Monday, 3 October 2016

rituximab


Generic Name: rituximab (ri TUX i mab)

Brand Names: Rituxan


What is rituximab?

Rituximab is a cancer medication that interferes with the growth of cancer cells and slows their growth and spread in the body.


Rituximab is used in combination with other cancer medicines to treat non-Hodgkin's lymphoma or chronic lymphocytic leukemia. Rituximab is also used in combination with another drug called methotrexate to treat symptoms of adult rheumatoid arthritis.


Rituximab is also used in combination with steroid medicines to treat certain rare disorders that cause inflammation of the blood vessels.


Rituximab may also be used for purposes not listed in this medication guide.


What is the most important information I should know about rituximab?


You should not receive this medication if you have ever had a severe allergic reaction to rituximab, or if you are allergic to mouse protein. Some people receiving a rituximab injection have had a reaction to the infusion (when the medicine is injected into the vein). Tell your caregiver right away if you feel dizzy, weak, nauseated, light-headed, itchy, or if you have a fever, chills, muscle pain, sneezing, sore throat, trouble breathing, or pain in your chest or shoulders. Infusion reactions often occur within the first 24 hours after the start of your rituximab infusion.

To be sure this medication is not causing harmful effects, your blood may need to be tested often. Your kidney or liver function may also need to be tested. Visit your doctor regularly.


If you have hepatitis B you may develop liver symptoms after you stop using this medication, even months after stopping. Your doctor may want to check your liver function at regular visits for several months after you stop using rituximab. Visit your doctor regularly.


Rituximab increases the risk of a serious viral infection of the brain that can lead to disability or death. This risk is higher if you have a weak immune system or are receiving certain medicines. Call your doctor right away if you have symptoms such as change in your mental state, problems with speech or walking, or decreased vision. These symptoms may start gradually and get worse quickly.

What should I discuss with my healthcare provider before receiving rituximab?


You should not receive this medication if you have ever had a severe allergic reaction to rituximab, or if you are allergic to mouse protein.

To make sure you can safely use rituximab, tell your doctor if you have any of these other conditions:



  • liver disease or hepatitis B (or if you are a carrier of hepatitis B);




  • kidney disease;




  • systemic lupus erythematosus (SLE);




  • lung disease or a breathing disorder;




  • a weak immune system;




  • a history of heart disease, angina (chest pain), or heart rhythm disorder; or




  • a recent or active infection, including herpes, shingles, cytomegalovirus, chickenpox, West Nile virus, hepatitis C, or any infection that keeps coming back or does not clear up.




FDA pregnancy category C. It is not known whether rituximab will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication. It is not known whether rituximab passes into breast milk or if it could harm a nursing baby. Do not take rituximab without telling your doctor if you are breast feeding a baby. Older adults may be more likely to have side effects from rituximab, causing breathing difficulty or heart rhythm problems.

How is rituximab given?


Rituximab is injected into a vein through an IV. You will receive this injection in a clinic or hospital setting.


Before you receive rituximab, you may be given other medications to prevent certain side effects that rituximab can cause.


The medicine is usually given once per week for 4 to 8 weeks. In the treatment of rheumatoid arthritis, you may receive only two injections of rituximab, with 2 weeks in between treatments.


To be sure this medication is not causing harmful effects, your blood may need to be tested often. Your kidney or liver function may also need to be tested. Visit your doctor regularly.


If you have hepatitis B you may develop liver symptoms after you stop using this medication, even months after stopping. Your doctor may want to check your liver function at regular visits for several months after you stop using rituximab. Do not miss any scheduled visits.


If you need surgery, tell the surgeon ahead of time that you are using rituximab.

What happens if I miss a dose?


Call your doctor if you miss an appointment for your rituximab injection.


What happens if I overdose?


Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I avoid while receiving rituximab?


Do not receive a "live" vaccine while using rituximab, and avoid coming into contact with anyone who has recently received a live vaccine. There is a chance that the virus could be passed on to you. Live vaccines include measles, mumps, rubella (MMR), Bacillus Calmette-Guérin (BCG), oral polio, rotavirus, smallpox, typhoid, yellow fever, varicella (chickenpox), H1N1 influenza, and nasal flu vaccine.


Rituximab side effects


Some people receiving a rituximab injection have had a reaction to the infusion (when the medicine is injected into the vein). Tell your caregiver right away if you feel dizzy, weak, nauseated, light-headed, itchy, or if you have a fever, chills, muscle pain, sneezing, sore throat, trouble breathing, or pain in your chest or shoulders. Infusion reactions often occur within the first 24 hours after the start of your rituximab infusion.


Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat. Rituximab increases the risk of a serious viral infection of the brain that can lead to disability or death. This risk is higher if you have a weak immune system or are receiving certain medicines. Call your doctor right away if you have symptoms such as change in your mental state, problems with speech or walking, or decreased vision. These symptoms may start gradually and get worse quickly. Call your doctor at once if you have any of these other serious side effects, even if they occur several months after you receive rituximab, or after your treatment ends.

  • lower back pain, blood in your urine, numbness or tingly feeling around your mouth;




  • urinating less than usual;




  • muscle weakness, tightness, or contraction, overactive reflexes;




  • fast or slow heart rate, weak pulse, feeling short of breath, fainting;




  • uneven heartbeats, wheezing or trouble breathing;




  • confusion, dizziness, loss of balance, sudden numbness or weakness, especially on one side of the body;




  • chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling;




  • fever, chills, cough, body aches, flu symptoms, ongoing cold symptoms such as stuffy nose, sneezing, sore throat;




  • easy bruising or bleeding;




  • pain or burning when you urinate;




  • earache, painful mouth ulcers, skin sores, warmth or swelling with skin redness;




  • a red, raised, blistering, scaly, itchy, or peeling skin rash;




  • severe constipation or stomach pain;




  • black, bloody, or tarry stools; or




  • nausea, upper stomach pain, itching, loss of appetite, dark urine, clay-colored stools, jaundice (yellowing of the skin or eyes).



Less serious side effects may include:



  • pain where the IV needle is placed;




  • mild stomach pain, nausea, or diarrhea;




  • swelling in your hands or feet;




  • muscle or joint pain; or




  • night sweats.



This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.


Rituximab Dosing Information


Usual Adult Dose for non-Hodgkin's Lymphoma:

Information for all healthcare professionals administering rituximab: Do not administer as an intravenous push or bolus. Administer only as an intravenous (IV) infusion. Premedicate before each infusion with acetaminophen and an antihistamine. For RA patients, methylprednisolone 100 mg IV or its equivalent is recommended 30 minutes prior to each infusion. Pneumocystis jiroveci pneumonia (PCP) and anti-herpetic viral prophylaxis is recommended for patients with CLL during treatment and for up to 12 months following treatment as appropriate.

First Infusion: Initiate infusion at a rate of 50 mg/hr. In the absence of infusion toxicity, increase infusion rate by 50 mg/hr increments every 30 minutes, to a maximum of 400 mg/hr.

Subsequent Infusions: Initiate infusion at a rate of 100 mg/hr. In the absence of infusion toxicity, increase rate by 100 mg/hr increments at 30 minute intervals, to a maximum of 400 mg/hr.

Interrupt the infusion or slow the infusion rate for infusion reactions. Continue the infusion at one-half the previous rate upon improvement of symptoms.

Relapsed or Refractory, low-grade or follicular, CD20-positive, B-cell non-Hodgkin's Lymphoma (NHL): 375 mg/m2 IV once weekly for 4 or 8 doses.

Retreatment for Relapsed or Refractory, low-grade or follicular, CD20-positive, B-cell NHL: 375 mg/m2 IV once weekly for 4 doses.

Previously untreated, follicular, CD20-positive, B-cell NHL: 375 mg/m2 IV, administered on Day 1 of each cycle of chemotherapy, for up to 8 doses. In patients with complete or partial response, initiate rituximab maintenance 8 weeks following completion of rituximab in combination with chemotherapy. Administer rituximab as a single agent every 8 weeks for 12 doses.

