


General Precautions


Hepatotoxicity

Asymptomatic elevations of hepatic aminotransferase concentrations reported.1


Consider periodic monitoring of liver function (aminotransferase, bilirubin, alkaline phosphatase concentrations); if severe elevations of test results occur, consider discontinuance.1


Specific Populations


Pregnancy

Category D.1 (See Fetal/Neonatal Morbidity and Mortality under Cautions.)


Lactation

Gefitinib and its metabolites are distributed into milk in rats; not known whether distributed into human milk.1 Women receiving gefitinib should not breast-feed.1


Pediatric Use

Safety and efficacy not established in children <18 years of age; therefore, not indicated for use in pediatric patients.1 9 CNS hemorrhage and death reported in pediatric patients receiving gefitinib alone or with radiation for primary CNS tumors.1


Geriatric Use

No substantial differences in safety and efficacy relative to younger adults.1


Hepatic Impairment

Possible increased exposure.1 (See Special Populations under Pharmacokinetics.)


Renal Impairment

Not studied in patients with severe renal impairment; use with caution.1


Common Adverse Effects


Diarrhea, rash, acne, dry skin, nausea, vomiting, pruritus, anorexia, asthenia.1


Interactions for Iressa


Metabolized principally by CYP3A4.1 Does not inhibit CYP isoenzymes 1A2, 2C9, or 3A4 in vitro, but may inhibit 2C19 and 2D6 at high drug concentrations.1


Drugs Affecting Hepatic Microsomal Enzymes


CYP3A4 inhibitors: Potential pharmacokinetic interaction (decreased gefitinib metabolism, increased plasma gefitinib concentrations).1 2 3 Possible increased risk of adverse effects.1 Use with caution.1


CYP3A4 inducers: Potential pharmacokinetic interaction (increased gefitinib metabolism, decreased plasma gefitinib concentrations).1 If used concomitantly with potent CYP3A4 inducer, consider increasing gefitinib dosage to 500 mg daily in the absence of severe adverse effects.1


Drugs Affecting Gastric Acidity


Possible pharmacokinetic interaction (decreased plasma gefitinib concentrations, possible reduction in gefitinib efficacy) with drugs that cause substantial, sustained gastric pH elevation.1 10


Specific Drugs






























Drug



Interaction



Comments



Antifungals, azoles (e.g., itraconazole, ketoconazole)



Decreased metabolism and increased plasma concentrations of gefitinib; possible increased risk of adverse effects1



Use with caution1



Histamine H2-receptor antagonists



Possible decreased plasma gefitinib concentrations and reduction in gefitinib efficacy1



Metoprolol



Increased systemic exposure to metoprolol1



Phenytoin



Increased metabolism and decreased plasma concentrations of gefitinib1



Consider increasing gefitinib dosage to 500 mg daily in the absence of severe adverse effects1



Proton-pump inhibitors



Possible decreased plasma gefitinib concentrations and reduction in gefitinib efficacy1 10



Rifampin



Increased metabolism and decreased plasma concentrations of gefitinib1



Consider increasing gefitinib dosage to 500 mg daily in the absence of severe adverse effects1



Vinorelbine



Possible exacerbation of vinorelbine-induced neutropenia1



Warfarin



Possible INR elevations and/or bleeding1



Monitor regularly for changes in PT or INR1


Iressa Pharmacokinetics


Absorption


Bioavailability


Slowly absorbed following oral administration, with peak plasma concentrations attained within 3–7 hours.1 Mean bioavailability is 60%.1


Food


Food does not substantially alter bioavailability.1


Distribution


Extent


Extensively distributed throughout the body.1


Crosses placenta.1 Gefitinib and its metabolites are distributed into milk in rats; not known whether distributed into human milk.1


Plasma Protein Binding


90% in vitro (albumin and α1-acid glycoprotein).1


Elimination


Metabolism


Extensively metabolized in liver, principally by CYP3A4.1 Five metabolites identified; only O-desmethyl gefitinib has exposure comparable to that of gefitinib, but potency is only 1/14 that of gefitinib.1


Elimination Route


Excreted in feces (86%) and urine (4%).1


Half-life


About 48 hours.1


Special Populations


In patients with hepatic impairment, systemic exposure to gefitinib may be increased, since drug is cleared principally by liver.1 However, in patients with moderate to severe elevations of hepatic enzymes and liver metastases, pharmacokinetic profile was similar to that in patients without hepatic abnormalities;1 9 effect of hepatic impairment unrelated to cancer not evaluated to date.1


