Sohotin

Sohotin may be available in the countries listed below.

Ingredient matches for Sohotin

Loratadine

Loratadine is reported as an ingredient of Sohotin in the following countries:

• Indonesia

International Drug Name Search

Next Choice Oral, Parenteral, Vaginal

Generic Name: progestin (Oral route, Parenteral route, Vaginal route)

Commonly used brand name(s)

In the U.S.

• Aygestin


• Camila


• Crinone


• Errin


• First-Progesterone VGS


• Jolivette


• Megace


• Megace ES


• Next Choice


• Ovrette


• Plan B


• Prochieve


• Prometrium

In Canada

• Alti-Mpa


• Megace Os

Available Dosage Forms:

• Tablet


• Suspension


• Capsule, Liquid Filled


• Gel/Jelly


• Cream


• Kit


• Suppository

Uses For Next Choice

Progestins are hormones. They are used by both men and women for different purposes.

Progestins are prescribed for several reasons:

• To properly regulate the menstrual cycle and treat unusual stopping of the menstrual periods (amenorrhea). Progestins work by causing changes in the uterus. After the amount of progestins in the blood drops, the lining of the uterus begins to come off and vaginal bleeding occurs (menstrual period). Progestins help other hormones start and stop the menstrual cycle. .


• To help a pregnancy occur during egg donor or infertility procedures in women who do not produce enough progesterone. Also, progesterone is given to help maintain a pregnancy when not enough of it is made by the body.


• To prevent estrogen from thickening the lining of the uterus (endometrial hyperplasia) in women around menopause who are being treated with estrogen for ovarian hormone therapy (OHT). OHT is also called hormone replacement therapy (HRT) and estrogen replacement therapy (ERT).


• To treat pain that is related to endometriosis, a condition where the endometrial tissue which lines the uterus becomes displaced in other female organs.


• To treat a condition called endometriosis, to help prevent endometrial hyperplasia, or to treat unusual and heavy bleeding of the uterus (dysfunctional uterine bleeding) by starting or stopping the menstrual cycle.


• To help treat cancer of the breast, kidney, or uterus. Progestins help change the cancer cell's ability to react to other hormones and proteins that cause tumor growth. In this way, progestins can stop the growth of a tumor.


• To test the body's production of certain hormones such as estrogen.


• To treat loss of appetite and severe weight or muscle loss in patients with acquired immunodeficiency syndrome (AIDS) or cancer by causing certain proteins to be produced that cause increased appetite and weight gain.

Progestins may also be used for other conditions as determined by your doctor.

Depending on how much and which progestin you use or take, a progestin can have different effects. For instance, high doses of progesterone are necessary for some women to continue a pregnancy while other progestins in low doses can prevent a pregnancy from occurring. Other effects include causing weight gain, increasing body temperature, developing the milk-producing glands for breast-feeding, and relaxing the uterus to maintain a pregnancy.

Progestins can help other hormones work properly. Progestins may help to prevent anemia (low iron in blood), too much menstrual blood loss, and cancer of the uterus.

Progestins are available only with your doctor's prescription.

Once a medicine has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although these uses are not included in product labeling, progestins are used in certain patients with the following medical conditions:

• Carcinoma of the prostate


• Corpus luteum insufficiency


• Hot flashes


• Polycystic ovary syndrome


• Precocious puberty

Before Using Next Choice

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

Although there is no specific information comparing use of progestins in children or teenagers with use in other age groups, this medicine is not expected to cause different side effects or problems in children or teenagers than it does in adults.

Geriatric

This medicine has been tested and has not been shown to cause different side effects or problems in older people than it does in younger adults.

Pregnancy

Progesterone, a natural hormone that the body makes during pregnancy, has not caused problems. In fact, it is sometimes used in women to treat a certain type of infertility and to aid in egg donor or infertility procedures.

Other progestins have not been studied in pregnant women. Be sure to tell your doctor if you become pregnant while using any of the progestins. It is best to use some kind of birth control method while you are receiving progestins in high doses. High doses of progestins are not recommended for use during pregnancy since there have been some reports that they may cause birth defects in the genitals (sex organs) of a male fetus. Also, some of these progestins may cause male-like changes in a female fetus and female-like changes in a male fetus, but these problems usually can be reversed. Low doses of progestins, such as those doses used for contraception, have not caused major problems when used accidentally during pregnancy.

Breast Feeding

Although progestins pass into the breast milk, they have not been shown to cause problems in nursing babies. However, progestins may change the quality or amount (increase or decrease) of the mother's breast milk. It may be necessary for you to take another medicine or to stop breast-feeding during treatment. Be sure you have discussed the risks and benefits of the medicine 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. When you are taking any of these medicines, 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 medicines in this class with any of the following medicines is not recommended. Your doctor may decide not to treat you with a medication in this class or change some of the other medicines you take.

• Boceprevir


• Dofetilide

Using medicines in this class 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.

• Felbamate


• Isotretinoin


• Theophylline


• Tizanidine


• Tranexamic Acid

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 medicines in this class. Make sure you tell your doctor if you have any other medical problems, especially:

• Asthma or


• Epilepsy (or history of) or


• Heart or circulation problems or


• Kidney disease (severe) or


• Migraine headaches—Progestins may cause fluid retention which may cause these conditions to become worse.

• Bleeding problems, undiagnosed, such as blood in the urine or changes in vaginal bleeding—May make diagnosis of these problems more difficult.

• Blood clots, or history of or


• Breast cancer, or history of or


• Deep vein thrombosis (blood clot in the leg), active or history of or


• Heart attack, active or history of or


• Liver disease, including jaundice, or history of or


• Pulmonary embolism (clot in the lung), active or history of or


• Stroke , active or history of or


• Venous thromboembolism (clot in the veins), or history of—Progestins should not be used in patients with these conditions.

• Breast disease (such as breast lumps or cysts), history of—May make this condition worse for diseases that do not react in a positive way to progestins.

• Diabetes mellitus—May cause an increase in your blood sugar and a change in the amount of medicine you take for diabetes; progestins in high doses are more likely to cause this problem.

• Memory loss (dementia)—May make this condition worse.

• Vision changes—This medicine may cause changes in vision; your medicine may need to be stopped if these conditions become worse.

Proper Use of progestin

This section provides information on the proper use of a number of products that contain progestin. It may not be specific to Next Choice. Please read with care.

To make the use of a progestin as safe and reliable as possible, you should understand how and when to take it and what effects may be expected. Progestins usually come with patient directions. Read them carefully before taking or using this medicine.

Take this medicine only as directed by your doctor. Do not take more of it and do not take it for a longer time than your doctor ordered. To do so may increase the chance of side effects. Try to take the medicine at the same time each day to reduce the possibility of side effects and to allow it to work better.

Progestins are often given together with certain medicines. If you are using a combination of medicines, make sure that you take each one at the proper time and do not mix them. Ask your health care professional to help you plan a way to remember to take your medicines at the right times.