Non-progressing, Low-grade, CD20-positive, B-cell NHL, after first-line CVP chemotherapy: Following completion of 6 to 8 cycles of CVP chemotherapy, administer 375 mg/m2 IV once weekly for 4 doses at 6 month intervals to a maximum of 16 doses.

Diffuse large B-cell NHL: 375 mg/m2 IV given on day 1 of each cycle of chemotherapy for up to 8 doses.

Chronic Lymphocytic Leukemia (CLL): 375 mg/m2 the day prior to initiation of FC chemotherapy, then 500 mg/m2 on Day 1 of cycles 2 through 6 (every 28 days).

As a required component of ibritumomab tiuxetan therapeutic regimen: rituximab 250 mg/m2 should be infused within 4 hours prior to the administration of Indium-111- (In-111-) ibritumomab tiuxetan and within 4 hours prior to the administration of Yttrium-90- (Y-90-) ibritumomab tiuxetan. Administration of rituximab and In-111-ibritumomab tiuxetan should precede rituximab and Y-90-ibritumomab tiuxetan by 7 to 9 days. (Note: The ibritumomab tiuxetan therapeutic regimen is indicated for the treatment of patients with relapsed or refractory low-grade or follicular B-cell non-Hodgkin's lymphoma, including patients with rituximab refractory follicular non-Hodgkin's lymphoma.)

Usual Adult Dose for Rheumatoid Arthritis:

Information for all healthcare professionals administering rituximab: Do not administer as an intravenous push or bolus. Administer only as an intravenous (IV) infusion. Premedicate before each infusion with acetaminophen and an antihistamine. For RA patients, methylprednisolone 100 mg IV or its equivalent is recommended 30 minutes prior to each infusion. Pneumocystis jiroveci pneumonia (PCP) and anti-herpetic viral prophylaxis is recommended for patients with CLL during treatment and for up to 12 months following treatment as appropriate.

First Infusion: Initiate infusion at a rate of 50 mg/hr. In the absence of infusion toxicity, increase infusion rate by 50 mg/hr increments every 30 minutes, to a maximum of 400 mg/hr.

Subsequent Infusions: Initiate infusion at a rate of 100 mg/hr. In the absence of infusion toxicity, increase rate by 100 mg/hr increments at 30 minute intervals, to a maximum of 400 mg/hr.

Interrupt the infusion or slow the infusion rate for infusion reactions. Continue the infusion at one-half the previous rate upon improvement of symptoms.

Rheumatoid Arthritis: Rituximab is given in combination with methotrexate. Rituximab is given as two 1000 mg IV infusions separated by 2 weeks. Glucocorticoids administered as methylprednisolone 100 mg IV or its equivalent 30 minutes prior to each infusion are recommended to reduce the incidence and severity of infusion reactions. Subsequent courses should be administered every 24 weeks or based on clinical evaluation, but not sooner than every 16 weeks.

Usual Adult Dose for Chronic Lymphocytic Leukemia:

Information for all healthcare professionals administering rituximab: Do not administer as an intravenous push or bolus. Administer only as an intravenous (IV) infusion. Premedicate before each infusion with acetaminophen and an antihistamine. For RA patients, methylprednisolone 100 mg IV or its equivalent is recommended 30 minutes prior to each infusion. Pneumocystis jiroveci pneumonia (PCP) and anti-herpetic viral prophylaxis is recommended for patients with CLL during treatment and for up to 12 months following treatment as appropriate.

First Infusion: Initiate infusion at a rate of 50 mg/hr. In the absence of infusion toxicity, increase infusion rate by 50 mg/hr increments every 30 minutes, to a maximum of 400 mg/hr.

Subsequent Infusions: Initiate infusion at a rate of 100 mg/hr. In the absence of infusion toxicity, increase rate by 100 mg/hr increments at 30 minute intervals, to a maximum of 400 mg/hr.

Interrupt the infusion or slow the infusion rate for infusion reactions. Continue the infusion at one-half the previous rate upon improvement of symptoms.

Chronic Lymphocytic Leukemia (CLL): 375 mg/m2 IV the day prior to the initiation of fludarabine and cyclophosphamide (FC) chemotherapy, then 500 mg/m2 on Day 1 of cycles 2 to 6 (every 28 days).

Pneumocystis jiroveci pneumonia (PCP) and anti-herpetic viral prophylaxis is recommended for patients with CLL during treatment and for up to 12 months following treatment as appropriate.

Usual Adult Dose for Wegener's Granulomatosus:

Information for all healthcare professionals administering rituximab: Do not administer as an intravenous push or bolus. Administer only as an intravenous (IV) infusion. Premedicate before each infusion with acetaminophen and an antihistamine. For RA patients, methylprednisolone 100 mg IV or its equivalent is recommended 30 minutes prior to each infusion. Pneumocystis jiroveci pneumonia (PCP) and anti-herpetic viral prophylaxis is recommended for patients with CLL during treatment and for up to 12 months following treatment as appropriate.

First Infusion: Initiate infusion at a rate of 50 mg/hr. In the absence of infusion toxicity, increase infusion rate by 50 mg/hr increments every 30 minutes, to a maximum of 400 mg/hr.

Subsequent Infusions: Initiate infusion at a rate of 100 mg/hr. In the absence of infusion toxicity, increase rate by 100 mg/hr increments at 30 minute intervals, to a maximum of 400 mg/hr.

Interrupt the infusion or slow the infusion rate for infusion reactions. Continue the infusion at one-half the previous rate upon improvement of symptoms.

Wegener's Granulomatosis (WG) and Microscopic Polyangiitis (MPA): 375 mg/m2 IV administered once weekly for 4 weeks.

Glucocorticoids administered as methylprednisolone 1000 mg IV daily for 1 to 3 days followed by oral prednisone 1 mg/kg/day (not to exceed 80 mg/day and tapered per clinical need) are recommended to treat severe vasculitis symptoms. This regimen should begin within 14 days prior to or with the initiation of rituximab and may continue during and after the 4 week course of rituximab treatment.

Safety and efficacy of treatment with subsequent courses of rituximab have not been established.

PCP prophylaxis is recommended for patients with WG and MPA during treatment and for at least 6 months following the last rituximab infusion.

Usual Adult Dose for Microscopic Polyangiitis:

Information for all healthcare professionals administering rituximab: Do not administer as an intravenous push or bolus. Administer only as an intravenous (IV) infusion. Premedicate before each infusion with acetaminophen and an antihistamine. For RA patients, methylprednisolone 100 mg IV or its equivalent is recommended 30 minutes prior to each infusion. Pneumocystis jiroveci pneumonia (PCP) and anti-herpetic viral prophylaxis is recommended for patients with CLL during treatment and for up to 12 months following treatment as appropriate.

First Infusion: Initiate infusion at a rate of 50 mg/hr. In the absence of infusion toxicity, increase infusion rate by 50 mg/hr increments every 30 minutes, to a maximum of 400 mg/hr.

Subsequent Infusions: Initiate infusion at a rate of 100 mg/hr. In the absence of infusion toxicity, increase rate by 100 mg/hr increments at 30 minute intervals, to a maximum of 400 mg/hr.

Interrupt the infusion or slow the infusion rate for infusion reactions. Continue the infusion at one-half the previous rate upon improvement of symptoms.

Wegener's Granulomatosis (WG) and Microscopic Polyangiitis (MPA): 375 mg/m2 IV administered once weekly for 4 weeks.

Glucocorticoids administered as methylprednisolone 1000 mg IV daily for 1 to 3 days followed by oral prednisone 1 mg/kg/day (not to exceed 80 mg/day and tapered per clinical need) are recommended to treat severe vasculitis symptoms. This regimen should begin within 14 days prior to or with the initiation of rituximab and may continue during and after the 4 week course of rituximab treatment.

Safety and efficacy of treatment with subsequent courses of rituximab have not been established.

PCP prophylaxis is recommended for patients with WG and MPA during treatment and for at least 6 months following the last rituximab infusion.


What other drugs will affect rituximab?


