Wednesday, October 19, 2016

Meperidine Tablets



Pronunciation: me-PER-i-deen
Generic Name: Meperidine
Brand Name: Examples include Demerol and Meperitab


Meperidine is used for:

Short-term treatment of moderate to severe pain. It may also be used for other conditions as determined by your doctor.


Meperidine is a narcotic analgesic. It works in the brain and nervous system to decrease pain.


Do NOT use Meperidine if:


  • you are allergic to any ingredient in Meperidine

  • you have severely slow or difficult breathing

  • you have taken a monoamine oxidase inhibitor (MAOI) (eg, phenelzine) within the last 14 days

  • you are taking ritonavir, sibutramine, or sodium oxybate (GHB)

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



Before using Meperidine:


Some medical conditions may interact with Meperidine. 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 had an allergic reaction to any codeine- or morphine-related medicine (eg, hydrocodone, oxycodone, dihydrocodeine, hydromorphone)

  • if you have a history of lung or breathing problems (eg, asthma, chronic obstructive pulmonary disease [COPD], cor pulmonale); low levels of oxygen or high levels of carbon dioxide in the blood; sickle cell anemia; adrenal gland problems (eg, Addison disease, pheochromocytoma); curvature of the spine (scoliosis); thyroid problems; low blood pressure; an enlarged prostate; urinary blockage or trouble urinating; lung, liver, or kidney problems; heart problems (eg, fast or irregular heartbeat); seizures; or stomach or bowels problems (eg, inflammatory bowel disease)

  • if you have or have recently had any head injury, brain tumor or other growths, or increased pressure in the brain

  • if you drink alcohol; are going through withdrawal from alcohol or other substances; or have a history of alcohol or substance abuse or dependence, mental or mood problems, or suicidal thoughts or attempts

  • if you have severe diarrhea due to taking an antibiotic (pseudomembranous colitis), constipation, stomach pain, low blood volume, dehydration, drowsiness, or severe weakness, or have had recent surgery

Some MEDICINES MAY INTERACT with Meperidine. Tell your health care provider if you are taking any other medicines, especially any of the following:


  • Mixed narcotic agonist/antagonists (eg, butorphanol, pentazocine), naltrexone, or rifamycins (eg, rifampin) because they may decrease Meperidine's effectiveness

  • Furazolidone or MAOIs (eg, phenelzine) because the risk of serious side effects, including coma, difficulty breathing, low blood pressure, seizures, and irregular heartbeat, may be increased

  • Selective serotonin reuptake inhibitors (SSRIs) (eg, fluoxetine) or sibutramine because the risk of side effects, including increased body temperature, mental or mood changes, muscle twitching, or severe drowsiness, may be increased

  • Acyclovir, cimetidine, phenothiazines (eg, chlorpromazine), phenytoin, or ritonavir because they may increase the risk of Meperidine's side effects

  • Muscle relaxers (eg, cyclobenzaprine) or sodium oxybate (GHB) because their actions and the risk of their side effects may be increased by Meperidine

This may not be a complete list of all interactions that may occur. Ask your health care provider if Meperidine 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 Meperidine:


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


  • Take Meperidine by mouth with or without food.

  • Tell your doctor if you still experience pain or if your pain gets worse while taking Meperidine.

  • If Meperidine is no longer needed, dispose of the unused tablets by flushing them down the toilet.

  • If you miss a dose of Meperidine and you are taking it regularly, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

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



Important safety information:


  • Meperidine may cause drowsiness, dizziness, or light-headedness. These effects may be worse if you take it with alcohol or certain medicines. Use Meperidine with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.

  • Meperidine may cause dizziness, light-headedness, or fainting; alcohol, hot weather, exercise, or fever can increase these effects. To prevent them, sit up or stand slowly, especially in the morning. Sit or lie down at the first sign of any of these effects.

  • Check with your doctor before you drink alcohol or use medicines that may cause drowsiness (eg, sleep aids, muscle relaxers) while you are using Meperidine; it may add to their effects. Ask your pharmacist if you have questions about which medicines may cause drowsiness.

  • Meperidine may cause constipation. Talk with your doctor or pharmacist about using a stool softener or laxative to prevent constipation. It is also important to maintain a diet adequate in fiber, drink plenty or water, and exercise to prevent constipation. If you become constipated while taking Meperidine, talk with your doctor or pharmacist.

  • Do NOT take more than the recommended dose or use for longer than prescribed without checking with your doctor. Prolonged use of Meperidine may increase the risk of toxicity, including seizures.

  • Do not suddenly stop taking Meperidine without first checking with your doctor. If you have been taking Meperidine for more than a few weeks and your doctor tells you to stop taking it, your dose may need to be gradually lowered as directed by your doctor to avoid side effects.

  • Tell your doctor or dentist that you take Meperidine before you receive any medical or dental care, emergency care, or surgery.

  • Use Meperidine with caution in the ELDERLY; they may be more sensitive to its effects.

  • Use Meperidine with extreme caution in CHILDREN; they may be more sensitive to its effects, especially slowed or difficult breathing.

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

When used for long periods of time or at high doses, Meperidine may not work as well and may require higher doses to obtain the same effect as when originally taken. This is known as TOLERANCE. Talk with your doctor if Meperidine stops working well. Do not take more than prescribed.


When used for long periods of time or at high doses, some people develop a need to continue taking Meperidine. This is known as DEPENDENCE or addiction.


If you suddenly stop taking Meperidine, you may experience WITHDRAWAL symptoms, including anxiety; appetite loss; backache; chills; diarrhea; enlarged pupils; fast heartbeat or breathing rate; increased tears; irritability; muscle or joint pain; nausea; restlessness; runny nose; severe or persistent dizziness; sleeplessness; stomach cramps; sweating; vomiting; weakness; and yawning.



Possible side effects of Meperidine:


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; dizziness; drowsiness; flushing; light-headedness; loss of appetite; nausea; sweating; 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); chest pain; confusion; difficulty urinating; fainting; fast, slow, or irregular heartbeat; hallucinations; mental or mood changes; numbness of an arm or a leg; seizure; severe or persistent constipation or stomach pain; severe or persistent dizziness or light-headedness; slowed, shallow, or difficult breathing; sudden, severe headache, nausea, or vomiting; tremor; uncontrolled muscle movements; vision changes.



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: Meperidine 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. Symptoms may include chest pain; cold and clammy skin; fainting; limp muscles; loss of consciousness; low body temperature; seizures; severe dizziness or light-headedness; severe drowsiness; slowed heartbeat; slowed, shallow, or difficult breathing; small pupils.


Proper storage of Meperidine:

Store Meperidine at 77 degrees F (25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Meperidine out of the reach of children and away from pets.


General information:


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

  • Meperidine 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 Meperidine. 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 Meperidine resources


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


Compare Meperidine with other medications


  • Light Sedation
  • Pain

Micardis



Pronunciation: TEL-mi-SAR-tan
Generic Name: Telmisartan
Brand Name: Micardis

Micardis may cause injury or death to the fetus if taken after the third month of pregnancy. If you think you may be pregnant, contact your doctor right away.





Micardis is used for:

Treating high blood pressure alone or with other medicines. It is also used to reduce the risk of heart attack, stroke, or death due to heart problems in certain patients. It may also be used for other conditions as determined by your doctor.


Micardis is an angiotensin II receptor blocker (ARB). It works by relaxing blood vessels, which helps to lower blood pressure.