Dosing

The dose medicines in this class 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 these medicines. 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 medroxyprogesterone


• For oral dosage form (tablets):
  
  • For controlling unusual and heavy bleeding of the uterus (dysfunctional uterine bleeding) or treating unusual stopping of menstrual periods (amenorrhea):
    
    • Adults and teenagers—5 to 10 milligrams (mg) per day for five to ten days as directed by your doctor.
    
    
  
  
  • For preparing the uterus for the menstrual period:
    
    • Adults and teenagers—10 milligrams (mg) per day for five or ten days as directed by your doctor.
    
    
  
  
  • For preventing estrogen from thickening the lining of the uterus (endometrial hyperplasia) when taking estrogen for ovarian hormone therapy in postmenopausal women:
    
    • Adults—When taking estrogen each day on Days 1 through 25: Oral, 5 to 10 milligrams (mg) of medroxyprogesterone per day for ten to fourteen or more days each month as directed by your doctor. Or, your doctor may want you to take 2.5 or 5 mg per day without stopping. Your doctor will help decide the number of tablets that is best for you and when to take them.
    
    
  
  


• For intramuscular injection dosage form:
  
  • For treating cancer of the kidneys or uterus:
    
    • Adults and teenagers—At first, 400 to 1000 milligrams (mg) injected into a muscle as a single dose once a week. Then, your doctor may lower your dose to 400 mg or more once a month.
    
    
  
  


• For subcutaneous injection dosage form:
  
  • For treating pain related to endometriosis:
    
    • Adults and teenagers—104 milligrams (mg) injected under the skin of the anterior thigh or abdomen every three months (12 to 14 weeks) for not more than 2 years.
    
    
  
  

• For megestrol


• For oral dosage form (suspension):
  
  • For treating loss of appetite (anorexia), muscles (cachexia), or weight caused by acquired immunodeficiency syndrome (AIDS):
    
    • Adults and teenagers—800 milligrams (mg) a day for the first month. Then your doctor may want you to take 400 or 800 mg a day for three more months.
    
    
  
  


• For oral dosage form (tablets):
  
  • For treating cancer of the breast:
    
    • Adults and teenagers—160 milligrams (mg) a day as a single dose or in divided doses for two or more months.
    
    
  
  
  • For treating cancer of the uterus:
    
    • Adults and teenagers—40 to 320 milligrams (mg) a day for two or more months.
    
    
  
  
  • For treating loss of appetite (anorexia), muscles (cachexia), or weight caused by cancer:
    
    • Adults and teenagers—400 to 800 milligrams (mg) a day.
    
    
  
  

• For norethindrone


• For oral dosage form (tablets):
  
  • For controlling unusual and heavy bleeding of the uterus (dysfunctional uterine bleeding) or treating unusual stopping of menstrual periods (amenorrhea):
    
    • Adults and teenagers—2.5 to 10 milligrams (mg) a day from Day 5 through Day 25 (counting from the first day of the last menstrual cycle). Or, your doctor may want you to take the medicine only for five to ten days as directed.
    
    
  
  
  • For treating endometriosis:
    
    • Adults and teenagers—At first, 5 milligrams (mg) a day for two weeks. Then, your doctor may increase your dose slowly up to 15 mg a day for six to nine months. Let your doctor know if your menstrual period starts. Your doctor may want you to take more of the medicine or may want you to stop taking the medicine for a short period of time.
    
    
  
  

• For progesterone


• For oral dosage form (capsules):
  
  • For preventing estrogen from thickening the lining of the uterus (endometrial hyperplasia) when taking estrogen for ovarian hormone therapy in postmenopausal women:
    
    • Adults—200 milligrams (mg) per day at bedtime for 12 continuous days per 28-day cycle of estrogen treatment each month.
    
    
  
  
  • For treating unusual stopping of menstrual periods (amenorrhea):
    
    • Adults—400 milligrams (mg) per day at bedtime for ten days.
    
    
  
  


• For vaginal dosage form (gel):
  
  • For treating unusual stopping of menstrual periods (amenorrhea):
    
    • Adults and teenagers—45 milligrams (mg) (one applicatorful of 4% gel) once every other day for up to six doses. Dose may be increased to 90 mg (one applicatorful of 8% gel) once every other day for up to six doses if needed.
    
    
  
  
  • For use with infertility procedures:
    
    • Adults and teenagers—90 milligrams (mg) (one applicatorful of 8% gel) one or two times a day. If pregnancy occurs, treatment can continue for up to ten to twelve weeks.
    
    
  
  


• For injection dosage form:
  
  • For controlling unusual and heavy bleeding of the uterus (dysfunctional uterine bleeding) or treating unusual stopping of menstrual periods (amenorrhea):
    
    • Adults and teenagers—5 to 10 milligrams (mg) a day injected into a muscle for six to ten days. Or, your doctor may want you to receive 100 or 150 mg injected into a muscle as a single dose. Sometimes your doctor may want you first to take another hormone called estrogen. If your menstrual period starts, your doctor will want you to stop taking the medicine.
    
    
  
  


• For vaginal dosage form (suppositories):
  
  • For maintaining a pregnancy (at ovulation and at the beginning of pregnancy):
    
    • Adults and teenagers—25 mg to 100 milligrams (mg) (one suppository) inserted into the vagina one or two times a day beginning near the time of ovulation. Your doctor may want you to receive the medicine for up to eleven weeks.
    
    
  
  

Missed Dose

If you miss a dose of this medicine, 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.

For all progestins, except for progesterone capsules for postmenopausal women: If you miss a dose of this medicine, take the missed dose 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.

For progesterone capsules for postmenopausal women: If you miss a dose of 200 mg of progesterone capsules at bedtime, take 100 mg in the morning then go back to your regular dosing schedule. If you take 300 mg of progesterone a day and you miss your morning and evening doses, you should not take the missed dose. Return to your regular dosing schedule.

Storage

Keep out of the reach of children.

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

Do not keep outdated medicine or medicine no longer needed.

Precautions While Using Next Choice

It is very important that your doctor check your progress at regular visits. This will allow for your dosage to be adjusted and for any unwanted effects to be detected. These visits will usually be every 6 to 12 months, but some doctors require them more often.

The Prometrium® capsules contain peanut oil. If you have an allergy to peanuts, make sure your doctor knows this before you take this brand of progestin.

Progestins may cause some people to become dizzy. For oral or vaginal progesterone, dizziness or drowsiness may occur 1 to 4 hours after taking or using it. Make sure you know how you react to this medicine before you drive, use machines, or do anything else that could be dangerous if you are not alert.

Unusual or unexpected vaginal bleeding of various amounts may occur between your regular menstrual periods during the first 3 months of use. This is sometimes called spotting when slight, or breakthrough menstrual bleeding when heavier. If this should occur, continue on your regular dosing schedule. Check with your doctor:

• If unusual or unexpected vaginal bleeding continues for an unusually long time.


• If your menstrual period has not started within 45 days of your last period.

Missed menstrual periods may occur. If you suspect a pregnancy, you should stop taking this medicine immediately and call your doctor. Your doctor will let you know if you should continue taking the progestin.