Tell your doctor about all other medicines you use, especially:



  • cisplatin (Platinol);




  • adalimumab (Humira);




  • auranofin (Ridaura);




  • azathioprine (Imuran);




  • cyclosporine (Gengraf, Neoral, Sandimmune);




  • etanercept (Enbrel);




  • infliximab (Remicade);




  • leflunomide (Arava);




  • minocycline (Dynacin, Minocin, Vectrin);




  • sulfasalazine (Azulfidine);




  • blood pressure medications; or




  • medication to treat malaria, such as chloroquine (Aralen) or hydroxychloroquine (Plaquenil, Quineprox).



This list is not complete and other drugs may interact with rituximab. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.



More rituximab resources


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


  • rituximab Intravenous Advanced Consumer (Micromedex) - Includes Dosage Information

  • Rituxan Prescribing Information (FDA)

  • Rituxan Consumer Overview

  • Rituximab Professional Patient Advice (Wolters Kluwer)

  • Rituximab Monograph (AHFS DI)

  • Rituximab MedFacts Consumer Leaflet (Wolters Kluwer)



Compare rituximab with other medications


  • Bullous Pemphigoid
  • Chronic Lymphocytic Leukemia
  • Evan's Syndrome
  • Focal Segmental Glomerulosclerosis
  • Follicular Lymphoma
  • Idiopathic Thrombocytopenic Purpura
  • Microscopic polyangiitis
  • Non-Hodgkin's Lymphoma
  • Pemphigoid
  • Pemphigus
  • Rheumatoid Arthritis
  • Wegener's Granulomatosus


Where can I get more information?


  • Your doctor or pharmacist can provide more information about rituximab.

See also: rituximab side effects (in more detail)


ritodrine Oral, Intravenous


RIT-oh-dreen


Available Dosage Forms:


  • Solution

  • Tablet

Therapeutic Class: Uterine Relaxant


Pharmacologic Class: Beta-2 Adrenergic Agonist


Uses For ritodrine

Ritodrine is used to stop premature labor. ritodrine was available only with your doctor's prescription.


Ritodrine is no longer available in the United States.


Before Using ritodrine


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 ritodrine, the following should be considered:


Allergies


Tell your doctor if you have ever had any unusual or allergic reaction to ritodrine 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.


Pregnancy








Pregnancy CategoryExplanation
All TrimestersBAnimal studies have revealed no evidence of harm to the fetus, however, there are no adequate studies in pregnant women OR animal studies have shown an adverse effect, but adequate studies in pregnant women have failed to demonstrate a risk to the fetus.

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 ritodrine, 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 ritodrine 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.


  • Acebutolol

  • Alprenolol

  • Arotinolol

  • Atenolol

  • Befunolol

  • Betaxolol

  • Bevantolol

  • Bisoprolol

  • Bopindolol

  • Brofaromine

  • Bucindolol

  • Bupranolol

  • Carteolol

  • Carvedilol

  • Celiprolol

  • Clorgyline

  • Dilevalol

  • Esmolol

  • Furazolidone

  • Iproniazid

  • Isocarboxazid

  • Labetalol

  • Landiolol

  • Lazabemide

  • Levobetaxolol

  • Levobunolol

  • Linezolid

  • Mepindolol

  • Metipranolol

  • Metoprolol

  • Moclobemide

  • Nadolol

  • Nebivolol

  • Nialamide

  • Nipradilol

  • Oxprenolol

  • Pargyline

  • Penbutolol

  • Phenelzine

  • Pindolol

  • Procarbazine

  • Propranolol

  • Rasagiline

  • Selegiline

  • Sotalol

  • Talinolol

  • Tertatolol

  • Timolol

  • Toloxatone

  • Tranylcypromine

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. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.


Other Medical Problems


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


  • Diabetes or

  • High blood pressure (hypertension), uncontrolled, or

  • Migraine headaches (or history of)—May make these conditions worse.

  • Heart or blood vessel disease or

  • Overactive thyroid, uncontrolled—May cause serious side effects on the heart, including irregular heartbeat.

Proper Use of ritodrine


Dosing


The dose of ritodrine 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 ritodrine. 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 form (extended-release capsules):
    • Adults: In the first twenty-four hours after the doctor stops your intravenous ritodrine, your dose may be as high as 40 milligrams (mg) every eight hours. After that, the dose is usually 40 mg every eight to twelve hours. Your doctor may want you to take oral ritodrine up until it is time for you to deliver your baby or until your 37th week of pregnancy.


  • For oral dosage form (tablets):
    • Adults: In the first twenty-four hours after the doctor stops your intravenous ritodrine, your dose may be as high as 10 milligrams (mg) every two hours. After that, the dose is usually 10 to 20 mg every four to six hours. Your doctor may want you to take oral ritodrine up until it is time for you to deliver your baby or until your 37th week of pregnancy.


  • For injection dosage form:
    • Adults: 50 to 350 micrograms per minute, injected into a vein.


Missed Dose


If you miss a dose of ritodrine, 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.


Precautions While Using ritodrine


Check with your doctor right away if your contractions begin again or your water breaks.


Do not take other medicines unless they have been discussed with your doctor. This especially includes over-the-counter (nonprescription) medicines for appetite control, asthma, colds, cough, hay fever, or sinus problems since they may increase the unwanted effects of ritodrine.


ritodrine 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
  • Blurred vision

  • chest pain or tightness

  • dizziness or lightheadedness

  • drowsiness

  • dry mouth

  • fast or irregular heartbeat—rare with oral form

  • flushed and dry skin

  • fruit-like breath odor

  • increased urination

  • loss of appetite

  • nausea

  • severe pounding or racing heartbeat—rare with oral form

  • shortness of breath—rare with oral form

  • sleepiness

  • stomachache

  • tiredness

  • troubled breathing (rapid and deep)

  • unusual thirst

  • vomiting

Rare
  • Sore throat or fever

  • yellow eyes or skin

Get emergency help immediately if any of the following symptoms of overdose occur:


  • Fast or irregular heartbeat (severe)

  • nausea or vomiting (severe)

  • nervousness or trembling (severe)

  • shortness of breath (severe)

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
  • Headache

  • reddened skin

  • tremors

Less common or rare
  • Anxiety

  • emotional upset

  • jitteriness, nervousness, or restlessness

  • skin rash

After you stop using ritodrine, it may still produce some side effects that need attention. During this period of time, check with your doctor immediately if you notice the following side effects:


  • Shortness of breath

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: ritodrine Oral, Intravenous side effects (in more detail)



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More ritodrine Oral, Intravenous resources


  • Ritodrine Oral, Intravenous Side Effects (in more detail)
  • Ritodrine Oral, Intravenous Use in Pregnancy & Breastfeeding
  • Ritodrine Oral, Intravenous Drug Interactions
  • Ritodrine Oral, Intravenous Support Group
  • 0 Reviews for Ritodrine Oral, Intravenous - Add your own review/rating


Compare ritodrine Oral, Intravenous with other medications


  • Premature Labor

radiopaque agent- diagnostic Oral, Rectal, Intravenous, Intra-arterial, Intraspinal


Class Name: radiopaque agent- diagnostic (Oral route, Rectal route, Intravenous route, Intra-arterial route, Intraspinal route)


Commonly used brand name(s)

In the U.S.


  • Cystografin

  • Cystografin-Dilute

  • Feridex IV

  • Gastrografin

  • Glofil-125

  • Hypaque Meglumine

  • Hypaque Sodium

  • MD-Gastroview

  • Multihance

  • Perchloracap

  • Renocal-76

  • Sinografin

In Canada


  • Hypaque

  • Renografin-Dip

Available Dosage Forms:


  • Solution

  • Powder for Suspension

  • Capsule

  • Tablet

  • Suspension

Uses For This Medicine


Radiopaque agents are drugs used to help diagnose certain medical problems. They contain iodine, which absorbs x-rays. Depending on how they are given, radiopaque agents build up in a particular area of the body. The resulting high level of iodine allows the x-rays to make a "picture" of the area.