Do NOT use Micardis if:


  • you are allergic to any ingredient in Micardis

  • you are in your second or third trimester of pregnancy

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



Before using Micardis:


Some medical conditions may interact with Micardis. 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 are able to become pregnant

  • if you have a history of angioedema (eg, swelling of the hands, face, lips, eyes, throat, or tongue; difficulty swallowing or breathing; hoarseness), including angioedema caused by treatment with an angiotensin-converting enzyme (ACE) inhibitor (eg, lisinopril)

  • if you have a history of heart problems (eg, heart failure), blood vessel problems, blood flow problems, liver or kidney problems, or gallbladder problems

  • if you have a history of stroke or recent heart attack

  • if you are dehydrated or have low blood volume

  • if you have electrolyte problems (eg, high blood potassium levels, low blood sodium levels) or are on a low-salt (sodium) diet

  • if you have diabetes, especially if you are also taking aliskiren

  • if you are on dialysis or are scheduled to have major surgery

  • if you take another medicine for blood pressure or heart problems

Some MEDICINES MAY INTERACT with Micardis. Tell your health care provider if you are taking any other medicines, especially any of the following:


  • Diuretics (eg, furosemide, hydrochlorothiazide) because the risk of low blood pressure may be increased

  • Aliskiren, potassium-sparing diuretics (eg, spironolactone, triamterene), or potassium supplements because the risk of high blood potassium levels may be increased

  • ACE inhibitors (eg, lisinopril, ramipril) because the risk of kidney problems and high blood potassium levels may be increased

  • ACE inhibitors (eg, lisinopril, ramipril) because the risk of kidney problems may be increased

  • Nonsteroidal anti-inflammatory drugs (NSAIDs) (eg, celecoxib, indomethacin) because they may decrease Micardis's effectiveness

  • Digoxin or lithium because the risk of their side effects may be increased by Micardis

This may not be a complete list of all interactions that may occur. Ask your health care provider if Micardis 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 Micardis:


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


  • Take Micardis by mouth with or without food.

  • Do not remove the tablet from the blister seal until you are ready to take your dose.

  • Take Micardis on a regular schedule to get the most benefit from it. Taking Micardis at the same time each day will help you remember to take it.

  • Continue to take Micardis even if you feel well. Do not miss any doses.

  • If you miss a dose of Micardis, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

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



Important safety information:


  • Micardis may cause dizziness, lightheadedness, or fainting. These effects may be worse if you take it with alcohol or certain medicines. Use Micardis with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.

  • Micardis may cause dizziness, lightheadedness, or fainting; alcohol, hot weather, exercise, or fever may increase these effects. To prevent them, sit up or stand slowly, especially in the morning. Sit or lie down at the first sign of any of these effects.

  • Micardis may cause a serious side effect called angioedema. Contact your doctor at once if you develop swelling of the hands, face, lips, eyes, throat, or tongue; difficulty swallowing or breathing; or hoarseness.

  • Micardis may not work as well in black patients. Discuss any questions or concerns with your doctor.

  • Dehydration, excessive sweating, vomiting, or diarrhea may increase the risk of low blood pressure. Contact your health care provider at once if any of these occur.

  • Check with your doctor before you use a salt substitute or a product that has potassium in it.

  • Tell your doctor or dentist that you take Micardis before you receive any medical or dental care, emergency care, or surgery.

  • Patients who take medicine for high blood pressure often feel tired or run down for a few weeks after starting treatment. Be sure to take your medicine even if you may not feel "normal." Tell your doctor if you develop any new symptoms.

  • If you have high blood pressure, do not use nonprescription products that contain stimulants. These products may include diet pills or cold medicines. Contact your doctor if you have any questions or concerns.

  • Lab tests, including blood pressure, blood electrolyte levels, and heart, kidney, or liver function, may be performed while you use Micardis. These tests may be used to monitor your condition or check for side effects. Be sure to keep all doctor and lab appointments.

  • Micardis should be used with extreme caution in CHILDREN; safety and effectiveness in children have not been confirmed.

  • PREGNANCY and BREAST-FEEDING: Micardis may cause birth defects or fetal death if you take it while you are pregnant. If you think you may be pregnant, contact your doctor right away. It is not known if Micardis is found in breast milk. Do not breast-feed while taking Micardis.


Possible side effects of Micardis:


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:



Back pain; diarrhea; dizziness; sinus pain or congestion; sore throat; upper respiratory tract infection.



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; unusual hoarseness); change in the amount of urine produced or painful urination; chest pain; difficulty swallowing; fast, slow, or irregular heartbeat; fever, chills, or persistent sore throat; increased or excessive sweating; muscle pain or cramps; severe or persistent vomiting or diarrhea; severe or persistent weakness; shortness of breath; swelling of the arms or legs; symptoms of low blood pressure (eg, fainting, lightheadedness, severe dizziness); tendon or joint pain.



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: Micardis 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. Symptoms may include fast or slow heartbeat; severe dizziness.


Proper storage of Micardis:

Store Micardis at 77 degrees F (25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Micardis out of the reach of children and away from pets.


General information:


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

  • Micardis 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 Micardis. 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 Micardis resources


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


  • Micardis Prescribing Information (FDA)

  • Micardis Consumer Overview

  • Micardis Monograph (AHFS DI)

  • Micardis Advanced Consumer (Micromedex) - Includes Dosage Information

  • Telmisartan Professional Patient Advice (Wolters Kluwer)



Compare Micardis with other medications


  • Cardiovascular Risk Reduction
  • High Blood Pressure
  • Prevention of Cardiovascular Disease

Mepron


Generic Name: atovaquone (Oral route)

a-TOE-va-kwone

Commonly used brand name(s)

In the U.S.


  • Mepron

Available Dosage Forms:


  • Tablet

  • Suspension

Therapeutic Class: Antiprotozoal


Chemical Class: Ubiquinone


Uses For Mepron


Atovaquone is used to treat and to prevent Pneumocystis carinii pneumonia (PCP), a very serious kind of pneumonia. This particular kind of pneumonia occurs commonly in patients whose immune systems are not working normally, such as cancer patients, transplant patients, and patients with acquired immune deficiency syndrome (AIDS).


This medicine is available only with your doctor's prescription.


Before Using Mepron


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 this medicine, the following should be considered:


Allergies


Tell your doctor if you have ever had any unusual or allergic reaction to this medicine 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 atovaquone in children 1 month to 13 years of age. Safety and efficacy have not been established .


Geriatric


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


Pregnancy








Pregnancy CategoryExplanation
All TrimestersCAnimal 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 this medicine, 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 this medicine 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.


  • Rifampin

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


  • Indinavir

  • Rifabutin

  • Tetracycline

  • Warfarin

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


  • Liver disease, severe or

  • Stomach or intestinal disorders—Atovaquone may not work properly in patients with these conditions .

Proper Use of Mepron


Make certain your doctor knows if you are on any special diet. This medicine must be taken with balanced meals so that it can work properly.


It is important that you take atovaquone with a balanced meal. This is to make sure the medicine is fully absorbed into the body and will work properly.


Atovaquone tablets may be crushed if necessary to make it easier to swallow.


Because atovaquone tablets and oral suspension do not produce the same amount of medicine in the blood, the tablets and the suspension cannot be switched and used in place of each other.


For patients taking the oral liquid form of this medicine:


  • Shake the bottle gently before using atovaquone.

  • This medicine is to be taken by mouth. Use a specially marked measuring spoon or other device to measure each dose accurately. The average household teaspoon may not hold the right amount of liquid.

  • Do not use after the expiration date on the label since the medicine may not work properly after that date. Check with your pharmacist if you have any questions about this .

To help clear up your infection completely, keep taking your medicine for the full time of treatment, even if you begin to feel better after a few days. If you stop taking this medicine too soon, your symptoms may return.


Atovaquone works best when there is a constant amount in the blood. To help keep the amount constant, do not miss any doses.


Dosing


The dose of this medicine 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 this medicine. 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 prevention of Pneumocystis carinii pneumonia (PCP):
    • For oral dosage form (suspension):
      • Adults and teenagers—1,500 milligrams (mg) or 10 milliliters (mL) once a day with a meal.

      • Children—Use and dose must be determined by your doctor .



  • For treatment of Pneumocystis carinii pneumonia (PCP):
    • For oral dosage form (suspension):
      • Adults and teenagers—750 milligrams (mg) or 5 milliliters (mL) taken with a meal two times a day for 21 days.

      • Children—Use and dose must be determined by your doctor .


    • For oral dosage form (tablets):
      • Adults and teenagers—750 milligrams (mg) taken with a meal three times a day for 21 days.

      • Children—Use and dose must be determined by your doctor.



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.


Storage


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


Keep out of the reach of children.


Do not keep outdated medicine or medicine no longer needed.


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


Precautions While Using Mepron


It is very important that your doctor check your progress at regular visits to make sure that this medicine is working properly. Blood tests may be needed to check for unwanted effects .


If your symptoms do not improve within a few days, or if they become worse, check with your doctor.