If you are scheduled for any laboratory tests, tell your health care professional that you are taking a progestin. Progestins can change certain test results.

In some patients, tenderness, swelling, or bleeding of the gums may occur. Brushing and flossing your teeth carefully and regularly and massaging your gums may help prevent this. See your dentist regularly to have your teeth cleaned. Check with your medical doctor or dentist if you have any questions about how to take care of your teeth and gums, or if you notice any tenderness, swelling, or bleeding of your gums.

You will need to use a birth control method while taking progestins for noncontraceptive use if you are fertile and sexually active.

If you are using vaginal progesterone, avoid using other vaginal products for 6 hours before and for 6 hours after inserting the vaginal dose of progesterone.

Since it is possible that certain doses of progestins may cause temporary thinning of the bones by changing your hormone balance, it is important that your doctor know if you have an increased risk of osteoporosis. Some things that can increase your risk for having osteoporosis include cigarette smoking, abusing alcohol, taking or drinking large amounts of caffeine, and having a family history of osteoporosis or easily broken bones. Some medicines, such as glucocorticoids (cortisone-like medicines) or anticonvulsants (seizure medicine), can also cause thinning of the bones. However, it is thought that progestins can help protect against osteoporosis in postmenopausal women.

Next Choice Side Effects

Along with their needed effects, progestins used in high doses sometimes cause some unwanted effects such as blood clots, heart attacks, and strokes, or problems of the liver and eyes. Although these effects are rare, some of them can be very serious and cause death. It is not clear if these problems are due to the progestin. They may be caused by the disease or condition for which progestins are being used.

The following side effects may be caused by blood clots. Although not all of these side effects may occur, if they do occur they need immediate medical attention.

Get emergency help immediately if any of the following side effects occur:

Rare

• Symptoms of blood clotting problems, usually severe or sudden, such as:


• headache or migraine


• loss of or change in speech, coordination, or vision


• numbness of or pain in chest, arm, or leg


• unexplained shortness of breath

Check with your doctor as soon as possible if any of the following side effects occur:

More common

• Changes in vaginal bleeding (increased amounts of menstrual bleeding occurring at regular monthly periods, lighter vaginal bleeding between menstrual periods, heavier vaginal bleeding between regular monthly periods, or stopping of menstrual periods)


• symptoms of blood sugar problems (dry mouth, frequent urination, loss of appetite, or unusual thirst)

Less common

• Mental depression


• skin rash


• unexpected or increased flow of breast milk

RareFor megestrol—During chronic treatment

• Backache


• dizziness


• filling or rounding out of the face


• irritability


• mental depression


• nausea or vomiting


• unusual decrease in sexual desire or ability in men


• unusual tiredness or weakness

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

• Abdominal pain or cramping


• bloating or swelling of ankles or feet


• blood pressure increase (mild)


• dizziness


• drowsiness (progesterone only)


• headache (mild)


• mood changes


• nervousness


• pain or irritation at place of injection site


• swelling of face, ankles, or feet


• unusual or rapid weight gain

Less common

• Acne


• breast pain or tenderness


• brown spots on exposed skin, possibly long-lasting


• hot flashes


• loss or gain of body, facial, or scalp hair


• loss of sexual desire


• trouble in sleeping

Not all of the side effects listed above have been reported for each of these medicines, but they have been reported for at least one of them. All of the progestins are similar, so any of the above side effects may occur with any of these medicines.

After you stop using this medicine, your body may need time to adjust. The length of time this takes depends on the amount of medicine you were using and how long you used it. During this period of time check with your doctor if you notice the following side effect:

For megestrol

• Dizziness


• nausea or vomiting


• unusual tiredness or weakness

• Delayed return to fertility


• stopping of menstrual periods


• unusual menstrual bleeding (continuing)

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 Reuters 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 Reuters 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 Reuters 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 REUTERS 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 REUTERS HEALTHCARE PRODUCTS. ALL IMPLIED WARRANTIES OF MERCHANTABILITY AND FITNESS FOR A PARTICULAR PURPOSE OR USE ARE HEREBY EXCLUDED. Thomson Reuters Healthcare does not assume any responsibility or risk for your use of the Thomson Reuters Healthcare products.

Carfentanil

In some countries, this medicine may only be approved for veterinary use.

Scheme

Rec.INN

CAS registry number (Chemical Abstracts Service)

0059708-52-0

Chemical Formula

C24-H30-N2-O3

Molecular Weight

394

Therapeutic Category

Opioid analgesic

Chemical Names

4-Piperidinecarboxylic acid, 4((1-oxopropyl)phenylamino)-1-(2-phenylethyl)-, methyl ester

4-Piperidinecarboxylic acid, 4-((1-oxopropyl)phenylamino)-1-(2-phenylethyl)-, methyl ester, 2-hydroxy-1,2,3-propanetricarboxylate (1:1)

Methyl 1-phenethyl-4-(N-phenylpropionamido)-4-piperidylcarboxylat (IUPAC)

Methyl 1-phenethyl-4-(N-phenylpropionamido)isonipecotate (WHO)

Foreign Names

• Carfentanilum (Latin)
• Carfentanil (German)
• Carfentanil (French)
• Carfentanilo (Spanish)

Generic Names

• 5-22-13-00537 (IS)
• BRN 0456976 (IS)
• R 31833 (IS: Janssen)
• Carfentanil Citrate (OS: USAN)
• EINECS 262-748-6 (IS)
• R 33799 (IS: Janssen)

Brand Name

• Wildnil (veterinary use)
  Wildlife, United States

International Drug Name Search

Glossary

IUPAC	International Union of Pure and Applied Chemistry
IS	Inofficial Synonym
OS	Official Synonym
Rec.INN	Recommended International Nonproprietary Name (World Health Organization)
USAN	United States Adopted Name
WHO	World Health Organization

Click for further information on drug naming conventions and International Nonproprietary Names.

Zinoximor

Zinoximor may be available in the countries listed below.

Ingredient matches for Zinoximor

Cefuroxime

Cefuroxime axetil (a derivative of Cefuroxime) is reported as an ingredient of Zinoximor in the following countries:

• Oman

International Drug Name Search

Pantoprazole Teva

Pantoprazole Teva may be available in the countries listed below.

Ingredient matches for Pantoprazole Teva

Pantoprazole

Pantoprazole sodium (a derivative of Pantoprazole) is reported as an ingredient of Pantoprazole Teva in the following countries:

• France


• Ireland

International Drug Name Search

Aciclovir Sala

Aciclovir Sala may be available in the countries listed below.

Ingredient matches for Aciclovir Sala

Acyclovir

Aciclovir sodium salt (a derivative of Aciclovir) is reported as an ingredient of Aciclovir Sala in the following countries:

• Spain

International Drug Name Search

Rituxan

Generic Name: rituximab

Dosage Form: injection, solution
FULL PRESCRIBING INFORMATION

WARNING: FATAL INFUSION REACTIONS, TUMOR LYSIS SYNDROME (TLS), SEVERE MUCOCUTANEOUS REACTIONS, and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML)

Infusion Reactions

  Rituxan administration can result in serious, including fatal infusion reactions. Deaths within 24 hours of Rituxan infusion have occurred. Approximately 80% of fatal infusion reactions occurred in association with the first infusion. Carefully monitor patients during infusions. Discontinue Rituxan infusion and provide medical treatment for Grade 3 or 4 infusion reactions [see Warnings and Precautions (5.1), Adverse Reactions, (6.1)].