Effect of severe renal impairment on pharmacokinetics not determined.1


Stability


Storage


Oral


Tablets

20–25°C.1


ActionsActions



  • Inhibits intracellular phosphorylation of numerous tyrosine kinases associated with transmembrane cell surface receptors, including epidermal growth factor receptor (EGFR) tyrosine kinase;1 2 3 4 activation of EGFR tyrosine kinase may initiate cascade of intracellular signaling events leading to cell proliferation and influencing processes critical to cell survival and tumor progression (e.g., angiogenesis, apoptosis, metastasis).2 4




  • Precise mechanism of antineoplastic activity not fully elucidated; further study needed to determine if correlation exists between EGFR receptor expression and response to gefitinib.1



Advice to Patients



  • Importance of promptly reporting any conditions that can be associated with dehydration (e.g., severe or persistent diarrhea, nausea, anorexia, vomiting), new onset or worsening of pulmonary symptoms (e.g., shortness of breath, cough), ocular irritation, or other new symptoms.1




  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed; necessity of advising women to avoid pregnancy and nursing during therapy.1 Advise pregnant women of risk to the fetus.1




  • Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements, as well as any concomitant illnesses.1




  • Importance of informing patients of other important precautionary information.1 (See Cautions.)



Preparations


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.


No longer available through community pharmacies.12 13 Currently available through the Iressa Access Program for selected patients.12 13 (See Restricted Distribution Program under Dosage and Administration.)













Gefitinib

Routes



Dosage Forms



Strengths



Brand Names



Manufacturer



Oral



Tablets, film-coated



250 mg



Iressa (with povidone)



AstraZeneca



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The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

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References



1. AstraZeneca Pharmaceuticals. Iressa (gefitinib) tablets prescribing information. Wilmington, DE; 2005 Jun.



2. Culy CR, Faulds D. Gefitinib. Drugs. 2002; 62:2237-48. [PubMed 12381224]



3. Anon. Gefitinib (Iressa) for advanced non-small cell lung cancer. Med Lett Drugs Ther. 2002; 44:77-8. [PubMed 12205428]



4. Baselga J, Averbuch SD. ZD1839 (Iressa) as an anticancer agent. Drugs. 2000; 60 (suppl 1):33-40. [PubMed 11129170]



5. Kris MG, Natale RB, Herbst RS et al. A phase II trial of ZD1839 (Iressa) in advanced non-small cell lung cancer (NSCLC) patients who had failed platinum- and docetaxel-based regimens (IDEAL 2). 38th Annual Meeting of the American Society of Clinical Oncology (ASCO), Orlando, FL, May 2002. Abstract No. 1166.



6. US Food and Drug Administration. Briefing document NDA 21-399. From FDA website. Accessed 2003 May 22.



7. Inoue A, Saijo Y, Maemondo M et al. Severe acute interstitial pneumonia and gefitinib. Lancet. 2003; 361:137-9. [IDIS 491838] [PubMed 12531582]



8. Kinoshita A, Fukuda M, Nagashima S, et al. Pulmonary damage during gefitinib monotherapy in patients with non-small cell lung cancer. 39th Annual Meeting of the American Society of Clinical Oncology (ASCO), Chicago, IL, May 2003. Abstract No. 2809.



9. AstraZeneca Pharmaceuticals, Wilmington, DE: Personal communication.



10. Zucchero FJ, Hogan MJ, Sommer CD, eds. Evaluations of Drug Interactions. St. Louis, MO: FirstDatabank; 2003:18/902.00.



11. FDA public health advisory: new labeling and distribution program for gefitinib (Iressa). Rockville, MD; 2005 Jun 17. From FDA website.



12. Questions and answers on Iressa (gefitinib). Rockville, MD: Food and Drug Administration; 2005 Jun 17. From FDA website.



13. AstraZeneca Pharmaceuticals. Information for healthcare professionals from website for Iressa.



More Iressa resources


  • Iressa Side Effects (in more detail)
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  • Iressa Prescribing Information (FDA)

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  • Non-Small Cell Lung Cancer

Wednesday, 29 February 2012

Iodinated contrast media


A drug may be classified by the chemical type of the active ingredient or by the way it is used to treat a particular condition. Each drug can be classified into one or more drug classes.