The radiopaque agents are used in the diagnosis of:


  • Biliary tract problems—Diatrizoates, Iodipamide, Iohexol, Iothalamate

  • Blood vessel diseases—Diatrizoates, Iohexol, Iopamidol, Iothalamate, Ioversol, Ioxaglate, Metrizamide

  • Blood vessel diseases of the brain—Diatrizoates, Iohexol, Iopamidol, Iothalamate, Ioversol, Ioxaglate

  • Blood vessel diseases of the heart—Diatrizoates, Iohexol, Iopamidol, Iothalamate, Ioversol, Ioxaglate, Metrizamide

  • Brain diseases and tumors—Diatrizoates, Iohexol, Iopamidol, Iothalamate, Ioversol, Ioxaglate, Metrizamide

  • Breast lesions—Diatrizoates

  • Heart disease—Diatrizoates, Iohexol, Iopamidol, Iothalamate, Ioversol, Ioxaglate, Metrizamide

  • Impaired flow of cerebrospinal fluid in brain—Iohexol, Iopamidol, Metrizamide

  • Kidney diseases—Diatrizoates, Iothalamate, Ioversol, Ioxaglate

  • Joint diseases—Diatrizoates, Iohexol, Iothalamate, Ioxaglate, Metrizamide

  • Liver diseases—Diatrizoates, Iohexol, Iothalamate, Ioversol, Ioxaglate

  • Pancreas disease—Diatrizoates, Iohexol, Iothalamate, Ioversol, Ioxaglate

  • Spinal disk diseases—Diatrizoates

  • Spleen diseases—Diatrizoates, Iothalamate

  • Stomach and intestinal problems—Diatrizoates, Iohexol

  • Urinary tract problems—Diatrizoates, Iohexol, Iopamidol, Iothalamate, Ioversol, Ioxaglate, Metrizamide

Radiopaque agents are taken by mouth or given by enema or injection. X-rays are then used to check if there are any problems with the stomach, intestines, kidneys, or other parts of the body.


Some radiopaque agents, such as iohexol, iopamidol, and metrizamide are given by injection into the spinal canal. X-rays are then used to help diagnose problems or diseases in the head, spinal canal, and nervous system.


The doses of radiopaque agents will be different for different patients and depend on the type of test. The strength of the solution is determined by how much iodine it contains. Different tests will require a different strength and amount of solution depending on the age of the patient, the contrast needed, and the x-ray equipment used.


A catheter or syringe is used to put the solution of the radiopaque agent into the bladder or ureters to help diagnose problems or diseases of the kidneys or other areas of the urinary tract. It may also be placed into the uterus and fallopian tubes to help diagnose problems or disease of those organs. After the test is done, the patient expels most of the solution by urinating (after bladder or ureter studies) or from the vagina (after uterine or fallopian tube studies).


Radiopaque agents are to be used only by or under the direct supervision of a doctor.


Before Using This Medicine


In deciding to receive a diagnostic test, the risks of taking the test must be weighed against the good it will do. This is a decision you and your doctor will make. For these tests, the following should be considered:


Allergies


Tell your doctor if you have ever had any unusual or allergic reaction to medicines in this group 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


Children, especially those with other medical problems, may be especially sensitive to the effects of radiopaque agents. This may increase the chance of side effects.


Geriatric


Elderly people are especially sensitive to the effects of radiopaque agents. This may increase the chance of side effects.


Pregnancy


Studies have not been done in humans with most of the radiopaque agents. However, iohexol, iopamidol, iothalamate, ioversol, ioxaglate, and metrizamide have not been shown to cause birth defects or other problems in animal studies. Some of the radiopaque agents, such as diatrizoates have, on rare occasions, caused hypothyroidism (underactive thyroid) in the baby when they were taken late in the pregnancy. Also, x-rays of the abdomen are usually not recommended during pregnancy. This is to avoid exposing the fetus to radiation. Be sure you have discussed this with your doctor.


Breast Feeding


Although some of these radiopaque agents pass into the breast milk, they have not been shown to cause problems in nursing babies. However, it may be necessary for you to stop breast-feeding temporarily after receiving a radiopaque agent. Be sure you have discussed this with your doctor.


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. Tell your healthcare professional if you are taking any other prescription or nonprescription (over-the-counter [OTC]) medicine.


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. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.


Other Medical Problems


The presence of other medical problems may affect the use of diagnostic tests in this class. Make sure you tell your doctor if you have any other medical problems, especially:


  • Acute kidney problems due to a severe liver disorder (hepato-renal syndrome [HRS]) or

  • Acute kidney problems before, during, or after a liver transplant or

  • Severe kidney problems, acute or chronic—The use of a gadolinium-based contrast agent (GBCA) should be avoided in patients with severe kidney problems. The risk of nephrogenic systemic fibrosis (NSF), a very serious disease affecting the skin, muscle, and internal organs, may be increased .

  • Asthma, hay fever, or other allergies (history of)—If you have a history of these conditions, the risk of having a reaction, such as an allergic reaction to the radiopaque agent, is greater.

  • High blood pressure (severe) or

  • Pheochromocytoma (PCC)—Injection of the radiopaque agent may cause a dangerous rise in blood pressure.

  • Liver disease—The radiopaque agent may build up in the body and cause side effects.

  • Multiple myeloma (bone cancer)—Serious kidney problems may develop in patients with this condition.

  • Overactive thyroid—A sudden increase in symptoms, such as fast heartbeat or palpitations, unusual tiredness or weakness, nervousness, excessive sweating, or muscle weakness may occur.

  • Sickle cell disease—The radiopaque agent may promote the formation of abnormal blood cells.

  • Type 2 diabetes mellitus—There is a greater risk of having kidney problems.

Proper Use of This Medicine


Your doctor may have special instructions for you in preparation for your test. He or she might prescribe a special diet or use of a laxative, depending on the type of test. If you have not received such instructions or if you do not understand them, check with your doctor in advance.


For some tests your doctor may tell you not to eat for several hours before having the test. This is to prevent any food from coming back up and entering your lungs during the test. You may be allowed to drink small amounts of clear liquids; however, check first with your doctor.


If you are on hemodialysis and treated with a gadolinium-based contrast agent (GBCA), your doctor may perform hemodialysis immediately after you receive the contrast agent .


Precautions While Using This Medicine


Make sure your doctor knows if you are planning to have any thyroid tests in the near future. Even after several weeks or months the results of the thyroid test may be affected by the iodine in this agent.


Seek immediate medical attention if you experience burning or itching of the skin; reddened or darkened patches; skin swelling, hardening and/or tightening; yellow raised spots on the whites of the eyes; joint stiffness; limited range of motion in the arms and legs; pain that is deep in the hip bone or ribs; or muscle weakness. These may be symptoms of a very serious disease called nephrogenic systemic fibrosis (NSF) .


Side Effects of This Medicine


Along with its needed effects, radiopaque agents can cause serious side effects such as allergic reactions. These effects may occur almost immediately or a few minutes after the radiopaque agent is given. Although these serious side effects appear only rarely, your health care professional will be prepared to give you immediate medical attention if needed. If you have any questions about this, check with your doctor.


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


With injection into the spinal canalRare
  • Hallucinations (seeing hearing, or feeling things that are not there)

  • paralysis of one side of body or of legs and arms

For patients receiving gadolinium-based contrast agents (GBCAs)Incidence not known
  • Burning or itching of the skin

  • joint stiffness

  • limited range of motion in the arms, hands, legs, or feet

  • muscle weakness

  • pain deep in the hip bone or ribs

  • reddened or darkened patches on the skin

  • skin swelling, hardening and/or tightening

  • yellow raised spots on the whites of the eyes

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:


With oral or rectal useLess common
  • Diarrhea or laxative effect

With injection into a vein or an arteryMore common
  • Unusual warmth and flushing of skin

Less common
  • Chills

  • dizziness or lightheadedness

  • headache

  • nausea or vomiting

  • pain or burning at the place of injection

  • sweating

  • unusual or metallic taste

  • unusual thirst

With injection into the spinal canalMore common
  • Backache

  • dizziness

  • headache (mild to moderate)

  • nausea and vomiting (mild to moderate)

  • stiffness of neck

Less common or rare
  • Difficult urination

  • drowsiness

  • headache (severe)

  • increased sensitivity of eyes to light

  • increased sweating

  • loss of appetite

  • ringing or buzzing in ears

  • unusual tiredness or weakness

Not all of the side effects listed above have been reported for each of these agents, but they have been reported for at least one of them. There are some similarities among these agents, so many of the above side effects may occur with any of them.