Tumor Lysis Syndrome (TLS)

  Acute renal failure requiring dialysis with instances of fatal outcome can occur in the setting of TLS following treatment of non Hodgkin’s lymphoma (NHL) with Rituxan monotherapy [see Warnings and Precautions (5.2), Adverse Reactions (6)].

Severe Mucocutaneous Reactions

  Severe, including fatal, mucocutaneous reactions can occur in patients receiving Rituxan [see Warnings and Precautions (5.3), Adverse Reactions (6)].

Progressive Multifocal Leukoencephalopathy (PML)

  JC virus infection resulting in PML and death can occur in patients receiving Rituxan [see Warnings and Precautions (5.4), Adverse Reactions (6)].

Indications and Usage for Rituxan

   Non‑Hodgkin’s Lymphoma (NHL)

Rituxan® (rituximab) is indicated for the treatment of patients with:

• Relapsed or refractory, low‑grade or follicular, CD20‑positive, B‑cell NHL as a single agent


•  Previously untreated follicular, CD20‑positive, B‑cell NHL in combination with first line chemotherapy and, in patients achieving a complete or partial response to Rituxan in combination with chemotherapy, as single-agent maintenance therapy.


• Non‑progressing (including stable disease), low‑grade, CD20‑positive, B‑cell NHL as a single agent after first‑line CVP chemotherapy


• Previously untreated diffuse large B‑cell, CD20‑positive NHL in combination with CHOP or other anthracycline‑based chemotherapy regimens

   Chronic Lymphocytic Leukemia (CLL)

Rituxan® (rituximab) is indicated, in combination with fludarabine and cyclophosphamide (FC), for the treatment of patients with previously untreated and previously treated CD20-positive CLL.

   Rheumatoid Arthritis (RA)

Rituxan® (rituximab) in combination with methotrexate is indicated for the treatment of adult patients with moderately‑to severely‑ active rheumatoid arthritis who have had an inadequate response to one or more TNF antagonist therapies.

   Wegener’s Granulomatosis (WG) and Microscopic Polyangiitis (MPA)

 Rituxan® (rituximab), in combination with glucocorticoids, is indicated for the treatment of adult patients with Wegener’s Granulomatosis (WG) and Microscopic Polyangiitis (MPA).

   Limitations of Use

Rituxan is not recommended for use in patients with severe, active infections.

Rituxan Dosage and Administration

   Administration

DO NOT ADMINISTER AS AN INTRAVENOUS PUSH OR BOLUS.

Premedicate before each infusion [see Dosage and Administration (2.7)]. Administer only as an intravenous (IV) infusion [see Dosage and Administration (2.7)].

• 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 [see Boxed Warning, Warnings and Precautions (5.1)]. Continue the infusion at one half the previous rate upon improvement of symptoms.

   Recommended Dose for Non‑Hodgkin’s Lymphoma (NHL)

The recommended dose is 375 mg/m2 as an intravenous infusion according to the following schedules:

• Relapsed or Refractory, Low‑Grade or Follicular, CD20‑Positive, B‑Cell NHL
  
  Administer once weekly for 4 or 8 doses.


• Retreatment for Relapsed or Refractory, Low‑Grade or Follicular, CD20‑Positive, B‑Cell NHL
  
  Administer once weekly for 4 doses.


• Previously Untreated, Follicular, CD20‑Positive, B‑Cell NHL
   Administer on Day 1 of each cycle of chemotherapy, for up to 8 doses. In patients with complete or partial response, initiate Rituxan maintenance eight weeks following completion of Rituxan in combination with chemotherapy. Administer Rituxan 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 6–8 cycles of CVP chemotherapy, administer once weekly for 4 doses at 6‑month intervals to a maximum of 16 doses.


• Diffuse Large B‑Cell NHL
  
  Administer on Day 1 of each cycle of chemotherapy for up to 8 infusions.

   Recommended Dose for Chronic Lymphocytic Leukemia (CLL)

 The recommended dose is:

•  375 mg/m2 the day prior to the initiation of FC chemotherapy, then 500 mg/m2 on Day 1 of cycles 2-6 (every 28 days).

   Recommended Dose as a Component of Zevalin®

• Infuse rituximab 250 mg/m2 within 4 hours prior to the administration of Indium‑111‑(In‑111‑) Zevalin and within 4 hours prior to the administration of Yttrium‑90‑ (Y‑90‑) Zevalin.


• Administer Rituxan and In‑111‑Zevalin 7–9 days prior to Rituxan and Y‑90‑ Zevalin.


• Refer to the Zevalin package insert for full prescribing information regarding the Zevalin therapeutic regimen.

   Recommended Dose for Rheumatoid Arthritis (RA)

• Administer Rituxan as two-1000 mg intravenous infusions separated by 2 weeks.


• Glucocorticoids administered as methylprednisolone 100 mg intravenous 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.


• Rituxan is given in combination with methotrexate.

   Recommended Dose for Wegener’s Granulomatosis (WG) and Microscopic Polyangiitis (MPA)

•  Administer Rituxan as a 375 mg/m2 intravenous infusion once weekly for 4 weeks.


•  Glucocorticoids administered as methylprednisolone 1000 mg intravenously per day 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 Rituxan and may continue during and after the 4 week course of Rituximab treatment.


•  Safety and efficacy of treatment with subsequent courses of Rituxan have not been established [see Warnings and Precautions (5.14)].

   Recommended Concomitant Medications

Premedicate before each infusion with acetaminophen and an antihistamine.

For RA patients, methylprednisolone 100 mg intravenously or its equivalent is recommended 30 minutes prior to each infusion.

 For WG and MPA patients, glucocorticoids are given in combination with Rituxan [see Dosage and Administration (2.6)].

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.

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

   Preparation for Administration

Use appropriate aseptic technique. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration. Do not use vial if particulates or discoloration is present. Withdraw the necessary amount of Rituxan and dilute to a final concentration of 1 to 4 mg/mL in an infusion bag containing either 0.9% Sodium Chloride, USP, or 5% Dextrose in Water, USP. Gently invert the bag to mix the solution. Do not mix or dilute with other drugs. Discard any unused portion left in the vial.

Dosage Forms and Strengths

100 mg/10 mL single‑use vial

500 mg/50 mL single‑use vial

Contraindications

None.

Warnings and Precautions

   Infusion Reactions

Rituxan can cause severe, including fatal, infusion reactions. Severe reactions typically occurred during the first infusion with time to onset of 30–120 minutes. Rituxan‑induced infusion reactions and sequelae include urticaria, hypotension, angioedema, hypoxia, bronchospasm, pulmonary infiltrates, acute respiratory distress syndrome, myocardial infarction, ventricular fibrillation, cardiogenic shock, anaphylactoid events, or death.