Mepron 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
  • Cough or hoarseness

  • difficult or labored breathing

  • fever or chills

  • lower back or side pain

  • painful or difficult urination

  • shortness of breath

  • tightness in chest

  • wheezing

Incidence not known
  • Black, tarry stools

  • bleeding gums

  • bloating

  • blood in urine or stools

  • bluish-colored lips, fingernails, or palms

  • constipation

  • dark urine

  • dizziness or lightheadedness

  • fast heartbeat

  • headache

  • indigestion

  • large, hive-like swelling on face, eyelids, lips, tongue, throat, hands, legs, feet, or sex organs

  • light-colored stools

  • loss of appetite

  • nausea

  • noisy breathing

  • pains in stomach, side, or abdomen, possibly radiating to the back

  • pale skin

  • pinpoint red spots on skin

  • rapid heart rate

  • sore throat

  • unusual bleeding or bruising

  • unusual tiredness or weakness

  • vomiting

  • yellow eyes or skin

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 or stomach pain

  • diarrhea

  • lack or loss of strength

  • runny nose

  • skin rash

  • sleeplessness

  • sneezing

  • sore mouth or tongue

  • stuffy nose

  • sweating

  • trouble in sleeping

  • unable to sleep

  • white patches in mouth, tongue, or throat

Incidence not known
  • Blistering, peeling, or loosening of skin

  • eye irritation or redness

  • itching

  • joint or muscle pain

  • red skin lesions, often with a purple center

  • 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: Mepron side effects (in more detail)



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.


More Mepron resources


  • Mepron Side Effects (in more detail)
  • Mepron Use in Pregnancy & Breastfeeding
  • Drug Images
  • Mepron Drug Interactions
  • Mepron Support Group
  • 1 Review for Mepron - Add your own review/rating


  • Mepron Prescribing Information (FDA)

  • Mepron Concise Consumer Information (Cerner Multum)

  • Mepron Monograph (AHFS DI)

  • Mepron MedFacts Consumer Leaflet (Wolters Kluwer)

  • Atovaquone Professional Patient Advice (Wolters Kluwer)

  • Atovaquone and Proguanil Hydrochloride Monograph (AHFS DI)



Compare Mepron with other medications


  • Babesiosis
  • Malaria
  • Pneumocystis Pneumonia
  • Pneumocystis Pneumonia Prophylaxis
  • Toxoplasmosis

Tuesday, October 18, 2016

M2 Zinc 50


Generic Name: zinc supplement (Oral route, Parenteral route)


Commonly used brand name(s)

In the U.S.


  • Galzin

  • M2 Zinc 50

  • Orazinc 110

  • Orazinc 220

  • Zinc-220

  • Zinc Chelated

  • Zn Plus Protein

In Canada


  • Prostavan

Available Dosage Forms:


  • Tablet

  • Capsule

  • Tablet, Extended Release

Uses For M2 Zinc 50


Zinc supplements are used to prevent or treat zinc deficiency.


The body needs zinc for normal growth and health. For patients who are unable to get enough zinc in their regular diet or who have a need for more zinc, zinc supplements may be necessary. They are generally taken by mouth but some patients may have to receive them by injection.


Zinc supplements may be used for other conditions as determined by your health care professional.


Lack of zinc may lead to poor night vision and wound-healing, a decrease in sense of taste and smell, a reduced ability to fight infections, and poor development of reproductive organs.


  • Acrodermatitis enteropathica (a lack of absorption of zinc from the intestine)

  • Alcoholism

  • Burns

  • Type 2 diabetes mellitus

  • Down's syndrome

  • Eating disorders

  • Intestine diseases

  • Infections (continuing or chronic)

  • Kidney disease

  • Liver disease

  • Pancreas disease

  • Sickle cell disease

  • Skin disorders

  • Stomach removal

  • Stress (continuing)

  • Thalassemia

  • Trauma (prolonged)

In addition, premature infants may need additional zinc.


Increased need for zinc should be determined by your health care professional.


Claims that zinc is effective in preventing vision loss in the elderly have not been proven. Zinc has not been proven effective in the treatment of porphyria.


Injectable zinc is given by or under the supervision of a health care professional. Other forms of zinc are available without a prescription.


Once a medicine or dietary supplement has been approved for marketing for a certain use, experience may show that it is also useful for other medical problems. Although this use is not included in product labeling, zinc supplements are used in certain patients with the following medical condition:


  • Wilson's disease (a disease of too much copper in the body)

Importance of Diet


For good health, it is important that you eat a balanced and varied diet. Follow carefully any diet program your health care professional may recommend. For your specific dietary vitamin and/or mineral needs, ask your health care professional for a list of appropriate foods. If you think that you are not getting enough vitamins and/or minerals in your diet, you may choose to take a dietary supplement.


Zinc is found in various foods, including lean red meats, seafood (especially herring and oysters), peas, and beans. Zinc is also found in whole grains; however, large amounts of whole-grains have been found to decrease the amount of zinc that is absorbed. Additional zinc may be added to the diet through treated (galvanized) cookware. Foods stored in uncoated tin cans may cause less zinc to be available for absorption from food.


The daily amount of zinc needed is defined in several different ways.


  • For U.S.—

  • Recommended Dietary Allowances (RDAs) are the amount of vitamins and minerals needed to provide for adequate nutrition in most healthy persons. RDAs for a given nutrient may vary depending on a person's age, sex, and physical condition (e.g., pregnancy).

  • Daily Values (DVs) are used on food and dietary supplement labels to indicate the percent of the recommended daily amount of each nutrient that a serving provides. DV replaces the previous designation of United States Recommended Daily Allowances (USRDAs).

  • For Canada—

  • Recommended Nutrient Intakes (RNIs) are used to determine the amounts of vitamins, minerals, and protein needed to provide adequate nutrition and lessen the risk of chronic disease.

Normal daily recommended intakes in milligrams (mg) for zinc are generally defined as follows:


























PersonsU.S. (mg)Canada (mg)
Infants and children birth to

3 years of age
5–102–4
Children 4 to 6 years of age105
Children 7 to 10 years of age107–9
Adolescent and adult males159–12
Adolescent and adult females129
Pregnant females1515
Breast-feeding females16–1915

Before Using M2 Zinc 50


If you are taking a dietary supplement without a prescription, carefully read and follow any precautions on the label. For these supplements, 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


Problems in children have not been reported with intake of normal daily recommended amounts.


Geriatric


Problems in older adults have not been reported with intake of normal daily recommended amounts. There is some evidence that the elderly may be at risk of becoming deficient in zinc due to poor food selection, decreased absorption of zinc by the body, or medicines that decrease absorption of zinc or increase loss of zinc from the body.


Pregnancy


It is especially important that you are receiving enough vitamins and minerals when you become pregnant and that you continue to receive the right amount of vitamins and minerals throughout your pregnancy. The healthy growth and development of the fetus depend on a steady supply of nutrients from the mother. There is evidence that low blood levels of zinc may lead to problems in pregnancy or defects in the baby. However, taking large amounts of a dietary supplement in pregnancy may be harmful to the mother and/or fetus and should be avoided.


Breast Feeding


It is important that you receive the right amounts of vitamins and minerals so that your baby will also get the vitamins and minerals needed to grow properly. However, taking large amounts of a dietary supplement while breast-feeding may be harmful to the mother and/or baby and should be avoided.


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 dietary supplements, 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 dietary supplements 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.


  • Amygdalin

  • Deferoxamine

  • Eltrombopag

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


  • Copper deficiency—Zinc supplements may make this condition worse.

Proper Use of zinc supplement

This section provides information on the proper use of a number of products that contain zinc supplement. It may not be specific to M2 Zinc 50. Please read with care.


Zinc supplements are most effective if they are taken at least 1 hour before or 2 hours after meals. However, if zinc supplements cause stomach upset, they may be taken with a meal. You should tell your health care professional if you are taking your zinc supplement with meals.


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 oral dosage forms (capsules, lozenges, tablets, extended-release tablets):
    • To prevent deficiency, the amount taken by mouth is based on normal daily recommended intakes (Note that the normal daily recommended intakes are expressed as an actual amount of zinc. The dosage form [e.g., zinc gluconate, zinc sulfate] has a different strength):
      • For the U.S

      • Adult and teenage males—15 milligrams (mg) per day.