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.



The information contained in the Thomson Healthcare (Micromedex) products as delivered by Drugs.com is intended as an educational aid only. It is not intended as medical advice for individual conditions or treatment. It is not a substitute for a medical exam, nor does it replace the need for services provided by medical professionals. Talk to your doctor, nurse or pharmacist before taking any prescription or over the counter drugs (including any herbal medicines or supplements) or following any treatment or regimen. Only your doctor, nurse, or pharmacist can provide you with advice on what is safe and effective for you.


The use of the Thomson Healthcare products is at your sole risk. These products are provided "AS IS" and "as available" for use, without warranties of any kind, either express or implied. Thomson Healthcare and Drugs.com make no representation or warranty as to the accuracy, reliability, timeliness, usefulness or completeness of any of the information contained in the products. Additionally, THOMSON HEALTHCARE MAKES NO REPRESENTATION OR WARRANTIES AS TO THE OPINIONS OR OTHER SERVICE OR DATA YOU MAY ACCESS, DOWNLOAD OR USE AS A RESULT OF USE OF THE THOMSON HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Healthcare does not assume any responsibility or risk for your use of the Thomson Healthcare products.

Rasburicase


Pronunciation: ras-BURE-i-kase
Generic Name: Rasburicase
Brand Name: Elitek

Rasburicase can cause a severe allergic reaction. If you develop new symptoms such as chest pain, trouble breathing, severe dizziness, a rash, or hives, stop using Rasburicase and seek immediate medical attention. Do not restart Rasburicase if a severe allergic reaction has occurred. Consult your doctor or pharmacist for more details.


Do not use Rasburicase if you have a metabolic condition called glucose-6-phosphate dehydrogenase (G6PD) deficiency because it can severely damage your red blood cells, leading to anemia (hemolysis). If you are of African or Mediterranean descent, you may be at higher risk for G6PD deficiency and should be tested to see if you have this condition before starting Rasburicase.


Rasburicase can cause a condition that affects the ability of your red blood cells to carry oxygen (methemoglobinemia). Do not restart Rasburicase if this effect occurs. Consult your doctor for more details.


Rasburicase can interfere with accurate measurements of uric acid in the blood, resulting in falsely low levels. Be sure to tell all lab personnel that you are using Rasburicase.





Rasburicase is used for:

Preventing high blood levels of uric acid from occurring in patients with certain types of cancer (eg, leukemia, lymphoma, solid malignant tumors) who are receiving cancer chemotherapy treatment.


Rasburicase is a urate-oxidase enzyme. When chemotherapy is given, cancer cells are destroyed, releasing large amounts of uric acid into the blood. Rasburicase works by allowing uric acid to be more easily removed from the body by the kidneys.


Do NOT use Rasburicase if:


  • you are allergic to any ingredient in Rasburicase

  • you have a history of blood problems such as methemoglobinemia (a bluish discoloration to the skin and mucous membranes) or hemolysis after receiving Rasburicase

  • you have a metabolic condition called G6PD deficiency

Contact your doctor or health care provider right away if any of these apply to you.



Before using Rasburicase:


Some medical conditions may interact with Rasburicase. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:


  • if you are pregnant, planning to become pregnant, or are breast-feeding

  • if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement

  • if you have allergies to medicines, foods, or other substances

  • if you have kidney disease or are dehydrated

Some MEDICINES MAY INTERACT with Rasburicase. However, no specific interactions with Rasburicase are known at this time.


Ask your health care provider if Rasburicase may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.


How to use Rasburicase:


Use Rasburicase as directed by your doctor. Check the label on the medicine for exact dosing instructions.


  • Rasburicase is usually given as an injection at your doctor's office, hospital, or clinic. Ask your doctor or pharmacist any questions that you may have about Rasburicase.

  • Do not shake Rasburicase.

  • Do not use Rasburicase if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged.

  • Keep this product, as well as syringes and needles, out of the reach of children and pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.

  • If you miss a dose of Rasburicase, contact your doctor immediately to establish a new dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Rasburicase.



Important safety information:


  • Rasburicase may interfere with certain lab tests, including uric acid tests. Be sure your doctor and lab personnel know you are using Rasburicase because they must follow special procedures to process your blood samples.

  • Lab tests, including uric acid levels, may be performed while you use Rasburicase. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.

  • Use Rasburicase with extreme caution in CHILDREN younger than 2 years old; they may be more sensitive to its effects.

  • PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Rasburicase while you are pregnant. It is not known if Rasburicase is found in breast milk. Do not breast-feed while taking Rasburicase.


Possible side effects of Rasburicase:


All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:



Constipation; diarrhea; headache; mouth sores or ulcers; nausea; stomach pain; vomiting.



Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blue or gray skin color; chest pain; chills; coughing up blood; dark urine; fever; irregular heartbeat; numbness or tingling of the skin; persistent sore throat; severe dizziness; shortness of breath, trouble breathing, or wheezing; swelling of the hands or feet; weakness; yellowing of the eyes and skin.



This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.


See also: Rasburicase side effects (in more detail)


If OVERDOSE is suspected:


Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately.


Proper storage of Rasburicase:

Rasburicase is usually handled and stored by a health care provider. If you are using Rasburicase at home, store Rasburicase as directed by your pharmacist or health care provider. Keep Rasburicase out of the reach of children and away from pets.


General information:


  • If you have any questions about Rasburicase, please talk with your doctor, pharmacist, or other health care provider.

  • Rasburicase is to be used only by the patient for whom it is prescribed. Do not share it with other people.

  • If your symptoms do not improve or if they become worse, check with your doctor.

  • Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Rasburicase. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.



Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Rasburicase resources


  • Rasburicase Side Effects (in more detail)
  • Rasburicase Use in Pregnancy & Breastfeeding
  • Rasburicase Support Group
  • 0 Reviews for Rasburicase - Add your own review/rating


  • Rasburicase Monograph (AHFS DI)

  • Rasburicase Professional Patient Advice (Wolters Kluwer)

  • rasburicase Concise Consumer Information (Cerner Multum)

  • rasburicase Intravenous Advanced Consumer (Micromedex) - Includes Dosage Information

  • Elitek Prescribing Information (FDA)



Compare Rasburicase with other medications


  • Hyperuricemia Secondary to Chemotherapy

Renagel



sevelamer hydrochloride

Dosage Form: tablet
FULL PRESCRIBING INFORMATION

Indications and Usage for Renagel


Renagel®1 (sevelamer hydrochloride) is indicated for the control of serum phosphorus in patients with chronic kidney disease (CKD) on dialysis. The safety and efficacy of Renagel in CKD patients who are not on dialysis have not been studied.



1

  Renagel is a Registered Trademark of Genzyme Corporation.


Renagel Dosage and Administration


Patients Not Taking a Phosphate Binder. The recommended starting dose of Renagel is 800 to 1600 mg, which can be administered as one or two 800 mg Renagel® Tablets or two to four 400 mg Renagel® Tablets, with meals based on serum phosphorus level. Table 1 provides recommended starting doses of Renagel for patients not taking a phosphate binder.
















Table 1. Starting Dose for Dialysis Patients Not Taking a Phosphate Binder
Serum PhosphorusRenagel® 800 mgRenagel® 400 mg

> 5.5 and < 7.5 mg/dL



1 tablet three times daily with meals



2 tablets three times daily with meals



≥ 7.5 and < 9.0 mg/dL



2 tablets three times daily with meals



3 tablets three times daily with meals



≥ 9.0 mg/dL



2 tablets three times daily with meals



4 tablets three times daily with meals


Patients Switching From Calcium Acetate. In a study in 84 CKD patients on hemodialysis, a similar reduction in serum phosphorus was seen with equivalent doses (approximately mg for mg) of Renagel and calcium acetate. Table 2 gives recommended starting doses of Renagel based on a patient’s current calcium acetate dose.
