Premedicate patients with an antihistamine and acetaminophen prior to dosing. For RA patients, methylprednisolone 100 mg intravenously or its equivalent is recommended 30 minutes prior to each infusion. Institute medical management (e.g. glucocorticoids, epinephrine, bronchodilators, or oxygen) for infusion reactions as needed. Depending on the severity of the infusion reaction and the required interventions, temporarily or permanently discontinue Rituxan. Resume infusion at a minimum 50% reduction in rate after symptoms have resolved. Closely monitor the following patients: those with pre‑existing cardiac or pulmonary conditions, those who experienced prior cardiopulmonary adverse reactions, and those with high numbers of circulating malignant cells ( ≥ 25,000/mm3). [See Boxed Warning, Warnings and Precautions (5.7), Adverse Reactions (6.1).]

   Tumor Lysis Syndrome (TLS)  

Acute renal failure, hyperkalemia, hypocalcemia, hyperuricemia, or hyperphosphatemia from tumor lysis, some fatal, can occur within 12–24 hours after the first infusion of Rituxan in patients with NHL. A high number of circulating malignant cells ( ≥ 25,000/mm3) or high tumor burden, confers a greater risk of TLS.

Administer aggressive intravenous hydration and anti-hyperuricemic therapy in patients at high risk for TLS. Correct electrolyte abnormalities, monitor renal function and fluid balance, and administer supportive care, including dialysis as indicated. [See Boxed Warning, Warnings and Precautions (5.8).]

   Severe Mucocutaneous Reactions

Mucocutaneous reactions, some with fatal outcome, can occur in patients treated with Rituxan. These reactions include paraneoplastic pemphigus, Stevens‑Johnson syndrome, lichenoid dermatitis, vesiculobullous dermatitis, and toxic epidermal necrolysis. The onset of these reactions has varied from 1–13 weeks following Rituxan exposure. Discontinue Rituxan in patients who experience a severe mucocutaneous reaction. The safety of readministration of Rituxan to patients with severe mucocutaneous reactions has not been determined. [See Boxed Warning, Adverse Reactions (6, 6.1).]

   Progressive Multifocal Leukoencephalopathy (PML)

JC virus infection resulting in PML and death can occur in Rituxan‑treated patients with hematologic malignancies or with autoimmune diseases. The majority of patients with hematologic malignancies diagnosed with PML received Rituxan in combination with chemotherapy or as part of a hematopoietic stem cell transplant. The patients with autoimmune diseases had prior or concurrent immunosuppressive therapy. Most cases of PML were diagnosed within 12 months of their last infusion of Rituxan.

Consider the diagnosis of PML in any patient presenting with new‑onset neurologic manifestations. Evaluation of PML includes, but is not limited to, consultation with a neurologist, brain MRI, and lumbar puncture. Discontinue Rituxan and consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML. [See Boxed Warning, Adverse Reactions (6).]

   Hepatitis B Virus (HBV) Reactivation

 Hepatitis B virus (HBV) reactivation with fulminant hepatitis, hepatic failure, and death can occur in patients treated with Rituxan. The median time to the diagnosis of hepatitis among patients with hematologic malignancies was approximately 4 months after the initiation of Rituxan and approximately one month after the last dose.

Screen patients at high risk of HBV infection before initiation of Rituxan. Closely monitor carriers of hepatitis B for clinical and laboratory signs of active HBV infection for several months following Rituxan therapy. Discontinue Rituxan and any concomitant chemotherapy in patients who develop viral hepatitis, and institute appropriate treatment including antiviral therapy. Insufficient data exist regarding the safety of resuming Rituxan in patients who develop hepatitis subsequent to HBV reactivation. [See Adverse Reactions (6.5).]

   Infections

Serious, including fatal, bacterial, fungal, and new or reactivated viral infections can occur during and up to one year following the completion of Rituxan-based therapy. New or reactivated viral infections included cytomegalovirus, herpes simplex virus, parvovirus B19, varicella zoster virus, West Nile virus, and hepatitis B and C. Discontinue Rituxan for serious infections and institute appropriate anti-infective therapy. [See Adverse Reactions (6, 6.1).]

   Cardiovascular

Discontinue infusions for serious or life‑threatening cardiac arrhythmias. Perform cardiac monitoring during and after all infusions of Rituxan for patients who develop clinically significant arrhythmias, or who have a history of arrhythmia or angina. [See Adverse Reactions (6).]

   Renal

Severe, including fatal, renal toxicity can occur after Rituxan administration in patients with NHL. Renal toxicity has occurred in patients who experience tumor lysis syndrome and in patients with NHL administered concomitant cisplatin therapy during clinical trials. The combination of cisplatin and Rituxan is not an approved treatment regimen. Monitor closely for signs of renal failure and discontinue Rituxan in patients with a rising serum creatinine or oliguria. [See Warnings and Precautions (5.2).]

   Bowel Obstruction and Perforation

Abdominal pain, bowel obstruction and perforation, in some cases leading to death, can occur in patients receiving Rituxan in combination with chemotherapy. In postmarketing reports, the mean time to documented gastrointestinal perforation was 6 (range 1–77) days in patients with NHL. Perform a thorough diagnostic evaluation and institute appropriate treatment for complaints of abdominal pain. [See Adverse Reactions (6).]

Immunization

The safety of immunization with live viral vaccines following Rituxan therapy has not been studied and vaccination with live virus vaccines is not recommended.

For RA patients, physicians should follow current immunization guidelines and administer non‑live vaccines at least 4 weeks prior to a course of Rituxan.

The effect of Rituxan on immune responses was assessed in a randomized, controlled study in patients with RA treated with Rituxan and methotrexate (MTX) compared to patients treated with MTX alone.

A response to pneumococcal vaccination (a T‑cell independent antigen) as measured by an increase in antibody titers to at least 6 of 12 serotypes was lower in patients treated with Rituxan plus MTX as compared to patients treated with MTX alone (19% vs. 61%). A lower proportion of patients in the Rituxan plus MTX group developed detectable levels of anti‑keyhole limpet hemocyanin antibodies (a novel protein antigen) after vaccination compared to patients on MTX alone (47% vs. 93%).

A positive response to tetanus toxoid vaccine (a T‑cell dependent antigen with existing immunity) was similar in patients treated with Rituxan plus MTX compared to patients on MTX alone (39% vs. 42%). The proportion of patients maintaining a positive Candida skin test (to evaluate delayed type hypersensitivity) was also similar (77% of patients on Rituxan plus MTX vs. 70% of patients on MTX alone).

Most patients in the Rituxan‑treated group had B‑cell counts below the lower limit of normal at the time of immunization. The clinical implications of these findings are not known.