      • Adult and teenage females—12 mg per day.

      • Pregnant females—15 mg per day.

      • Breast-feeding females—16 to 19 mg per day.

      • Children 4 to 10 years of age—10 mg per day.

      • Children birth to 3 years of age—5 to 10 mg per day.

      • For Canada

      • Adult and teenage males—9 to 12 mg per day.

      • Adult and teenage females—9 mg per day.

      • Pregnant females—15 mg per day.

      • Breast-feeding females—15 mg per day.

      • Children 7 to 10 years of age—7 to 9 mg per day.

      • Children 4 to 6 years of age—5 mg per day.

      • Children birth to 3 years of age—2 to 4 mg per day.


    • To treat deficiency:
      • Adults, teenagers, and children—Treatment dose is determined by prescriber for each individual based on severity of deficiency.



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.


If you miss taking zinc supplements for one or more days there is no cause for concern, since it takes some time for your body to become seriously low in zinc. However, if your health care professional has recommended that you take zinc, try to remember to take it as directed every day.


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 M2 Zinc 50


When zinc combines with certain foods it may not be absorbed into your body and it will do you no good. If you are taking zinc, the following foods should be avoided or taken 2 hours after you take zinc:


  • Bran

  • Fiber-containing foods

  • Phosphorus-containing foods such as milk or poultry

  • Whole-grain breads and cereals

Do not take zinc supplements and copper, iron, or phosphorus supplements at the same time. It is best to space doses of these products 2 hours apart, to get the full benefit from each dietary supplement.


M2 Zinc 50 Side Effects


Along with its needed effects, a dietary supplement 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 as soon as possible if any of the following side effects occur:


Rare - With large doses
  • Chills

  • continuing ulcers or sores in mouth or throat

  • fever

  • heartburn

  • indigestion

  • nausea

  • sore throat

  • unusual tiredness or weakness

Symptoms of overdose
  • Chest pain

  • dizziness

  • fainting

  • shortness of breath

  • vomiting

  • yellow eyes or skin

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.

Maalox Quick Dissolve Maximum Strength



Generic Name: calcium carbonate (KAL see um KAR boe nate)

Brand Names: Alka-Mints, Cal-Gest, Calcarb, Calci Mix, Calci-Chew, Calci-Mix, Calcium Concentrate, Calcium Liquid Softgel, Calcium Oyster Shell, Caltrate, Chooz, Extra Strength Mylanta Calci Tabs, Icar Prenatal Chewable Calcium, Maalox Antacid Barrier, Maalox Childrens', Maalox Quick Dissolve, Maalox Quick Dissolve Maximum Strength, Maalox Regular Strength, Mylanta Child, Nephro Calci, Os-Cal 500, Oysco 500, Oyst Cal 500, Oyster Cal, Oyster Calcium, Oyster Shell, Pepto Children's, Rolaids Sodium Free, Rolaids Soft Chew, Titralac, Tums, Tums 500, Tums E-X, Tums Kids, Tums QuikPak, Tums Ultra


What is Maalox Quick Dissolve Maximum Strength (calcium carbonate)?

Calcium is a mineral that is found naturally in foods. Calcium is necessary for many normal functions of the body, especially bone formation and maintenance. Calcium can also bind to other minerals (such as phosphate) and aid in their removal from the body.


Calcium carbonate is used to prevent and to treat calcium deficiencies.


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


What is the most important information I should know about Maalox Quick Dissolve Maximum Strength (calcium carbonate)?


Do not take calcium carbonate or antacids that contain calcium without first asking your doctor if you also take other medicines. Calcium can make it harder for your body to absorb certain medicines. Calcium carbonate works best if you take it with food.

What should I discuss with my healthcare provider before taking Maalox Quick Dissolve Maximum Strength (calcium carbonate)?


To make sure you can safely take calcium carbonate, tell your doctor if you have any of these other conditions:



  • a history of kidney stones; or




  • a parathyroid gland disorder.




Talk to your doctor before taking calcium carbonate if you are pregnant. Talk to your doctor before taking calcium carbonate if you are breast-feeding a baby.

How should I take Maalox Quick Dissolve Maximum Strength (calcium carbonate)?


Use exactly as directed on the label, or as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended.


Calcium carbonate works best if you take it with food. Swallow the calcium carbonate tablet or capsule with a full glass of water.

The chewable tablet should be chewed before you swallow it.


Use the calcium carbonate powder as directed. Allow the powder to dissolve completely, then consume the mixture.


Shake the oral suspension (liquid) well just before you measure a dose. Measure the liquid with a special dose-measuring spoon or medicine cup, not with a regular table spoon. If you do not have a dose-measuring device, ask your pharmacist for one. Store at room temperature away from moisture and heat.

What happens if I miss a dose?


Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.


What happens if I overdose?


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

Overdose symptoms may include nausea, vomiting, decreased appetite, constipation, confusion, delirium, stupor, and coma.


What should I avoid while taking Maalox Quick Dissolve Maximum Strength (calcium carbonate)?


Follow your healthcare provider's instructions about any restrictions on food, beverages, or activity.


Maalox Quick Dissolve Maximum Strength (calcium carbonate) side effects


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.

Less serious side effects may include:



  • nausea or vomiting;




  • decreased appetite;




  • constipation;




  • dry mouth or increased thirst; or




  • urinating more than usual.



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.


What other drugs can affect Maalox Quick Dissolve Maximum Strength (calcium carbonate)?


Calcium carbonate can make it harder for your body to absorb other medications you take by mouth. Tell your doctor if you are taking:



  • digoxin (Lanoxin, Lanoxicaps);




  • antacids or other calcium supplements;




  • calcitriol (Rocaltrol) or vitamin D supplements; or




  • doxycycline (Adoxa, Doryx, Oracea, Vibramycin), minocycline (Dynacin, Minocin, Solodyn, Vectrin), or tetracycline (Brodspec, Panmycin, Sumycin, Tetracap).



This list is not complete and other drugs may interact with calcium carbonate. 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 Maalox Quick Dissolve Maximum Strength resources


  • Maalox Quick Dissolve Maximum Strength Side Effects (in more detail)
  • Maalox Quick Dissolve Maximum Strength Use in Pregnancy & Breastfeeding
  • Drug Images
  • Maalox Quick Dissolve Maximum Strength Drug Interactions
  • Maalox Quick Dissolve Maximum Strength Support Group
  • 4 Reviews for Maalox Quick Dissolve Maximum Strength - Add your own review/rating


  • Calcium Carbonate MedFacts Consumer Leaflet (Wolters Kluwer)

  • Titralac Consumer Overview

  • Titralac MedFacts Consumer Leaflet (Wolters Kluwer)

  • Tums Chewable Tablets MedFacts Consumer Leaflet (Wolters Kluwer)



Compare Maalox Quick Dissolve Maximum Strength with other medications


  • Duodenal Ulcer
  • Erosive Esophagitis
  • GERD
  • Hypocalcemia
  • Indigestion
  • Osteopenia
  • Osteoporosis
  • Stomach Ulcer


Where can I get more information?


  • Your doctor or pharmacist can provide more information about calcium carbonate.

See also: Maalox Quick Dissolve Maximum Strength side effects (in more detail)


Mitoxantrone Injection Concentrate





Dosage Form: injection, solution, concentrate
mitoXANTRONE Injection USP (concentrate)

Rx only


4680


4685


4686




Mitoxantrone injection USP (concentrate) should be administered under the supervision of a physician experienced in the use of cytotoxic chemotherapy agents.


Mitoxantrone injection USP (concentrate) should be given slowly into a freely flowing intravenous infusion. It must never be given subcutaneously, intramuscularly, or intra-arterially. Severe local tissue damage may occur if there is extravasation during administration (see ADVERSE REACTIONS, General, Cutaneous and DOSAGE AND ADMINISTRATION, Preparation and Administration Precautions).


NOT FOR INTRATHECAL USE. Severe injury with permanent sequelae can result from intrathecal administration (seeWARNINGS, General).


Except for the treatment of acute nonlymphocytic leukemia, mitoxantrone injection USP (concentrate) therapy generally should not be given to patients with baseline neutrophil counts of less than 1,500 cells/mm3. In order to monitor the occurrence of bone marrow suppression, primarily neutropenia, which may be severe and result in infection, it is recommended that frequent peripheral blood cell counts be performed on all patients receiving mitoxantrone injection USP (concentrate).