Drug List:

Monday, 27 February 2012

Eloxatin





Dosage Form: injection, solution, concentrate
FULL PRESCRIBING INFORMATION
WARNING: ANAPHYLACTIC REACTIONS

Anaphylactic reactions to Eloxatin have been reported, and may occur within minutes of Eloxatin administration. Epinephrine, corticosteroids, and antihistamines have been employed to alleviate symptoms of anaphylaxis [see Warnings and Precautions (5.1)].




Indications and Usage for Eloxatin


Eloxatin, used in combination with infusional 5-fluorouracil/leucovorin, is indicated for:


  • adjuvant treatment of stage III colon cancer in patients who have undergone complete resection of the primary tumor.

  • treatment of advanced colorectal cancer.


DOSAGE and ADMINISTRATION


Eloxatin (oxaliplatin injection) should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Appropriate management of therapy and complications is possible only when adequate diagnostic and treatment facilities are readily available.



Dosage



Administer Eloxatin in combination with 5-fluorouracil/leucovorin every 2 weeks. For advanced disease, treatment is recommended until disease progression or unacceptable toxicity. For adjuvant use, treatment is recommended for a total of 6 months (12 cycles):


Day 1: Eloxatin 85 mg/m2 intravenous infusion in 250–500 mL 5% Dextrose injection, USP and leucovorin 200 mg/m2 intravenous infusion in 5% Dextrose Injection, USP both given over 120 minutes at the same time in separate bags using a Y-line, followed by 5-fluorouracil 400 mg/m2 intravenous bolus given over 2–4 minutes, followed by 5-fluorouracil 600 mg/m2 intravenous infusion in 500 mL 5% Dextrose Injection, USP (recommended) as a 22-hour continuous infusion.


Day 2: Leucovorin 200 mg/m2 intravenous infusion over 120 minutes, followed by 5-fluorouracil 400 mg/m2 intravenous bolus given over 2–4 minutes, followed by 5-fluorouracil 600 mg/m2 intravenous infusion in 500 mL 5% Dextrose Injection, USP (recommended) as a 22-hour continuous infusion.


Figure 1



The administration of Eloxatin does not require prehydration. Premedication with antiemetics, including 5-HT3 blockers with or without dexamethasone, is recommended.


For information on 5-fluorouracil and leucovorin, see the respective package inserts.



Dose Modification Recommendations


Prior to subsequent therapy cycles, patients should be evaluated for clinical toxicities and recommended laboratory tests [see Warnings and Precautions (5.6)]. Prolongation of infusion time for Eloxatin from 2 hours to 6 hours may mitigate acute toxicities. The infusion times for 5-fluorouracil and leucovorin do not need to be changed.



Adjuvant Therapy in Patients with Stage III Colon Cancer


Neuropathy and other toxicities were graded using the NCI CTC scale version 1 [see Warnings and Precautions (5.2)].


For patients who experience persistent Grade 2 neurosensory events that do not resolve, a dose reduction of Eloxatin to 75 mg/m2 should be considered. For patients with persistent Grade 3 neurosensory events, discontinuing therapy should be considered. The infusional 5-fluorouracil/leucovorin regimen need not be altered.


A dose reduction of Eloxatin to 75 mg/m2 and infusional 5-fluorouracil to 300 mg/m2 bolus and 500 mg/m2 22 hour infusion is recommended for patients after recovery from grade 3/4 gastrointestinal (despite prophylactic treatment) or grade 4 neutropenia or grade 3/4 thrombocytopenia. The next dose should be delayed until: neutrophils ≥1.5 × 109/L and platelets ≥75 × 109/L.



Dose Modifications in Therapy in Previously Untreated and Previously Treated Patients with Advanced Colorectal Cancer


Neuropathy was graded using a study-specific neurotoxicity scale [see Warnings and Precautions (5.2)]. Other toxicities were graded by the NCI CTC, Version 2.0.


For patients who experience persistent Grade 2 neurosensory events that do not resolve, a dose reduction of Eloxatin to 65 mg/m2 should be considered. For patients with persistent Grade 3 neurosensory events, discontinuing therapy should be considered. The 5-fluorouracil/leucovorin regimen need not be altered.


A dose reduction of Eloxatin to 65 mg/m2 and 5-fluorouracil by 20% (300 mg/m2 bolus and 500 mg/m2 22-hour infusion) is recommended for patients after recovery from grade 3/4 gastrointestinal (despite prophylactic treatment) or grade 4 neutropenia or grade 3/4 thrombocytopenia. The next dose should be delayed until: neutrophils ≥1.5 × 109/L and platelets ≥75 × 109/L.