Laboratory Monitoring

In patients with lymphoid malignancies, during treatment with Rituxan monotherapy, obtain complete blood counts (CBC) and platelet counts prior to each Rituxan course. During treatment with Rituxan and chemotherapy, obtain CBC and platelet counts at weekly to monthly intervals and more frequently in patients who develop cytopenias [see Adverse Reactions (6.1)]. In patients with RA,  WG or MPA, obtain CBC and platelet counts at two to four month intervals during Rituxan therapy. The duration of cytopenias caused by Rituxan can extend months beyond the treatment period.

Concomitant Use with Biologic Agents and DMARDS other than Methotrexate in RA,  WG and MPA

Limited data are available on the safety of the use of biologic agents or DMARDs other than methotrexate in RA patients exhibiting peripheral B‑cell depletion following treatment with rituximab. Observe patients closely for signs of infection if biologic agents and/or DMARDs are used concomitantly.  Use of concomitant immunosuppressants other than corticosteroids has not been studied in WG or MPA patients exhibiting peripheral B-cell depletion following treatment with Rituxan.

Use in RA Patients Who Have Not Had Prior Inadequate Response to Tumor Necrosis Factor (TNF) Antagonists

While the efficacy of Rituxan was supported in four controlled trials in patients with RA with prior inadequate responses to non‑biologic DMARDs, and in a controlled trial in MTX‑naïve patients, a favorable risk‑benefit relationship has not been established in these populations. The use of Rituxan in patients with RA who have not had prior inadequate response to one or more TNF antagonists is not recommended [see Clinical Studies (14.5)].

 5.14 Retreatment in Patients with Wegener’s Granulomatosis (WG) and Microscopic Polyangiitis (MPA)

 Limited data are available on the safety and efficacy of subsequent courses of Rituxan in patients with WG and MPA. The safety and efficacy of retreatment with Rituxan have not been established [see Dosage and Administration (2.6), Adverse Reactions (6.3), and Clinical Studies (14.6)].

Adverse Reactions

The following serious adverse reactions are discussed in greater detail in other sections of the labeling:

• Infusion reactions [see Warnings and Precautions (5.1)]


• Tumor lysis syndrome [see Warnings and Precautions (5.2)]


• Mucocutaneous reactions [see Warnings and Precautions (5.3)]


• Progressive multifocal leukoencephalopathy [see Warnings and Precautions (5.4)]


• Hepatitis B reactivation with fulminant hepatitis [see Warnings and Precautions (5.5)]


• Infections [see Warnings and Precautions (5.6)]


• Cardiac arrhythmias[see Warnings and Precautions (5.7)]


• Renal toxicity[see Warnings and Precautions (5.8)]


• Bowel obstruction and perforation [see Warnings and Precautions (5.9)]

The most common adverse reactions of Rituxan (incidence ≥ 25%) observed in clinical trials of patients with NHL were infusion reactions, fever, lymphopenia, chills, infection, and asthenia.

The most common adverse reactions of Rituxan (incidence ≥ 25%) observed in clinical trials of patients with CLL were infusion reactions and neutropenia.

   Clinical Trials Experience in Lymphoid Malignancies

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.

The data described below reflect exposure to Rituxan in 2783 patients, with exposures ranging from a single infusion up to 2 years. Rituxan was studied in both single-arm and controlled trials (n = 356 and n = 2427=1926). The population included 1180 patients with low grade or follicular lymphoma, 927 patients with DLBCL, and 676 patients with CLL. Most NHL patients received Rituxan as an infusion of 375 mg/m2 per infusion, given as a single agent weekly for up to 8 doses, in combination with chemotherapy for up to 8 doses, or following chemotherapy for up to 16 doses. CLL patients received Rituxan 375 mg/m2 as an initial infusion followed by 500 mg/m2 for up to 5 doses, in combination with fludarabine and cyclophosphamide. Seventy-one percent of CLL patients received 6 cycles and 90% received at least 3 cycles of Rituxan-based therapy.

Infusion Reactions

In the majority of patients with NHL, infusion reactions consisting of fever, chills/rigors, nausea, pruritus, angioedema, hypotension, headache, bronchospasm, urticaria, rash, vomiting, myalgia, dizziness, or hypertension occurred during the first Rituxan infusion. Infusion reactions typically occurred within 30 to 120 minutes of beginning the first infusion and resolved with slowing or interruption of the Rituxan infusion and with supportive care (diphenhydramine, acetaminophen, and intravenous saline). The incidence of infusion reactions was highest during the first infusion (77%) and decreased with each subsequent infusion. [See Boxed Warning, Warnings and Precautions (5.1).]

Infections

Serious infections (NCI CTCAE Grade 3 or 4), including sepsis, occurred in less than 5% of patients with NHL in the single‑arm studies. The overall incidence of infections was 31% (bacterial 19%, viral 10%, unknown 6%, and fungal 1%). [See Warnings and Precautions (5.4), (5.5), (5.6).]

In randomized, controlled studies where Rituxan was administered following chemotherapy for the treatment of follicular or low‑grade NHL, the rate of infection was higher among patients who received Rituxan. In diffuse large B‑cell lymphoma patients, viral infections occurred more frequently in those who received Rituxan.

Cytopenias and hypogammaglobulinemia

In patients with NHL receiving rituximab monotherapy, NCI‑CTC Grade 3 and 4 cytopenias were reported in 48% of patients. These included lymphopenia (40%), neutropenia (6%), leukopenia (4%), anemia (3%), and thrombocytopenia (2%). The median duration of lymphopenia was 14 days (range, 1–588 days) and of neutropenia was 13 days (range, 2–116 days). A single occurrence of transient aplastic anemia (pure red cell aplasia) and two occurrences of hemolytic anemia following Rituxan therapy occurred during the single‑arm studies.

In studies of monotherapy, Rituxan‑induced B‑cell depletion occurred in 70% to 80% of patients with NHL. Decreased IgM and IgG serum levels occurred in 14% of these patients.

Relapsed or Refractory, Low-Grade NHL

Adverse reactions in Table 1 occurred in 356 patients with relapsed or refractory, low‑grade or follicular, CD20‑positive, B‑cell NHL treated in single‑arm studies of Rituxan administered as a single agent [see Clinical Studies (14.1)]. Most patients received Rituxan 375 mg/m2 weekly for 4 doses.

Table 1: Incidence of Adverse Reactions in ≥ 5% of Patients with Relapsed or Refractory, Low‑Grade or Follicular NHL, Receiving Single‑agent Rituxan (N=356)a,b

	All Grades (%)	Grade 3 and 4 (%)
a Adverse reactions observed up to 12 months following Rituxan. b Adverse reactions graded for severity by NCI‑CTC criteria.
Any Adverse Reactions	99	57
Body as a Whole	86	10
Fever	53	1
Chills	33	3
Infection	31	4
Asthenia	26	1
Headache	19	1
Abdominal Pain	14	1
Pain	12	1
Back Pain	10	1
Throat Irritation	9	0
Flushing	5	0
Heme and Lymphatic System	67	48
Lymphopenia	48	40
Leukopenia	14	4
Neutropenia	14	6
Thrombocytopenia	12	2
Anemia	8	3
Skin and Appendages	44	2
Night Sweats	15	1
Rash	15	1
Pruritus	14	1
Urticaria	8	1
Respiratory System	38	4
Increased Cough	13	1
Rhinitis	12	1
Bronchospasm	8	1
Dyspnea	7	1
Sinusitis	6	0
Metabolic and Nutritional Disorders	38	3
Angioedema	11	1
Hyperglycemia	9	1
Peripheral Edema	8	0
LDH Increase	7	0
Digestive System	37	2
Nausea	23	1
Diarrhea	10	1
Vomiting	10	1
Nervous System	32	1
Dizziness	10	1
Anxiety	5	1
Musculoskeletal System	26	3
Myalgia	10	1
Arthralgia	10	1
Cardiovascular System	25	3
Hypotension	10	1
Hypertension	6	1

In these single‑arm Rituxan studies, bronchiolitis obliterans occurred during and up to 6 months after Rituxan infusion.