Cardiotoxicity


Congestive heart failure (CHF), potentially fatal, may occur either during therapy with mitoxantrone injection USP (concentrate) or months to years after termination of therapy. Cardiotoxicity risk increases with cumulative mitoxantrone dose and may occur whether or not cardiac risk factors are present. Presence or history of cardiovascular disease, radiotherapy to the mediastinal/pericardial area, previous therapy with other anthracyclines or anthracenediones, or use of other cardiotoxic drugs may increase this risk. In cancer patients, the risk of symptomatic CHF was estimated to be 2.6% for patients receiving up to a cumulative dose of 140 mg/m2. To mitigate the cardiotoxicity risk with mitoxantrone, prescribers should consider the following:


All Patients


 

- All patients should be assessed for cardiac signs and symptoms by history, physical examination, and ECG prior to start of mitoxantrone injection USP (concentrate) therapy.

 

- All patients should have baseline quantitative evaluation of left ventricular ejection fraction (LVEF) using appropriate methodology (ex. Echocardiogram, multi-gated radionuclide angiography (MUGA), MRI, etc.).

Multiple Sclerosis Patient


 

- MS patients with a baseline LVEF below the lower limit of normal should not be treated with mitoxantrone injection USP (concentrate).

 

- MS patients should be assessed for cardiac signs and symptoms by history, physical examination and ECG prior to each dose.

 

- MS patients should undergo quantitative reevaluation of LVEF prior to each dose using the same methodology that was used to assess baseline LVEF. Additional doses of mitoxantrone injection USP (concentrate) should not be administered to multiple sclerosis patients who have experienced either a drop in LVEF to below the lower limit of normal or a clinically significant reduction in LVEF during mitoxantrone injection USP (concentrate) therapy.

 

- MS patients should not receive a cumulative mitoxantrone dose greater than 140 mg/m2.

 

- MS patients should undergo yearly quantitative LVEF evaluation after stopping mitoxantrone to monitor for late occurring cardiotoxicity.

Secondary Leukemia


Mitoxantrone injection USP (concentrate) therapy in patients with MS and in patients with cancer increases the risk of developing secondary acute myeloid leukemia.


For additional information, see WARNINGSandDOSAGE AND ADMINISTRATION.



Mitoxantrone Injection Concentrate Description

Mitoxantrone injection USP (concentrate) is a synthetic antineoplastic anthracenedione for intravenous use. It is supplied as a concentrate that MUST BE DILUTED PRIOR TO INJECTION. The concentrate is a sterile, nonpyrogenic, dark blue aqueous solution containing mitoxantrone hydrochloride USP equivalent to 2 mg/mL mitoxantrone free base, with sodium chloride (0.80% w/v), sodium acetate (0.005% w/v), and acetic acid (0.046% w/v) as inactive ingredients. The solution has a pH of 3 to 4.5 and contains 0.14 mEq of sodium per mL. The product does not contain preservatives. The chemical name is 1,4-dihydroxy-5,8-bis[[2-[(2-hydroxyethyl) amino]ethyl]amino]-9,10-anthracenedione dihydrochloride and the structural formula is:


C22H28N4O6•2HCl M.W. 517.41




Mitoxantrone Injection Concentrate - Clinical Pharmacology



Mechanism of Action


Mitoxantrone, a DNA-reactive agent that intercalates into deoxyribonucleic acid (DNA) through hydrogen bonding, causes crosslinks and strand breaks. Mitoxantrone also interferes with ribonucleic acid (RNA) and is a potent inhibitor of topoisomerase II, an enzyme responsible for uncoiling and repairing damaged DNA. It has a cytocidal effect on both proliferating and nonproliferating cultured human cells, suggesting lack of cell cycle phase specificity.


Mitoxantrone injection (concentrate) has been shown in vitro to inhibit B cell, T cell, and macrophage proliferation and impair antigen presentation, as well as the secretion of interferon gamma, TNFα, and IL-2.



Pharmacokinetics


Pharmacokinetics of mitoxantrone in patients following a single intravenous administration of mitoxantrone injection (concentrate) can be characterized by a three-compartment model. The mean alpha half-life of mitoxantrone is 6 to 12 minutes, the mean beta half-life is 1.1 to 3.1 hours and the mean gamma (terminal or elimination) half-life is 23 to 215 hours (median approximately 75 hours). Pharmacokinetic studies have not been performed in humans receiving multiple daily dosing. Distribution to tissues is extensive: steady-state volume of distribution exceeds 1,000 L/m2. Tissue concentrations of mitoxantrone appear to exceed those in the blood during the terminal elimination phase. In the healthy monkey, distribution to brain, spinal cord, eye, and spinal fluid is low.


In patients administered 15 to 90 mg/m2 of mitoxantrone intravenously, there is a linear relationship between dose and the area under the concentration-time curve (AUC).


Mitoxantrone is 78% bound to plasma proteins in the observed concentration range of 26 to 455 ng/mL. This binding is independent of concentration and is not affected by the presence of phenytoin, doxorubicin, methotrexate, prednisone, prednisolone, heparin, or aspirin.



Metabolism and Elimination


Mitoxantrone is excreted in urine and feces as either unchanged drug or as inactive metabolites. In human studies, 11% and 25% of the dose were recovered in urine and feces, respectively, as either parent drug or metabolite during the 5-day period following drug administration. Of the material recovered in urine, 65% was unchanged drug. The remaining 35% was composed of monocarboxylic and dicarboxylic acid derivatives and their glucuronide conjugates. The pathways leading to the metabolism of mitoxantrone have not been elucidated.



Special Populations


Gender

The effect of gender on mitoxantrone pharmacokinetics is unknown.


Geriatric

In elderly patients with breast cancer, the systemic mitoxantrone clearance was 21.3 L/hr/m2, compared with 28.3 L/hr/m2 and 16.2 L/hr/m2 for non-elderly patients with nasopharyngeal carcinoma and malignant lymphoma, respectively.


Pediatric

Mitoxantrone pharmacokinetics in the pediatric population are unknown.


Race

The effect of race on mitoxantrone pharmacokinetics is unknown.


Renal Impairment

Mitoxantrone pharmacokinetics in patients with renal impairment are unknown.


Hepatic Impairment

Mitoxantrone clearance is reduced by hepatic impairment. Patients with severe hepatic dysfunction (bilirubin > 3.4 mg/dL) have an AUC more than three times greater than that of patients with normal hepatic function receiving the same dose. Patients with multiple sclerosis who have hepatic impairment should ordinarily not be treated with mitoxantrone. Other patients with hepatic impairment should be treated with caution and dosage adjustment may be required.



Drug Interactions


In vitro drug interaction studies have demonstrated that mitoxantrone did not inhibit CYP450 1A2, 2A6, 2C9, 2C19, 2D6, 2E1, and 3A4 across a broad concentration range. The results of in vitro induction studies are inconclusive, but suggest that mitoxantrone may be a weak inducer of CYP450 2E1 activity.


Pharmacokinetic studies of the interaction of mitoxantrone with concomitantly administered medications in humans have not been performed. The pathways leading to the metabolism of mitoxantrone have not been elucidated. To date, post-marketing experience has not revealed any significant drug interactions in patients who have received mitoxantrone for treatment of cancer. Information on drug interactions in patients with multiple sclerosis is limited.



Clinical Trials



Multiple Sclerosis


The safety and efficacy of mitoxantrone in multiple sclerosis were assessed in two randomized, multicenter clinical studies.


One randomized, controlled study (Study 1) was conducted in patients with secondary progressive or progressive relapsing multiple sclerosis. Patients in this study demonstrated significant neurological disability based on the Kurtzke Expanded Disability Status Scale (EDSS). The EDSS is an ordinal scale with 0.5 point increments ranging from 0 to 10 (increasing score indicates worsening) and based largely on ambulatory impairment in its middle range (EDSS 4.5 to 7.5 points). Patients in this study had experienced a mean deterioration in EDSS of about 1.6 points over the 18 months prior to enrollment.