 Dose Modifications in Therapy for Patients with Renal Impairment


 In patients with normal renal function or mild to moderate renal impairment, the recommended dose of Eloxatin is 85 mg/m2. In patients with severe renal impairment, the initial recommended Eloxatin dose should be reduced to 65 mg/m2 [see Use in Specific Populations (8.6) and Clinical Pharmacology (12.3)].



Preparation of Infusion Solution


Powder for solution for infusion

Reconstitution or final dilution must never be performed with a sodium chloride solution or other chloride containing solutions.

The lyophilized powder is reconstituted by adding 10 mL (for the 50 mg vial) or 20 mL (for the 100 mg vial) of Water for Injection, USP or 5% Dextrose Injection, USP. Do not administer the reconstituted solution without further dilution. The reconstituted solution must be further diluted in an infusion solution of 250–500 mL of 5% Dextrose Injection, USP.

After reconstitution in the original vial, the solution may be stored up to 24 hours under refrigeration [2–8°C (36–46°F)]. After final dilution with 250–500 mL of 5% Dextrose Injection, USP, the shelf life is 6 hours at room temperature [20–25°C (68–77°F)] or up to 24 hours under refrigeration [2–8°C (36–46°F)].

Eloxatin is not light sensitive.


Concentrate for solution for infusion

Do not freeze and protect from light the concentrated solution.

A final dilution must never be performed with a sodium chloride solution or other chloride-containing solutions.

The solution must be further diluted in an infusion solution of 250-500 mL of 5% Dextrose Injection, USP.

After dilution with 250-500 mL of 5% Dextrose Injection, USP, the shelf life is 6 hours at room temperature [20-25°C (68-77°F)] or up to 24 hours under refrigeration [2-8°C (36-46°F)].

After final dilution, protection from light is not required.



Eloxatin is incompatible in solution with alkaline medications or media (such as basic solutions of 5-fluorouracil) and must not be mixed with these or administered simultaneously through the same infusion line. The infusion line should be flushed with 5% Dextrose Injection, USP prior to administration of any concomitant medication.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration and discarded if present.


Needles or intravenous administration sets containing aluminum parts that may come in contact with Eloxatin should not be used for the preparation or mixing of the drug. Aluminum has been reported to cause degradation of platinum compounds.



Dosage Forms and Strengths


Eloxatin is supplied in single-use vials containing 50 mg or 100 mg of oxaliplatin as a sterile, preservative-free lyophilized powder for reconstitution.



Eloxatin is supplied in single-use vials containing 50 mg, 100 mg or 200 mg of oxaliplatin as a sterile, preservative-free, aqueous solution at a concentration of 5 mg/ml.



Contraindications


Eloxatin should not be administered to patients with a history of known allergy to Eloxatin or other platinum compounds [see Warnings and Precautions (5.1)].



Warnings and Precautions



Allergic Reactions


See boxed warning


Grade 3/4 hypersensitivity, including anaphylactic/anaphylactoid reactions, to Eloxatin has been observed in 2–3% of colon cancer patients. These allergic reactions which can be fatal, can occur within minutes of administration and at any cycle, and were similar in nature and severity to those reported with other platinum-containing compounds, such as rash, urticaria, erythema, pruritus, and, rarely, bronchospasm and hypotension. The symptoms associated with hypersensitivity reactions reported in the previously untreated patients were urticaria, pruritus, flushing of the face, diarrhea associated with oxaliplatin infusion, shortness of breath, bronchospasm, diaphoresis, chest pains, hypotension, disorientation and syncope. These reactions are usually managed with standard epinephrine, corticosteroid, antihistamine therapy, and require discontinuation of therapy.  Rechallenge is contraindicated in these patients [see Contraindications (4)]. Drug-related deaths associated with platinum compounds from anaphylaxis have been reported.