Table 2. Starting Dose for Dialysis Patients Switching From Calcium Acetate to Renagel
Calcium Acetate 667 mg

(Tablets per meal)
Renagel® 800 mg

(Tablets per meal)
Renagel® 400 mg

(Tablets per meal)

1 tablet



1 tablet



2 tablets



2 tablets



2 tablets



3 tablets



3 tablets



3 tablets



5 tablets


Dose Titration for All Patients Taking Renagel. Dosage should be adjusted based on the serum phosphorus concentration with a goal of lowering serum phosphorus to 5.5 mg/dL or less. The dose may be increased or decreased by one tablet per meal at two week intervals as necessary. Table 3 gives a dose titration guideline. The average dose in a Phase 3 trial designed to lower serum phosphorus to 5.0 mg/dL or less was approximately three Renagel 800 mg tablets per meal. The maximum average daily Renagel dose studied was 13 grams.












Table 3. Dose Titration Guideline
Serum Phosphorus
Renagel® Dose

>5.5 mg/dL



Increase 1 tablet per meal at 2 week intervals



3.5 - 5.5 mg/dL



Maintain current dose



<3.5 mg/dL



Decrease 1 tablet per meal



Dosage Forms and Strengths


800 mg and 400 mg Tablets.



Contraindications


Renagel is contraindicated in patients with bowel obstruction.



Warnings and Precautions



Gastrointestinal Adverse Events


Cases of dysphagia and esophageal tablet retention have been reported in association with use of the tablet formulation of sevelamer, some requiring hospitalization and intervention. Consider using sevelamer suspension in patients with a history of swallowing disorders.


Cases of bowel obstruction and perforation have also been reported with sevelamer use.


Patients with dysphagia, swallowing disorders, severe gastrointestinal (GI) motility disorders including severe constipation, or major GI tract surgery were not included in the Renagel clinical studies.



Monitor Serum Chemistries


Bicarbonate and chloride levels should be monitored.



Monitor for Reduced Vitamins D, E, K (clotting factors) and Folic Acid Levels


In preclinical studies in rats and dogs, sevelamer hydrochloride reduced vitamins D, E, and K (coagulation parameters) and folic acid levels at doses of 6-10 times the recommended human dose. In short-term clinical trials, there was no evidence of reduction in serum levels of vitamins.  However, in a one-year clinical trial, 25-hydroxyvitamin D (normal range 10 to 55 ng/mL) fell from 39 ± 22 ng/mL to 34 ± 22 ng/mL (p<0.01) with sevelamer hydrochloride treatment. Most (approximately 75%) patients in sevelamer hydrochloride clinical trials received vitamin supplements, which is typical of patients on dialysis.



Adverse Reactions



Clinical Trials Experience


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


In a parallel design study of sevelamer hydrochloride with treatment duration of 52 weeks, adverse reactions reported for sevelamer hydrochloride (n=99) were similar to those reported for the active-control group (n=101). Overall adverse reactions among those treated with sevelamer hydrochloride occurring in > 5% of patients included: vomiting (22%), nausea (20%), diarrhea (19%), dyspepsia (16%), abdominal pain (9%), flatulence (8%) and constipation (8%). A total of 27 patients treated with sevelamer and 10 patients treated with comparator withdrew from the study due to adverse reactions.


Based on studies of 8-52 weeks, the most common reason for withdrawal from Renagel was gastrointestinal adverse reactions (3-16%).


In one hundred and forty-three peritoneal dialysis patients studied for 12 weeks most adverse reactions were similar to adverse reactions observed in hemodialysis patients. The most frequently occurring treatment emergent serious adverse reaction was peritonitis (8 reactions in 8 patients [8%] in the sevelamer group and 2 reactions in 2 patients [4%] on active-control). Thirteen patients (14%) in the sevelamer group and 9 patients (20%) in the active-control group discontinued, mostly for gastrointestinal adverse reactions. Patients on peritoneal dialysis should be closely monitored to ensure the reliable use of appropriate aseptic technique with the prompt recognition and management of any signs and symptoms associated with peritonitis.



Postmarketing Experience


The following adverse reactions have been identified during post-approval use of sevelamer hydrochloride (Renagel®): pruritus, rash, abdominal pain, fecal impaction and uncommon cases of ileus, intestinal obstruction, and intestinal perforation. Appropriate medical management should be given to patients who develop constipation or have worsening of existing constipation to avoid severe complications.


Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency or to establish a causal relationship to drug exposure.



Drug Interactions


Renagel has been studied in human drug-drug interaction studies with ciprofloxacin, digoxin, warfarin, enalapril, metoprolol and iron.



Ciprofloxacin


In a study of 15 healthy subjects, a co-administered single dose of 7 Renagel capsules (approximately 2.8 g) decreased the bioavailability of ciprofloxacin by approximately 50%.



Digoxin


In 19 healthy subjects receiving 6 Renagel capsules three times a day with meals for 2 days, Renagel did not alter the pharmacokinetics of a single dose of digoxin.



Warfarin


In 14 healthy subjects receiving 6 Renagel capsules three times a day with meals for 2 days, Renagel did not alter the pharmacokinetics of a single dose of warfarin.



Enalapril


In 28 healthy subjects a single dose of 6 Renagel capsules did not alter the pharmacokinetics of a single dose of enalapril.



Metoprolol


In 31 healthy subjects a single dose of 6 Renagel capsules did not alter the pharmacokinetics of a single dose of metoprolol.



Iron


In 23 healthy subjects, a single dose of 7 Renagel capsules did not alter the absorption of a single oral dose of iron as 200 mg exsiccated ferrous sulfate tablet.



Other Concomitant Drug Therapy


There are no empirical data on avoiding drug interactions between Renagel® and most concomitant drugs. During postmarketing experience, very rare cases of increased thyroid stimulating hormone (TSH) levels have been reported in patients co-administered sevelamer hydrochloride and levothyroxine. Closer monitoring of TSH levels is therefore recommended in patients receiving both medications.


When administering an oral medication where a reduction in the bioavailability of that medication would have a clinically significant effect on its safety or efficacy, the drug should be administered at least one hour before or three hours after Renagel, or the physician should consider monitoring blood levels of the drug. Patients taking anti-arrhythmic medications for the control of arrhythmias and anti-seizure medications for the control of seizure disorders were excluded from the clinical trials. Special precautions should be taken when prescribing Renagel to patients also taking these medications.



USE IN SPECIFIC POPULATIONS



Pregnancy


Pregnancy Category C: The effect of Renagel on the absorption of vitamins and other nutrients has not been studied in pregnant women. Requirements for vitamins and other nutrients are increased in pregnancy. In pregnant rats given doses of Renagel during organogenesis, reduced or irregular ossification of fetal bones, probably due to a reduced absorption of fat-soluble vitamin D, occurred. In pregnant rabbits given oral doses of Renagel by gavage during organogenesis, an increase of early resorptions occurred. [See NONCLINICAL TOXICOLOGY (13.1)]



Labor and Delivery


No Renagel treatment-related effects on labor and delivery were seen in animal studies. The effects of Renagel on labor and delivery in humans are not known. [See NONCLINICAL TOXICOLOGY (13.1)]



Pediatric Use


The safety and efficacy of Renagel has not been established in pediatric patients.



Geriatric Use


Clinical studies of Renagel did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range.



Overdosage


Renagel has been given to normal healthy volunteers in doses of up to 14 grams per day for eight days with no adverse effects. Renagel has been given in average doses up to 13 grams per day to hemodialysis patients. There are no reports of overdosage with Renagel in patients. Since Renagel is not absorbed, the risk of systemic toxicity is low.



Renagel Description


The active ingredient in Renagel Tablets is sevelamer hydrochloride, a polymeric amine that binds phosphate and is meant for oral administration. Sevelamer hydrochloride is poly(allylamine hydrochloride) crosslinked with epichlorohydrin in which forty percent of the amines are protonated. It is known chemically as poly(allylamine-co-N,N’-diallyl-1,3-diamino-2-hydroxypropane) hydrochloride. Sevelamer hydrochloride is hydrophilic, but insoluble in water. The structure is represented in Figure 1.