Patients were randomized to receive placebo, 5 mg/m2 mitoxantrone, or 12 mg/m2 mitoxantrone administered IV every 3 months for 2 years. High-dose methylprednisolone was administered to treat relapses. The intent-to-treat analysis cohort consisted of 188 patients; 149 completed the 2-year study. Patients were evaluated every 3 months, and clinical outcome was determined after 24 months. In addition, a subset of patients was assessed with magnetic resonance imaging (MRI) at baseline, Month 12, and Month 24. Neurologic assessments and MRI reviews were performed by evaluators blinded to study drug and clinical outcome, although the diagnosis of relapse and the decision to treat relapses with steroids were made by unblinded treating physicians. A multivariate analysis of five clinical variables (EDSS, Ambulation Index [AI], number of relapses requiring treatment with steroids, months to first relapse needing treatment with steroids, and Standard Neurological Status [SNS]) was used to determine primary efficacy. The AI is an ordinal scale ranging from 0 to 9 in one point increments to define progressive ambulatory impairment. The SNS provides an overall measure of neurologic impairment and disability, with scores ranging from 0 (normal neurologic examination) to 99 (worst possible score).


Results of Study 1 are summarized in Table 1.




































































Table 1: Efficacy Results at Month 24 Study 1
Treatment Groupsp-value
Mitoxantrone



Primary Endpoints
Placebo

(N = 64)
5 mg/m2

(N = 64)
12 mg/m2

(N = 60)
Placebo vs. 12 mg/m2 Mitoxantrone
NR = not reached within 24 months; MRI = magnetic resonance imaging.

*

Wei-Lachin test.


Month 24 value minus baseline.


A subset of 110 patients was selected for MRI analysis. MRI results were not available for all patients at all time points.

Primary efficacy multivariate analysis*---< 0.0001
Primary clinical variables analyzed:
EDSS change (mean)0.23-0.23-0.130.0194
Ambulation Index change (mean)0.770.410.300.0306
Mean number of relapses per patient requiring corticosteroid treatment (adjusted for discontinuation)1.200.730.400.0002
Months to first relapse requiring corticosteroid treatment (median [1st quartile])14.2 [6.7]NR [6.9]NR [20.4]0.0004
Standard Neurological Status change (mean)0.77-0.38-1.070.0269
MRI
No. of patients with new GD-enhancing lesions5/32 (16%)4/37 (11%)0/310.022
Change in number of T2-weighted lesions, mean (n)1.94 (32)0.68 (34)0.29 (28)0.027

A second randomized, controlled study (Study 2) evaluated mitoxantrone in combination with methylprednisolone (MP) and was conducted in patients with secondary progressive or worsening relapsing-remitting multiple sclerosis who had residual neurological deficit between relapses. All patients had experienced at least two relapses with sequelae or neurological deterioration within the previous 12 months. The average deterioration in EDSS was 2.2 points during the previous 12 months. During the screening period, patients were treated with two monthly doses of 1 g of IV MP and underwent monthly MRI scans. Only patients who developed at least one new Gd-enhancing MRI lesion during the 2-month screening period were eligible for randomization. A total of 42 evaluable patients received monthly treatments of 1 g of IV MP alone (n = 21) or ~12 mg/m2 of IV mitoxantrone plus 1 g of IV MP (n = 21) (MIT + MP) for 6 months. Patients were evaluated monthly, and study outcome was determined after 6 months. The primary measure of effectiveness in this study was a comparison of the proportion of patients in each treatment group who developed no new Gd-enhancing MRI lesions at 6 months; these MRIs were assessed by a blinded panel. Additional outcomes were measured, including EDSS and number of relapses, but all clinical measures in this trial were assessed by an unblinded treating physician. Five patients, all in the MP alone arm, failed to complete the study due to lack of efficacy.


The results of this trial are displayed in Table 2.






























Table 2: Efficacy Results Study 2
Primary EndpointMP alone

(N = 21)
MIT + MP

(N = 21)
p-value
MP = Methylprednisolone; MIT + MP = Mitoxantrone plus Methylprednisolone.

*

Results at Month 6, not including data for 5 withdrawals in the MP alone group.

Patients (%) without new Gd-enhancing lesions on MRIs (primary endpoint)*5 (31%)19 (90%)0.001
Secondary Endpoints
EDSS change (Month 6 minus baseline)* (mean)-0.1-1.10.013
Annualized relapse rate (mean per patient)30.70.003
Patients (%) without relapses7 (33%)14 (67%)0.031

Advanced Hormone-Refractory Prostate Cancer


A multicenter Phase 2 trial of mitoxantrone and low-dose prednisone (M + P) was conducted in 27 symptomatic patients with hormone-refractory prostate cancer. Using NPCP (National Prostate Cancer Project) criteria for disease response, there was one partial responder and 12 patients with stable disease. However, nine patients or 33% achieved a palliative response defined on the basis of reduction in analgesic use or pain intensity.


These findings led to the initiation of a randomized multicenter trial (CCI-NOV22) comparing the effectiveness of (M + P) to low-dose prednisone alone (P). Eligible patients were required to have metastatic or locally advanced disease that had progressed on standard hormonal therapy, a castrate serum testosterone level, and at least mild pain at study entry. Mitoxantrone was administered at a dose of 12 mg/m2 by short IV infusion every 3 weeks. Prednisone was administered orally at a dose of 5 mg twice a day. Patients randomized to the prednisone arm were crossed over to the M + P arm if they progressed or if they were not improved after a minimum of 6 weeks of therapy with prednisone alone.


A total of 161 patients were randomized, 80 to the M + P arm and 81 to the P arm. The median mitoxantrone dose administered was 12 mg/m2 per cycle. The median cumulative mitoxantrone dose administered was 73 mg/m2 (range of 12 to 212 mg/m2).


A primary palliative response (defined as a 2-point decrease in pain intensity in a 6-point pain scale, associated with stable analgesic use, and lasting a minimum of 6 weeks) was achieved in 29% of patients randomized to M + P compared to 12% of patients randomized to P alone (p = 0.011). Two responders left the study after meeting primary response criterion for two consecutive cycles. For the purposes of this analysis, these two patients were assigned a response duration of zero days. A secondary palliative response was defined as a 50% or greater decrease in analgesic use, associated with stable pain intensity, and lasting a minimum of 6 weeks. An overall palliative response (defined as primary plus secondary responses) was achieved in 38% of patients randomized to M + P compared to 21% of patients randomized to P (p = 0.025).


The median duration of primary palliative response for patients randomized to M + P was 7.6 months compared to 2.1 months for patients randomized to P alone (p = 0.0009). The median duration of overall palliative response for patients randomized to M + P was 5.6 months compared to 1.9 months for patients randomized to P alone (p = 0.0004).


Time to progression was defined as a 1-point increase in pain intensity, or a > 25% increase in analgesic use, or evidence of disease progression on radiographic studies, or requirement for radiotherapy. The median time to progression for all patients randomized to M + P was 4.4 months compared to 2.3 months for all patients randomized to P alone (p = 0.0001). Median time to death was 11.3 months for all patients on the M + P arm compared to 10.8 months for all patients on P alone (p = 0.2324).


Forty-eight patients on the P arm crossed over to receive M + P. Of these, thirty patients had progressed on P, while 18 had stable disease on P. The median cycle of crossover was 5 cycles (range of 2 to 16 cycles). Time trends for pain intensity prior to crossover were significantly worse for patients who crossed over than for those who remained on P alone (p = 0.012). Nine patients (19%) demonstrated a palliative response on M + P after crossover. The median time to death for patients who crossed over to M + P was 12.7 months.


The clinical significance of a fall in prostate-specific antigen (PSA) concentrations after chemotherapy is unclear. On the CCI-NOV22 trial, a PSA fall of 50% or greater for two consecutive follow-up assessments after baseline was reported in 33% of all patients randomized to the M + P arm and 9% of all patients randomized to the P arm. These findings should be interpreted with caution since PSA responses were not defined prospectively. A number of patients were inevaluable for response, and there was an imbalance between treatment arms in the numbers of evaluable patients. In addition, PSA reduction did not correlate precisely with palliative response, the primary efficacy endpoint of this study. For example, among the 26 evaluable patients randomized to the M + P arm who had a ≥ 50% reduction in PSA, only 13 had a primary palliative response. Also, among 42 evaluable patients on this arm who did not have this reduction in PSA, 8 nonetheless had a primary palliative response.