Neurologic Toxicity



Neuropathy


Eloxatin is associated with two types of neuropathy:


An acute, reversible, primarily peripheral, sensory neuropathy that is of early onset, occurring within hours or one to two days of dosing, that resolves within 14 days, and that frequently recurs with further dosing.The symptoms may be precipitated or exacerbated by exposure to cold temperature or cold objects and they usually present as transient paresthesia, dysesthesia and hypoesthesia in the hands, feet, perioral area, or throat. Jaw spasm, abnormal tongue sensation, dysarthria, eye pain, and a feeling of chest pressure have also been observed. The acute, reversible pattern of sensory neuropathy was observed in about 56% of study patients who received Eloxatin with 5-fluorouracil/leucovorin. In any individual cycle acute neurotoxicity was observed in approximately 30% of patients. In adjuvant patients the median cycle of onset for grade 3 peripheral sensory neuropathy was 9 in the previously treated patients the median number of cycles administered on the Eloxatin with 5-fluorouracil/leucovorin combination arm was 6.


An acute syndrome of pharyngolaryngeal dysesthesia seen in 1–2% (grade 3/4) of patients previously untreated for advanced colorectal cancer, and the previously treated patients, is characterized by subjective sensations of dysphagia or dyspnea, without any laryngospasm or bronchospasm (no stridor or wheezing). Ice (mucositis prophylaxis) should be avoided during the infusion of Eloxatin because cold temperature can exacerbate acute neurological symptoms.


A persistent (>14 days), primarily peripheral, sensory neuropathy that is usually characterized by paresthesias, dysesthesias, hypoesthesias, but may also include deficits in proprioception that can interfere with daily activities (e.g., writing, buttoning, swallowing, and difficulty walking from impaired proprioception). These forms of neuropathy occurred in 48% of the study patients receiving Eloxatin with 5-fluorouracil/leucovorin. Persistent neuropathy can occur without any prior acute neuropathy event. The majority of the patients (80%) who developed grade 3 persistent neuropathy progressed from prior Grade 1 or 2 events. These symptoms may improve in some patients upon discontinuation of Eloxatin.


In the adjuvant colon cancer trial, neuropathy was graded using a prelisted module derived from the Neuro-Sensory section of the National Cancer Institute Common Toxicity Criteria (NCI CTC) scale, Version 1, as follows:















Table 1 - NCI CTC Grading for Neuropathy in Adjuvant Patients
GradeDefinition
Grade 0No change or none
Grade 1Mild paresthesias, loss of deep tendon reflexes
Grade 2Mild or moderate objective sensory loss, moderate paresthesias
Grade 3Severe objective sensory loss or paresthesias that interfere with function
Grade 4Not applicable

Peripheral sensory neuropathy was reported in adjuvant patients treated with the Eloxatin combination with a frequency of 92% (all grades) and 13% (grade 3). At the 28-day follow-up after the last treatment cycle, 60% of all patients had any grade (Grade 1=40%, Grade 2=16%, Grade 3=5%) peripheral sensory neuropathy decreasing to 39% at 6 months follow-up (Grade 1=31%, Grade 2=7%, Grade 3=1%) and 21% at 18 months of follow-up (Grade 1=17%, Grade 2=3%, Grade 3=1%).


In the advanced colorectal cancer studies, neuropathy was graded using a study-specific neurotoxicity scale, which was different from the NCI CTC scale, Version 2.0 (see below).













Table 2 - Grading Scale for Paresthesias/Dysesthesias in Advanced Colorectal Cancer Patients
GradeDefinition
Grade 1Resolved and did not interfere with functioning
Grade 2Interfered with function but not daily activities
Grade 3Pain or functional impairment that interfered with daily activities
Grade 4Persistent impairment that is disabling or life-threatening

Overall, neuropathy was reported in patients previously untreated for advanced colorectal cancer in 82% (all grades) and 19% (grade 3/4), and in the previously treated patients in 74% (all grades) and 7% (grade 3/4) events. Information regarding reversibility of neuropathy was not available from the trial for patients who had not been previously treated for colorectal cancer.



 Reversible Posterior Leukoencephalopathy Syndrome


 Reversible Posterior Leukoencephalopathy Syndrome (RPLS, also known as PRES, Posterior Reversible Encephalopathy Syndrome) has been observed in clinical trials (< 0.1%) and postmarketing experience. Signs and symptoms of RPLS could be headache, altered mental functioning, seizures, abnormal vision from blurriness to blindness, associated or not with hypertension [see Adverse Reactions (6.2)]. Diagnosis of RPLS is based upon confirmation by brain imaging.