Figure 1. Chemical Structure of Sevelamer Hydrochloride



      a, b = number of primary amine groups                 a + b = 9


      c = number of crosslinking groups                         c = 1


      n = fraction of protonated amines                          n = 0.4


      m = large number to indicate extended polymer network


The primary amine groups shown in the structure are derived directly from poly(allylamine hydrochloride). The crosslinking groups consist of two secondary amine groups derived from poly(allylamine hydrochloride) and one molecule of epichlorohydrin.


Renagel® Tablets: Each film-coated tablet of Renagel contains either 800 mg or 400 mg of sevelamer hydrochloride on an anhydrous basis. The inactive ingredients are hypromellose, diacetylated monoglyceride, colloidal silicon dioxide, and stearic acid. The tablet imprint contains iron oxide black ink.



Renagel - Clinical Pharmacology


Patients with chronic kidney disease (CKD) on dialysis retain phosphorus and can develop hyperphosphatemia. High serum phosphorus can precipitate serum calcium resulting in ectopic calcification. When the product of serum calcium and phosphorus concentrations (Ca x P) exceeds 55 mg2/dL2, there is an increased risk that ectopic calcification will occur. Hyperphosphatemia plays a role in the development of secondary hyperparathyroidism in renal insufficiency.


Treatment of hyperphosphatemia includes reduction in dietary intake of phosphate, inhibition of intestinal phosphate absorption with phosphate binders, and removal of phosphate with dialysis. Renagel taken with meals has been shown to decrease serum phosphorus concentrations in patients with CKD who are on dialysis.



Mechanism of Action


Renagel contains sevelamer hydrochloride, a non-absorbed binding crosslinked polymer. It contains multiple amines separated by one carbon from the polymer backbone. These amines exist in a protonated form in the intestine and interact with phosphate molecules through ionic and hydrogen bonding. By binding phosphate in the dietary tract and decreasing absorption, sevelamer hydrochloride lowers the phosphate concentration in the serum.



Pharmacodynamics


In addition to effects on serum phosphate levels, sevelamer hydrochloride has been shown to bind bile acids in vitro and in vivo in experimental animal models. Bile acid binding by ion exchange resins is a well-established method of lowering blood cholesterol. Because sevelamer binds bile acids, it may interfere with normal fat absorption and thus may reduce absorption of fat-soluble vitamins such as A, D and K. In clinical trials of sevelamer hydrochloride, both the mean total and LDL cholesterol declined by 15-31%. This effect is observed after 2 weeks. Triglycerides, HDL cholesterol and albumin did not change.



Pharmacokinetics


A mass balance study using 14C-sevelamer hydrochloride in 16 healthy male and female volunteers showed that sevelamer hydrochloride is not systemically absorbed. No absorption studies have been performed in patients with renal disease.



Nonclinical Toxicology



Carcinogenesis, Mutagenesis, Impairment of Fertility


Standard lifetime carcinogenicity bioassays were conducted in mice and rats. Rats were given sevelamer hydrochloride by diet at 0.3, 1, or 3 g/kg/day. There was an increased incidence of urinary bladder transitional cell papilloma in male rats of the high dose group (human equivalent dose twice the maximum clinical trial dose of 13 g). Mice received dietary administration of sevelamer hydrochloride at doses of up to 9 g/kg/day (human equivalent dose 3 times the maximum clinical trial dose). There was no increased incidence of tumors observed in mice.


In an in vitro mammalian cytogenetic test with metabolic activation, sevelamer hydrochloride caused a statistically significant increase in the number of structural chromosome aberrations. Sevelamer hydrochloride was not mutagenic in the Ames bacterial mutation assay.


Sevelamer hydrochloride did not impair the fertility of male or female rats in a dietary administration study in which the females were treated from 14 days prior to mating through gestation and the males were treated for 28 days prior to mating. The highest dose in this study was 4.5 g/kg/day (human equivalent dose 3 times the maximum clinical trial dose of 13 g).


In pregnant rats given dietary doses of 0.5, 1.5 or 4.5 g/kg/day of sevelamer hydrochloride during organogenesis, reduced or irregular ossification of fetal bones, probably due to a reduced absorption of fat-soluble vitamin D, occurred in mid- and high-dose groups (human equivalent doses less than the maximum clinical trial dose of 13 g). In pregnant rabbits given oral doses of 100, 500 or 1000 mg/kg/day of sevelamer hydrochloride by gavage during organogenesis, an increase of early resorptions occurred in the high-dose group (human equivalent dose twice the maximum clinical trial dose).



Clinical Studies


The ability of Renagel to lower serum phosphorus in CKD patients on dialysis was demonstrated in six clinical trials: one double-blind placebo controlled 2-week study (Renagel N=24); two open-label uncontrolled 8-week studies (Renagel N=220) and three active-controlled open-label studies with treatment durations of 8 to 52 weeks (Renagel N=256). Three of the active-controlled studies are described here. One is a crossover study with two 8-week periods comparing Renagel to an active-control. The second is a 52-week parallel study comparing Renagel with active-control. The third is a 12-week parallel study comparing Renagel and active-control in peritoneal dialysis patients.



Active-Control, Cross-Over Study in Hemodialysis Patients


Eighty-four CKD patients on hemodialysis who were hyperphosphatemic (serum phosphorus > 6.0 mg/dL) following a two-week phosphate binder washout period received Renagel and active-control for eight weeks each in random order. Treatment periods were separated by a two-week phosphate binder washout period. Patients started on treatment three times per day with meals. Over each eight-week treatment period, at three separate time points the dose of Renagel could be titrated up 1 capsule or tablet per meal (3 per day) to control serum phosphorus, the dose of active-control could also be altered to attain phosphate control. Both treatments significantly decreased mean serum phosphorus by about 2 mg/dL (Table 4).

















Table 4. Mean Serum Phosphorus (mg/dL) at Baseline and Endpoint

Renagel®

(N=81)
 Active-Control

(N=83)

*

p<0.0001, within treatment group comparison


Baseline at End of Washout



8.4



8.0



Endpoint



6.4



5.9



Change from Baseline at Endpoint


(95% Confidence Interval)



-2.0*


(-2.5, -1.5)



-2.1*


(-2.6, -1.7)


The distribution of responses is shown in Figure 2 . The distributions are similar for sevelamer hydrochloride and active control. The median response is a reduction of about 2 mg/dL in both groups. About 50% of subjects have reductions between 1 and 3 mg/dL.


Figure 2. Percentage of patients (Y-axis) attaining a phosphorus reduction from baseline (mg/dL) at least as great as the value of the X-axis.



Average daily Renagel dose at the end of treatment was 4.9 g (range of 0.0 to 12.6 g).



Active-Control, Parallel Study in Hemodialysis Patients


Two hundred CKD patients on hemodialysis who were hyperphosphatemic (serum phosphorus >5.5 mg/dL) following a two-week phosphate binder washout period were randomized to receive Renagel 800 mg tablets (N=99) or an active-control (N=101). The two treatments produced similar decreases in serum phosphorus. At week 52, using last-observation-carried-forward, Renagel and active-control both significantly decreased mean serum phosphorus (Table 5).













Table 5. Mean Serum Phosphorus (mg/dL) and Ion Product at Baseline and Change from Baseline to End of Treatment

Renagel®

(N=94)
Active-Control

(N=98)

Phosphorus


Baseline


Change from Baseline at Endpoint



7.5


-2.1



7.3


-1.8



Ca x Phosphorus Ion Product


Baseline


Change from Baseline at Endpoint



 70.5


-19.4



 68.4


-14.2


Sixty-one percent of Renagel patients and 73% of the control patients completed the full 52 weeks of treatment.


Figure 3, a plot of the phosphorus change from baseline for the completers, illustrates the durability of response for patients who are able to remain on treatment.


Figure 3. Mean Phosphorus Change from Baseline for Patients who Completed 52 Weeks of Treatment



Average daily Renagel dose at the end of treatment was 6.5 g (range of 0.8 to 13 g).