Investigators at Cancer and Leukemia Group B (CALGB) conducted a Phase 3 comparative trial of mitoxantrone plus hydrocortisone (M + H) versus hydrocortisone alone (H) in patients with hormone-refractory prostate cancer (CALGB 9182). Eligible patients were required to have metastatic disease that had progressed despite at least one hormonal therapy. Progression at study entry was defined on the basis of progressive symptoms, increases in measurable or osseous disease, or rising PSA levels. Mitoxantrone was administered intravenously at a dose of 14 mg/m2 every 21 days and hydrocortisone was administered orally at a daily dose of 40 mg. A total of 242 subjects were randomized, 119 to the M + H arm and 123 to the H arm. There were no differences in survival between the two arms, with a median of 11.1 months in the M + H arm and 12 months in the H arm (p = 0.3298).


Using NPCP criteria for response, partial responses were achieved in 10 patients (8.4%) randomized to the M + H arm compared with 2 patients (1.6%) randomized to the H arm (p = 0.018). The median time to progression, defined by NPCP criteria, for patients randomized to the M + H arm was 7.3 months compared to 4.1 months for patients randomized to H alone (p = 0.0654).


Approximately 60% of patients on each arm required analgesics at baseline. Analgesic use was measured in this study using a 5-point scale. The best percent change from baseline in mean analgesic use was -17% for 61 patients with available data on the M + H arm, compared with +17% for 61 patients on H alone (p = 0.014). A time trend analysis for analgesic use in individual patients also showed a trend favoring the M + H arm over H alone but was not statistically significant.


Pain intensity was measured using the Symptom Distress Scale (SDS) Pain Item 2 (a 5-point scale). The best percent change from baseline in mean pain intensity was -14% for 37 patients with available data on the M + H arm, compared with +8% for 38 patients on H alone (p = 0.057). A time trend analysis for pain intensity in individual patients showed no difference between treatment arms.



Acute Nonlymphocytic Leukemia


In two large randomized multicenter trials, remission induction therapy for acute nonlymphocytic leukemia (ANLL) with mitoxantrone 12 mg/m2 daily for 3 days as a 10-minute intravenous infusion and cytarabine 100 mg/m2 for 7 days given as a continuous 24-hour infusion was compared with daunorubicin 45 mg/m2 daily by intravenous infusion for 3 days plus the same dose and schedule of cytarabine used with mitoxantrone. Patients who had an incomplete antileukemic response received a second induction course in which mitoxantrone or daunorubicin was administered for 2 days and cytarabine for 5 days using the same daily dosage schedule. Response rates and median survival information for both the U.S. and international multicenter trials are given in Table 3.






























Table 3: Response Rates, Time to Response, and Survival in U.S. and International Trials


Trial
% Complete

Response (CR)
Median Time

to CR (days)


Survival (days)
MIT = Mitoxantrone Injection USP (concentrate) + Cytarabine

DAUN = Daunorubicin + Cytarabine
MITDAUNMITDAUNMITDAUN
U.S.63 (62/98)53 (54/102)3542312237
International50 (56/112)51 (62/123)3642192230

In these studies, two consolidation courses were administered to complete responders on each arm. Consolidation therapy consisted of the same drug and daily dosage used for remission induction, but only 5 days of cytarabine and 2 days of mitoxantrone or daunorubicin were given. The first consolidation course was administered 6 weeks after the start of the final induction course if the patient achieved a complete remission. The second consolidation course was generally administered 4 weeks later. Full hematologic recovery was necessary for patients to receive consolidation therapy. For the U.S. trial, median granulocyte nadirs for patients receiving mitoxantrone + cytarabine for consolidation courses 1 and 2 were 10/mm3 for both courses, and for those patients receiving daunorubicin + cytarabine nadirs were 170/mm3 and 260/mm3, respectively. Median platelet nadirs for patients who received mitoxantrone + cytarabine for consolidation courses 1 and 2 were 17,000/mm3 and 14,000/mm3, respectively, and were 33,000/mm3 and 22,000/mm3 in courses 1 and 2 for those patients who received daunorubicin + cytarabine. The benefit of consolidation therapy in ANLL patients who achieve a complete remission remains controversial. However, in the only well-controlled prospective, randomized multicenter trials with mitoxantrone in ANLL, consolidation therapy was given to all patients who achieved a complete remission. During consolidation in the U.S. study, two myelosuppression-related deaths occurred on the mitoxantrone arm and one on the daunorubicin arm. However, in the international study there were eight deaths on the mitoxantrone arm during consolidation which were related to the myelosuppression and none on the daunorubicin arm where less myelosuppression occurred.



Indications and Usage for Mitoxantrone Injection Concentrate


Mitoxantrone injection USP (concentrate) is indicated for reducing neurologic disability and/or the frequency of clinical relapses in patients with secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis (i.e., patients whose neurologic status is significantly abnormal between relapses). Mitoxantrone injection USP (concentrare) is not indicated in the treatment of patients with primary progressive multiple sclerosis.


The clinical patterns of multiple sclerosis in the studies were characterized as follows: secondary progressive and progressive relapsing disease were characterized by gradual increasing disability with or without superimposed clinical relapses, and worsening relapsing-remitting disease was characterized by clinical relapses resulting in a step-wise worsening of disability.


Mitoxantrone injection USP (concentrate) in combination with corticosteroids is indicated as initial chemotherapy for the treatment of patients with pain related to advanced hormone-refractory prostate cancer.


Mitoxantrone injection USP (concentrate) in combination with other approved drug(s) is indicated in the initial therapy of acute nonlymphocytic leukemia (ANLL) in adults. This category includes myelogenous, promyelocytic, monocytic, and erythroid acute leukemias.



Contraindications


Mitoxantrone is contraindicated in patients who have demonstrated prior hypersensitivity to it.



Warnings


WHEN MITOXANTRONE IS USED IN HIGH DOSES (> 14 mg/m2/d × 3 days) SUCH AS INDICATED FOR THE TREATMENT OF LEUKEMIA, SEVERE MYELOSUPPRESSION WILL OCCUR. THEREFORE, IT IS RECOMMENDED THAT MITOXANTRONE BE ADMINISTERED ONLY BY PHYSICIANS EXPERIENCED IN THE CHEMOTHERAPY OF THIS DISEASE. LABORATORY AND SUPPORTIVE SERVICES MUST BE AVAILABLE FOR HEMATOLOGIC AND CHEMISTRY MONITORING AND ADJUNCTIVE THERAPIES, INCLUDING ANTIBIOTICS. BLOOD AND BLOOD PRODUCTS MUST BE AVAILABLE TO SUPPORT PATIENTS DURING THE EXPECTED PERIOD OF MEDULLARY HYPOPLASIA AND SEVERE MYELOSUPPRESSION. PARTICULAR CARE SHOULD BE GIVEN TO ASSURING FULL HEMATOLOGIC RECOVERY BEFORE UNDERTAKING CONSOLIDATION THERAPY (IF THIS TREATMENT IS USED) AND PATIENTS SHOULD BE MONITORED CLOSELY DURING THIS PHASE. MITOXANTRONE ADMINISTERED AT ANY DOSE CAN CAUSE MYELOSUPPRESSION.



General


Patients with preexisting myelosuppression as the result of prior drug therapy should not receive mitoxantrone unless it is felt that the possible benefit from such treatment warrants the risk of further medullary suppression.


The safety of mitoxantrone injection (concentrate) in patients with hepatic insufficiency is not established (see CLINICAL PHARMACOLOGY).


Safety for use by routes other than intravenous administration has not been established.


Mitoxantrone is not indicated for subcutaneous, intramuscular, or intra-arterial injection. There have been reports of local/regional neuropathy, some irreversible, following intra-arterial injection.


Mitoxantrone must not be given by intrathecal injection. There have been reports of neuropathy and neurotoxicity, both central and peripheral, following intrathecal injection. These reports have included seizures leading to coma and severe neurologic sequelae, and paralysis with bowel and bladder dysfunction.


Topoisomerase II inhibitors, including mitoxantrone, have been associated with the development of secondary acute myeloid leukemia and myelosuppression.