Pulmonary Toxicity


Eloxatin has been associated with pulmonary fibrosis (<1% of study patients), which may be fatal. The combined incidence of cough and dyspnea was 7.4% (any grade) and <1% (grade 3) with no grade 4 events in the Eloxatin plus infusional 5-fluorouracil/leucovorin arm compared to 4.5% (any grade) and no grade 3 and 0.1% grade 4 events in the infusional 5-fluorouracil/leucovorin alone arm in adjuvant colon cancer patients. In this study, one patient died from eosinophilic pneumonia in the Eloxatin combination arm. The combined incidence of cough, dyspnea and hypoxia was 43% (any grade) and 7% (grade 3 and 4) in the Eloxatin plus 5-fluorouracil/leucovorin arm compared to 32% (any grade) and 5% (grade 3 and 4) in the irinotecan plus 5-fluorouracil/leucovorin arm of unknown duration for patients with previously untreated colorectal cancer. In case of unexplained respiratory symptoms such as non-productive cough, dyspnea, crackles, or radiological pulmonary infiltrates, Eloxatin should be discontinued until further pulmonary investigation excludes interstitial lung disease or pulmonary fibrosis.



Hepatotoxicity


Hepatotoxicity as evidenced in the adjuvant study, by increase in transaminases (57% vs. 34%) and alkaline phosphatase (42% vs. 20%) was observed more commonly in the Eloxatin combination arm than in the control arm. The incidence of increased bilirubin was similar on both arms. Changes noted on liver biopsies include: peliosis, nodular regenerative hyperplasia or sinusoidal alterations, perisinusoidal fibrosis, and veno-occlusive lesions. Hepatic vascular disorders should be considered, and if appropriate, should be investigated in case of abnormal liver function test results or portal hypertension, which cannot be explained by liver metastases [see Clinical Trials Experience (6.1)].



Use in Pregnancy


Pregnancy Category D


Eloxatin may cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies of Eloxatin in pregnant women. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with Eloxatin. [see Use in Specific Populations (8.1)].



Recommended Laboratory Tests


Standard monitoring of the white blood cell count with differential, hemoglobin, platelet count, and blood chemistries (including ALT, AST, bilirubin and creatinine) is recommended before each Eloxatin cycle [see Dosage and Administration (2)].


There have been reports while on study and from post-marketing surveillance of prolonged prothrombin time and INR occasionally associated with hemorrhage in patients who received Eloxatin plus 5-fluorouracil/leucovorin while on anticoagulants. Patients receiving Eloxatin plus 5-fluorouracil/leucovorin and requiring oral anticoagulants may require closer monitoring.



Adverse Reactions



Clinical Trials Experience


Serious adverse reactions including anaphylaxis and allergic reactions, neuropathy, pulmonary toxicities and hepatotoxicities can occur [See Warnings and Precautions (5.1)].


Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.


More than 1100 patients with stage II or III colon cancer and more than 4,000 patients with advanced colorectal cancer have been treated in clinical studies with Eloxatin. The most common adverse reactions in patients with stage II or III colon cancer receiving adjuvant therapy were peripheral sensory neuropathy, neutropenia, thrombocytopenia, anemia, nausea, increase in transaminases and alkaline phosphatase, diarrhea, emesis, fatigue and stomatitis. The most common adverse reactions in previously untreated and treated patients were peripheral sensory neuropathies, fatigue, neutropenia, nausea, emesis, and diarrhea [see Warnings and Precautions (5)].



Combination Adjuvant Therapy with Eloxatin and Infusional 5-fluorouracil/leucovorin in Patients with Colon Cancer


One thousand one hundred and eight patients with stage II or III colon cancer, who had undergone complete resection of the primary tumor, have been treated in a clinical study with Eloxatin in combination with infusional 5-fluorouracil/leucovorin [see Clinical Studies (14)]. The incidence of grade 3 or 4 adverse reactions was 70% on the Eloxatin combination arm, and 31% on the infusional 5-fluorouracil/leucovorin arm. The adverse reactions in this trial are shown in the tables below. Discontinuation of treatment due to adverse reactions occurred in 15% of the patients receiving Eloxatin and infusional 5-fluorouracil/leucovorin. Both 5-fluorouracil/leucovorin and Eloxatin are associated with gastrointestinal or hematologic adverse reactions. When Eloxatin is administered in combination with infusional 5-fluorouracil/leucovorin, the incidence of these events is increased.