Previously Untreated, Low-Grade or Follicular, NHL

In Study 4, patients in the R‑CVP arm experienced a higher incidence of infusional toxicity and neutropenia compared to patients in the CVP arm. The following adverse reactions occurred more frequently ( ≥ 5%) in patients receiving R‑CVP compared to CVP alone: rash (17% vs. 5%), cough (15% vs. 6%), flushing (14% vs. 3%), rigors (10% vs. 2%), pruritus (10% vs. 1%), neutropenia (8% vs. 3%), and chest tightness (7% vs. 1%). [See Clinical Studies (14.2).]

In Study 5, detailed safety data collection was limited to serious adverse reactions, Grade ≥ 2 infections, and Grade ≥ 3 adverse reactions. In patients receiving Rituxan as single-agent maintenance therapy following Rituxan plus chemotherapy, infections were reported more frequently compared to the observation arm (37% vs. 22%). Grade 3-4 adverse reactions occurring at a higher incidence (≥2%) in the Rituxan group were infections (4% vs. 1%) and neutropenia (4% vs. <1%).

In Study 6, the following adverse reactions were reported more frequently ( ≥ 5%) in patients receiving Rituxan following CVP compared to patients who received no further therapy: fatigue (39% vs. 14%), anemia (35% vs. 20%), peripheral sensory neuropathy (30% vs. 18%), infections (19% vs. 9%), pulmonary toxicity (18% vs. 10%), hepato‑biliary toxicity (17% vs. 7%), rash and/or pruritus (17% vs. 5%), arthralgia (12% vs. 3%), and weight gain (11% vs. 4%). Neutropenia was the only Grade 3 or 4 adverse reaction that occurred more frequently ( ≥ 2%) in the Rituxan arm compared with those who received no further therapy (4% vs. 1%). [See Clinical Studies (14.3).]

DLBCL

In Studies 7 and 8, [see Clinical Studies (14.3)], the following adverse reactions, regardless of severity, were reported more frequently ( ≥ 5%) in patients age ≥ 60 years receiving R‑CHOP as compared to CHOP alone: pyrexia (56% vs. 46%), lung disorder (31% vs. 24%), cardiac disorder (29% vs. 21%), and chills (13% vs. 4%). Detailed safety data collection in these studies was primarily limited to Grade 3 and 4 adverse reactions and serious adverse reactions.

In Study 8, a review of cardiac toxicity determined that supraventricular arrhythmias or tachycardia accounted for most of the difference in cardiac disorders (4.5% for R‑CHOP vs. 1.0% for CHOP).

The following Grade 3 or 4 adverse reactions occurred more frequently among patients in the R‑CHOP arm compared with those in the CHOP arm: thrombocytopenia (9% vs. 7%) and lung disorder (6% vs. 3%). Other Grade 3 or 4 adverse reactions occurring more frequently among patients receiving R‑CHOP were viral infection (Study 8), neutropenia (Studies 8 and 9), and anemia (Study 9).

CLL

The data below reflect exposure to Rituxan in combination with fludarabine and cyclophosphamide in 676 patients with CLL in Study 10 or Study 11 [see Clinical Studies (14.4)]. The age range was 30-83 years and 71% were men. Detailed safety data collection in Study 10 was limited to Grade 3 and 4 adverse reactions and serious adverse reactions.

Infusion-related adverse reactions were defined by any of the following adverse events occurring during or within 24 hours of the start of infusion: nausea, pyrexia, chills, hypotension, vomiting, and dyspnea.

In Study 10, the following Grade 3 and 4 adverse reactions occurred more frequently in R-FC-treated patients compared to FC-treated patients: infusion reactions (9% in R-FC arm), neutropenia (30% vs. 19%), febrile neutropenia (9% vs. 6%), leukopenia (23% vs. 12%), and pancytopenia (3% vs. 1%).

In Study 11, the following Grade 3 or 4 adverse reactions occurred more frequently in R-FC-treated patients compared to FC-treated patients: infusion reactions (7% in R-FC arm), neutropenia (49% vs. 44%), febrile neutropenia (15% vs. 12%), thrombocytopenia (11% vs. 9%), hypotension (2% vs. 0%), and hepatitis B (2% vs. < 1%). Fifty-nine percent of R-FC-treated patients experienced an infusion reaction of any severity.

   Clinical Trials Experience in Rheumatoid Arthritis

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in 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.

The data presented below reflect the experience in 2578 RA patients treated with Rituxan in controlled and long‑term studies with a total exposure of 5014 patient‑years.

Among all exposed patients, adverse reactions reported in greater than 10% of patients include infusion related reactions, upper respiratory tract infection, nasopharyngitis, urinary tract infection, and bronchitis.

In placebo‑controlled studies, patients received 2 x 500 mg or 2 x 1000 mg intravenous infusions of Rituxan or placebo, in combination with methotrexate, during a 24‑week period. From these studies, 938 patients treated with Rituxan (2 x 1000 mg) or placebo have been pooled (see Table 2). Adverse reactions reported in ≥ 5% of patients were hypertension, nausea, upper respiratory tract infection, arthralgia, pyrexia and pruritus (see Table 2). The rates and types of adverse reactions in patients who received Rituxan 2 x 500 mg were similar to those observed in patients who received Rituxan 2 x 1000 mg.