Cardiac Effects


Because of the possible danger of cardiac effects in patients previously treated with daunorubicin or doxorubicin, the benefit-to-risk ratio of mitoxantrone therapy in such patients should be determined before starting therapy.


Functional cardiac changes including decreases in left ventricular ejection fraction (LVEF) and irreversible congestive heart failure can occur with mitoxantrone. Cardiac toxicity may be more common in patients with prior treatment with anthracyclines, prior mediastinal radiotherapy, or with preexisting cardiovascular disease. Such patients should have regular cardiac monitoring of LVEF from the initiation of therapy. Cancer patients who received cumulative doses of 140 mg/m2 either alone or in combination with other chemotherapeutic agents had a cumulative 2.6% probability of clinical congestive heart failure. In comparative oncology trials, the overall cumulative probability rate of moderate or severe decreases in LVEF at this dose was 13%.


Multiple Sclerosis

Changes in cardiac function may occur in patients with multiple sclerosis treated with mitoxantrone. In one controlled trial (Study 1, see CLINICAL TRIALS, Multiple Sclerosis ), two patients (2%) of 127 receiving mitoxantrone, one receiving a 5 mg/m2 dose and the other receiving the 12 mg/m2 dose, had LVEF values that decreased to below 50%. An additional patient receiving 12 mg/m2, who did not have LVEF measured, had a decrease in another echocardiographic measurement of ventricular function (fractional shortening) that led to discontinuation from the trial (see ADVERSE REACTIONS, Multiple Sclerosis). There were no reports of congestive heart failure in either controlled trial.


MS patients should be assessed for cardiac signs and symptoms by history, physical examination, ECG, and quantitative LVEF evaluation using appropriate methodology (ex. Echocardiogram, MUGA, MRI, etc.) prior to the start of mitoxantrone therapy. MS patients with a baseline LVEF below the lower limit of normal should not be treated with mitoxantrone. Subsequent LVEF and ECG evaluations are recommended if signs or symptoms of congestive heart failure develop and prior to every dose administered to MS patients. Mitoxantrone should not be administered to MS patients who experience a reduction in LVEF to below the lower limit of normal, to those who experience a clinically significant reduction in LVEF, or to those who have received a cumulative lifetime dose of 140 mg/m2. MS patients should have yearly quantitative LVEF evaluation after stopping mitoxantrone to monitor for late-occurring cardiotoxicity.


Leukemia

Acute congestive heart failure may occasionally occur in patients treated with mitoxantrone for ANLL. In first-line comparative trials of mitoxantrone + cytarabine vs. daunorubicin + cytarabine in adult patients with previously untreated ANLL, therapy was associated with congestive heart failure in 6.5% of patients on each arm. A causal relationship between drug therapy and cardiac effects is difficult to establish in this setting since myocardial function is frequently depressed by the anemia, fever and infection, and hemorrhage that often accompany the underlying disease.


Hormone-Refractory Prostate Cancer

Functional cardiac changes such as decreases in LVEF and congestive heart failure may occur in patients with hormone-refractory prostate cancer treated with mitoxantrone. In a randomized comparative trial of mitoxantrone plus low-dose prednisone vs. low-dose prednisone, 7 of 128 patients (5.5 %) treated with mitoxantrone had a cardiac event defined as any decrease in LVEF below the normal range, congestive heart failure (n = 3), or myocardial ischemia. Two patients had a prior history of cardiac disease. The total mitoxantrone dose administered to patients with cardiac effects ranged from > 48 to 212 mg/m2.


Among 112 patients evaluable for safety on the mitoxantrone + hydrocortisone arm of the CALGB trial, 18 patients (19%) had a reduction in cardiac function, 5 patients (5%) had cardiac ischemia, and 2 patients (2%) experienced pulmonary edema. The range of total mitoxantrone doses administered to these patients is not available.



Pregnancy


Mitoxantrone may cause fetal harm when administered to a pregnant woman. Women of childbearing potential should be advised to avoid becoming pregnant. Mitoxantrone is considered a potential human teratogen because of its mechanism of action and the developmental effects demonstrated by related agents. Treatment of pregnant rats during the organogenesis period of gestation was associated with fetal growth retardation at doses ≥ 0.1 mg/kg/day (0.01 times the recommended human dose on a mg/m2 basis). When pregnant rabbits were treated during organogenesis, an increased incidence of premature delivery was observed at doses ≥ 0.1 mg/kg/day (0.01 times the recommended human dose on a mg/m2 basis). No teratogenic effects were observed in these studies, but the maximum doses tested were well below the recommended human dose (0.02 and 0.05 times in rats and rabbits, respectively, on a mg/m2 basis). There are no adequate and well-controlled studies in pregnant women. Women with multiple sclerosis who are biologically capable of becoming pregnant should have a pregnancy test prior to each dose, and the results should be known prior to administration of the drug. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential risk to the fetus.



Secondary Leukemia


Mitoxantrone injection (concentrate) therapy increases the risk of developing secondary leukemia in patients with cancer and in patients with multiple sclerosis.


In a study of patients with prostate cancer, acute myeloid leukemia occurred in 1% (5/487) of mitoxantrone-treated patients versus no cases in the control group (0/496) not receiving mitoxantrone at 4.7 years follow-up.


In a prospective, open-label, tolerability and safety monitoring study of mitoxantrone  treated MS patients followed for up to five years (median of 2.8 years), leukemia occurred in 0.6% (3/509) of patients. Publications describe leukemia risks of 0.25% to 2.8% in cohorts of patients with MS treated with mitoxantrone and followed for varying periods of time. This leukemia risk exceeds the risk of leukemia in the general population. The most commonly reported types were acute promyelocytic leukemia and acute myelocytic leukemia.


In 1774 patients with breast cancer who received mitoxantrone concomitantly with other cytotoxic agents and radiotherapy, the cumulative risk of developing treatment-related acute myeloid leukemia was estimated as 1.1% and 1.6% at 5 and 10 years, respectively. The second largest report involved 449 patients with breast cancer treated with mitoxantrone, usually in combination with radiotherapy and/or other cytotoxic agents. In this study, the cumulative probability of developing secondary leukemia was estimated to be 2.2% at 4 years.


Secondary acute myeloid leukemia has also been reported in cancer patients treated with anthracyclines. Mitoxantrone is an anthracenedione, a related drug. The occurrence of secondary leukemia is more common when anthracyclines are given in combination with DNA-damaging antineoplastic agents, when patients have been heavily pretreated with cytotoxic drugs, or when doses of anthracyclines have been escalated.


Symptoms of acute leukemia may include excessive bruising, bleeding, and recurrent infections.



Precautions



General


Therapy with mitoxantrone should be accompanied by close and frequent monitoring of hematologic and chemical laboratory parameters, as well as frequent patient observation.


Systemic infections should be treated concomitantly with or just prior to commencing therapy with mitoxantrone.



Information for Patients


Mitoxantrone may impart a blue-green color to the urine for 24 hours after administration, and patients should be advised to expect this during therapy. Bluish discoloration of the sclera may also occur. Patients should be advised of the signs and symptoms of myelosuppression.


Patients with multiple sclerosis should be provided with the Patient Package Insert at the time that the decision is made to treat with mitoxantrone and prior to and in close temporal proximity to each treatment. In addition, the physician should discuss the issues addressed in the Patient Package Insert with the patient.



Laboratory Tests


A complete blood count, including platelets, should be obtained prior to each course of mitoxantrone and in the event that signs and symptoms of infection develop. Liver function tests should also be performed prior to each course of therapy. Mitoxantrone therapy in multiple sclerosis patients with abnormal liver function tests is not recommended because mitoxantrone clearance is reduced by hepatic impairment and no laboratory measurement can predict drug clearance and dose adjustments.


In leukemia treatment, hyperuricemia may occur as a result of rapid lysis of tumor cells by mitoxantrone. Serum uric acid levels should be monitored and hypouricemic therapy instituted prior to the initiation of antileukemic therapy.


Women with multiple sclerosis who are biologically capable of becoming pregnant, even if they are using birth control, should have a pregnancy test, and the results should be known, before receiving each dose of mitoxantrone (see WARNINGS, Pregnancy).



Carcinogenesis, Mutagenesis, Impair