The incidence of death within 28 days of last treatment, regardless of causality, was 0.5% (n=6) in both the Eloxatin combination and infusional 5-fluorouracil/leucovorin arms, respectively. Deaths within 60 days from initiation of therapy were 0.3% (n=3) in both the Eloxatin combination and infusional 5-fluorouracil/leucovorin arms, respectively. On the Eloxatin combination arm, 3 deaths were due to sepsis/neutropenic sepsis, 2 from intracerebral bleeding and one from eosinophilic pneumonia. On the 5-fluorouracil/leucovorin arm, one death was due to suicide, 2 from Steven-Johnson Syndrome (1 patient also had sepsis), 1 unknown cause, 1 anoxic cerebral infarction and 1 probable abdominal aorta rupture.


The following table provides adverse reactions reported in the adjuvant therapy colon cancer clinical trial [see Clinical Studies (14)] by body system and decreasing order of frequency in the Eloxatin and infusional 5-fluorouracil/leucovorin arm for events with overall incidences ≥ 5% and for NCI grade 3/4 events with incidences ≥ 1%.
























































































Table 3 - Adverse Reactions Reported in Patients with Colon Cancer receiving Adjuvant Treatment (≥5% of all patients and with ≥1% NCI Grade 3/4 events)
Eloxatin + 5-FU/LV

N=1108
5-FU/LV

N=1111
Adverse reaction

(WHO/Pref)
All Grades

(%)
Grade 3/4

(%)
All Grades

(%)
Grade 3/4

(%)

*

Includes thrombosis related to the catheter

Any Event100709931
Allergy/Immunology
Allergic Reaction1032<1
Constitutional Symptoms/Pain
Fatigue444381
Abdominal Pain181172
Dermatology/Skin
Skin Disorder322362
Injection Site Reaction*113103
Gastrointestinal
Nausea745612
Diarrhea5611487
Vomiting476241
Stomatitis423402
Anorexia1318<1
Fever/Infection
Fever271121
Infection254253
Neurology
Overall Peripheral Sensory Neuropathy921216<1

The following table provides adverse reactions reported in the adjuvant therapy colon cancer clinical trial [see Clinical Studies (14)] by body system and decreasing order of frequency in the Eloxatin and infusional 5-fluorouracil/leucovorin arm for events with overall incidences ≥ 5% but with incidences <1% NCI grade 3/4 events.

























































Table 4 - Adverse Reactions Reported in Patients with Colon Cancer receiving Adjuvant Treatment (≥ 5% of all patients, but with <1% NCI Grade 3/4 events)
Eloxatin + 5-FU/LV

N=1108
5-FU/LV

N=1111
Adverse reaction

(WHO/Pref)
All Grades (%)All Grades (%)
Allergy/Immunology
Rhinitis68
Constitutional Symptoms/Pain/Ocular/Visual
Epistaxis1612
Weight Increase1010
Conjunctivitis915
Headache75
Dyspnea53
Pain55
Lacrimation Abnormal412
Dermatology/Skin
Alopecia3028
Gastrointestinal
Constipation2219
Taste Perversion128
Dyspepsia85
Metabolic
Phosphate Alkaline increased4220
Neurology
Sensory Disturbance81

Although specific events can vary, the overall frequency of adverse reactions was similar in men and women and in patients <65 and ≥65 years. However, the following grade 3/4 events were more common in females: diarrhea, fatigue, granulocytopenia, nausea and vomiting. In patients ≥65 years old, the incidence of grade 3/4 diarrhea and granulocytopenia was higher than in younger patients. Insufficient subgroup sizes prevented analysis of safety by race. The following additional adverse reactions, were reported in ≥2% and <5% of the patients in the Eloxatin and infusional 5-fluorouracil/leucovorin combination arm (listed in decreasing order of frequency): pain, leukopenia, weight decrease, coughing.


The number of patients who developed secondary malignancies was similar; 62 in the Eloxatin combination arm and 68 in the infusional 5-fluorouracil/leucovorin arm. An exploratory analysis showed that the number of deaths due to secondary malignancies was 1.96% in the Eloxatin combination arm and 0.98% in infusional 5-fluorouracil/leucovorin arm. In addition, the number of cardiovascular deaths was 1.4% in the Eloxatin combination arm as compared to 0.7% in the infusional 5-fluorouracil/leucovorin arm. Clinical significance of these findings is unknown.



Patients Previously Untreated for Advanced Colorectal Cancer


Two hundred and fifty-nine patients were treated in the Eloxatin and 5-fluorouracil/leucovorin combination arm of the randomized trial in patients previously untreated for advanced colorectal cancer [see Clinical Studies (14)]. The adverse reaction profile in this study was similar to that seen in other studies and the adverse reactions in this trial are shown in the tables below.