Active-Control, Parallel Study in Peritoneal Dialysis Patients


One hundred and forty-three patients on peritoneal dialysis who were hyperphosphatemic (serum phosphorus > 5.5 mg/dL) following a two-week phosphate binder washout period were randomized to receive Renagel® (N=97) or active-control (N=46) open label for 12 weeks. Average daily Renagel dose at the end of treatment was 5.9 g (range 0.8 to 14.3 g). There were statistically significant changes in serum phosphorus (p<0.001) for Renagel (-1.6 mg/dL from baseline of 7.5 mg/dL), similar to the active-control.



How Supplied/Storage and Handling


Renagel® 800 mg Tablets are supplied as oval, film-coated, compressed tablets, imprinted with “Renagel 800” containing 800 mg of sevelamer hydrochloride on an anhydrous basis, hypromellose, diacetylated monoglyceride, colloidal silicon dioxide, and stearic acid. Renagel® 800 mg Tablets are packaged in bottles of 180 tablets.


Renagel® 400 mg Tablets are supplied as oval, film-coated, compressed tablets, imprinted with “Renagel 400” containing 400 mg of sevelamer hydrochloride on an anhydrous basis, hypromellose, diacetylated monoglyceride, colloidal silicon dioxide, and stearic acid. Renagel® 400 mg Tablets are packaged in bottles of 360 tablets.


1 Bottle of 30 ct 800 mg Tablets (NDC 58468-0021-3)


1 Bottle of 180 ct 800 mg Tablets (NDC 58468-0021-1)


1 Bottle of 360 ct 400 mg Tablets (NDC 58468-0020-1)


Storage Store at 25°C (77°F): excursions permitted to 15-30°C (59-86°F).


Do not use Renagel® after the expiration date on the bottle.


[See USP controlled room temperature]


Protect from moisture.



Patient Counseling Information



Dosing Recommendations


The prescriber should inform patients to take Renagel with meals and adhere to their prescribed diets. Instructions should be given on concomitant medications that should be dosed apart from Renagel.



Adverse Reactions


Renagel may cause constipation that if left untreated, may lead to severe complications. Patients should be cautioned to report new onset or worsening of existing constipation promptly to their physician.


Distributed by:


Genzyme Corporation


500 Kendall Street


Cambridge, MA 02142 USA




Bottle Label - Principal Display Panel – 400 mg - U.S. Source


EACH TABLET CONTAINS:


Active Ingredient: Sevelamer hydrochloride….400 mg.


Inactive Ingredients:


Hypromellose, diacetylated monoglyceride, colloidal silicon dioxide, and stearic acid.


Dispense in a tight container.


Protect from moisture.


Store at 25ºC (77ºF).


GENZYME



NDC 58468-0020-1


Renagel® Tablets


(sevelamer hydrochloride) 400 mg


360 Tablets


Rx only


Manufactured by:


Genzyme Ireland Ltd.


For: Genzyme Corporation


500 Kendall Street


Cambridge, MA 02142 USA


400 mg



USUAL DOSAGE:


SEE PACKAGE INSERT FOR DOSAGE INFORMATION.





Bottle Label - Principal Display Panel – 400 mg - U.K. Source


EACH TABLET CONTAINS:


Active Ingredient: Sevelamer hydrochloride….400 mg.


Inactive Ingredients:


Hypromellose, diacetylated monoglyceride, colloidal silicon dioxide, and stearic acid.


Dispense in a tight container.


Protect from moisture.


Store at 25ºC (77ºF).


GENZYME



NDC 58468-0020-1


Renagel® Tablets


(sevelamer hydrochloride) 400 mg


360 Tablets


Rx only


Manufactured by:


Genzyme Ireland Ltd.


For: Genzyme Corporation


500 Kendall Street


Cambridge, MA 02142 USA


Country of origin: U.K.


400 mg



USUAL DOSAGE:


SEE PACKAGE INSERT FOR DOSAGE INFORMATION.





Bottle Label - Principal Display Panel – 800 mg - U.S. Source


EACH TABLET CONTAINS:


Active Ingredient: Sevelamer hydrochloride….800 mg.


Inactive Ingredients:


Hypromellose, diacetylated monoglyceride, colloidal silicon dioxide, and stearic acid.


Dispense in a tight container.


Protect from moisture.


Store at 25ºC (77ºF).


GENZYME



NDC 58468-0021-1


Renagel® Tablets


(sevelamer hydrochloride) 800 mg


180 Tablets


Rx only


Manufactured by:


Genzyme Ireland Ltd.


For: Genzyme Corporation


500 Kendall Street


Cambridge, MA 02142 USA


800 mg



USUAL DOSAGE:


SEE PACKAGE INSERT FOR DOSAGE INFORMATION.





Bottle Label - Principal Display Panel – 800 mg - U.K. Source


EACH TABLET CONTAINS:


Active Ingredient: Sevelamer hydrochloride….800 mg.


Inactive Ingredients:


Hypromellose, diacetylated monoglyceride, colloidal silicon dioxide, and stearic acid.


Dispense in a tight container.


Protect from moisture.


Store at 25ºC (77ºF).


GENZYME



NDC 58468-0021-1


Renagel® Tablets


(sevelamer hydrochloride) 800 mg


180 Tablets


Rx only


Manufactured by:


Genzyme Ireland Ltd.


For: Genzyme Corporation


500 Kendall Street


Cambridge, MA 02142 USA


800 mg


Country of origin: U.K.



USUAL DOSAGE:


SEE PACKAGE INSERT FOR DOSAGE INFORMATION.











Renagel 
Renagel  tablet










Product Information
Product TypeHUMAN PRESCRIPTION DRUGNDC Product Code (Source)58468-0020
Route of AdministrationORALDEA Schedule    








Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
SEVELAMER HYDROCHLORIDE (SEVELAMER)SEVELAMER HYDROCHLORIDE400 mg




















Inactive Ingredients
Ingredient NameStrength
COLLOIDAL SILICON DIOXIDE1.6 mg
STEARIC ACID1.6 mg
WATER32.3 mg
HYPROMELLOSE 2910 (5 MPA.S)8.35 mg
HYPROMELLOSE 2910 (15 MPA.S)8.35 mg
FERROSOFERRIC OXIDE 
PROPYLENE GLYCOL 
ISOPROPYL ALCOHOL 


















Product Characteristics
ColorWHITE (WHITE)Scoreno score
ShapeOVAL (OVAL)Size15mm
FlavorImprint CodeRenagel;400
Contains      










Packaging
#NDCPackage DescriptionMultilevel Packaging
158468-0020-1360 TABLET In 1 BOTTLE, PLASTICNone










Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
NDANDA02117906/06/2008







Renagel 
Renagel  tablet










Product Information
Product TypeHUMAN PRESCRIPTION DRUGNDC Product Code (Source)58468-0021
Route of AdministrationORALDEA Schedule    








Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
SEVELAMER HYDROCHLORIDE (SEVELAMER)SEVELAMER HYDROCHLORIDE800 mg




















Inactive Ingredients
Ingredient NameStrength
COLLOIDAL SILICON DIOXIDE3.2 mg
STEARIC ACID3.2 mg
WATER64.6 mg
HYPROMELLOSE 2910 (5 MPA.S)16.7 mg
HYPROMELLOSE 2910 (15 MPA.S)16.7 mg
FERROSOFERRIC OXIDE 
PROPYLENE GLYCOL 
ISOPROPYL ALCOHOL 


















Product Characteristics
ColorWHITE (WHITE)Scoreno score
ShapeOVAL (OVAL)Size19mm
FlavorImprint CodeRenagel;800
Contains      














Packaging
#NDCPackage DescriptionMultilevel Packaging
158468-0021-1180 TABLET In 1 BOTTLE, PLASTICNone
258468-0021-330 TABLET In 1 BOTTLE, PLASTICNone










Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
NDANDA02117906/06/2008


Labeler - Genzyme Corporation (025322157)









Establishment
NameAddressID/FEIOperations
Genzyme Limited Haverhill229522842API MANUFACTURE









Establishment
NameAddressID/FEIOperations
Dow Chemical Company171862600API MANUFACTURE









Establishment
NameAddressID/FEIOperations
Genzyme Ireland Limited985127419ANALYSIS, MANUFACTURE
Revised: 05/2011Genzyme Corporation

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