Table 2*: Incidence of All Adverse Reactions** Occurring in ≥ 2% and at Least 1% Greater than Placebo Among Rheumatoid Arthritis Patients in Clinical Studies Up to Week 24 (Pooled)

Preferred Term	Placebo + MTX N = 398 n (%)	Rituxan + MTX N = 540 n (%)
*These data are based on 938 patients treated in Phase 2 and 3 studies of Rituxan (2 × 1000 mg) or placebo administered in combination with methotrexate.
**Coded using MedDRA.
Hypertension	21 (5)	43 (8)
Nausea	19 (5)	41 (8)
Upper Respiratory Tract Infection	23 (6)	37 (7)
Arthralgia	14 (4)	31 (6)
Pyrexia	8 (2)	27 (5)
Pruritus	5 (1)	26 (5)
Chills	9 (2)	16 (3)
Dyspepsia	3 (<1)	16 (3)
Rhinitis	6 (2)	14 (3)
Paresthesia	3 (<1)	12 (2)
Urticaria	3 (<1)	12 (2)
Abdominal Pain Upper	4 (1)	11 (2)
Throat Irritation	0 (0)	11 (2)
Anxiety	5 (1)	9 (2)
Migraine	2 (<1)	9 (2)
Asthenia	1 (<1)	9 (2)

Infusion Reactions

In the Rituxan RA pooled placebo‑controlled studies, 32% of Rituxan‑treated patients experienced an adverse reaction during or within 24 hours following their first infusion, compared to 23% of placebo‑treated patients receiving their first infusion. The incidence of adverse reactions during the 24‑hour period following the second infusion, Rituxan or placebo, decreased to 11% and 13%, respectively. Acute infusion reactions (manifested by fever, chills, rigors, pruritus, urticaria/rash, angioedema, sneezing, throat irritation, cough, and/or bronchospasm, with or without associated hypotension or hypertension) were experienced by 27% of Rituxan‑treated patients following their first infusion, compared to 19% of placebo‑treated patients receiving their first placebo infusion. The incidence of these acute infusion reactions following the second infusion of Rituxan or placebo decreased to 9% and 11%, respectively. Serious acute infusion reactions were experienced by < 1% of patients in either treatment group. Acute infusion reactions required dose modification (stopping, slowing, or interruption of the infusion) in 10% and 2% of patients receiving rituximab or placebo, respectively,

AHD Iodine

AHD Iodine may be available in the countries listed below.

In some countries, this medicine may only be approved for veterinary use.

Ingredient matches for AHD Iodine

Povidone Iodine

Povidone-Iodine is reported as an ingredient of AHD Iodine in the following countries:

• New Zealand

International Drug Name Search

opium

OH-pee-um

Commonly used brand name(s)

In Canada

• Pantopon

Available Dosage Forms:

• Tincture

Therapeutic Class: Analgesic

Chemical Class: Opium (class)

Uses For opium

Opium tincture is used to treat diarrhea. opium belongs to the group of medicines called narcotics.

When a narcotic is used for a long time, it may become habit-forming, causing mental or physical dependence. Physical dependence may lead to withdrawal side effects if treatment is stopped suddenly. However, severe withdrawal side effects can usually be prevented by gradually reducing the dose over a period of time before treatment is stopped completely.

opium is available only with your doctor's prescription.

Before Using opium

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 opium, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to opium 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 opium tincture in the pediatric population. Use in children is not recommended.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of opium tincture in the elderly. However, elderly patients are more likely to have age-related liver, lung, or breathing problems which may require caution for patients receiving opium tincture.

Pregnancy

	Pregnancy Category	Explanation
All Trimesters	C	Animal studies have shown an adverse effect and there are no adequate studies in pregnant women OR no animal studies have been conducted and there are no adequate studies in pregnant women.

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 opium, 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 opium 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.

• Alfentanil


• Anileridine


• Codeine


• Fentanyl


• Hydrocodone


• Hydromorphone


• Levorphanol


• Meperidine


• Morphine


• Morphine Sulfate Liposome


• Opium


• Oxycodone


• Oxymorphone


• Propoxyphene


• Remifentanil


• Sufentanil

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 opium. Make sure you tell your doctor if you have any other medical problems, especially:

• Alcohol abuse, history of or


• Brain disease (e.g., cerebral arteriosclerosis) or


• Breathing problems (e.g., asthma, emphysema) or


• Drug dependence, especially narcotic abuse or dependence, or history of or


• Head injuries or


• Increased pressure in your head or


• Liver disease (e.g., cirrhosis) or


• Stomach or bowel bleeding or


• Underactive thyroid—Use with caution. May increase risk for more serious side effects.

• Diarrhea caused by poisoning—Should not be used in patients with this condition.

Proper Use of opium

Take opium only as directed by your doctor. Do not take more of it, do not take it more often, and do not take it for a longer time than your doctor ordered. This is especially important for young children and for elderly patients, who are especially sensitive to the effects of opium preparations. If too much is taken, opium may become habit-forming (causing mental or physical dependence) or lead to problems because of an overdose.

opium is to be taken by mouth even if it comes in a dropper bottle. The amount you should take is to be measured with the special dropper provided with your prescription and diluted with water just before you take each dose.

Dosing

The dose of opium 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 opium. 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 (tincture):
  
  • For diarrhea:
    
    • Adults—0.6 milliliters (mL) four times a day.
    
    
    • Children—Use is not recommended.
    
    
  
  

Missed Dose

If you miss a dose of opium, 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.

Keep the bottle tightly closed after use.

Precautions While Using opium

It is very important that your doctor check your progress while you are taking opium. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it.

opium will add to the effects of alcohol and other CNS depressants (medicines that can make you drowsy or less alert). Some examples of CNS depressants are antihistamines or medicine for allergies or colds; sedatives, tranquilizers, or sleeping medicine; other prescription pain medicine or narcotics; medicine for seizures or barbiturates; muscle relaxants; or anesthetics, including some dental anesthetics. Check with your doctor before taking any of the other medicines listed above while you are using opium.

opium may be habit-forming. If you feel that the medicine is not working as well, do not use more than your prescribed dose.

Do not change your dose or suddenly stop using opium without first checking with your doctor. Your doctor may want you to gradually reduce the amount you are using before stopping it completely. This may help prevent worsening of your condition and reduce the possibility of withdrawal symptoms, such as abdominal or stomach cramps, anxiety, fever, nausea, runny nose, sweating, tremors, or trouble with sleeping.

opium 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:

Incidence not known

• Difficulty having a bowel movement (stool)


• hives or welts


• nausea


• vomiting

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

Symptoms of overdose

• Anxiety


• blurred vision


• blue lips and fingernails


• chest pain or discomfort


• chills


• cold sweats


• coma


• confusion


• constricted, pinpoint, or small pupils (black part of eye)


• cool, clammy skin


• coughing that sometimes produces a pink frothy sputum


• depression


• difficult, fast, or noisy breathing, sometimes with wheezing


• difficult or troubled breathing


• difficulty sleeping


• disorientation


• dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly


• drowsiness to profound coma


• fast heartbeat


• hallucination


• headache


• increased hunger


• increased sweating


• irregular, fast or slow, or shallow breathing


• lethargy


• lightheadedness


• mood or other mental changes


• nervousness


• nightmares


• no blood pressure or pulse


• no muscle tone or movement


• not breathing


• pale or blue lips, fingernails, or skin


• seizures


• shakiness


• shortness of breath


• slow or irregular heartbeat


• slurred speech


• stopping of heart


• swelling in legs and ankles


• unconsciousness


• unusual tiredness or weakness

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:

Incidence not known

• Itching skin


• redness of skin


• skin rash

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: opium side effects (in more detail)

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More opium resources

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

• Opium Monograph (AHFS DI)


• Opium Tincture MedFacts Consumer Leaflet (Wolters Kluwer)


• Opium Deodorized Concise Consumer Information (Cerner Multum)


• Paregoric MedFacts Consumer Leaflet (Wolters Kluwer)

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