Both 5-fluorouracil and Eloxatin are associated with gastrointestinal and hematologic adverse reactions. When Eloxatin is administered in combination with 5-fluorouracil, the incidence of these events is increased.


The incidence of death within 30 days of treatment in the previously untreated for advanced colorectal cancer study, regardless of causality, was 3% with the Eloxatin and 5-fluorouracil/leucovorin combination, 5% with irinotecan plus 5-fluorouracil/leucovorin, and 3% with Eloxatin plus irinotecan. Deaths within 60 days from initiation of therapy were 2.3% with the Eloxatin and 5-fluorouracil/leucovorin combination, 5.1% with irinotecan plus 5-fluorouracil/leucovorin, and 3.1% with Eloxatin plus irinotecan.

The following table provides adverse reactions reported in the previously untreated for advanced colorectal cancer study [see Clinical Studies (14)] by body system and decreasing order of frequency in the Eloxatin and 5-fluorouracil/leucovorin combination arm for events with overall incidences ≥5% and for grade 3/4 events with incidences ≥1%.


































































































































































































































































































Table 5 – Adverse Reactions Reported in Patients Previously Untreated for Advanced Colorectal Cancer Clinical Trial (≥5% of all patients and with ≥1% NCI Grade 3/4 events)
Eloxatin + 5-FU/LV

N=259
irinotecan + 5-FU/LV

N=256
Eloxatin + irinotecan

N=258
Adverse reaction

(WHO/Pref)
All Grades

(%)
Grade 3/4

(%)
All Grades

(%)
Grade 3/4

(%)
All Grades

(%)
Grade 3/4

(%)

*

Not otherwise specified


Absolute neutrophil count

Any Event998298709976
Allergy/Immunology
Hypersensitivity1225061
Cardiovascular
Thrombosis656633
Hypotension536343
Constitutional Symptoms/Pain/Ocular/Visual
Fatigue70758116616
Abdominal Pain2983173910
Myalgia1426092
Pain715161
Vision abnormal502161
Neuralgia500021
Dermatology/Skin
Skin reaction – hand/foot712110
Injection site reaction601041
Gastrointestinal
Nausea71667158319
Diarrhea561265297625
Vomiting41443136423
Stomatitis380251191
Anorexia352254275
Constipation324272212
Diarrhea-colostomy132167163
Gastrointestinal NOS*524232
Hematology/Infection
Infection normal ANC1045172
Infection low ANC88121198
Lymphopenia624152
Febrile neutropenia4415141211
Hepatic/Metabolic/Laboratory/Renal
Hyperglycemia142113123
Hypokalemia1137462
Dehydration951611147
Hypoalbuminemia805291
Hyponatremia827441
Urinary frequency512131
Neurology
Overall Neuropathy8219182697
Paresthesias7718162626
Pharyngo-laryngeal dysesthesias38210281
Neuro-sensory1212091
Neuro NOS*101010
Pulmonary
Cough351252171
Dyspnea187143112
Hiccups512032

The following table provides adverse reactions reported in the previously untreated for advanced colorectal cancer study [see Clinical Studies (14)] by body system and decreasing order of frequency in the Eloxatin and 5-fluorouracil/leucovorin combination arm for events with overall incidences ≥5% but with incidences <1% NCI Grade 3/4 events.

















Table 6 - Adverse Reactions Reported in Patients Previously Untreated for Advanced Colorectal Cancer Clinical Trial (≥5% of all patients but with < 1% NCI Grade 3/4 events)
Eloxatin + 5-FU/LV

N=259
irinotecan + 5-FU/LV

N=256
Eloxatin + irinotecan

N=258
Adverse reaction

(WHO/Pref)
All Grades

(%)
All Grades

(%)
All Grades

(%)

*

Absolute neutrophil count

Allergy/Immunology
Rash1147

Tuesday, 6 December 2011

Foligan




Foligan may be available in the countries listed below.


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Allopurinol

Allopurinol is reported as an ingredient of Foligan in the following countries:


  • Germany

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Saturday, 3 December 2011

Umbra MD




Umbra MD may be available in the countries listed below.


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Barium Sulfate

Barium Sulfate is reported as an ingredient of Umbra MD in the following countries:


  • Japan

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Saturday, 5 November 2011

Bevonazole




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Itraconazole

Itraconazole is reported as an ingredient of Bevonazole in the following countries:


  • Greece

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